{"paper_id":"1e71f21b-a15e-4771-bd2c-46cff9748c8f","body_text":"Amsterdam UMC\nFresh versus frozen embryo transfers in assisted reproduction\nZaat, Tjitske; Zagers, Miriam; Mol, Femke; Goddijn, Mariëtte; van Wely, Madelon;\nMastenbroek, Sebastiaan\nPublished in:\nCochrane database of systematic reviews (Online)\nDOI:\n10.1002/14651858.CD011184.pub3\nPublished: 04/02/2021\nDocument Version\nPublisher's PDF, also known as Version of record\nDocument license\nCC BY\nLink to publication\nCitation for pulished version (APA):\nZaat, T., Zagers, M., Mol, F., Goddijn, M., van Wely, M., & Mastenbroek, S. (2021). Fresh versus frozen embryo\ntransfers in assisted reproduction. Cochrane database of systematic reviews (Online), 2021(2), CD011184.\nArticle CD011184. https://doi.org/10.1002/14651858.CD011184.pub3\nGeneral rights\nIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s),\nother than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).\nDisclaimer/Complaints regulations\nIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Amsterdam UMC\nMedical Library know, stating your reasons. In case of a legitimate complaint, the Medical Library will make the material inaccessible and/or\nremove it from the website. Contact address: outputregistratie@amsterdamumc.nl\nDownload date: 01. Aug. 2026\n\nCochrane\nLibrary\n/uni00A0\nCochrane Database of Systematic Reviews\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction\n(Review)\n/uni00A0\n/uni00A0Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S /uni00A0\n/uni00A0 Zaat/uni00A0T, Zagers/uni00A0M, Mol/uni00A0F, Goddijn/uni00A0M, van/uni00A0Wely/uni00A0M, Mastenbroek/uni00A0S. \nFresh versus frozen embryo transfers in assisted reproduction. \nCochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD011184. \nDOI: 10.1002/14651858.CD011184.pub3.\n/uni00A0\n/uni00A0 www.cochranelibrary.com /uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)/uni00A0\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nT A B L E /uni00A0 O F /uni00A0 C O N T E N T S\nABSTRACT..................................................................................................................................................................................................... 1\nPLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2\nSUMMARY OF FINDINGS .............................................................................................................................................................................. 4\nBACKGROUND.............................................................................................................................................................................................. 7\nOBJECTIVES.................................................................................................................................................................................................. 8\nMETHODS..................................................................................................................................................................................................... 8\nFigure 1.................................................................................................................................................................................................. 10\nRESULTS........................................................................................................................................................................................................ 12\nFigure 2.................................................................................................................................................................................................. 17\nFigure 3.................................................................................................................................................................................................. 18\nFigure 4.................................................................................................................................................................................................. 20\nFigure 5.................................................................................................................................................................................................. 21\nFigure 6.................................................................................................................................................................................................. 22\nFigure 7.................................................................................................................................................................................................. 23\nFigure 8.................................................................................................................................................................................................. 24\nFigure 9.................................................................................................................................................................................................. 25\nDISCUSSION.................................................................................................................................................................................................. 25\nAUTHORS' CONCLUSIONS........................................................................................................................................................................... 28\nACKNOWLEDGEMENTS................................................................................................................................................................................ 28\nREFERENCES................................................................................................................................................................................................ 29\nCHARACTERISTICS OF STUDIES.................................................................................................................................................................. 34\nDATA AND ANALYSES.................................................................................................................................................................................... 64\nAnalysis 1.1. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 1: Cumulative live birth rate..... 68\nAnalysis 1.2. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 2: Ovarian hyperstimulation\nsyndrome (OHSS)..................................................................................................................................................................................\n68\nAnalysis 1.3. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 3: Cumulative ongoing\npregnancy rate......................................................................................................................................................................................\n69\nAnalysis 1.4. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 4: Cumulative clinical\npregnancy rate......................................................................................................................................................................................\n69\nAnalysis 1.5. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 5: Ectopic pregnancy.............. 70\nAnalysis 1.6. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 6: Miscarriage.......................... 70\nAnalysis 1.7. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 7: Multiple pregnancy............. 71\nAnalysis 1.8. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 8: Gestational diabetes\nmellitus..................................................................................................................................................................................................\n71\nAnalysis 1.9. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 9: Hypertensive disorders of\npregnancy..............................................................................................................................................................................................\n72\nAnalysis 1.10. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 10: Preterm delivery (< 37\nweeks of gestational age).....................................................................................................................................................................\n72\nAnalysis 1.11. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 11: Perinatal and neonatal\ndeath......................................................................................................................................................................................................\n73\nAnalysis 1.12. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 12: Neonatal hospitalisation\n(> 3 days or neonatal intensive care unit admission).........................................................................................................................\n73\nAnalysis 1.13. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 13: Large for gestational age\n(birth weight > 90th percentile)...........................................................................................................................................................\n74\nAnalysis 1.14. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 14: Small for gestational age\n(birth weight < 10th percentile)...........................................................................................................................................................\n74\nAnalysis 1.15. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 15: Congenital abnormalities\nper live-born children...........................................................................................................................................................................\n75\nAnalysis 1.16. Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 16: Birth weight of babies\nborn........................................................................................................................................................................................................\n75\nAnalysis 2.1. Comparison 2: Freeze-all versus conventional IVF, adverse events per clinical pregnancy, Outcome 1: Multiple\npregnancy: a/f_ter first embryo transfer................................................................................................................................................\n76\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\ni\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 2.2. Comparison 2: Freeze-all versus conventional IVF, adverse events per clinical pregnancy, Outcome 2: Miscarriage:\na/f_ter first embryo transfer....................................................................................................................................................................\n76\nAnalysis 3.1. Comparison 3: Additional analysis: freeze-all versus conventional IVF, live birth rate a/f_ter first transfer, Outcome 1:\nAdditional analysis: live birth rate a/f_ter first transfer per randomised woman/uni00A0...............................................................................\n77\nADDITIONAL TABLES.................................................................................................................................................................................... 77\nAPPENDICES................................................................................................................................................................................................. 78\nWHAT'S NEW................................................................................................................................................................................................. 83\nHISTORY........................................................................................................................................................................................................ 83\nCONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 83\nDECLARATIONS OF INTEREST..................................................................................................................................................................... 83\nSOURCES OF SUPPORT............................................................................................................................................................................... 84\nDIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 84\nINDEX TERMS............................................................................................................................................................................................... 84\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\nii\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n[Intervention Review]\nFresh versus frozen embryo transfers in assisted reproduction\nTjitske Zaat1, Miriam Zagers1, Femke Mol1, Mariëtte Goddijn1, Madelon van Wely1, Sebastiaan Mastenbroek1\n1Amsterdam UMC, University of Amsterdam, Center for Reproductive Medicine, Amsterdam Reproduction & Development Research\nInstitute, Amsterdam, Netherlands\nContact: Tjitske Zaat, t.zaat@amsterdamumc.nl.\nEditorial group: Cochrane Gynaecology and Fertility Group.\nPublication status and date: New search for studies and content updated (no change to conclusions), published in Issue 2, 2021.\nCitation: Zaat/uni00A0T, Zagers/uni00A0M, Mol/uni00A0F, Goddijn/uni00A0M, van/uni00A0Wely/uni00A0M, Mastenbroek/uni00A0S. Fresh versus frozen embryo transfers in assisted reproduction.\nCochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD011184. DOI: 10.1002/14651858.CD011184.pub3.\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\nA B S T R A C T\nBackground\nIn vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments conventionally consist of a fresh embryo transfer, possibly\nfollowed by one or more cryopreserved embryo transfers in subsequent cycles. An alternative option is to freeze all suitable embryos\nand transfer cryopreserved embryos in subsequent cycles only, which is known as the 'freeze all' strategy. This is the first update of the\nCochrane Review on this comparison.\nObjectives\nTo evaluate the effectiveness and safety of the freeze all strategy compared to the conventional IVF/ICSI strategy in women undergoing\nassisted reproductive technology.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two\nregisters of ongoing trials from inception until 23 September/uni00A02020 for relevant studies, checked references of publications found, and\ncontacted study authors to obtain additional data.\nSelection criteria\nTwo review authors (TZ and MZ) independently selected studies for inclusion, assessed risk of bias, and extracted study data. We included\nrandomised controlled trials comparing a 'freeze all' strategy with a conventional IVF/ICSI strategy including a fresh embryo transfer in\nwomen undergoing IVF or ICSI treatment.\nData collection and analysis\nThe primary outcomes were cumulative live birth rate and ovarian hyperstimulation syndrome (OHSS). Secondary outcomes included\neffectiveness outcomes (including ongoing pregnancy rate and clinical pregnancy rate), time to pregnancy and obstetric, perinatal and\nneonatal outcomes.\nMain results\nWe included 15/uni00A0studies in the systematic review and eight/uni00A0studies with a total of 4712/uni00A0women in the meta-analysis. The overall evidence\nwas of moderate to low quality. We graded all the outcomes and downgraded due to serious risk of bias, serious imprecision and serious\nunexplained heterogeneity. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study during\nthe interim analysis, unit of analysis error, and absence of adequate study termination rules. There was an absence of high-quality evidence\naccording to GRADE assessments for our primary outcomes, which is reflected in the cautious language below.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n1\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nThere is probably little or no difference in cumulative live birth rate between the 'freeze all' strategy and the conventional IVF/ICSI strategy\n(odds ratio (OR) 1.08, 95% CI 0.95 to 1.22; I2 = 0%; 8/uni00A0RCTs, 4712 women; moderate-quality evidence). This suggests that for a cumulative\nlive birth rate of 58% following the conventional strategy, the cumulative live birth rate following the 'freeze all' strategy would be between\n57% and 63%.\nWomen might develop less OHSS a/f_ter the 'freeze all' strategy compared to the conventional IVF/ICSI strategy (OR 0.26, 95% CI 0.17/uni00A0to 0.39;\nI2 = 0%; 6/uni00A0RCTs, 4478 women; low-quality evidence). These data suggest that for an OHSS rate of 3% following the conventional strategy,\nthe rate following the 'freeze all' strategy would be 1%.\nThere is probably little or no difference between the two strategies in the cumulative ongoing pregnancy rate (OR 0.95, 95% CI 0.75 to 1.19;\nI2 = 31%; 4 RCTs, 1245 women; moderate-quality evidence).\nWe could not analyse time to pregnancy; by design, time to pregnancy is shorter in the conventional strategy than in the 'freeze all' strategy\nwhen the cumulative live birth rate is comparable, as embryo transfer is delayed in a 'freeze all' strategy. We are uncertain whether the\ntwo strategies differ in cumulative miscarriage rate because the evidence is very low quality (Peto OR 1.06, 95% CI 0.72 to 1.55; I2 = 55%; 2\nRCTs, 986 women; very low-quality evidence) and cumulative multiple-pregnancy rate (Peto OR 0.88, 95% CI 0.61 to 1.25; I2 = 63%; 2 RCTs,\n986 women; very low-quality evidence). The risk of hypertensive disorders of pregnancy (Peto OR 2.15, 95% CI 1.42 to 3.25; I2 = 29%; 3\nRCTs, 3940 women; low-quality evidence), having a large-for-gestational-age baby (Peto OR 1.96, 95% CI 1.51 to 2.55; I2 = 0%; 3 RCTs, 3940\nwomen; low-quality evidence) and a higher birth weight of the children born (mean difference (MD) 127 g, 95% CI 77.1 to 177.8; I2 = 0%; 5\nRCTs, 1607/uni00A0singletons; moderate-quality evidence) may be increased following the 'freeze all' strategy. We are uncertain whether the two\nstrategies differ in the risk of having a small-for-gestational-age baby because the evidence is low quality (Peto OR 0.82, 95% CI 0.65 to 1.05;\nI2 = 64%; 3 RCTs, 3940 women; low-quality evidence).\nAuthors' conclusions\nWe found moderate-quality evidence showing that one strategy is probably not superior to the other in terms of cumulative live birth rate\nand ongoing pregnancy rate. The risk of OHSS may be decreased in the 'freeze all' strategy. Based on the results of the included studies,\nwe could not analyse time to pregnancy. It is likely to be shorter using a conventional IVF/ICSI strategy with fresh embryo transfer in the\ncase of similar cumulative live birth rate, as embryo transfer is delayed in a 'freeze all' strategy. The risk of maternal hypertensive disorders\nof pregnancy, of having a large-for-gestational-age baby and a higher birth weight of the children born may be increased following the\n'freeze all' strategy. We are uncertain if 'freeze all' strategy reduces the risk of miscarriage, multiple pregnancy rate or having a small-for-\ngestational-age baby compared to conventional IVF/ICSI.\nP L A I N /uni00A0 L A N G U A G E /uni00A0 S U M M A R Y\nFresh versus frozen embryo transfers for assisted reproduction\nReview question\nIs a freeze-all strategy in IVF and ICSI treatments safe and effective in comparison to conventional IVF and ICSI treatment?\nBackground\nConventionally, in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments consist of a fresh embryo transfer directly\na/f_ter ovarian hyperstimulation, which is used in order to retrieve oocytes in the IVF/ICSI procedure. In the conventional IVF/ICSI treatment\nfresh embryo transfer is possibly followed by one or more frozen embryo transfers in subsequent cycles when enough embryos are\navailable. Alternatively, one can opt to 'freeze all' suitable embryos, and transfer frozen embryos in subsequent cycles only, which is also\nknown as the 'freeze all' strategy. In the \"freeze all\" strategy all embryos are frozen to be transferred at later time point when the ovaries\nare not stimulated. Therefore, this method could reduce the risk of ovarian hyperstimulation syndrome (OHSS, an overreaction to fertility\ndrugs) as OHSS is more severe when pregnancy occurs. Furthermore, studies have suggested that a woman's hormonal response to fertility\ndrugs could affect the lining of the womb making it difficult for an embryo to implant. Thus, it could be beneficial to freeze the embryos\nand transfer them later when the lining of the womb is not affected by fertility drugs.\nIn the past decade, an increasing number of clinics have applied the 'freeze all' strategy as a standard treatment strategy in their practice.\nIn practice, the 'freeze all' strategy and the conventional strategy can vary technically.\nWe compared the effectiveness and safety of these treatment strategies in women undergoing assisted reproductive technology.\nStudy characteristics\nWe examined all research published in the scientific literature up to 23 September 2020.\nWe included 15 randomised controlled trials (experiments where each person has an equal chance of being chosen to receive the treatment\nor a comparator) in the review. We were able to combine and analyse the results of eight trials, with a total of 4712 women.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n2\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nKey results\nThere is probably little or no difference in cumulative live birth rate and ongoing pregnancy rate between the 'freeze all' strategy and the\nconventional IVF/ICSI strategy. Our findings suggest that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy,\nthe rate following a 'freeze all' strategy would be between 57% and 63%. Not performing a fresh transfer, as is done in a freeze-all strategy,\nmight lower the OHSS risk for women at risk of OHSS. Our findings suggest that if the OHSS rate is 3% following a conventional IVF/ICSI\nstrategy, the rate following a 'freeze all' strategy would be 1%. We are uncertain whether the 'freeze all' strategy has any effect on the risk\nof miscarriage, multiple pregnancy rate, and time to pregnancy compared to conventional IVF/ICSI.\nWe also evaluated differences in risks for mother and child. The 'freeze all' strategy may increase the risk of hypertensive disorders of\npregnancy, the risk of having a large-for-gestational-age baby, and may result in a higher birth weight of the children born. Caution is\nneeded in drawing conclusions from this as the analysis is based on very low number of events.\nQuality of the evidence\nThe evidence was of moderate quality for cumulative live birth rate and low quality for safety outcomes. The low quality was generally due\nto serious imprecision in view of the relatively few/uni00A0events, serious unexplained heterogeneity, meaning that the results across trials varied\nwidely, and due to risk of bias within the included trials.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n3\n\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n4\nS U M M A R Y /uni00A0 O F /uni00A0 F I N D I N G S\n/uni00A0\nSummary of findings 1. /uni00A0 Fresh compared to frozen embryo transfer (cumulatively) in assisted reproduction\nFresh compared to frozen embryo transfer (cumulatively) in assisted reproduction\nPatient or population: women undergoing assisted reproduction\nSetting: assisted reproduction clinic\nIntervention: frozen embryo transfers only\nComparison: fresh and frozen embryo transfers (conventional IVF)\nAnticipated absolute effects* (95% CI)Outcomes\nRisk with fresh\nand frozen embryo\ntransfers\nRisk with frozen embryo\ntransfer only\nRelative effect\n(95% CI)\n/uni2116 of partici-\npants\n(studies)\nQuality of the evi-\ndence\n(GRADE)\nComments\nLive birth rate: cumula-\ntively\n579 per 1000 589/uni00A0per 1000\n(567/uni00A0to 627)\nOR 1.08\n(0.95 to 1.22)\n4712\n(8/uni00A0RCTs)\n⊕⊕⊕⊝\nModeratea\n/uni00A0\nOHSS: per cycle with ovar-\nian hyperstimulation\n33/uni00A0per 1000 9 per 1000\n(6 to 13)\nOR 0.26\n(0.17/uni00A0to 0.39)\n4478\n(6/uni00A0RCTs)\n⊕⊕⊝⊝\nLowa,b\n/uni00A0\nOngoing pregnancy rate:\ncumulatively\n508 per 1000 495 per 1000\n(436 to 551)\nOR 0.95\n(0.75 to 1.19)\n1245\n(4 RCTs)\n⊕⊕⊕⊝\nModeratea\n/uni00A0\nMiscarriage rate: cumula-\ntively\n118 per 1000 124 per 1000\n(88 to 171)\nOR 1.06\n(0.72 to 1.55)\n986\n(2 RCTs)\n⊕⊝⊝⊝\nVery lowa,b,c\n/uni00A0\nMultiple pregnancy rate:\ncumulatively\n156 per 1000 140 per 1000\n(101 to 188)\nOR 0.88\n(0.61 to 1.25)\n986\n(2 RCTs)\n⊕⊝⊝⊝\nVery lowa,b,c\n/uni00A0\nTime to pregnancy Outcome could not be analysed.\nBy design, time to pregnancy is shorter in the conventional strategy compared to the 'freeze all' strategy when the cumulative live birth rate is\ncomparable, as embryo transfer is delayed in a 'freeze all' strategy.\n*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and\nits 95% CI).\nCI: confidence interval; IVF: in vitro fertilisation; OHSS: ovarian hyperstimulation syndrome; OR: odds ratio; RCT: randomised controlled trial; RR: risk ratio\nGRADE Working Group grades of evidence\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n5\nHigh quality: further research is very unlikely to change our confidence in the estimate of effect.\nModerate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.\nLow quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.\nVery low quality: we are very uncertain about the estimate.\naDowngraded one level due to serious risk of bias associated with lack of power calculation (unclear what determined end of study) and/or use of interim analysis that was\ncalculated per transfer (unit of analysis error) with absence of adequate stopping rules (possible overestimation of treatment effect).\nbDowngraded one level due to serious imprecision: event rate less than 300.\ncDowngraded one level due to serious unexplained heterogeneity.\n/uni00A0\n/uni00A0\nSummary of findings 2. /uni00A0 Fresh compared to frozen embryo transfers in assisted reproduction regarding pregnancy and neonatal outcomes\nFresh compared to frozen embryo transfers in assisted reproduction regarding pregnancy and neonatal outcomes (cumulatively and after first embryo transfer)\nPatient or population: women undergoing assisted reproduction\nSetting: assisted reproduction clinic\nIntervention: frozen embryo transfers only\nComparison: fresh and frozen embryo transfers (conventional IVF)\nAnticipated absolute effects* (95% CI)Outcomes\nRisk with fresh\nand frozen em-\nbryo transfers\nRisk with frozen embryo\ntransfer only\nRelative effect\n(95% CI)\n/uni2116 of partici-\npants\n(studies)\nQuality of the\nevidence\n(GRADE)\nComments\nHypertensive disorders of pregnancy: cu-\nmulatively\n26 per 1000 18 per 1000\n(7 to 46)\nOR 0.70\n(0.27 to 1.82)\n782\n(1 RCT)\n⊕⊕⊝⊝\nLowa,b\n/uni00A0\nHypertensive disorders of pregnancy: after\nfirst ET\n15 per 1000 31 per 1000\n(21 to 46)\nOR 2.15\n(1.42 to 3.25)\n3940\n(3 RCTs)\n⊕⊕⊝⊝\nLowa,b\n/uni00A0\nLarge for gestational age (birth weight\nabove 90th percentile): cumulatively\n10 per 1000 20 per 1000\n(6 to 60)\nOR 1.97\n(0.63 to 6.15)\n782\n(1 RCT)\n⊕⊕⊝⊝\nLowa,b\n/uni00A0\nLarge for gestational age (birth weight\nabove 90th percentile): after first ET\n42 per 1000 79 per 1000\n(62 to 100)\nOR 1.96\n(1.51 to 2.55)\n3940\n(3 RCTs)\n⊕⊕⊝⊝\nLowa,b,c\n/uni00A0\nSmall for gestational age (birth weight be-\nlow 10th percentile): cumulatively\n46 per 1000 17 per 1000\n(8 to 37)\nOR 0.36\n(0.16 to 0.80)\n782\n(1 RCT)\n⊕⊕⊝⊝\nLowa,b\n/uni00A0\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n6\nSmall for gestational age (birth weight be-\nlow 10th percentile): after first ET\n82 per 1000 68 per 1000\n(55 to 86)\nOR 0.82\n(0.65 to 1.05)\n3940\n(3 RCTs)\n⊕⊝⊝⊝\nVery lowa,b,c\n/uni00A0\nBirth weight of babies born: singletons /uni00A0 MD 127.4 g higher\n(77.1 higher to 177.1 high-\ner)\n- 1607\n(5 RCTs)\n⊕⊕⊕⊝\nModeratea\n/uni00A0\nBirth weight of babies born: multiples /uni00A0 MD 49.5 g higher\n(21.1 lower to 120.1 high-\ner)\n- 804\n(4 RCTs)\n⊕⊕⊝⊝\nLowa,c\n/uni00A0\n*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and\nits 95% CI).\nCI: confidence interval; IVF: in vitro fertilisation; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial; RR: risk ratio\nGRADE Working Group grades of evidence\nHigh quality: further research is very unlikely to change our confidence in the estimate of effect.\nModerate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.\nLow quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.\nVery low quality: we are very uncertain about the estimate.\naDowngraded one level due to serious risk of bias associated with lack of power calculation (unclear what determined end of study) and/or use of interim analysis that was\ncalculated per transfer (unit of analysis error) with absence of adequate stopping rules (possible overestimation of treatment effect).\nbDowngraded one level due to serious imprecision: event rate: less than 300.\ncDowngraded one level due to serious unexplained heterogeneity.\n/uni00A0\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nB A C K G R O U N D\nDescription of the condition\nSubfertility is defined as the failure to conceive a/f_ter 12 months\nof regular unprotected intercourse (Van Voorhis 2007; Zegers-\nHochschild 2017 ). One in six couples experience subfertility at\nleast once during their reproductive lifetime, and approximately\n10% of couples worldwide are subfertile (CDC 2016 ; ESHRE\n2018). Common causes of infertility include poor semen quality,\nobstruction of the fallopian tubes or absence of ovulation (Hull\n1985). Poor semen quality can manifest itself as low sperm\nconcentration, as low as no sperm (azoospermia), low motility, or\nlow numbers of sperm with normal morphology. Fallopian tubes\ncan be blocked or damaged by infection, for example, chlamydia,\nor there can be adhesions of the tubes or ovaries caused by surgery,\ninfection or endometriosis. Couples who fail to conceive naturally\nare diagnosed as having unexplained infertility if no cause can\nbe found a/f_ter standard fertility tests. Numbers of couples with\nunexplained fertility have increased recently, which may be due\nto an increase in older women undergoing ART. Also genetic and\nenvironmental factors might play a role in unexplained infertility.\nDescription of the intervention\nAssisted reproductive technology (ART) has rapidly evolved as an\nintervention to improve pregnancy rates. It is now estimated that\nmore than 8 million babies have been born worldwide with assisted\nreproduction since the first ART baby was born in 1978 (ESHRE\n2018). ART involves the handling of gametes and embryos outside\nthe human body and consists of in vitro fertilisation (IVF) with or\nwithout intracytoplasmic sperm injection (ICSI). A/f_ter fertilisation,\nfresh transfer of the morphologically best embryo(s) into the\nuterine cavity is performed. Embryos suitable for transfer, but not\ntransferred fresh, are cryopreserved for future use. If a woman does\nnot get pregnant a/f_ter the fresh transfer or has a wish for a second\nchild the frozen embryo(s) can be thawed and transferred.\nIn some cases, pregnancy a/f_ter a fresh embryo transfer can lead to\novarian hyperstimulation syndrome (OHSS). OHSS is characterised\nby a fluid shi/f_t from blood vessels to the abdominal cavity,\nresulting in, for example, abdominal bloating, high risk of clots\nwithin the blood vessels (thrombosis) and decreased blood supply\nto important organs such as kidneys and liver. Severe OHSS is\npotentially life-threatening and can lead to lethal complications.\nThe development of OHSS is mainly an iatrogenic side effect\nof the high doses of gonadotropin used for ovarian stimulation,\nresulting in multi-follicular growth. Multiple follicles will in their\nturn produce vascular endothelial growth factor, which induces\nhyperpermeability of ovarian blood vessels, leading to a fluid shi/f_t\nfrom the intravascular to the third space. The administration of\nhuman chorionic gonadotrophin (hCG) can trigger OHSS. Moreover,\nthe extra hCG rise accompanying (multiple) pregnancy a/f_ter a fresh\nembryo transfer can aggravate already existing OHSS or induce\nlate-onset OHSS (Mourad 2017; Youssef 2016).\nIn order to reduce OHSS by avoiding fresh embryo transfer, in 2011\nDevroey and colleagues promoted the option to 'freeze all' suitable\nembryos a/f_ter IVF/ICSI treatment, and transfer cryopreserved\nembryos in subsequent cycles only, which is also known as the\n'freeze all' strategy (Devroey 2011).\nRecent technical improvements in cryopreservation have led\nto increased chances of embryo survival a/f_ter thawing and\nsubsequently increased pregnancy rates per cryopreserved\nembryo transfer (CDC 2016 ; ESHRE 2018 ; Wong 2014 ). In fact,\npregnancy rates a/f_ter cryopreserved embryo transfer are now\nalmost equal to pregnancy rates a/f_ter fresh transfer when\ncalculated per transfer. This has fuelled the idea that the 'freeze all'\nstrategy might increase the cumulative live birth rate. Therefore,\nthe 'freeze all' strategy has become a strategy that possibly\nincreases effectiveness in IVF/ICSI treatment, with safety not its\nonly objective (Devroey 2011; Griesinger 2011; Maheshwari 2013;\nMastenbroek 2011; Roque 2019).\nHow the intervention might work\nIn contrast to the conventional strategy, in a 'freeze all'\nstrategy there are no fresh embryo transfers in the cycle with\novarian stimulation with exogenous gonadotropins, but only\ncryopreserved embryo transfers in subsequent cycles without\novarian stimulation. This avoids possible adverse effects of ovarian\nstimulation on the endometrial environment.\nDuring ovarian stimulation for IVF/ICSI, the development of\nmultiple follicles leads to elevated oestradiol (Kosmas 2004), and\nprogesterone levels (Venetis 2013; Venetis 2015). This endocrine\nmilieu may reduce endometrial receptivity for the implanting\nembryo (Bourgain 2003; Kolibianakis 2002; Roque 2017; Fatemi\n2015; Venetis 2013; Venetis 2016). Studies on the molecular level\ncomparing stimulated with unstimulated endometrium samples\nhave shown distinct gene-expression profiles between the two\nconditions (Haouzi 2009 ; Van Vaerenbergh 2009; Fatemi 2015).\nTransfer of cryopreserved embryos only would thus circumvent a\npossible negative effect of gonadotropins on the endometrium in\nthe cycle with ovarian stimulation, and consequently increase live\nbirth rates, the main outcome of interest to subfertile couples.\nOvarian stimulation with exogenous gonadotropins in IVF increases\nthe risk of OHSS when a pregnancy occurs right a/f_ter the\novarian stimulation. Avoiding a pregnancy in the cycle with\novarian stimulation by only transferring cryopreserved embryos in\nsubsequent unstimulated cycles would eliminate or significantly\nreduce the risks of OHSS.\nIn order to evaluate the efficacy of the 'freeze all' strategy, we\nhave to compare the 'freeze all' cumulative live birth rate with the\nconventional IVF/ICSI strategy cumulative live birth rate. Currently,\nsome studies primarily compare live birth rate a/f_ter first transfer.\nThis possibly shows differences in outcome for a stimulated versus\nunstimulated uterus, although this does not take the number of\nembryos that were thawed for transfer into account. For women,\nthe live birth rate per first transfer is less relevant, since at the\nsame time of first transfer in a 'freeze all' strategy, they would\nalready have received the second transfer in a conventional IVF/ICSI\nstrategy. Considering the important perspective of time, it would\nonly be fair to compare cumulative live birth rate between groups\ninstead of live birth rate a/f_ter first transfer (Zaat 2019).\nWhy it is important to do this review\nAn increasing number of clinics apply the 'freeze all' strategy as a\nstandard treatment strategy in their practice (Pereira 2016; Pereira\n2019). Data from the Centers for Disease Control and Prevention\n(CDC) in the USA indicate that there has been a very steep rise of the\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n7\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n'freeze all' strategy from almost none of the cycles in 2007 to 25%\nof all IVF/ICSI cycles in 2016 (CDC 2016). Data from the European\nSociety of Human Reproduction and Embryology (ESHRE) from the\nEuropean IVF-monitoring Consortium, presented provisionally for\n2015 at last year's Annual Meeting, also revealed strong growth in\nthe number of 'freeze all' cycles (up 7% on the previous year), and\naccounting for 15% of all IVF cycles in 2015 (Focus on Reproduction\n2019). The Human Fertilisation & Embryology Authority (HFEA) of\nthe UK states that 'freeze all' cycles have increased by 39% since\n2014 (Focus on Reproduction 2019).\nHowever, despite its increasing use, the relative effectiveness and\nsafety of IVF treatment with the 'freeze all' strategy compared to\nthe conventional IVF/ICSI strategy is unclear. It is important to do\nthis review in order to evaluate the effectiveness and safety of the\n'freeze all' strategy compared to the conventional IVF/ICSI strategy\nincluding fresh embryo transfer in women undergoing ART.\nThe previous version of this Cochrane review included data from\n1892 women comparing a 'freeze all' strategy with a conventional\nIVF/ICSI strategy. Concerning effectiveness, moderate-quality\nevidence showed that one strategy is not superior to the other\nin terms of cumulative live birth rate. With respect to safety, low-\nquality evidence suggested that not performing a fresh transfer\nlowers the OHSS risk for women at risk of OHSS (Wong 2017).\nO B J E C T I V E S\nTo evaluate the effectiveness and safety of the 'freeze all'\nstrategy compared to the conventional IVF/ICSI strategy in women\nundergoing assisted reproductive technology.\nM E T H O D S\nCriteria for considering studies for this review\nTypes of studies\nWe included published RCTs comparing the 'freeze all' strategy\nwith the conventional IVF/ICSI strategy with fresh embryo transfer\nregardless of the context of the evaluation (OHSS or susceptibility\nof the endometrium). We excluded quasi- and pseudo-randomised\ncontrolled trials. We excluded trials published only as abstracts. We\nplanned to include cross-over trials for completeness, but would\nonly pool the data from the first phase in the meta-analysis (Vail\n2003).\nTypes of participants\nAll women undergoing IVF or ICSI irrespectively of the reason for\n'freeze all', the infertility factor, age, ethnicity, number of previous\nIVF cycles, type of stimulation protocol and type of embryo transfer\nprotocol.\nTypes of interventions\nTrials comparing the 'freeze all' strategy with transfer of\ncryopreserved embryos only versus the conventional IVF/ICSI\nstrategy with transfer of fresh and subsequent cryopreserved\nembryos until a live birth occurred or until all embryos from the\ninitial cycle were transferred.\nTypes of outcome measures\nPrimary outcomes\n1. Effectiveness: cumulative live birth rate per randomised woman.\nThat is, the rate of live birth following the transfer of all (fresh or\ncryopreserved) embryos within the time horizon of the follow-\nup defined by the authors of the original study\n2. Safety: OHSS per randomised woman\nSecondary outcomes\n1. Cumulative ongoing pregnancy rate, defined as the number of\nongoing pregnancies per woman randomised (demonstrated\nby the presence of a gestational sac with fetal heartbeat on\nultrasound at 10 to 12 weeks of gestation)\n2. Cumulative clinical pregnancy rate, defined as the cumulative\nnumber of clinical pregnancies per woman randomised\n(demonstrated by a pregnancy confirmed by ultrasonographic\nvisualisation of one or more gestational sacs)\n3. Time to pregnancy, defined as the time between randomisation\nand ongoing pregnancy\n4. Pregnancy outcomes and obstetric, perinatal and neonatal\noutcomes per woman.\na. Ectopic pregnancy, defined as a pregnancy in which\nimplantation takes place outside the uterine cavity\nb. Miscarriage rate, defined as the spontaneous demise of\na pregnancy before the fetus reaches viability. The term\ntherefore includes all pregnancy losses from the time of\nconception until 24 weeks of gestation\nc. Multiple pregnancy rate, defined as presence of more than\none sac at early pregnancy ultrasound six to eight weeks'\ngestation\nd. Gestational diabetes mellitus\ne. Hypertensive disorders of pregnancy, comprising pregnancy-\ninduced hypertension (PIH), pre-eclampsia (PE) and\nhaemolysis, elevated liver enzymes, and low platelets in the\nblood (HELLP syndrome)\nf. Preterm delivery, defined as delivery more than 24 and less\nthan 37 weeks of gestational age\ng. Perinatal and neonatal death, defined as stillbirths and the\ndeath of a newborn within 28 days a/f_ter delivery\nh. Neonatal hospitalisation, defined as admission for longer\nthan three days or admission to the neonatal intensive care\nunit (NICU)\ni. Large for gestational age, defined as birth weight above 90th\npercentile\nj. Small for gestational age, defined as birth weight below 10th\npercentile\nk. Congenital abnormalities per live-born children, defined as\nthe number of congenital abnormalities at birth per live-born\nchildren plus number of foetuses therapeutically terminated\nl. Birth weight of babies born, per baby\nWe also provide multiple pregnancy rate and miscarriage rate per\nclinical pregnancy.\nAs an additional analysis we calculated the live birth rate per\nwoman a/f_ter first embryo transfer only.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n8\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nSearch methods for identification of studies\nWe searched for all published randomised controlled trials on the\n'freeze all' strategy, without language or date restriction and in\nconsultation with the Cochrane Gynaecology and Fertility (CGF)\nInformation Specialist.\nElectronic searches\nWe searched the following electronic databases, trials registers,\nand websites from their inception to 23 September 2020 in\nconsultation with the CGF Information Specialist:\n1. Cochrane Gynaecology and Fertility Group Specialised Register,\nProcite platform (searched 23 September 2020; Appendix 1);\n2. CENTRAL via the Cochrane Central Register of Studies Online\n(CRSO), Web platform (searched 23 September 2020; Appendix\n2);\n3. MEDLINE, Ovid platform (searched 1946 to 23 September 2020;\nAppendix 3);\n4. Embase, Ovid platform (searched 1980 to 23 September 2020;\nAppendix 4);\n5. PsycINFO, Ovid platform (searched 1806 to 23 September 2020;\nAppendix 5);\n6. CINAHL, Ebsco platform (searched 1961 to 23 September 2020;\nAppendix 6).\nOther electronic sources of trials included:\n1. trials registers for ongoing and registered trials:\na. US National Institutes of Health Ongoing Trials Register\nClinicalTrials.gov (clinicaltrials.gov/ct2/home; searched 23\nSeptember 2020; Appendix 7);\nb. World Health Organization International Clinical Trials\nRegistry Platform (WHO ICTRP) (www.who.int/trialsearch/\nDefault.aspx; searched 23 September 2020; Appendix 8);\n2. DARE (Database of Abstracts of Reviews of Effects) in\nthe Cochrane Library for reference lists from relevant\nnon-Cochrane reviews (onlinelibrary.wiley.com/o/cochrane/\ncochrane_cldare_articles_fs.html);\n3. PubMed (www.ncbi.nlm.nih.gov/pubmed/).\nSearching other resources\nWe examined the reference lists of eligible articles and contacted\nstudy authors where necessary to obtain additional relevant data\nand handsearched relevant journals and conference abstracts that\nwere not covered in the CGF Register.\nData collection and analysis\nSelection of studies\nTwo review authors (TZ and MZ) screened the titles and abstracts\nretrieved by the search and retrieved the full texts of all potentially\neligible studies using Covidence. We independently examined\nthese full-text articles for compliance with the inclusion criteria\nand selected studies eligible for inclusion in the review. We\ncorresponded with study investigators as required to clarify study\neligibility. We resolved any disagreements about study eligibility\nby discussion or by consulting a third review author (SM). We\ndocumented the selection process with a PRISMA flow chart (Moher\n2009; Figure 1).\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n9\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 1.\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n10\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 1. /uni00A0 (Continued)\n/uni00A0\nData extraction and management\nTwo review authors (TZ and MZ) independently extracted data\nfrom the eligible studies using a data extraction form designed and\npilot-tested by the review authors. We resolved any discrepancies\nby discussion. The data extraction forms included methodological\nquality and allocation information. We included this information\nin the review and presented it in the Characteristics of included\nstudies and Characteristics of excluded studies tables.\nWe corresponded with study investigators to request further data\non methods or results, or both, as required. Whenever we did not\nreceive a response within six weeks we sent a reminder email to the\nstudy authors.\nAssessment of risk of bias in included studies\nTwo review authors (TZ and MZ) independently assessed the\nincluded studies for risk of bias using the Cochrane 'Risk of bias'\nassessment tool for the following domains (Higgins 2011).\nSequence generation\nWe allocated a low risk of bias if the investigators described a\nrandom component in the sequence generation process, such as:\n1. using a computerised random number generator;\n2. using a random numbers table.\nAllocation concealment\nWe allocated a low risk of bias if the participants and investigators\nenrolling participants could not foresee assignment because one\nof the following, or an equivalent method, was used to conceal\nallocation:\n1. central computer randomisation;\n2. serially numbered, sealed, opaque envelopes.\nBlinding\nIn this study design it was not possible to blind participants and\nclinicians and therefore the risk of performance bias will be low.\nCompleteness of outcome data\nWe allocated a low risk of bias if there were no missing data, which\nmeant live birth rate and length of follow-up were stated, loss to\nfollow-up was accounted for, and an intention-to-treat analysis had\nbeen carried out.\nSelective outcome reporting\nWe allocated a low risk of bias if all of the study's primary,\nsecondary, and additional outcomes that were of interest in the\nreview had been reported in a prespecified way.\nOther sources of bias\nWe allocated a low risk of bias if the study:\n1. was free of commercial funding;\n2. had no other source of bias identified (e.g. imbalance in\nprognostic factors at baseline).\nTwo review authors (TZ and MZ) assessed these domains and\nresolved any disagreements by consensus or by consulting a third\nreview author (SM). We described the judgements and presented\nthe conclusions in the 'Risk of bias' figures. We took into account all\njudgements in the interpretation of review findings.\nMeasures of treatment effect\nFor dichotomous data (e.g. live birth rates), we used the numbers\nof events in the 'freeze all' strategy and in the conventional IVF/\nICSI strategy group of each study to calculate Mantel-Haenszel odds\nratios (ORs) with 95% confidence intervals (CI). We used Peto ORs\nwhere the event was very rare (less than 1%) or in the case of zero\ncell counts. For continuous data (e.g. birth weight), we calculated\nmean difference (MD) between treatment groups provided that the\nsame measure was used. We reversed the direction of effect of\nindividual studies if required to ensure consistency across studies.\nWe treated ordinal data as continuous data. Where data to calculate\nORs or MDs were not available, we utilised the most detailed\nnumerical data available that would facilitate similar analyses of\nincluded studies (e.g. test statistics, P values). We compared the\nmagnitude and direction of effect reported by studies with how\nthey were presented in the review, taking into account legitimate\ndifferences.\nWe planned to analyse the outcome 'time to pregnancy' using\nhazard ratios (HRs). However, data were insufficient to conduct\nthese analyses. Should more data become available in the future,\nwe will conduct HR analyses of time to pregnancy in later updates\nof this review.\nUnit of analysis issues\nWe performed the analyses with data per woman randomised,\napart from birth weight, which we analysed per baby. If data of the\nprimary analysis were reported per embryo, per oocyte, per cycle,\nor per transfer, we contacted the authors of the studies for per-\nwoman data for completeness.\nWe counted reported multiple live births as one live birth event.\nWe planned to include only first-phase data from cross-over trials.\nWe also performed secondary analyses for multiple pregnancy,\nmiscarriage, pregnancy complications, and birth weight per\npregnancy since these conditions only occur in pregnant women.\nDealing with missing data\nWe analysed the data on an intention-to-treat basis. In case of\nmissing data we contacted authors of studies to request more data.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n11\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nWe assumed that live births had not occurred in women without\na reported outcome. If studies reported sufficient detail to\ncalculate MDs, but provided no information on associated standard\ndeviations (SD), we assumed that the outcome had a SD equal to\nthe highest SD from other studies within the same analysis.\nAssessment of heterogeneity\nWe considered heterogeneity when the clinical and methodological\ncharacteristics of the included studies were sufficiently similar for\na meta-analysis to provide a clinically meaningful summary. We\nperformed statistical analyses in accordance with the guidelines\ndeveloped by Cochrane (Deeks 2020). We assessed heterogeneity\nbetween the results of different studies by the I2 statistic (Higgins\n2003), considering an I2 value greater than 50% to indicate\nsubstantial heterogeneity (Deeks 2020).\nAssessment of reporting biases\nWe aimed to minimise the potential impact of publication and\nreporting biases by performing a comprehensive search for eligible\nstudies and looking for duplication of data. We planned to perform\na funnel plot to investigate the possibility of small-study effects if\nwe included 10 or more studies in an analysis.\nIf included studies reported neither the primary outcome measure\nof live birth nor interim outcomes such as clinical pregnancy, we\nundertook informal assessment as to whether studies reporting\nthe primary outcome measures reflected typical findings for the\ninterim outcomes. We considered within-study reporting bias by\nlooking at the protocols.\nWe addressed the assessment of reporting biases in the Risk of bias\nin included studies section of the Results.\nData synthesis\nWe used Review Manager 5 so/f_tware to perform the meta-analyses\nwith a fixed-effect model to calculate pooled ORs and 95% CIs\n(Review Manager 2020).\nTo aid interpretation, we translated findings for primary outcomes\nto absolute risks, expressed as percentages based on the 95% CIs.\nWe combined results for continuous outcomes using MDs.\nProspectively, we planned to present the analyses as:\n1. cumulative live birth rates for conventional IVF cycles and 'freeze\nall' cycles;\n2. OHSS rate for conventional IVF cycles and 'freeze all' cycles;\n3. cumulative rate for secondary outcomes for conventional IVF\ncycles and 'freeze all' cycles;\n4. time to pregnancy.\nWe included an additional table (Table 1) with pregnancy and\nlive birth rates for one IVF/ICSI cycle a/f_ter the first cryopreserved\nembryo transfer in the 'freeze all' strategy versus one IVF/ICSI\ncycle a/f_ter the first fresh embryo transfer in the conventional IVF/\nICSI strategy. In the current literature it is usual to report on\noutcomes only a/f_ter the first cryopreserved embryo transfer, but\nthis comparison could easily result in the wrong conclusion (Zaat\n2019).\nSubgroup analysis and investigation of heterogeneity\nWe had planned to perform subanalyses on timing of\ncryopreservation (e.g. day of embryo development) and method\nof cryopreservation (e.g. slow freezing or vitrification). However,\ndata were insufficient to conduct all planned subgroup analyses.\nShould more data become available in the future, we will conduct\nadditional subgroup analyses in later updates of this review.\nSensitivity analysis\nWe conducted sensitivity analyses for the primary outcomes\n(cumulative live birth rate and OHSS). These analyses included\nconsideration of whether the review conclusions would have\ndiffered if:\n1. eligibility was restricted to studies without high risk of bias;\n2. a random-effects model had been adopted;\n3. the summary effect measure was risk ratio rather than OR.\nSummary of findings and assessment of the certainty of the\nevidence\nWe prepared a 'Summary of findings' table using GRADEpro GDT\nso/f_tware and following Cochrane methods (Schünemann 2020 ).\nThis table evaluates the overall quality of the body of evidence\nfor the main review outcomes. Two review authors independently\nevaluated the overall quality of the evidence for the outcomes\n(live birth, OHSS, multiple pregnancy, miscarriage, pregnancy\ncomplications and time to pregnancy) using GRADE criteria (study\nlimitations such as risk of bias, consistency of effect, imprecision,\nindirectness, and publication bias). We justified, documented,\nand took into account judgements about evidence quality (high,\nmoderate, low, or very low) in the results for each outcome.\nR E S U L T S\nDescription of studies\nResults of the search\nResults of the previous search\nOur searches on 14 November 2016/uni00A0revealed 2401/uni00A0reports, of which\n785/uni00A0were duplicates, leaving 1622/uni00A0reports. A/f_ter screening the title\nand abstract, we found 12/uni00A0reports to be potentially eligible, and\nretrieved these reports in full text.\nIn the first version of our review (Wong 2017 ), we included\nfour studies (Chen 2016 ; Ferraretti 1999; Shapiro 2011a; Shapiro\n2011b). We excluded four studies: (Absalan 2013; Aflatoonian 2010;\nBoostanfar 2016; Yang 2015)). We classified one study as awaiting\nassessment because it did not clearly report the methods it used\n(Chandel 2016).\nFor the previous version of the review, we contacted the authors\nof three included studies reporting on the primary outcomes\nFerraretti 1999; Shapiro 2011a; Shapiro 2011b and one excluded\nstudy, Absalan 2013, for missing data. We asked the study authors\nabout these missing data and about bias (e.g. randomisation and\nblinding). One author did not reply to our request for information\n(Absalan 2013 ). The remaining authors very kindly responded to\nour request for additional information, and we were able to include\nthese data in our analysis.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n12\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nResults of the current search\nOur searches on 23 September 2020/uni00A0revealed 2395/uni00A0reports, of which\n1127 were duplicates, leaving 1268/uni00A0reports. A/f_ter screening the title\nand abstract, we found 13/uni00A0reports to be potentially eligible, and\nretrieved these reports in full text.\nWe excluded three studies: one we considered not properly\nrandomised/uni00A0(Magdi 2017); one randomised women to a different\nintervention that was not clear from the abstract (Simon 2020); and\none was not the correct study design, which was not clear from the\nabstract screening (Beyer 2016).\nSix studies were ongoing and awaiting data\n(ACTRN12612000422820; ACTRN12616000643471;\nISRCTN61225414; NCT02133950; NCT02570386; NCT03349905).\nWe contacted the authors of five/uni00A0studies (Aflatoonian 2018;\nAghahosseini 2017 ; Coates 2017; Shi 2018 ; Stormlund 2020),\nincluded in the additional analysis regarding live birth rate a/f_ter first\nembryo transfer for cumulative live birth rate. None of the study\nauthors responded to our request for this additional information.\nWe included 11/uni00A0new randomised controlled trials (RCTs) in the\nupdate.\nWe reassessed Chandel 2016 , which was awaiting assessment\nfrom the previous version of the review (Wong 2017 ). We have\nexcluded this study because we did not consider it to be properly\nrandomised.\nThe current review includes 15 studies in total: four studies from\nthe first version of the review (Chen 2016; Ferraretti 1999; Shapiro\n2011a; Shapiro 2011b), and 11 new studies (Aflatoonian 2018;\nAghahosseini 2017 ; Coates 2017; Santos-Ribeiro 2020; Shapiro\n2016; Shi 2018; Stormlund 2020; Vuong 2018; Wei 2019; Wong 2021;\nZhang 2018). We included eight studies in the meta-analyses, which\nare the eight primary reports of the RCTs (Chen 2016 ; Ferraretti\n1999; Santos-Ribeiro 2020; Shapiro 2011a; Shapiro 2011b; Vuong\n2018; Wei 2019; Wong 2021).\nSee the study flow diagram (Figure 1) and study tables\n(Characteristics of included studies; Characteristics of excluded\nstudies; Characteristics of ongoing studies).\nIncluded studies\nStudy design and setting\nOf the 15/uni00A0studies included in the systematic review, eight were the\nprimary reports of the RCTs and had data on primary and secondary\noutcomes and therefore included in the meta-analysis. Six of\nthese eight were single-centre studies, conducted in reproductive\nmedical centres in Belgium, Italy, the Netherlands, USA and\nVietnam (Ferraretti 1999; Santos-Ribeiro 2020; Shapiro 2011a;\nShapiro 2011b; Vuong 2018; Wong 2021), and two were multicentre\nstudies conducted in reproductive medical centres throughout\nChina (Chen 2016; Wei 2019).\nWe included two studies for secondary outcomes (Shapiro 2016;\nZhang 2018). Both studies are follow-up studies of included RCTs.\nShapiro 2016 reports on the follow-up data of Shapiro 2011a and\nShapiro 2011b. Zhang 2018 reports on the follow-up data of Chen\n2016.\nThirteen studies supplied data for the additional analysis – live birth\na/f_ter a first embryo transplant (Aflatoonian 2018; Aghahosseini\n2017; Chen 2016; Coates 2017; Ferraretti 1999; Santos-Ribeiro 2020;\nShapiro 2011a; Shapiro 2011b; Shi 2018 ; Stormlund 2020; Vuong\n2018; Wei 2019; Wong 2021).\nParticipants\nThe eight/uni00A0studies reporting on the primary outcome enrolled a\ntotal of 4712/uni00A0women, with 2342/uni00A0women undergoing the 'freeze all'\nstrategy and 2370/uni00A0women undergoing the conventional IVF/ICSI\nstrategy with fresh embryo transfer.\nFerraretti 1999/uni00A0 and Santos-Ribeiro 2020/uni00A0evaluated the 'freeze all'\nstrategy in the context of prevention of OHSS. Shapiro 2011a;\nShapiro 2011b; Vuong 2018; Wei 2019 and Wong 2021 evaluated the\n'freeze all' strategy in the context of an offered approach to improve\nsusceptibility of the endometrium. Chen 2016 evaluated the 'freeze\nall' strategy in the context of both an offered approach to improve\nsusceptibility of the endometrium and prevention of OHSS.\nThe inclusion criteria of the two Shapiro studies were based on\nthe number of antral follicles observed at baseline ultrasound\nexamination: Shapiro 2011a included normal responders (8 to\n15 antral follicles), and Shapiro 2011b included high responders\n(> 15 antral follicles). Ferraretti 1999 included women at risk of\ndeveloping OHSS, based on level of estradiol (E2) and number\nof retrieved eggs (≥ 15 oocytes)./uni00A0Santos-Ribeiro 2020/uni00A0 included\nwomen with an excessive response to ovarian stimulation (≥\n18 follicles/uni00A0measuring/uni00A0≥ 11 mm on the day of the GnRH\ntriggering)./uni00A0Chen 2016  included women with polycystic ovary\nsyndrome. Vuong 2018 and Wei 2019  included women without\npolycystic ovary syndrome. Wong 2021 included women with any\nIVF indication, independent of the number of follicles or available\nembryos.\nIn all studies, the baseline characteristics were comparable\nbetween the two strategies.\nThe ages of the women included by Shapiro 2011a and Shapiro\n2011b ranged from 18 to 41 years. The mean age for the women\nincluded in Ferraretti 1999 ranged from 31.4 to 31.6 years. Women\nin Chen 2016 were between the ages of 20 and 34 years. The mean\nage of women in Vuong 2018 was 32 years. In Wei 2019 the mean\nage of the participants was 28.8 years./uni00A0The mean age for the women\nincluded in/uni00A0Santos-Ribeiro 2020/uni00A0ranged from 30.4/uni00A0to 31.2 years./uni00A0The\nmean age for the women included in Wong 2021 ranged from 35.1\nto 35.2 years.\nFor details about the extra studies used for additional analysis\n(Aflatoonian 2018; Aghahosseini 2017 ; Coates 2017; Shi 2018 ;\nStormlund 2020), see Characteristics of included studies.\nInterventions\nIn Chen 2016 , women received recombinant FSH at a daily dose\nof 112.5 IU for those weighing less than 60 kg and 150 IU for\nthose weighing over 60 kg starting on day 2 or 3 of the menstrual\ncycle. This was adjusted following ovarian response. hCG could be\nadded when considered appropriate. On the day of oocyte retrieval,\nwomen had to have more than 3 and fewer than 30 oocytes with\na low risk of OHSS to be randomised. Intramuscular progesterone\nat a daily dose of 80 mg was administered for luteal-phase support\nin the fresh-transfer group. Embryos were cryopreserved at day 3\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n13\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nof development. Oral oestradiol valerate was used for endometrial\npreparation on day 2 or 3 of the second menstrual cycle a/f_ter oocyte\nretrieval. Intramuscular progesterone (80 mg/day) was added when\nendometrial thickness reached 8 mm or more or at the physician’s\ndiscretion. On day 4 of progesterone administration, two day-3\nfrozen embryos were thawed and transferred. Luteal-phase\nsupport with oestradiol valerate and intramuscular progesterone\nfor endometrium preparation continued until 10 weeks a/f_ter\nconception.\nWomen in Ferraretti 1999 received a down-regulation protocol\nwith gonadotropin-releasing hormone (GnRH) analogue (0.3 mg\nsubcutaneous buserelin acetate (Suprefact) twice a day) and\novarian stimulation with urinary gonadotropin (4 ampoules\nof follicle-stimulating hormone (FSH) on the first and second\ndays of treatment, and 2 ampoules of FSH plus 2 ampoules\nof human menopausal gonadotropins on the third and fourth\ntreatment days). This was followed by an adjusted dosage of\ngonadotropins according to the individual response measured by\nplasma concentration of E2 and follicular growth assessed by\nultrasound (Ferraretti 1996). Human chorionic gonadotropin (hCG)\nwas administered 34 to 36 hours before follicle aspiration followed\nby 20 g of intravenous albumin. Embryos were frozen at the\npronuclear stage. All embryos were transferred at the early cleavage\nstage (day 3) in artificial cycles. The artificial cycle treatment\nincluded oral administration of oestradiol valerate, 2 mg daily for\nthe first 5 days of the cycle; 4 mg/day from day 6 to day 10; 6 mg/\nday from day 11 to day 13; then 4 mg/day from day 14 onward. On\nday 15 of the cycle, 50 mg of progesterone in oil was administered\ndaily, and on day 17 the dose was increased to 100 mg/day.\nIn women in Santos-Ribeiro 2020, ovarian stimulation commenced\na/f_ter confirmation that the woman was not pregnant and that\nshe had basal serum levels of estradiol (< 80 pg/mL) and\nprogesterone (< 1.5 ng/mL). Treating physicians decided which\nexogenous gonadotropins should be used according to the\nwoman’s profile and preference, including either recombinant\nFSH (Gonal-FVR or Puregon) or highly purified urinary human\nmenopausal gonadotropins (MenopurVR). All women included\nunderwent exogenous ovarian stimulation using GnRH antagonist\nsuppression from day 6 of stimulation onwards with daily injections\nof either ganirelix or cetrorelix. Final oocyte maturation was\ntriggered with 0.2 mg triptorelin as soon as at least three follicles\nof larger than 17 mm were observed. A GnRH agonist was the\npreferred triggering agent for both groups in order to avoid the\nelevated risk of OHSS associated with hCG triggering in high\nresponders. Oocyte retrieval was performed approximately 36\nhours a/f_ter the GnRH agonist administration. In the fresh transfer\narm, following oocyte retrieval, intensified luteal phase support\nwas provided with a single administration of 1500 IU of exogenous\nhCG approximately one hour a/f_ter oocyte retrieval followed by 200\nmg of vaginal micronized progesterone (UtrogestanVR) three times\na day plus 2 mg of oral estradiol valerate (ProgynovaVR) twice daily.\nThe embryo transfer was performed on day 3 or 5 of development\nwith preference to the latter whenever at least four good-quality\nembryos were available on day 3. The choice to transfer one or\ntwo embryos was decided by the clinician at consultation prior\nto commencing the ART treatment, mainly depending on the\nwoman’s age and the number of embryos replaced in the previous\ntreatment cycles, according to Belgian law. All remaining good-\nquality embryos were vitrified. In the 'freeze all' arm, no fresh luteal\nphase support was provided following oocyte retrieval. Instead, all\nviable embryos were vitrified, preferably at blastocyst stage (day 5\nor 6), according to the same, before-mentioned threshold of good-\nquality embryos available on day 3. Women started with exogenous\nhormone therapy for endometrial preparation in the next cycle.\nThis therapy was initiated only a/f_ter confirmation that the woman\nhad basal serum levels of estradiol/progesterone and consisted\nof 2 mg of oral estradiol valerate (ProgynovaVR ) twice daily for\nseven days followed by three times a day for another six days.\nEndometrial development was assessed using ultrasound and if the\nendometrium was 7 mm or more, 200 mg of vaginal Utrogestan\nthree times a day was added to the treatment scheme. The frozen\nembryo transfer was scheduled according to the developmental\nstage of the embryo.\nIn Shapiro 2011a and Shapiro 2011b, women received down-\nregulation with a GnRH antagonist and a combination of\nrecombinant FSH and highly purified urinary FSH. hCG was\nadministered 34 to 36 hours prior to follicle aspiration. In those\nwomen with greater ovarian response, 4 mg leuprolide acetate\nwas added concomitant to the hCG. Embryos were vitrified at\nthe pronuclear stage. All embryos were transferred as blastocysts\nin artificial cycles. Women with fresh embryo transfers received\n6.0 mg daily E2 and daily progesterone injections (100 mg),\nwith progesterone supplementation beginning one to two days\na/f_ter follicle aspiration and E2 initiated as needed. Women\nwith cryopreserved embryo transfers were down-regulated with\nleuprolide acetate in a subsequent cycle and received oral 6.0 mg\ndaily E2 and E2 patches as needed starting 10 to 14 days before\nthawing to achieve a target endometrial thickness of at least 8\nmm. Daily progesterone injections (typically 100 mg) were started\nthe day before thawing. In both groups, E2 and progesterone\nsupplements were adjusted as needed to sustain serum levels of at\nleast 200 pg/mL and 15 ng/mL, respectively, until increasing serum\nlevels indicated placental production, at 9 to 10 weeks’ gestation.\nWomen in Vuong 2018 underwent ovarian hyperstimulation\naccording to the protocol for the use of FSH and GnRH antagonists.\nThe dose of recombinant FSH ranged from 150 to 300 IU per day,\ndepending on the woman’s age, anti-Müllerian hormone levels, and\nresponse to FSH in any prior IVF cycle. When the mean diameter of\nat least two leading follicles was 17 mm, 250 /uni03BCg of recombinant hCG\nwas administered, and oocyte retrieval was performed 36 hours\nlater. Embryos were cryopreserved at day 3 of development. In the\nfollowing cycle, the endometrium was prepared with the use of\noral estradiol valerate at a dose of 8 mg per day, starting on the\nsecond or third day of the menstrual cycle. Endometrial thickness\nwas monitored from day 6 onward, and vaginal progesterone at a\ndose of 800 mg per day was started when the endometrial thickness\nreached 8 mm or more. A maximum of two embryos of grade 1\nor 2 were thawed on the day of embryo transfer, three days a/f_ter\nthe start of progesterone. Luteal-phase support with oestradiol\nvalerate and vaginal progesterone for endometrium preparation\ncontinued until seven weeks a/f_ter conception.\nIn Wei 2019 women were given GnRH antagonist (ganirelix) regimen\nfor ovarian stimulation. Recombinant FSH (Puregon) was started on\nday 1 to 3 of the menstrual cycle. When at least two follicles were 18\nmm or greater in mean diameter, hCG at a dose of 4000 IU to 10000\nIU was administered to induce the final maturation of oocytes.\nOocyte retrieval was done 34 hours to 36 hours a/f_ter hCG injection.\nLuteal phase support was started from the day of oocyte retrieval\nwith vaginal progesterone gel (Crinone) 90 mg per day and oral\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n14\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\ndydrogesterone (Duphaston) 10 mg twice daily. On day 3 of embryo\nculture, embryos were graded by morphological criteria. Women\nwho had four or more high-grade embryos were randomly assigned\nto the fresh or frozen blastocyst transfer group. In the 'freeze all'\ngroup, luteal phase support was stopped a/f_ter randomisation. On\nday 3, embryos were removed from cleavage media and replaced\nin blastocyst media. All blastocysts were vitrified on day 5 or day\n6 according to embryo development. At least 4 weeks later, the\nendometrium was prepared either with a natural cycle regimen\nor artificial cycle regimen, at the discretion of local investigators.\nFor the natural ovulatory cycle regimen, ovulation was determined\nby ultrasound monitoring. Oral dydrogesterone (Duphaston) 10\nmg three times daily was administered for luteal phase support\na/f_ter ovulation. A single cryopreserved blastocyst was transferred\non the fi/f_th day a/f_ter ovulation. If pregnancy was achieved, luteal\nphase support was continued until 10 weeks’ gestation. For the\nartificial cycle regimen, oral oestradiol valerate (Progynova) at\na dose of 4 mg to 8 mg daily was started on day 1 to 3 of\nthe menstrual cycle. Vaginal progesterone gel (Crinone) 90 mg\nper day and oral dydrogesterone 10 mg twice daily were added\nwhen the endometrial thickness reached 7 mm or more. A single\nfrozen-thawed blastocyst was transferred on the fi/f_th day a/f_ter\nprogesterone initiation. If pregnancy was achieved, oral oestradiol\nvalerate was continued until eight weeks’ gestation, and vaginal\nprogesterone gel and oral dydrogesterone were continued until 10\nweeks’ gestation.\nWomen in Wong 2021  underwent pituitary downregulation with\na long GnRH agonist protocol with or without oral contraceptive\npill pre-treatment. Ovarian stimulation was conducted with\nhuman menopausal gonadotrophin (Menopur) or recombinant FSH\n(Puregon or Gonal-F) in women with polycystic ovary syndrome\nstarting from the seventh day without oral contraceptive pill\npre-treatment. The starting dose depended on the antral follicle\ncount. Ovarian stimulation was continued until three or more\nfollicles with a diameter of 18 mm had developed. Ovulation was\ntriggered with 5000 or 10,000 IU hCG (Pregnyl). A single embryo\ntransfer was performed for women below 38 years of age and\na double embryo transfer policy for women of 38 years of age\nand above, if two or more embryos were available. Embryos\nwere cryopreserved on day 6 of culture. Women started with oral\noestrogen supplementation of 6 mg daily on the first day of their\nfirst menstruation a/f_ter the follicular aspiration. If the endometrium\nhad reached 8 mm, women started vaginal progesterone of 600\nmg daily and continued the oral oestrogen. At the seventh day\nof vaginal progesterone administration, the cryopreserved embryo\ntransfer was performed. If pregnancy occurred, oestrogen and\nprogesterone supplementation was continued until the eleventh\nweek of gestation.\nOutcomes\nData were extracted from study reports or provided by authors for\nthe following outcomes.\nPrimary outcomes\n1. Effectiveness: cumulative live birth rate per woman. Two studies\ndid not report on live birth in their published article (Shapiro\n2011a; Shapiro 2011b), but we were able to obtain these data\nby personal communication with the study authors. One study\ndid not report on live birth rate a/f_ter the first embryo transfer\n(Ferraretti 1999), but we were able to obtain these data by\npersonal communication with the study authors. Chen 2016 ;\nSantos-Ribeiro 2020; Vuong 2018; Wei 2019  and Wong 2021\nreported these data. Five studies did not report on cumulative\nlive birth rate but only on live birth rate a/f_ter the first embryo\ntransfer (Aflatoonian 2018; Aghahosseini 2017; Coates 2017; Shi\n2018; Stormlund 2020). We contacted the authors for cumulative\nlive birth rate but did not receive any response. We used these\nstudies in the additional analysis on live birth rate per woman\na/f_ter the first embryo transfer.\n2. Safety: OHSS. Two studies reported OHSS per woman if\nhospitalisation was required (Ferraretti 1999; Wong 2021 ).\nTwo studies did not report on OHSS (Shapiro 2011a; Shapiro\n2011b), but we were able to obtain these data by personal\ncommunication with the study authors. However, we did not\ninclude the data from these two studies in the analysis, as\nwomen with high risk of OHSS were excluded and received the\n'freeze all' strategy as standard. Chen 2016; Santos-Ribeiro 2020;\nVuong 2018; Wei 2019 and Wong 2021 reported these data.\nSecondary outcomes\n1. Four studies reported ongoing pregnancy rate determined at 10\nto 12 weeks of gestational age (Shapiro 2011a; Shapiro 2011b;\nVuong 2018; Wong 2021).\n2. Four studies reported cumulative clinical pregnancy rate\n(Ferraretti 1999; Santos-Ribeiro 2020; Vuong 2018; Wong 2021).\n3. Four of the studies reported time to pregnancy, each in a\ndifferent way. Santos-Ribeiro 2020 reported the mean time\nfrom randomisation to detection of clinical pregnancy a/f_ter\nthe first embryo transfer and the overall cumulative time to\nclinical pregnancy; Vuong 2018 reported on the median time\nto conception; Wei 2019 reported on the time to live birth;/uni00A0and\nWong 2021 reported on the time to ongoing pregnancy.\n4. The following studies reported obstetric, perinatal and neonatal\ncomplications per woman.\na. Two studies reported on cumulative ectopic pregnancy rate\n(Vuong 2018; Wong 2021 ). Five studies reported ectopic\npregnancy a/f_ter first embryo transfer (Chen 2016; Ferraretti\n1999; Santos-Ribeiro 2020; Vuong 2018; Wei 2019).\nb. Two studies reported on cumulative miscarriage rate (Vuong\n2018; Wong 2021). All eight studies reported the number of\nmiscarriages a/f_ter first embryo transfer (Chen 2016; Ferraretti\n1999; Santos-Ribeiro 2020; Shapiro 2011a; Shapiro 2011b;\nVuong 2018; Wei 2019; Wong 2021).\nc. Two studies reported on cumulative multiple-pregnancy rate\n(Vuong 2018; Wong 2021 ). Five studies reported multiple-\npregnancy rate a/f_ter first embryo transfer (Chen 2016 ;\nShapiro 2011b; Vuong 2018; Wei 2019; Wong 2021).\nd. One study reported on cumulative diabetes mellitus rate\n(Vuong 2018). Three studies reported on gestational diabetes\nmellitus a/f_ter first embryo transfer (Vuong 2018; Wei 2019 ;\nZhang 2018).\ne. One study reported on cumulative rate of hypertensive\ndisorders of pregnancy (Vuong 2018). Three studies reported\non hypertensive disorders of pregnancy a/f_ter first embryo\ntransfer (Chen 2016; Vuong 2018; Wei 2019).\nf. Two studies reported on cumulative rate of preterm delivery\n(Vuong 2018; Wong 2021). Three studies reported on preterm\ndelivery a/f_ter first embryo transfer (Chen 2016; Vuong 2018;\nWei 2019).\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n15\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\ng. Only one study reported on cumulative rate of perinatal\nand neonatal death (Vuong 2018). Two studies reported\non perinatal and neonatal death a/f_ter first embryo transfer\n(Chen 2016; Vuong 2018).\nh. One study reported on cumulative rate of neonatal\nhospitalisation (Vuong 2018). Three studies reported on\nneonatal hospitalisation a/f_ter first embryo transfer (Vuong\n2018; Wei 2019; Zhang 2018).\ni. One study reported on cumulative rate of large for gestational\nage (Vuong 2018). Three studies reported on the rate of\nbabies who were large for gestational age a/f_ter first embryo\ntransfer (Vuong 2018; Wei 2019; Zhang 2018).\nj. One study reported on cumulative rate of small for\ngestational age (Vuong 2018). Three studies reported on the\nrate of babies who were small for gestational age a/f_ter first\nembryo transfer (Vuong 2018; Wei 2019; Zhang 2018).\nk. None of the studies reported on the cumulative rate of babies\nborn with congenital abnormalities. Three studies reported\non the rate of babies born with congenital abnormalities a/f_ter\nfirst embryo transfer (Chen 2016; Wei 2019; Wong 2021).\nl. Five studies reported on the birth weight of babies born\n(Chen 2016; Shapiro 2016; Vuong 2018; Wei 2019; Wong 2021).\nExcluded studies\nWe excluded eight potentially eligible studies from the review, for\nthe following reasons.\n• Aflatoonian 2010: this study was retracted.\n• Absalan 2013: it was unclear whether this study was truly a RCT.\nThis study compared the clinical and delivery rates between the\n'freeze all' strategy and the conventional strategy in women at\nrisk for OHSS. The abstract stated that women with OHSS were\nrandomly divided into two groups, with fresh embryo transfer\nand with frozen transfer. However, the methods section does not\nmention the method of randomisation (sequence generation\nor allocation concealment) nor which method was used to\ndivide women into the two groups. Nothing was reported on the\noccurrence of OHSS in these women. The study authors did not\nrespond to our request for additional information.\n• Beyer 2016: this study was not the correct study design, which\nwas not clear from the abstract screening.\n• Boostanfar 2016 randomised women to a different intervention\nthat was not clear from the abstract.\n• Chandel 2016 /uni00A0randomised women but, based on results,\nswitched women to the other randomisation group (pseudo-\nRCT).\n• Magdi 2017 stated it was a prospective cohort study, however,\nrandomly assigned women into two groups using a computer-\nbased Microso/f_t Excel spreadsheet. We did not consider the\nstudy to be a properly randomised RCT.\n• Simon 2020/uni00A0randomised women to a different intervention that\nwas not clear from the abstract.\n• Yang 2015: one-third of all randomised women chose to\nbe in group 3 (fresh transfer of a day-3 embryo followed\nby cryopreserved embryos) a/f_ter randomisation. We did not\nconsider the study to be a properly randomised RCT.\nAwaiting classification\nCurrently there are no studies awaiting classification.\nOngoing studies\nWe identified six ongoing studies from trials registers\nthat may have results for inclusion in future versions\nof this review (ACTRN12612000422820; ACTRN12616000643471;\nISRCTN61225414; NCT02133950; NCT02570386; NCT03349905).\nNote that studies that we did not include studies that were\nregistered in the trials registers but that were not started or that\nwere withdrawn or stopped.\nRisk of bias in included studies\nSee the 'Risk of bias’ summary (Figure 2) and graph (Figure 3) for the\nincluded trials (eight RCTs for the primary outcomes, two follow-up\nstudies for the secondary outcomes and five extra for the additional\nanalysis). See also Characteristics of included studies.\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n16\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 2. /uni00A0 'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study\nRandom sequence generation (selection bias)\nAllocation concealment (selection bias)\nBlinding of participants and personnel (performance bias): All outcomes\nBlinding of outcome assessment (detection bias): All outcomes\nIncomplete outcome data (attrition bias): All outcomes\nSelective reporting (reporting bias)\nOther bias\nAflatoonian 2018+ + + + + ? ?\nAghahosseini 2017? ? + + + ? ?\nChen 2016+ + + + + - ?\nCoates 2017+ ? + + + ? ?\nFerraretti 1999? ? + + + ? -\nSantos-Ribeiro 2020+ + + + + + +\nShapiro 2011a ? + + + ? + ?\nShapiro 2011b ? + + + ? + ?\nShapiro 2016+ + + + ? + ?\nShi 2018+ + + + + + ?\nStormlund 2020+ + + + + + ?\nVuong 2018 + ? + + + + ?\nWei 2019 + + + + + + ?\nWong 2021 + + + + + + ?\nZhang 2018+ + + + + + ?\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n17\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 3. /uni00A0 'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages\nacross all included studies\nRandom sequence generation (selection bias)\nAllocation concealment (selection bias)\nBlinding of participants and personnel (performance bias): All outcomes\nBlinding of outcome assessment (detection bias): All outcomes\nIncomplete outcome data (attrition bias): All outcomes\nSelective reporting (reporting bias)\nOther bias\n0% 25% 50% 75% 100%\nLow risk of bias Unclear risk of bias High risk of bias\n/uni00A0\nAllocation\nSequence generation\nFerraretti 1999 did not describe the method of randomisation in\nthe published article, but replied in a personal communication that\nthe method of randomisation was performed with random sealed\nenvelopes; we judged this study to be at unclear risk of this bias.\nShapiro 2011a and Shapiro 2011b did not report on the method\nfor random sequence generation; we judged these two studies at\nunclear risk of bias.\nSequence generation in Chen 2016 was well described; an online\ncentral randomisation system was used. We considered risk of\nselection bias related to sequence generation to be low. Vuong\n2018 performed sequence generation randomly by an independent\nstudy co-ordinator by means of block randomisation using a\ncomputer-generated random list and therefore we considered\nrisk of selection bias related to sequence generation to be\nlow. Risk of selection bias related to sequence generation in\nWei 2019  was also considered low based on the use of block\nrandomisation using a computer-generated random list./uni00A0Santos-\nRibeiro 2020/uni00A0randomised women by means of a computer-\ngenerated randomisation list./uni00A0Wong 2021 randomised women with\nan online randomisation program using block randomisation with\na maximum block size of 6, stratified for age (18 years through 35\nand 35 through 43 years) and study centre. Couples were allocated\nin a 1:1 ratio to the 'freeze all' strategy or the conventional strategy.\nWe judged these two studies at low risk of bias.\nAllocation concealment\nShapiro 2011a and Shapiro 2011b performed allocation\nconcealment by drawing randomly among identical, opaque,\nunmarked, sealed envelopes, and we therefore judged both studies\nto be at low risk of selection bias related to allocation concealment.\nChen 2016  used an online central randomisation system\n(www.medresman.org) to generate the assignment sequence\nautomatically, which was unknown to the clinical investigators.\nSantos-Ribeiro 2020 sealed each entry of the list in a sequentially\nnumbered opaque envelope and allocated participants in that\norder. Participating physicians did not have access to the\nrandomisation list. Wei 2019 used a sequence that was entered into\ntheir central online database, secured by username and password\nlog-in. Wong 2021  used a randomisation program to generate\na unique study number with allocation code a/f_ter entry of the\nparticipant’s date of birth and randomisation date. We also judged\nthese four studies to be at low risk of bias.\nThe first author of the Ferraretti 1999 study provided additional\ninformation on allocation concealment. This study performed\nparticipant allocation by sealed envelopes, and we therefore\njudged it to be unclear risk of bias for this domain. Vuong\n2018 randomised patients by means of block randomisation by\nan independent study co-ordinator using a computer-generated\nrandom list, there was no further explanation about allocation\nconcealment. We also judged this study to be at unclear risk of bias.\nBlinding\nPerformance bias\nBlinding of doctors and participants was not possible due to the\nnature of the intervention. Therefore the risk of performance bias\nwas low in all eight studies.\nDetection bias\nAs described in the Methods section, blinding of the participant or\nthe clinician is technically not possible due to the nature of the\nintervention in this study design. We felt that lack of blinding was\nnot likely to influence findings for the primary outcomes live birth\nor OHSS. The risk of performance bias was low in all eight studies.\nIncomplete outcome data\nThree studies did not report intention-to-treat analysis in the\nmethodological or analysis sections (Ferraretti 1999; Shapiro\n2011a; Shapiro 2011b), while five studies did report intention-to-\ntreat analysis (Chen 2016 ; Santos-Ribeiro 2020; Vuong 2018; Wei\n2019; Wong 2021).\nWe initially judged the studies by Shapiro 2011a and Shapiro 2011b\nto be at high risk of attrition bias. These studies did not take\ninto account withdrawals or exclusions of randomised women in\nthe reported analyses. Both studies also analysed the outcomes\nper embryo transferred instead of per woman. However, sufficient\ndata were available for analysis per woman in meta-analysis. We\nprespecified ongoing pregnancy as a viable pregnancy at 12 weeks'\ngestation. These two studies defined ongoing pregnancy at 10\nweeks' gestation, which could slightly overestimate the results for\nthis outcome. Taking these issues into account, we considered the\nrisk of bias to be unclear in these two studies.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n18\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFerraretti 1999; Santos-Ribeiro 2020; Vuong 2018; Wei 2019 /uni00A0 and\nWong 2021 did analyse all randomised women. The risk of attrition\nbias was low.\nSelective reporting\nFour studies were registered in a prospective trials register under\nthe following numbers: NCT01841528 (Chen 2016 ), NCT02471573\n(Vuong 2018),/uni00A0ChiCTR-IOR-14005405 (Wei 2019) and/uni00A0NCT02148393\n(Santos-Ribeiro 2020), including an automatically indexed link on\nthe published report on the study, and the study protocol was\npublished beforehand (Chen 2016 ; Santos-Ribeiro 2020; Vuong\n2018; Wei 2019). Wong 2021 was registered in a prospective trials\nregister with the trial number NTR3187. Prespecified outcomes\nwere generally reported, although in Chen 2016 some prespecified\noutcomes (e.g. time to pregnancy) were missing from the report.\nConsidering this, we judged Santos-Ribeiro 2020; Vuong 2018; Wei\n2019 and Wong 2021 to be at low risk of reporting bias and Chen\n2016 to be at high risk of reporting bias. Two studies were registered\nin a prospective trials register with the respective trial numbers\nNCT00963625 and NCT00963079 (Shapiro 2011a; Shapiro 2011b).\nData on the follow-up of the studies were available in the trials\nregister. The prespecified outcomes of interest were reported in the\ntwo studies, and we judged these studies to be at low risk of this\nbias. We could not assess reporting bias for Ferraretti 1999, as trials\nregisters did not exist at that time, therefore the risk of reporting\nbias for this study was unclear.\nOther potential sources of bias\nWe judged fourteen studies to be at unclear risk of other bias\nand Ferraretti 1999 to be at high risk of other bias. Three of the\nstudies did not clearly report their prespecified criteria for early\ntermination of their trial. Ferraretti 1999 did not prespecify rules\nas to when to terminate the study. In the two studies by Shapiro\n2011a; Shapiro 2011b, an interim analysis was planned a/f_ter 100\ncompleted blastocyst transfers. While women were randomised,\nthe interim analyses were based on completed blastocyst transfers\n(unit of analysis error). They did not report whether the interim\nanalysis was performed by an independent committee that was\nblinded for the primary outcome. In addition, Shapiro 2011b\nterminated the study early a/f_ter an interim analysis based on\ndifferences in embryo quality between the two strategies. This\nreason was not mentioned as one of the criteria to terminate the\nstudy. All three studies cryopreserved embryos at the two pro-\nnucleate (2pn) stage with slow freezing, which is not currently a\ncommon freezing protocol in IVF centres.\nA/f_ter freezing and thawing, the eight studies transferred embryos\nat a different developmental stage: Chen 2016 ; Ferraretti 1999\nand Vuong 2018 transferred cleavage embryos, and Santos-\nRibeiro 2020; Shapiro 2011a; Shapiro 2011b; Wei 2019 /uni00A0 and/uni00A0 Wong\n2021 transferred blastocysts. Four studies reported a form of\ntime to pregnancy: Vuong 2018 reported the median time to\nconception,/uni00A0Wei 2019 reported the mean time to live birth,/uni00A0Santos-\nRibeiro 2020/uni00A0reported the mean time from randomisation to\ndetection of clinical pregnancy a/f_ter the first embryo transfer\nand/uni00A0Wong 2021 reported the time to ongoing pregnancy. None of\nthe eight studies reported on blinding of doctors to interim analyses\nof outcomes of the study.\nEffects of interventions\nSee: Summary of findings 1 Fresh compared to frozen embryo\ntransfer (cumulatively) in assisted reproduction; Summary of\nfindings 2 Fresh compared to frozen embryo transfers in assisted\nreproduction regarding pregnancy and neonatal outcomes\nWe included eight studies involving 4,712/uni00A0women in this review. See\nSummary of findings 1.\n1. Comparison of the 'freeze all' strategy versus the\nconventional IVF/ICSI strategy\n1.1 Effectiveness: cumulative live birth rate per woman\nAll studies included in the meta-analysis collected data on\ncumulative live birth rates (Chen 2016 ; Ferraretti 1999; Santos-\nRibeiro 2020; Shapiro 2011a; Shapiro 2011b; Vuong 2018; Wei 2019;\nWong 2021).\nThere is probably little or no difference between the 'freeze all'\nstrategy and the conventional IVF/ICSI strategy in cumulative live\nbirth rate (OR 1.08, 95% CI 0.95 to 1.22; I2 = 0%; 8/uni00A0RCTs, 4712\nwomen; moderate-quality evidence). The evidence suggests that\nfor a cumulative live birth rate of 58% following the conventional\nstrategy, the cumulative live birth rate following the 'freeze all'\nstrategy would be between/uni00A057% and 63%.\nAs there was no indication of statistical heterogeneity an identical\nestimate for the OR was found when using the random-effects\nmodel. The corresponding RR was 1.03/uni00A0(95% CI 0.99/uni00A0to 1.08; Table 2).\nA sensitivity analysis including only studies without risk of selection\nbias (Chen 2016; Santos-Ribeiro 2020; Vuong 2018; Wei 2019; Wong\n2021), found a comparable result (OR 1.09, 95% CI 0.95 to 1.23; I2 =\n0%; 4/uni00A0RCTs, 4328 women). A sensitivity analysis adopting a random-\neffects model or using risk ratio did not lead to a change in result.\nThere is also probably no difference between the two strategies\nin cumulative live birth rate when the studies are analysed per\ncleavage stage (OR 1.09, 95% CI 0.93 to 1.29; I2 = 0%; 3 RCTs,\n2415 women; moderate-quality evidence) or blastocyst transfer\nstage (OR 1.06, 95% CI 0.88/uni00A0to 1.27; I2 =14%; 5/uni00A0RCTs, 2297 women;\nmoderate-quality evidence; Analysis 1.1; Figure 4).\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n19\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 4. /uni00A0 Forest plot of comparison 1. Freeze-all versus conventional IVF, outcomes per woman, outcome 1.1 live\nbirth rate\nStudy or Subgroup\n1.1.1 Live birth rate: cumulatively for cleavage stage transferChen 2016Ferraretti 1999\nVuong 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.10, df = 2 (P = 0.95); I² = 0%\nTest for overall effect: Z = 1.09 (P = 0.28)\n1.1.2 Live birth rate: cumulatively for blastocyst stage transferSantos-Ribeiro 2020\nShapiro 2011a\nShapiro 2011b\nWei 2019\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.66, df = 4 (P = 0.32); I² = 14%\nTest for overall effect: Z = 0.59 (P = 0.55)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.83, df = 7 (P = 0.68); I² = 0%\nTest for overall effect: Z = 1.21 (P = 0.23)\nTest for subgroup differences: Chi² = 0.07, df = 1 (P = 0.78), I² = 0%\nFreeze all IVFEvents\n46523191\n679\n65373762718\n784\n1463\nTotal\n74658391\n1195\n907060825102\n1147\n2342\nConventional IVFEvents\n45526185\n666\n67353960429\n774\n1440\nTotal\n762673911220\n946762825102\n1150\n2370\nWeight\n34.1%2.9%19.0%56.0%\n3.7%3.4%3.0%29.1%4.8%44.0%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n1.12 [0.91 , 1.37]1.04 [0.50 , 2.13]1.06 [0.80 , 1.41]1.09 [0.93 , 1.29]\n1.05 [0.55 , 1.99]1.03 [0.52 , 2.00]0.95 [0.46 , 1.97]1.16 [0.93 , 1.45]0.54 [0.28 , 1.05]1.06 [0.88 , 1.27]\n1.08 [0.95 , 1.22]\nOdds RatioM-H, Fixed, 95% CI\n0.2 0.5 1 2 5Favours conventionalFavours freeze-all\nRisk of BiasA\n+?+\n+??++\nB\n+??\n+++++\nC\n+++\n+++++\nD\n+++\n+++++\nE\n+++\n+??++\nF\n-?+\n+++++\nG\n?-?\n+????\nRisk of bias legend(A) Random sequence generation (selection bias)\n(B) Allocation concealment (selection bias)(C) Blinding of participants and personnel (performance bias)(D) Blinding of outcome assessment (detection bias)(E) Incomplete outcome data (attrition bias)(F) Selective reporting (reporting bias)(G) Other bias\n/uni00A0\n1.2 Safety: ovarian hyperstimulation syndrome (OHSS) per\nwoman\nTwo studies reported on OHSS per woman if hospitalisation was\nrequired (Ferraretti 1999; Wong 2021). Two studies did not report\non OHSS (Shapiro 2011a; Shapiro 2011b), but we were able to\nobtain these data by personal communication with the authors.\nHowever, we did not include the data from these two studies in\nthe analysis, as women with high risk of OHSS were excluded and\nreceived the 'freeze all' strategy as standard. Chen 2016 ; Santos-\nRibeiro 2020; Vuong 2018 and/uni00A0 Wei 2019/uni00A0reported these data. The\nrisk for developing OHSS may be lower a/f_ter the 'freeze all' strategy\ncompared to the conventional IVF/ICSI strategy (Peto OR 0.26,\n95% CI 0.17 to 0.39; I2 = 0%; 6/uni00A0RCTs, 4478 women; low-quality\nevidence; Analysis 1.2 ; Figure 5). As there was no indication of\nstatistical heterogeneity, we found an identical estimate for the\nOR when using the random-effects model. The corresponding RR\nwas 0.25/uni00A0(95% CI 0.14 to 0.44; Table 2). A sensitivity analysis\nincluding only studies without risk of selection bias (Chen 2016 ;\nSantos-Ribeiro 2020; Vuong 2018; Wei 2019; Wong 2021), found a\ncomparable result (OR 0.27, 95% CI 0.18/uni00A0to 0.40; I2 = 12%; 5/uni00A0RCTs,\n4354 women). A sensitivity analysis adopting a random-effects\nmodel or using risk ratio did not lead to a change in result.\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n20\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 5. /uni00A0 Forest plot of comparison 1. Freeze-all versus conventional IVF, outcomes per woman, outcome 1.2\novarian hyperstimulation syndrome (OHSS)\nStudy or Subgroup\n1.2.1 Per cycle with ovarian hyperstimulationChen 2016Ferraretti 1999Santos-Ribeiro 2020\nVuong 2018\nWei 2019\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.85, df = 5 (P = 0.43); I² = 0%\nTest for overall effect: Z = 6.61 (P < 0.00001)\nFreeze all IVFEvents\n1000340\n17\nTotal\n746581043918251022226\nConventional IVFEvents\n5449493\n83\nTotal\n762671053918251022252\nWeight\n63.4%4.0%9.0%7.2%13.3%3.1%100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.24 [0.15 , 0.40]0.15 [0.02 , 1.08]0.13 [0.03 , 0.48]0.75 [0.17 , 3.32]0.46 [0.15 , 1.37]0.13 [0.01 , 1.29]0.26 [0.17 , 0.39]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours freeze-allFavours conventional\nRisk of BiasA\n+?++++\nB\n+?+?++\nC\n++++++\nD\n++++++\nE\n++++++\nF\n-?++++\nG\n?-+???\nRisk of bias legend(A) Random sequence generation (selection bias)\n(B) Allocation concealment (selection bias)(C) Blinding of participants and personnel (performance bias)(D) Blinding of outcome assessment (detection bias)(E) Incomplete outcome data (attrition bias)(F) Selective reporting (reporting bias)(G) Other bias\n/uni00A0\nSecondary outcomes\n1.3 Ongoing pregnancy rate per woman\nFour studies reported on the cumulative ongoing pregnancy rates\n(Shapiro 2011a; Shapiro 2011b; Vuong 2018; Wong 2021). There was\nprobably little or no difference between the two strategies in the\ncumulative ongoing pregnancy rate (OR 0.95, 95% CI 0.75 to 1.19;\nI2 = 31%; 4 RCTs, 1245 women; moderate-quality evidence; Analysis\n1.3).\n1.4 Clinical pregnancy rate per woman\nFour studies reported on cumulative clinical pregnancy rate\n(Ferraretti 1999; Santos-Ribeiro 2020; Vuong 2018; Wong 2021 ).\nThere may be no difference between the two strategies in clinical\npregnancy rate though the confidence interval of the estimate (OR\n0.92, 95% CI 0.72 to 1.16; I2 = 35%; 4 RCTs; 1320 women; low-quality\nevidence; Analysis 1.4).\nTime to pregnancy\nFour of the studies reported on time to pregnancy. Santos-Ribeiro\n2020 reported the mean time from randomisation to detection\nof clinical pregnancy a/f_ter the first embryo transfer (average\ntreatment effect 33.3 days, 95% CI 25.8 to 40.9; P < 0.01) and\nthe overall cumulative time to clinical pregnancy (Cox regression\nhazard ratio 0.92, 95% CI 0.68 to 1.24; P = 0.59). Vuong 2018\nreported median time to pregnancy of 3.6 months in the frozen\nembryo group and 2.2 months in the fresh embryo group (absolute\ndifference 1.4 months, 95% CI 0.95 to 1.84; P < 0.001). Wei 2019 did\nnot report time to live birth a/f_ter randomisation but a/f_ter embryo\ntransfer and is therefore not a fair comparison. All three studies\ncalculated time to pregnancy for the women who became pregnant\nand not for the entire study group. Therefore no valid analysis can\nbe performed based the results of these three studies. It was not\npossible to calculate the median time to pregnancy for Wong 2021\ndue to the limited number of ongoing pregnancies.\nSecondary outcomes per woman regarding obstetric, perinatal\nand neonatal complication\n1.5 Ectopic pregnancy rate\nTwo studies reported on the cumulative ectopic pregnancy rate\n(Vuong 2018; Wong 2021 ). We are uncertain whether there is\na difference between the two strategies in cumulative ectopic\npregnancy rate (Peto OR 0.61, 95% CI 0.31 to 1.22; I2 = 0%; 2 RCTs.\n986 women; low-quality evidence; Analysis 1.5).\nFive studies reported on ectopic pregnancy rate a/f_ter the first\nembryo transfer (Chen 2016; Ferraretti 1999; Vuong 2018; Wei 2019;\nSantos-Ribeiro 2020). We are uncertain whether there is a difference\nbetween the two strategies in ectopic rate a/f_ter the first embryo\ntransfer (Peto OR 0.64, 95% CI 0.39/uni00A0to 1.06; I2 = 0%; 5/uni00A0RCTs, 4274\nwomen; low-quality evidence; Analysis 1.5).\n1.6 Miscarriage rate\nTwo studies reported on the cumulative miscarriage rate (Vuong\n2018; Wong 2021 ). We are uncertain whether the two strategies\ndiffer in cumulative miscarriage rate (Peto OR 1.06, 95% CI 0.72\nto 1.55; I2 = 55%; 2 RCTs, 986 women; very low-quality evidence;\nAnalysis 1.6).\nAll eight studies reported on miscarriage rate a/f_ter the first embryo\ntransfer (Chen 2016; Ferraretti 1999; Santos-Ribeiro 2020; Shapiro\n2011a; Shapiro 2011b; Vuong 2018; Wei 2019; Wong 2021). We are\nuncertain about the existence of a difference between the two\nstrategies in miscarriage rate a/f_ter the first embryo transfer (Peto\nOR 0.90, 95% CI 0.76/uni00A0to 1.07; I2 = 64%; 8 RCTs, 4569 women; very\nlow-quality evidence; Analysis 1.6).\n1.7 Multiple pregnancy rate\nTwo studies reported on the cumulative multiple-pregnancy rate\n(Vuong 2018; Wong 2021 ). We are uncertain whether the two\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n21\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nstrategies differ in cumulative multiple-pregnancy rate (Peto OR\n0.88, 95% CI 0.61 to 1.25; I2 = 63%; 2 RCTs. 986 women; very low-\nquality evidence; Analysis 1.7).\nFive studies reported on multiple-pregnancy rate a/f_ter the first\nembryo transfer (Chen 2016; Shapiro 2011b; Vuong 2018; Wei 2019;\nWong 2021). We are uncertain whether the two strategies differ in\nmultiple-pregnancy rate a/f_ter the first embryo transfer (Peto OR\n1.18, 95% CI 0.96 to 1.45; I2 = 45%; 5 RCTs, 4266 women; very low-\nquality evidence; Analysis 1.7).\n1.8 Gestational diabetes\nOne study reported the cumulative rates of gestational diabetes\n(Vuong 2018), therefore pooling was not possible. We are uncertain\nwhether the two strategies differ in cumulative rates of gestational\ndiabetes (Peto OR 0.83, 95% CI 0.36 to 1.94; 1 RCT, 782 women; low-\nquality evidence; Analysis 1.8).\nThree studies reported on the rate of gestational diabetes a/f_ter the\nfirst embryo transfer (Vuong 2018; Wei 2019; Zhang 2018). We are\nuncertain whether the two strategies differ in gestational diabetes\na/f_ter the first embryo transfer (Peto OR 1.34, 95% CI 0.96 to 1.86; I2\n= 20%; 3 RCTs, 3940 women; low-quality evidence; Analysis 1.8).\n1.9 Hypertensive disorders of pregnancy\nOne study reported the cumulative rates of hypertensive disorders\nof pregnancy (Vuong 2018), therefore pooling was not possible. We\nare uncertain whether the two strategies differ in cumulative rates\nof hypertensive disorders of pregnancy (Peto OR 0.70, 95% CI 0.27 to\n1.82; 1 RCT, 782 women; low-quality evidence; Analysis 1.9; Figure\n6).\n/uni00A0\nFigure 6. /uni00A0 Forest plot of comparison: 1 Freeze-all versus conventional IVF, outcomes per woman, outcome 1.9\nhypertensive disorders of pregnancy\nStudy or Subgroup\n1.9.1 Hypertensive disorders of pregnancy: cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 0.74 (P = 0.46)\n1.9.2 Hypertensive disorders of pregnancy: after first embryo transferChen 2016\nVuong 2018\nWei 2019Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 2.84, df = 2 (P = 0.24); I² = 29%\nTest for overall effect: Z = 3.63 (P = 0.0003)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 7.30, df = 3 (P = 0.06); I² = 59%\nTest for overall effect: Z = 3.05 (P = 0.002)\nTest for subgroup differences: Chi² = 4.46, df = 1 (P = 0.03), I² = 77.6%\nFreeze-all IVFEvents\n7\n7\n29529\n63\n70\nTotal\n391391\n7463918251962\n2353\nConventional IVFEvents\n10\n10\n11612\n29\n39\nTotal\n391391\n7623918251978\n2369\nWeight\n15.6%15.6%\n36.6%10.2%37.6%84.4%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.70 [0.27 , 1.82]0.70 [0.27 , 1.82]\n2.57 [1.37 , 4.82]0.83 [0.25 , 2.73]2.34 [1.26 , 4.35]2.15 [1.42 , 3.25]\n1.80 [1.23 , 2.64]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze-all IVFFavours Conventional IVF\nRisk of BiasA\n+\n+++\nB\n?\n+?+\nC\n+\n+++\nD\n+\n+++\nE\n+\n+++\nF\n+\n-++\nG\n?\n???\nRisk of bias legend(A) Random sequence generation (selection bias)\n(B) Allocation concealment (selection bias)(C) Blinding of participants and personnel (performance bias)(D) Blinding of outcome assessment (detection bias)(E) Incomplete outcome data (attrition bias)(F) Selective reporting (reporting bias)(G) Other bias\n/uni00A0\nThree studies reported on the rate of hypertensive disorders of\npregnancy a/f_ter the first embryo transfer (Chen 2016; Vuong 2018;\nWei 2019 ). The risk of hypertensive disorders might be increased\nfollowing the 'freeze all' strategy (Peto OR 2.15, 95% CI 1.42 to 3.25;\nI2 = 29%; 3 RCTs, 3940 women; low-quality evidence; Analysis 1.9;\nFigure 6).\n1.10 Preterm delivery (less than 37 weeks of gestational age)\nTwo studies reported the cumulative rates of preterm delivery\n(Vuong 2018; Wong 2021 ). We are uncertain whether the two\nstrategies differ in cumulative rates of preterm delivery (Peto OR\n0.62, 95% CI 0.39 to 0.99; I2 = 0%; 2 RCTs, 986 women; low-quality\nevidence; Analysis 1.10).\nThree studies reported on the rate of preterm delivery a/f_ter the\nfirst embryo transfer (Chen 2016 ; Vuong 2018; Wei 2019 ). We are\nuncertain whether the two strategies differ in preterm delivery a/f_ter\nthe first embryo transfer (Peto OR 1.15, 95% CI 0.89 to 1.50; I2 = 0%;\n3 RCTs, 3940 women; low-quality evidence; Analysis 1.10).\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n22\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n1.11 Perinatal and neonatal death\nOne study reported the cumulative rates of perinatal and neonatal\ndeath (Vuong 2018), therefore pooling was not possible. Based on\nresults from this solitary study (not meta-analysis) we are uncertain\nwhether the two strategies differ in cumulative rates of perinatal\nand neonatal death (Peto OR 0.13, 95% CI 0.01 to 1.30; 1 RCT, 782\nwomen; very low-quality evidence; Analysis 1.11).\nTwo studies reported on the rate of perinatal and neonatal death\na/f_ter the first embryo transfer (Chen 2016 ; Vuong 2018). We\nare uncertain whether the two strategies differ in perinatal and\nneonatal death a/f_ter the first embryo transfer (Peto OR 2.27, 95%\nCI 0.65 to 7.84; I2 = 88%; 2 RCTs, 2290 women; very low-quality\nevidence; Analysis 1.11).\n1.12 Neonatal hospitalisation (for more than three days or NICU\nadmission)\nOne study reported the cumulative rates of neonatal\nhospitalisation (Vuong 2018), therefore pooling was not possible.\nWe are uncertain whether the two strategies differ in cumulative\nrates of neonatal hospitalisation (Peto OR 1.00, 95% CI 0.29 to 3.48;\n1 RCT, 782 women; very low-quality evidence; Analysis 1.12).\nThree studies reported on the rate of neonatal hospitalisation a/f_ter\nthe first embryo transfer (Vuong 2018; Wei 2019 ; Zhang 2018 ).\nWe are uncertain whether the two strategies differ in neonatal\nhospitalisation a/f_ter the first embryo transfer (Peto OR 1.37, 95%\nCI 1.07 to 1.75; I2 = 0%; 3 RCTs, 3940 women; low-quality evidence;\nAnalysis 1.12).\n1.13 Large for gestational age (birth weight above 90th\npercentile)\nOne study reported the cumulative rates of large-for-gestational-\nage babies (Vuong 2018). Based on the results from this solitary\nstudy we are uncertain whether the two strategies differ in\ncumulative rates of having a large-for-gestational-age baby (Peto\nOR 1.97, 95% CI 0.63 to 6.15; 1 RCT, 782 women; low-quality\nevidence; Analysis 1.13; Figure 7).\n/uni00A0\nFigure 7. /uni00A0 Forest plot of comparison 1. Freeze-all versus conventional IVF, outcomes per woman, outcome 1.13 large\nfor gestational age (birth weight above 90th percentile)\nStudy or Subgroup\n1.13.1 Large for gestational age (birth weight > 90th percentile): cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 1.16 (P = 0.24)\n1.13.2 Large for gestational age (birth weight > 90th percentile): after first embryo transfer\nVuong 2018\nWei 2019Zhang 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.42, df = 2 (P = 0.81); I² = 0%\nTest for overall effect: Z = 5.03 (P < 0.00001)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.42, df = 3 (P = 0.94); I² = 0%\nTest for overall effect: Z = 5.16 (P < 0.00001)\nTest for subgroup differences: Chi² = 0.00, df = 1 (P = 1.00), I² = 0%\nFreeze all IVFEvents\n8\n8\n78466\n157\n165\nTotal\n391391\n3918257461962\n2353\nConventional IVFEvents\n4\n4\n34139\n83\n87\nTotal\n391391\n3918257621978\n2369\nWeight\n5.0%5.0%\n4.2%49.2%41.6%95.0%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n1.97 [0.63 , 6.15]1.97 [0.63 , 6.15]\n2.25 [0.65 , 7.82]2.10 [1.46 , 3.03]1.78 [1.20 , 2.64]1.96 [1.51 , 2.55]\n1.96 [1.52 , 2.53]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze all IVFFavours Conventional IVF\nRisk of BiasA\n+\n+++\nB\n?\n?++\nC\n+\n+++\nD\n+\n+++\nE\n+\n+++\nF\n+\n+++\nG\n?\n???\nRisk of bias legend(A) Random sequence generation (selection bias)\n(B) Allocation concealment (selection bias)(C) Blinding of participants and personnel (performance bias)(D) Blinding of outcome assessment (detection bias)(E) Incomplete outcome data (attrition bias)(F) Selective reporting (reporting bias)(G) Other bias\n/uni00A0\nThree studies reported on the rate of large for gestational age a/f_ter\nthe first embryo transfer (Vuong 2018; Wei 2019; Zhang 2018). Based\non these studies the risk of having a large-for-gestational-age baby\nmight be increased following the 'freeze all' strategy (Peto OR 1.96,\n95% CI 1.51 to 2.55; I2 = 0%; 3 RCTs, 3940 women; low-quality\nevidence; Analysis 1.13; Figure 7).\n1.14 Small for gestational age (birth weight below 10th\npercentile)\nOne study reported the cumulative rates of small for gestational\nage babies (Vuong 2018), therefore pooling was not possible. The\nresults of this solitary study suggest that the cumulative risk of\nhaving a small-for-gestational-age baby might be lower following\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n23\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nthe 'freeze all' strategy (Peto OR 0.36, 95% CI 0.16 to 0.80; 1 RCT, 782;\nlow-quality evidence; Analysis 1.14; Figure 8).\n/uni00A0\nFigure 8. /uni00A0 Forest plot of comparison 1. Freeze-all versus conventional IVF, outcomes per woman, outcome 1.14 small\nfor gestational age (birth weight below 10th percentile)\nStudy or Subgroup\n1.14.1 Small for gestational age (birth weight < 10th percentile): cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 2.49 (P = 0.01)\n1.14.2 Small for gestational age (birth weight < 10th percentile): after first embryo transfer\nVuong 2018\nWei 2019Zhang 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 5.63, df = 2 (P = 0.06); I² = 64%\nTest for overall effect: Z = 1.59 (P = 0.11)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 9.36, df = 3 (P = 0.02); I² = 68%\nTest for overall effect: Z = 2.23 (P = 0.03)\nTest for subgroup differences: Chi² = 3.72, df = 1 (P = 0.05), I² = 73.1%\nFreeze-all IVFEvents\n6\n6\n329102\n134\n140\nTotal\n391391\n3918257461962\n2353\nConventional IVFEvents\n18\n18\n1433\n115\n162\n180\nTotal\n391391\n3918257621978\n2369\nWeight\n8.2%8.2%\n5.8%20.9%65.1%91.8%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.36 [0.16 , 0.80]0.36 [0.16 , 0.80]\n0.27 [0.10 , 0.70]0.87 [0.53 , 1.45]0.89 [0.67 , 1.19]0.82 [0.65 , 1.05]\n0.77 [0.61 , 0.97]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze-all IVFFavours Conventional IVF\nRisk of BiasA\n+\n+++\nB\n?\n?++\nC\n+\n+++\nD\n+\n+++\nE\n+\n+++\nF\n+\n+++\nG\n?\n???\nRisk of bias legend(A) Random sequence generation (selection bias)\n(B) Allocation concealment (selection bias)(C) Blinding of participants and personnel (performance bias)(D) Blinding of outcome assessment (detection bias)(E) Incomplete outcome data (attrition bias)(F) Selective reporting (reporting bias)(G) Other bias\n/uni00A0\nThree studies reported on the rate of small for gestational age a/f_ter\nthe first embryo transfer (Vuong 2018; Wei 2019; Zhang 2018). We\nare uncertain whether the two strategies differ in the risk of having a\nsmall-for-gestational-age baby a/f_ter the first embryo transfer (Peto\nOR 0.82, 95% CI 0.65 to 1.05; I2 = 64%; 3 RCTs, 3940 women; very\nlow-quality evidence; Analysis 1.14; Figure 8).\n1.15 Congenital abnormalities\nThree studies reported on congenital abnormalities (Chen 2016 ;\nWei 2019; Wong 2021). We are uncertain whether the two strategies\ndiffer in rates of congenital abnormalities per live-born children\nplus number of foetuses therapeutically terminated (OR 1.08,\n95% CI 0.65 to 1.78; I2 = 0%; 3 RCTs, 1789 live-born children\nplus number of foetuses therapeutically terminated; low-quality\nevidence; Analysis 1.15).\n1.16 Birth weight\nFive studies reported on birth weight (Chen 2016 ; Shapiro 2016;\nVuong 2018; Wei 2019; Wong 2021). The risk for having a higher birth\nweight of singleton babies born is probably increased following the\n'freeze all' strategy (MD 127 g, 95% CI 77.1 to 177.8; I2 = 0%; 5 RCTs,\n1607 singletons; moderate-quality evidence).\nWe are uncertain whether birth weight of multiples is higher in the\n'freeze all' strategy compared to the conventional IVF/ICSI strategy\n(MD 49.5, 95% CI −21.2 to 120.1; I2 = 17%; 4 RCTs, 804 children born\nfrom multiples; low-quality evidence; Analysis 1.16; Figure 9).\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n24\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nFigure 9. /uni00A0 Forest plot of comparison 1. Freeze-all versus conventional IVF, outcomes per woman, outcome 1.16 birth\nweight of babies born\nStudy or Subgroup\n1.16.1 Birth weight of singletons\nWong 2021Shapiro 2016\nVuong 2018Chen 2016\nWei 2019Subtotal (95% CI)\nHeterogeneity: Chi² = 1.25, df = 4 (P = 0.87); I² = 0%\nTest for overall effect: Z = 4.96 (P < 0.00001)\n1.16.2 Birth weight of multiples\nWei 2019Shapiro 2016\nVuong 2018Chen 2016Subtotal (95% CI)\nHeterogeneity: Chi² = 3.63, df = 3 (P = 0.30); I² = 17%\nTest for overall effect: Z = 1.37 (P = 0.17)\nTest for subgroup differences: Chi² = 3.10, df = 1 (P = 0.08), I² = 67.8%\nFreeze all IVFMean\n352832423151.3\n3511.23407.9\n2544.824102501.52479.7\nSD\n518701434.5593.6476.2\n468.9\n611502.6503.2\nTotal\n1841142250416867\n236798237425\nConventional IVFMean\n328330763048.53349.43293.1\n2523.822272388.22481.7\nSD\n704\n511466.8553.2513.5\n472.7516520.8496\nTotal\n2936134212329740\n1249102216379\nWeight\n2.1%3.4%22.3%23.1%49.0%100.0%\n4.6%\n11.8%24.8%58.8%100.0%\nMean Difference\nIV, Fixed, 95% CI\n245.00 [-105.59 , 595.59]166.00 [-105.85 , 437.85]102.80 [-3.76 , 209.36]\n161.80 [57.11 , 266.49]\n114.80 [42.88 , 186.72]127.44 [77.08 , 177.80]\n21.00 [-308.02 , 350.02]183.00 [-22.62 , 388.62]\n113.30 [-28.53 , 255.13]-2.00 [-94.08 , 90.08]49.46 [-21.15 , 120.08]\nMean Difference\nIV, Fixed, 95% CI\n-200-1000 100200Higher with ConventionalHigher with Freeze-all\nRisk of BiasA\n+++++\n++++\nB\n++?++\n++?+\nC\n+++++\n++++\nD\n+++++\n++++\nE\n+?+++\n+?++\nF\n+++-+\n+++-\nG\n?????\n????\nRisk of bias legend(A) Random sequence generation (selection bias)\n(B) Allocation concealment (selection bias)(C) Blinding of participants and personnel (performance bias)(D) Blinding of outcome assessment (detection bias)(E) Incomplete outcome data (attrition bias)(F) Selective reporting (reporting bias)(G) Other bias\n/uni00A0\nWong 2021 had three twin live-born in the conventional IVF strategy\nand none in the 'freeze all' strategy and could therefore not be\npooled in the analysis.\nOther analyses\nWe also analysed the adverse events, multiple pregnancy and\nmiscarriage per clinical pregnancy (Analysis 2.1; Analysis 2.2).\nIt is uncertain whether the two strategies differ in multiple\npregnancy per clinical pregnancy a/f_ter the first embryo transfer (OR\n1.09, 95% CI 0.87 to 1.36; 5 RCTs, 2223 clinical pregnancies; I2 = 14%;\nAnalysis 2.1 ). We are uncertain whether the two strategies differ\nin miscarriage rate/uni00A0per clinical pregnancy a/f_ter the first embryo\ntransfer (OR 0.82, 95% CI 0.66/uni00A0to 1.02; I2 = 63%; 8/uni00A0RCTs, 2451/uni00A0clinical\npregnancies; Analysis 2.2).\nAdditional analysis\nWe also calculated and presented the live birth rate a/f_ter the first\ntransfer (Table 1). Based on this calculation the live birth rate a/f_ter\nthe first transfer is increased following the 'freeze all' strategy (OR\n1.17, 95% CI 1.06/uni00A0to 1.28; 13/uni00A0RCTs, 7766 women) for all stages of\ntransfer.\nD I S C U S S I O N\nSummary of main results\nOur findings suggest that the 'freeze all' strategy results in\nsimilar cumulative live birth rate but lower OHSS rate than the\nconventional IVF/ICSI strategy. We could not analyse time to\npregnancy. We can assume that it is shorter with conventional\nIVF/ICSI strategy where cumulative live birth rate is similar, as\nembryo transfer is delayed in a 'freeze all' strategy (Zaat 2019).\nLow-quality evidence suggests that the 'freeze all' strategy might\nbe associated with increased risk of hypertensive disorders of\npregnancy, increased risk of having a large-for-gestational-age\nbaby and a higher birth weight of singleton babies.\nOverall completeness and applicability of evidence\nAll eight trials included in the meta-analysis provided data on the\nprimary outcome, live birth rate, but for OHSS we could use data\nfrom only five studies.\nFour of these studies involved a small number of women. All studies\nin the meta-analysis had specific and differing technical protocols,\nand studies had distinct inclusion criteria leading to the inclusion\nof select groups of women (women with a high risk of OHSS, good\nprognosis women, women with polycystic ovary syndrome, young\nwomen without polycystic ovary syndrome and in women with\nany IVF indication, including the women with possible low ovarian\nresponse). Four of the studies reported time to pregnancy, each in a\ndifferent way and therefore we could not pool these outcomes. One\nof these three studies (Wei 2019), did not report time to live birth\na/f_ter randomisation but a/f_ter embryo transfer and is therefore not\na fair comparison. Time to a pregnancy leading to a live birth needs\nto be reported with the date of randomisation as a starting point.\nQuality of the evidence\nWe rated the quality of evidence using GRADE methods and judged\nit to be moderate to low, due to serious risk of bias and (for\nsome outcomes) serious imprecision. Risk of bias was associated\nwith unclear blinding of investigators for preliminary outcomes of\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n25\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nthe study during the interim-analysis, unit of analysis error, and\nabsence of adequate study termination rules.\nThe eight included studies involved a total of 2342/uni00A0women\nundergoing the 'freeze all' strategy and 2370/uni00A0women undergoing\nthe conventional IVF/ICSI strategy. Varying protocols between\nstudies (some not common in routine practice), varying study\npopulation (select groups of women undergoing IVF), one study\nthat did not report power calculation (Ferraretti 1999: unclear\nwhat determined the end of study), two studies that calculated\ninterim analysis per transfer (Shapiro 2011a; Shapiro 2011b:\nunit of analysis error) with absence of adequate stopping rules\n(possible overestimation of treatment effect) and one study that\nreported cumulative live birth rate including a possible second\n('freeze all' 5.9%, conventional IVF 6.4%) or third ('freeze all' 0.5%,\nconventional IVF 0.8%) retrieval cycle (Vuong 2018), resulted in an\noverall judgement of the evidence as moderate to low quality.\nOur searches identified six ongoing studies. We anticipate that the\nevidence from these will provide a more definitive answer on the\nrelative effectiveness and safety of a 'freeze all' strategy.\nPotential biases in the review process\nWe tried to reduce potential bias in the review process to a\nminimum by identifying all eligible studies for inclusion in this\nmeta-analysis. We were able to retrieve additional information\non three included trials where required, which helped us in\nproviding accurate study outcomes. Unfortunately, we did not\nreceive additional information regarding cumulative data for four\nother studies, therefore these studies could only be included in the\nadditional analysis.\nAgreements and disagreements with other studies or\nreviews\nCumulative live birth rate\nFour out of eight studies included in the meta-analysis in this review\nreported higher pregnancy or live birth rates in favour of the 'freeze\nall' strategy (Chen 2016; Shapiro 2011a; Shapiro 2011b; Wei 2019),\nwhile our review concluded that there was no difference in live\nbirth rates between the strategies. This discrepancy in conclusion is\nattributed to the fact that these publications focused on outcomes\nthat were reported a/f_ter the first transfer, whereas in our review we\nfocused on the cumulative live birth rate per woman randomised.\nIn case cumulative live birth rates are comparable, as found in\nthis review, then the difference between strategies could be time\nto pregnancy and possible differences in pregnancy and neonatal\ncomplications. For illustrative purposes we also calculated and\npresented the live birth rate a/f_ter the first transfer (Table 1). Based\non this calculation the live birth rate a/f_ter the first transfer is\nincreased following the 'freeze all' strategy (OR 1.17, 95% CI 1.06/uni00A0to\n1.28; 13/uni00A0RCTs, 7766 women) for all stages of transfer. The live birth\nrate calculated a/f_ter the first transfer possibly shows differences\nin outcome for a stimulated and an unstimulated uterus, although\nthis does not take into account the number of embryos that were\nthawed for transfer.\nFor women, the live birth rate per first transfer is less relevant,\nsince at the same time of first transfer in a 'freeze all' strategy, they\nwould already have received the second transfer in a conventional\nIVF/ICSI strategy. Considering the important perspective of time, it\nwould only be fair to compare cumulative live birth rate between\ngroups instead of live birth rate a/f_ter first transfer (Zaat 2019).\nIn the additional calculation concerning live birth rate a/f_ter the\nfirst transfer, we included a study in which women underwent\npreimplantation genetic testing for aneuploidies (PGT-A) (Coates\n2017). The use of PGT-A could have an effect on the current\ncomparison under evaluation, as PGT-A affects the number of\nembryos available for transfer (Mastenbroek 2014).\nOne out of eight included studies reported lower cumulative\nongoing pregnancy rate or live birth rates for the 'freeze all'\nstrategy than for conventional IVF/ICSI treatment including fresh\ntransfer (Wong 2021 ). In this trial, an unselected cohort of\ncouples undergoing IVF was selected, including women with poor\nprognosis. This could explain the difference from the other included\ntrials, in which only women with a good prognosis (Santos-Ribeiro\n2020; Shapiro 2011a; Shapiro 2011b; Vuong 2018; Wei 2019), women\nwith polycystic ovary syndrome (Chen 2016 ), and women with\na high risk of OHSS were included (Ferraretti 1999). This should\nbe taken into account when considering the 'freeze all' strategy,\nwhether to use it in an unselected population or only in women\nwith a good prognosis, with a minimum number of good-quality\nembryos available. The current review does not provide an answer\nto this.\nTwo recently published systematic reviews and meta-analyses,\nRoque 2019 and Bosdou 2019  reported a higher live birth rate\na/f_ter the first transfer in the 'freeze all' strategy compared to\nconventional IVF/ICSI. No significant difference was found in\ncumulative live birth rate between both groups. In Roque 2019 this\nincreased live birth rate was only found in hyper-responders and\nin cycles with PGT-A. However, no significant difference was found\nin cumulative live birth rate between both groups. Santos-Ribeiro\n2020; Wei 2019/uni00A0and/uni00A0Wong 2021 had not been published when the\nreview by Roque 2019 was written. In Bosdou 2019, high responders\nhad a significantly higher probability of live birth in the 'freeze\nall' strategy based on the results a/f_ter the first transfer. However,\nthe probability of live birth was not significantly different between\nboth groups in normal responders a/f_ter the first embryo transfer.\nBosdou and colleagues did include the Absalan 2013 study, which\nwe excluded based on the unclear study design. No significant\ndifference was found in cumulative live birth rate between both\ngroups.\nOvarian hyperstimulation syndrome (OHSS)\nThe lower rate of OHSS found in our review is in agreement with\nprevious systematic reviews and studies (Bosdou 2019 ; D'Angelo\n2017; Evans 2014; Roque 2019; Takeshima 2016), and is to be\nexpected. Avoiding a pregnancy in the initial cycle with ovarian\nstimulation would eliminate the residual risks of OHSS, and OHSS\nwould therefore be self-limiting. Mild OHSS symptoms can still\noccur as a result of a hCG trigger in the hyperstimulated cycle in\nthe 'freeze all' strategy, but OHSS in its severe form should be\nrare and even close to zero when agonist trigger is used (D'Angelo\n2017; Youssef 2016). All the included studies in our review used hCG\ntrigger before oocyte aspiration.\nAlthough in agreement with previous studies and our expectations,\nthe quality of evidence for the lower rate of OHSS in the 'freeze all'\nstrategy was low. Definitions of OHSS vary widely in literature as in\nthe studies included in this review. Therefore, this result should be\ninterpreted with caution.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n26\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nTime to pregnancy\nThree of the studies reported on time to pregnancy, all in a different\nway. All three studies calculated time to pregnancy for the women\nwho became pregnant and not for the entire study group. Therefore\nno valid analysis can be performed based on the results of these\nthree studies. Reporting on time to pregnancy should be done\nbased on the entire study group, including presenting Kaplan-Meier\ncurves, calculating hazard ratios, or calculating median survival\ntimes. By design, time to pregnancy is shorter in the conventional\nstrategy than in the 'freeze all' strategy when the cumulative live\nbirth rate is comparable, as embryo transfer is delayed in a 'freeze\nall' strategy (Zaat 2019).\nSecondary outcomes concerning effectiveness\nAlthough we reported pregnancy and live birth rates only\ncumulatively; for other outcomes, such as the number of multiples,\nthe number of miscarriages and the obstetric, perinatal and\nneonatal outcomes, we reported the numbers cumulatively and\nalso a/f_ter the first embryo transfer. When the cumulative rates\nfor these outcomes were reported in one or two of the included\nstudies we also plotted the outcomes a/f_ter first embryo transfer.\nDefinitions used in the included studies for some of the secondary\noutcomes, especially miscarriages, differ between studies. The\nincluded data are insufficient to identify any differences in early or\nlate miscarriage between both strategies.\nSecondary outcomes concerning safety\nIn our review we found that women in the 'freeze all' strategy might\nhave an increased risk of hypertensive disorders of pregnancy.\nSeveral cohort studies (Ishihara 2014; Opdahl 2015 ; Sazonova\n2012), and two recent meta-analyses (Maheshwari 2018; Roque\n2019), reported increased risk of hypertensive disorders of\npregnancy a/f_ter frozen embryo transfer compared to fresh embryo\ntransfer. It is hypothesised that the risk of hypertensive disorders of\npregnancy may relate to endometrial preparation with exogenous\nprogesterone and prolonged estrogen use during artificial frozen\nembryo transfer cycles (Roque 2019). During the implantation\nperiod in early pregnancy, extravillous trophoblast cells are the\nkey cells involved in uterine spiral arteriole remodelling during\npregnancy, an event that is critical for a successful pregnancy\noutcome. Some studies suggest that aberrant progesterone levels\nin early pregnancy can lead to over-invasion or an invasion defect\nof the extravillous trophoblast, which may possibly lead to serious\ncomplications such as hypertensive disorders of pregnancy (Esh-\nBroder 2011; Schatz 2016).\nAnother hypothesis is/uni00A0that the increased risk of hypertensive\ndisorders of pregnancy may be due to the missing circulating\ncorpus luteum vasoactive products such as relaxin, vascular\nendothelial growth factor and angiogenic metabolites of estrogen.\nThe absence of these vasoactive factors may lead to deficient\ncirculatory adaptations during early gestation and therefore\nhypertensive disorders of pregnancy (Conrad 2011; Singh 2020; von\nVersen-Höynck 2019a; von Versen-Höynck/uni00A02019b). Recently, in line\nwith this possible biological explanation, the results of two large\ncohort studies showed that the risk of hypertensive disorders of\npregnancy is increased a/f_ter cryopreserved embryo transfer in an\nartificial cycle compared to cryopreserved embryo transfer in a\nnatural cycle (Ernstad 2019; Saito 2019).\nIn this review, seven of the included studies used only artificial\ncycles for frozen embryo transfer in the 'freeze all' strategy (Chen\n2016; Ferraretti 1999; Santos-Ribeiro 2020; Shapiro 2011a; Shapiro\n2011b; Vuong 2018; Wong 2021), of which two studies (Chen 2016;\nVuong 2018), reported on this outcome. Chen 2016 found a higher\nrate of pre-eclampsia in the 'freeze all' strategy, Vuong 2018 found\nno difference between both groups. Frozen embryo transfers in\nthe study by Wei 2019 were mainly performed in natural ovulatory\ncycles (63.7%) or in artificial cycles (36.4%); the type of treatment\ncycle was decided at the discretion of local physicians. Difference\nin hypertensive disorders of pregnancy between natural cycle\nfrozen embryo transfer and artificial cycle embryo transfer was not\nreported. All seven studies used progesterone for luteal support in\ncase of a pregnancy. Based on the results of the included studies in\nthis review it is unclear whether the type of frozen embryo transfer\nand endometrial preparation is associated with increased risk of\nhypertensive disorders of pregnancy or whether there could be\nanother explanation.\nAccording to these studies, this over-invasion or invasion defect\nof the extravillous trophoblast may also lead to abnormal\nplacentation such as placenta accrete (Esh-Broder 2011; Schatz\n2016). In our current review we could not investigate whether\nthe risk of abnormal placentation differs between the 'freeze all'\nstrategy and the conventional IVF/ICSI strategy because none of\nthe included RCTs reported on abnormal placentation. Regarding\nfuture research it would be of great interest to gain more\nknowledge about a possible difference between the strategies for\nthis pregnancy complication.\nThe 'freeze all' strategy is associated with an increased risk of/uni00A0a\nhigher birth weight in singleton babies. This finding is in agreement\nwith a recently published meta-analysis comparing frozen embryo\ntransfer to fresh embryo transfer (Maheshwari 2012; Maheshwari\n2018). The higher risk of large for gestational age a/f_ter frozen\nembryo transfer is also applicable when compared to the general\npopulation ( Luke 2017; Pinborg 2014; Spijkers 2017). It has been\nsuggested that artificial endometrial preparation is associated with\nhigher birth weights (Ernstad 2019; Roque 2019). In this review,\nseven of the included studies used only artificial cycles for frozen\nembryo transfer in the 'freeze all' strategy (Chen 2016 ; Ferraretti\n1999; Santos-Ribeiro 2020; Shapiro 2011a; Shapiro 2011b; Vuong\n2018; Wong 2021), of which four studies (Chen 2016; Shapiro 2016;\nWei 2019; Wong 2021), reported on this outcome. All of these five\nstudies found a higher birth weight of babies born a/f_ter the 'freeze\nall' strategy. Frozen embryo transfers in the study by Wei 2019\nwere mainly performed in natural ovulatory cycles (63.7%) or in\nartificial cycles (36.4%); the type of treatment cycle was decided\nat the discretion of local physicians. Difference in birth weight\nbetween natural cycle frozen embryo transfer and artificial cycle\nembryo transfer was not reported. All of the seven studies used\nprogesterone for luteal support in case of a pregnancy. Based on the\nresults of the included studies in this review it is unclear whether\nthe type of endometrial preparation for frozen embryo transfer is\nassociated with the increased risk of higher birth weight or whether\nthere could be another explanation.\nIt has also been suggested that the freezing and thawing\nprocedures or extended culture may play an independent role in\nthe growth potential of the foetus due to epigenetic alterations at\nthe early embryonic stages (Pinborg 2014).\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n27\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nThe lower rate of small for gestational age in the 'freeze all' strategy\nin our review is in agreement with the findings of a recent meta-\nanalysis (Maheshwari 2018). It has been hypothesised that because\nof a state of hyperestrogenism - due to hormonal stimulation of the\novaries - at time of fresh embryo transfer abnormal endometrial\nangiogenesis occurs and may lead to reduced implantation as\nwell as abnormal placentation. At the time of the frozen embryo\ntransfer, the effect of the ovarian stimulation is worn off and\ntherefore a frozen embryo transfer is performed in a more natural\nuterine environment compared to the fresh cycle (Healy 2010;\nKansal Kalra 2011). However, this hypothesis would also account\nfor findings such as more preterm deliveries and more low birth\nweight babies, which were not found in our meta-analysis.\nA U T H O R S ' /uni00A0 C O N C L U S I O N S\nImplications for practice\nWe found moderate-quality evidence showing that one strategy\nis probably not superior to the other in terms of cumulative\nlive birth rate and ongoing pregnancy rate. The risk of ovarian\nhyperstimulation syndrome (OHSS) may be decreased in the 'freeze\nall' strategy. We could not pool data for time to pregnancy. We\nassume it is shorter using a conventional in vitro fertilisation (IVF)\nor intracytoplasmic sperm injection (ICSI) strategy in the case of\nsimilar cumulative live birth rate, as embryo transfer is delayed in a\n'freeze all' strategy. The risk of maternal hypertensive disorders of\npregnancy, of having a large-for-gestational-age baby and a higher\nbirth weight of the children born may be increased following the\n'freeze all' strategy. We are uncertain if 'freeze all' strategy reduces\nthe risk of miscarriage or multiple pregnancy rate compared to\nconventional IVF/ICSI with fresh embryo transfer.\nImplications for research\nBased on moderate-quality evidence we state that one strategy\nis probably not superior to the other in terms of cumulative live\nbirth rate. In order to achieve high-quality evidence, well designed\nrandomised controlled trials (RCTs) reporting on cumulative\nlive birth rate instead of live birth rate a/f_ter the first transfer\nusing adequate and universal reporting of outcomes should be\nperformed. Time to a pregnancy leading to a live birth needs to\nbe reported with the date of randomisation as the starting point,\nin a way that incorporates the follow-up time of all randomised\nwomen. Time to pregnancy should be reported as Kaplan-Meier\ncurves, calculating hazard ratios, or calculating median survival\ntimes.\nRegarding pregnancy outcomes and obstetric, perinatal and\nneonatal outcomes, future RCTs and large cohort studies should\nconsider reporting neonatal outcomes not only per woman\nrandomised but also per (live) birth per randomised arm. In this\nway, the crude rates become more comparable across studies,\nwhereby better informed decisions can be made. To evaluate the\neffect of 'freeze all' on mothers and babies, an Individual Patient\nData analysis including both RCTs and cohort studies may gain\nmore insight into the differences in these outcomes we found in our\nreview. Another possibility may be to use registries.\nIn future studies, participant characteristics (e.g. women with good\nprognosis versus poor prognosis), treatment characteristics (e.g.\nnumber of available embryos, number of embryos transferred,\nresults for first and every subsequent transfer, time to pregnancy),\nand protocols used (e.g. timing/extended culture and method of\ncryopreservation, method of endometrial preparation for frozen\nembryo transfer) should be properly reported.\nA C K N O W L E D G E M E N T S\nWe would like to acknowledge the team at Cochrane Gynaecology\nand Fertility for their assistance, and especially Information\nSpecialist Marian Showell for the literature search. We acknowledge\nthe contribution of Kai Mee Wong to the previous version of this\nreview. We would like to acknowledge the valuable feedback of\nour peer reviewers – Dr. Paraskevi Vogiatzi, Wellington Martins,\nMamoona Javed and Jack Wilkinson. We would like to thank Kai\nMee Wong and Sjoerd Repping for their contribution to previous\nversions of the review.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n28\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nREFERENCES\n/uni00A0\nReferences to studies included in this review\nAflatoonian 2018 {published data only (unpublished sought but\nnot used)}\nAflatoonian/uni00A0A, Mansoori-Torshizi/uni00A0M, Mojtahedi/uni00A0MF,\nAflatoonian/uni00A0B, Khalili/uni00A0MA, Amir-Arjmand/uni00A0MH, et al. Fresh versus\nfrozen embryo transfer a/f_ter gonadotropin releasing hormone\nagonist trigger in gonadotropin releasing hormone antagonist\ncycles among high responder women: a randomized, multi-\ncenter study. International Journal of Reproductive BioMedicine\n2018;16(1):9-18.\nAghahosseini 2017 {published data only (unpublished sought but\nnot used)}\nAghahosseini/uni00A0M, Aleyasin/uni00A0A, Sarfjoo/uni00A0FS, Mahdavi/uni00A0A, Yaraghi/uni00A0M,\nSaeedabadi/uni00A0H. In vitro fertilization outcome in frozen versus\nfresh embryo transfer in women with elevated progesterone\nlevel on the day of HCG injection: an RCT. International Journal\nof Reproductive BioMedicine 2017;15(12):757-62.\nChen 2016 {published data only}\n*/uni00A0 Chen/uni00A0ZJ, Shi/uni00A0Y, Sun/uni00A0Y, Zhang/uni00A0B, Liang/uni00A0X, Cao/uni00A0Y, et al. Fresh\nversus frozen embryos for infertility in the polycystic ovary\nsyndrome. New England Journal of Medicine 2016;375(6):523-33.\n[DOI: 10.1056/NEJMoa1513873]\nZhang/uni00A0B, Wei/uni00A0D, Legro/uni00A0RS, Shi/uni00A0Y, Li/uni00A0J, Zhang/uni00A0L, et al. Obstetric\ncomplications a/f_ter frozen versus fresh embryo transfer\nin women with polycystic ovary syndrome: results from a\nrandomized trial. Fertility and Sterility 2018;109:324–9. [DOI:\nhttps://doi.org/10.1016/j.fertnstert.2017.10.020]\nCoates 2017 {published data only (unpublished sought but not\nused)}\nCoates/uni00A0A, Kung/uni00A0A, Mounts/uni00A0E, Hesla/uni00A0J, Bankowski/uni00A0B, Barbieri/uni00A0E,\net al. Optimal euploid embryo transfer strategy, fresh versus\nfrozen, a/f_ter preimplantation genetic screening with next\ngeneration sequencing: a randomized controlled trial. Fertility\nand Sterility 2017;107(3):723-30.\nFerraretti 1999 {published and unpublished data}\n*/uni00A0 Ferraretti/uni00A0AP, Gianaroli/uni00A0L, Magli/uni00A0C, Fortini/uni00A0D, Selman/uni00A0HA,\nFeliciani/uni00A0E. Elective cryopreservation of all pronucleate\nembryos in women at risk of ovarian hyperstimulation\nsyndrome: efficiency and safety. Human Reproduction\n1999;14:1457-60. [DOI: 10.1093/humrep/14.6.1457] [PMID:\n10357958 ]\nSantos-Ribeiro 2020 {published data only}\nSantos-Ribeiro/uni00A0S, Mackens/uni00A0S, Popovic-Todorovic/uni00A0B, Racca/uni00A0A,\nPolyzos/uni00A0NP, Van Landuyt/uni00A0L, et al. The freeze-all strategy versus\nagonist triggering with low-dose hCG for luteal phase support\nin IVF/ICSI for high responders: a randomized controlled trial.\nHuman Reproduction 2020;35(12):2808-18. [DOI: 10.1093/\nhumrep/deaa226]\nShapiro 2011a {published and unpublished data}\nShapiro/uni00A0BS, Daneshmand/uni00A0ST, Bedient/uni00A0CE, Garner/uni00A0FC.\nComparison of birth weights in patients randomly assigned\nto fresh or frozen-thawed embryo transfer. Fertility and\nSterility 2016;106:317–21. [DOI: http://dx.doi.org/10.1016/\nj.fertnstert.2016.03.049]\n*/uni00A0 Shapiro/uni00A0BS, Daneshmand/uni00A0ST, Garner/uni00A0FC, Aguirre/uni00A0M, Hudson/uni00A0C,\nThomas/uni00A0S. Evidence of impaired endometrial receptivity a/f_ter\novarian stimulation for in vitro fertilization: a prospective\nrandomized trial comparing fresh and frozen-thawed\nembryo transfer in normal responders. Fertility and Sterility\n2011;96:344-8. [DOI: 10.1016/j.fertnstert.2011.05.050] [PMID:\n21737072 ]\nShapiro 2011b {published and unpublished data}\nShapiro/uni00A0BS, Daneshmand/uni00A0ST, Bedient/uni00A0CE, Garner/uni00A0FC.\nComparison of birth weights inpatients randomly assigned\nto fresh or frozen-thawed embryo transfer. Fertility and\nSterility 2016;106:317–21. [DOI: http://dx.doi.org/10.1016/\nj.fertnstert.2016.03.049]\n*/uni00A0 Shapiro/uni00A0BS, Daneshmand/uni00A0ST, Garner/uni00A0FC, Aguirre/uni00A0M, Hudson/uni00A0C,\nThomas/uni00A0S. Evidence of impaired endometrial receptivity a/f_ter\novarian stimulation for in vitro fertilization: a prospective\nrandomized trial comparing fresh and frozen-thawed embryo\ntransfers in high responders. Fertility and Sterility 2011;96:516-8.\n[DOI: 10.1016/j.fertnstert.2011.02.059] [PMID: 21737071 ]\nShapiro 2016 {published data only}\nShapiro/uni00A0BS, Daneshmand/uni00A0ST, Bedient/uni00A0CE, Garner/uni00A0FC.\nComparison of birth weights inpatients randomly assigned to\nfresh or frozen-thawed embryo transfer. Fertility and Sterility\n2016;106:317-21.\nShi 2018 {published data only (unpublished sought but not used)}\nShi/uni00A0Y, Sun/uni00A0Y, Hao/uni00A0C, Zhang/uni00A0H, Wei/uni00A0D, Zhang/uni00A0Y, et al. Transfer of\nfresh versus frozen embryos in ovulatory women. New England\nJournal of Medicine 2018;378:126-38.\nStormlund 2020 {published data only}\nStormlund/uni00A0S, /uni00A0Sopa/uni00A0N, /uni00A0Zedeler/uni00A0A, Bogstad/uni00A0J, /uni00A0Prætorius/uni00A0L, Svarre\nNielsen/uni00A0H, /uni00A0et al. Freeze-all versus fresh blastocyst transfer\nstrategy during in vitro fertilisation in women with regular\nmenstrual cycles: multicentre randomised controlled trial. BMJ\n2020;370:m2519. [DOI: 10.1136/bmj.m2519]\nVuong 2018 {published data only}\nVuong/uni00A0LN, Dang/uni00A0VQ, Ho/uni00A0TM, Huynh/uni00A0BG, Ha/uni00A0DT, Pham/uni00A0TD,\net al. IVF transfer of fresh or frozen embryos in women\nwithout polycystic ovaries. New England Journal of Medicine\n2018;378(2):137-47. [DOI: 10.1056/NEJMoa1703768]\nWei 2019 {published data only}\nWei/uni00A0D, Liu J-Y, Sun/uni00A0Y, Shi/uni00A0Y, Zhang/uni00A0B, Liu J-Q, et al. Frozen\nversus fresh single blastocyst transfer in ovulatory\nwomen: a multicentre, randomised controlled trial. Lancet\n2019;393(10178):1310-18.\nWong 2021 {unpublished data only}\nWong/uni00A0KM, Van Wely/uni00A0M, Verhoeve/uni00A0HR, Kaaijk/uni00A0EM, Mol/uni00A0F, Van der\nVeen/uni00A0F, et al. Transfer of fresh or frozen embryos: a randomised\ncontrolled trial. Human Reproduction 2021:deaa305. [DOI:\ndoi.org/10.1093/humrep/deaa305]\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n29\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nZhang 2018 {published data only}\nZhang/uni00A0B, Wei/uni00A0D, Legro/uni00A0RS, Shi/uni00A0Y, Li/uni00A0J, Zhang/uni00A0L, et al. Obstetric\ncomplications a/f_ter frozen versus fresh embryo transfer\nin women with polycystic ovary syndrome: results from a\nrandomized trial. Fertility and Sterility 2018;109:324-9.\n/uni00A0\nReferences to studies excluded from this review\nAbsalan 2013 {published and unpublished data}\nAbsalan/uni00A0F, Ghannadi/uni00A0A, Kazerooni/uni00A0M. Reproductive outcome\nfollowing thawed embryo transfer in management of ovarian\nhyperstimulation syndrome. Journal of Reproduction and\nInfertility 2013;14(3):133-7. [PMID: 24163797 ]\nAflatoonian 2010 {published data only}\n*/uni00A0 Aflatoonian/uni00A0A, Oskouian/uni00A0H, Ahmadi/uni00A0S, Oskouian/uni00A0L. Can\nfresh embryo transfers be replaced by cryopreserved-thawed\nembryo transfers in assisted reproductive cycles? A randomized\ncontrolled trial. Journal of Assisted Reproduction and Genetics\n2010;27:357-63. [DOI: 10.1007/s10815-010-9412-9] [PMID:\n20373015 ]\nEditor and the ASRM Publications Committee. Retraction note\nto: Can fresh embryo transfers be replaced by cryopreserved-\nthawed embryo transfers in assisted reproductive cycles? A\nrandomized controlled trial. Journal of Assisted Reproduction\nand Genetics 2013;30(9):1245. [DOI: 10.1007] [PMID: 23975193 ]\nBeyer 2016 {published data only}\nBeyer/uni00A0DA, Griesinger/uni00A0G. Vitrified-warmed embryo transfer is\nassociated with mean higher singleton birth weight compared\nto fresh embryo transfer. European Journal of Obstetrics &\nGynecology and Reproductive Biology 2016;203:104–7.\nBoostanfar 2016 {published data only}\nBoostanfar/uni00A0R, Gates/uni00A0D, Guan/uni00A0Y, Gordon/uni00A0K, McCrary Sisk/uni00A0C,\nStegmann/uni00A0B. Efficacy and safety of frozen-thawed\nembryo transfer in women aged 35 to 42 years from the\nPURSUE randomized clinical trial. Fertility and Sterility\n2016;106(2):300-5.\nChandel 2016 {published data only}\nChandel/uni00A0NP, Bhat/uni00A0VV, Bhat/uni00A0BS, Chandel/uni00A0SS. Outcome analysis\nof day-3 frozen embryo transfer v/s fresh embryo transfer in\ninfertility: a prospective therapeutic study in Indian scenario.\nJournal of Obstetrics and Gynecology of India 2016;66(5):345–51.\nMagdi 2017 {published data only}\nMagdi/uni00A0Y, El-Damen/uni00A0A, Fathi/uni00A0AM, Abdelaziz/uni00A0AM, Youssef/uni00A0MA,\nAbd-Allah/uni00A0AA, et al. Revisiting the management of recurrent\nimplantation failure through freeze-all policy. Fertility and\nSterility 2017;108(1):72-7.\nSimon 2020 {published data only}NCT01954758\nSimón/uni00A0C, Gómez/uni00A0C, Cabanillas/uni00A0S, Vladimirov/uni00A0I, Castillón/uni00A0G,\nGiles/uni00A0J, et al, for the ERA-RCT Study Consortium Group. A\n5-year multicentre randomized controlled trial comparing\npersonalized, frozen and fresh blastocyst transfer in IVF.\nReproductive BioMedicine Online 2020;41(3):402-15. [DOI:\nhttps://doi.org/10.1016/j.rbmo.2020.06.002 1472- 6483/]\nYang 2015 {published data only}\nYang/uni00A0S, Pang/uni00A0T, Li/uni00A0R, Yang/uni00A0R, Zhen/uni00A0X, Chen/uni00A0X, et al. The\nindividualized choice of embryo transfer timing for patients\nwith elevated serum progesterone level on the HCG day in\nIVF/ICSI cycles: a prospective randomized clinical study.\nGynecological Endocrinology 2015;31(5):355-8. [PMID: 25558791]\n/uni00A0\nReferences to ongoing studies\nACTRN12612000422820 {unpublished data only}\nACTRN12612000422820. A randomised controlled trial to\ndetermine the effect of elective embryo cryopreservation and\nsubsequent transfer in a natural menstrual cycle on clinical\npregnancy rates in infertile females. www.anzctr.org.au/Trial/\nRegistration/TrialReview.aspx?id=362361 (first received 11 April\n2012).\nACTRN12616000643471 {unpublished data only}\nACTRN12616000643471. Fresh vs. elective frozen\nembryo transfer a/f_ter IVF: a randomised controlled trial.\nwww.anzctr.org.au/Trial/Registration/TrialReview.aspx?\nid=370373 (first received 24 March 2016).\nISRCTN61225414 {unpublished data only}\nISRCTN61225414. Freezing of embryos in assisted conception:\na randomised controlled trial evaluating the clinical and cost-\neffectiveness of a policy of freezing embryos followed by\nthawed frozen embryo transfer, compared with a policy of fresh\nembryo transfer in women undergoing in-vitro fertilization.\nwww.isrctn.com/ISRCTN61225414 (first received 24 December\n2015).\nNCT02133950 {unpublished data only}\nNCT02133950. Efficacy study of segmentation of PGD treatment.\nclinicaltrials.gov/ct2/show/NCT02133950 (first received 6 May\n2014).\nNCT02570386 {unpublished data only}\nNCT02570386. Clinical effectiveness of frozen thawed embryo\ntransfer compared to fresh embryo transfer. clinicaltrials.gov/\nct2/show/record/NCT02570386 (first received 29 September\n2015).\nNCT03349905 {published data only}\nNCT03349905. Deferred versus fresh embryo transfers\n(DEFETOSE). clinicaltrials.gov/ct2/show/NCT03349905 (first\nreceived September 2018).\n/uni00A0\nAdditional references\nBosdou 2019\nBosdou/uni00A0JK, Venetis/uni00A0CA, Tarlatzis/uni00A0BC, Grimbizis/uni00A0GF,\nKolibianakis/uni00A0EM. Higher probability of live-birth in high, but\nnot normal, responders a/f_ter first frozen-embryo transfer in a\nfreeze-only cycle strategy compared to fresh-embryo transfer: a\nmeta-analysis. Human Reproduction 2019;34:491-505.\nBourgain 2003\nBourgain/uni00A0C, Devroey/uni00A0P. The endometrium in stimulated cycles\nfor IVF. Human Reproduction Update 2003;9:515-22.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n30\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nCDC 2016\nCenters for Disease Control and Prevention. Assisted\nReproductive Technology Report; 2016. cdc.gov/nchs/fastats/\ninfertility.htm (accessed 15 July 2016).\nConrad 2011\nConrad/uni00A0KP. Emerging role of relaxin in the maternal adaptations\nto normal pregnancy: implications for preeclampsia. Seminars\nin Nephrology 2011;31:15-32.\nCovidence [Computer program]\nVeritas Health Innovation Covidence. Version accessed a/f_ter\n23 September 2020. Melbourne, Australia: Veritas Health\nInnovation. Available at covidence.org.\nD'Angelo 2017\nD'Angelo/uni00A0A, Amso/uni00A0NN, Hassan/uni00A0R. Coasting (withholding\ngonadotrophins) for preventing ovarian hyperstimulation\nsyndrome. Cochrane Database of Systematic Reviews 2017, Issue\n5. Art. No: CD002811. [DOI: 10.1002/14651858.CD002811.pub4]\nDeeks 2020\nDeeks/uni00A0JJ, Higgins/uni00A0JP, Altman DG (editors). Chapter 10: Analysing\ndata and undertaking meta-analyses. In: Higgins JP, Thomas\nJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA editor(s).\nCochrane Handbook for Systematic Reviews of Interventions\nVersion 6.1 (updated September 2020). Cochrane, 2020.\nAvailable from www.training.cochrane.org/handbook.\nDevroey 2011\nDevroey/uni00A0P, Polyzos/uni00A0NP, Blockeel/uni00A0C. An OHSS-free clinic\nby segmentation of IVF treatment. Human Reproduction\n2011;26:2593-7.\nErnstad 2019\nGinström Ernstad/uni00A0E, Wennerholm U-B, Khatibi/uni00A0A, Petzold/uni00A0M,\nChristina Bergh/uni00A0C. Neonatal and maternal outcome a/f_ter\nfrozen embryo transfer: increased risks in programmed\ncycles. American Journal of Obstetrics & Gynecology\n2019;221(2):126.e1-126.e18.\nEsh-Broder 2011\nEsh-Broder/uni00A0E, Ariel/uni00A0I, Abas-Bashir/uni00A0N, Bdolah/uni00A0Y, Celnikier/uni00A0DH.\nPlacenta accreta is associated with IVF pregnancies: a\nretrospective chart review. BJOG 2011;118:1084–9.\nESHRE 2018\nEuropean Society of Human Reproduction and Embryology\n(ESHRE). ART Fact Sheet; 2018. eshre.eu/~/media/sitecore-files/\nGuidelines/ART-fact-sheet_vFebr18_VG.pdf?la=en (accessed\nbefore 26 January 2021).\nEvans 2014\nEvans/uni00A0J, Hannan/uni00A0NJ, Edgell/uni00A0TA, Vollenhoven/uni00A0BJ, Lutjen/uni00A0PJ,\nOsianlis/uni00A0T, et al. Fresh versus frozen embryo transfer: backing\nclinical decisions with scientific and clinical evidence. Human\nReproduction Update 2014;20:808-21.\nFatemi 2015\nFatemi/uni00A0HM, Van Vaerenbergh/uni00A0I. Significance of premature\nprogesterone rise in IVF. Current Opinion in Obstetrics &\nGynecology 2015;3:242-8.\nFerraretti 1996\nFerraretti/uni00A0AP, Magli/uni00A0C, Feliciani/uni00A0E, Montanaro/uni00A0N, Gianaroli/uni00A0L.\nRelationship of timing of agonist administration in the cycle\nphase to the ovarian response to gonadotropins in the\nlong down-regulation protocols for assisted reproductive\ntechnologies. Fertility and Sterility 1996;65(1):114-21.\nFocus on Reproduction 2019\nFocus on Reproduction, ESHRE. The number of freeze-\nall cycles in IVF continues to increase 'dramatically'.\nfocusonreproduction.eu/article/ESHRE-News-Freeze-all-2\n(accessed before 26 January 2021).\nGRADEpro GDT [Computer program]\nMcMaster University (developed by Evidence Prime) GRADEpro\nGDT. Version accessed 18 november 2019. Hamilton (ON):\nMcMaster University (developed by Evidence Prime). Available\nat gradepro.org.\nGriesinger 2011\nGriesinger/uni00A0G, Schultz/uni00A0L, Bauer/uni00A0T, Broessner/uni00A0A, Frambach/uni00A0T,\nKissler/uni00A0S. Ovarian hyperstimulation syndrome prevention by\ngonadotropin-releasing hormone agonist triggering of final\noocyte maturation in a gonadotropin-releasing hormone\nantagonist protocol in combination with a \"freeze-all\"\nstrategy: a prospective multicentric study. Fertility and Sterility\n2011;6:2029-33, 2033 e1.\nHaouzi 2009\nHaouzi/uni00A0D, Assou/uni00A0S, Mahmoud/uni00A0K, Tondeur/uni00A0S, Reme/uni00A0T, Hedon/uni00A0B, et\nal. Gene expression profile of human endometrial receptivity:\ncomparison between natural and stimulated cycles for the\nsame patients. Human Reproduction 2009;24:1436-45.\nHealy 2010\nHealy/uni00A0DL, Breheny/uni00A0S, Halliday/uni00A0J, Jaques/uni00A0A, Rushford/uni00A0D, Garrett/uni00A0C,\net al. Prevalence and risk factors for obstetric haemorrhage in\n6730 singleton births a/f_ter assisted reproductive technology in\nVictoria Australia. Human Reproduction 2009;25:265-74.\nHiggins 2003\nHiggins/uni00A0JP, Thompson/uni00A0SG, Deeks/uni00A0JJ, Altman/uni00A0DG. Measuring\ninconsistency in meta-analyses. BMJ 2003;327:557-60.\nHiggins 2011\nHiggins/uni00A0JP, Altman/uni00A0DG, Sterne JA (editors). Chapter 8: Assessing\nrisk of bias in included studies. In: Higgins JP, Green S\n(editors). Cochrane Handbook for Systematic Reviews of\nInterventions Version 5.1.0 (updated March 2011). The Cochrane\nCollaboration, 2011. Available from training.cochrane.org/\nhandbook/archive/v5.1/.\nHull 1985\nHull/uni00A0MG, Glazener/uni00A0CM, Kelly/uni00A0NJ, Conway/uni00A0DI, Foster/uni00A0PA,\nHinton/uni00A0RA, et al. Population study of causes, treatment, and\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n31\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\noutcome of infertility. British Medical Journal (Clinical Research\nEd.) 1985;291:1693-7.\nIshihara 2014\nIshihara/uni00A0O, Araki/uni00A0R, Kuwahara/uni00A0A, Itakura/uni00A0A, Saito/uni00A0H, Adamson/uni00A0GD.\nImpact of frozen-thawed single-blastocyst transfer on maternal\nand neonatal outcome: an analysis of 277,042 single-embryo\ntransfer cycles from 2008 to 2010 in Japan. Fertility and Sterility\n2013;101:128-33.\nKansal Kalra 2011\nKansal Kalra/uni00A0S, Ratcliffe/uni00A0SJ, Milman/uni00A0L, Gracia/uni00A0CR, Coutifaris/uni00A0C,\nBarnhart/uni00A0KT. Perinatal morbidity a/f_ter in vitro fertilization\nis lower with frozen embryo transfer. Fertility and Sterility\n2011;95:548–53.\nKolibianakis 2002\nKolibianakis/uni00A0E, Bourgain/uni00A0C, Albano/uni00A0C, Osmanagaoglu/uni00A0K, Smitz/uni00A0J,\nVan Steirteghem/uni00A0A, et al. Effect of ovarian stimulation with\nrecombinant follicle-stimulating hormone, gonadotropin\nreleasing hormone antagonists, and human chorionic\ngonadotropin on endometrial maturation on the day of oocyte\npick-up. Fertility and Sterility 2002;78:1025-9.\nKosmas 2004\nKosmas/uni00A0IP, Kolibianakis/uni00A0EM, Devroey/uni00A0P. Association of estradiol\nlevels on the day of hCG administration and pregnancy\nachievement in IVF: a systematic review. Human Reproduction\n2004;19:2446-53.\nLuke 2017\nLuke/uni00A0B, Brown/uni00A0MB, Wantman/uni00A0E, Stern/uni00A0JE, Toner/uni00A0JP, Coddington\nCC 3rd. Increased risk of large-for-gestational age birthweight in\nsingleton siblings conceived with in vitro fertilization in frozen\nversus fresh cycles. Journal of Assisted/uni00A0Reproduction/uni00A0Genetics\n2016;34:191-200.\nMaheshwari 2012\nMaheshwari/uni00A0A, Pandey/uni00A0S, Shetty/uni00A0A, Hamilton/uni00A0M, Bhattacharya/uni00A0S.\nObstetric and perinatal outcomes in singleton pregnancies\nresulting from the transfer of frozen thawed versus fresh\nembryos generated through in vitro fertilization treatment:\na systematic review and meta-analysis. Fertility and Sterility\n2012;98:368-77.\nMaheshwari 2013\nMaheshwari/uni00A0A, Bhattacharya/uni00A0S. Elective frozen replacement\ncycles for all: ready for prime time? Human Reproduction\n2013;28:6-9.\nMaheshwari 2018\nMaheshwari/uni00A0A, Pandey/uni00A0S, Amalraj Raja/uni00A0E, Shetty/uni00A0A, Hamilton/uni00A0M,\nBhattacharya/uni00A0S. Is frozen embryo transfer better for mothers\nand babies? Can cumulative meta-analysis provide a definitive\nanswer? Human Reproduction Update 2017;24:35-58.\nMastenbroek 2011\nMastenbroek/uni00A0S, Van der Veen/uni00A0F, Aflatoonian/uni00A0A, Shapiro/uni00A0B,\nBossuyt/uni00A0P, Repping/uni00A0S. Embryo selection in IVF. Human\nReproduction 2011;26:964-6.\nMastenbroek 2014\nMastenbroek/uni00A0S, Repping/uni00A0S. Preimplantation genetic screening:\nback to the future. Human Reproduction 2014;29:1846-50.\nMoher 2009\nMoher/uni00A0D, Liberati/uni00A0A, Tetzlaff/uni00A0J, Altman/uni00A0DG. The PRISMA Group\n(2009). Preferred reporting items for systematic reviews\nand meta-analyses: the PRISMA Statement. PLoS Medicine\n6;7:e1000097. [DOI: 10.1371/journal.pmed1000097]\nMourad 2017\nMourad/uni00A0S, Brown/uni00A0J, Farquhar/uni00A0C. Interventions for the prevention\nof OHSS in ART cycles: an overview of Cochrane reviews.\nCochrane Database of Systematic Reviews 2017, Issue 1. Art. No:\nCD012103. [DOI: 10.1002/14651858.CD012103.pub2]\nOpdahl 2015\nOpdahl/uni00A0S, Henningsen/uni00A0AA, Tiitinen/uni00A0A, Bergh/uni00A0C, Pinborg/uni00A0A,\nRomundstad/uni00A0P, et al. Risk of hypertensive disorders in\npregnancies following assisted reproductive technology: a\ncohort study from the CoNARTaS group. Human Reproduction\n2015;30:1724-31.\nPereira 2016\nPereira/uni00A0N, Rosenwaks/uni00A0Z. A fresh(er) perspective on frozen\nembryo transfers. Ferility and Sterility 2016;106:257-8.\nPereira 2019\nPereira/uni00A0N, Petrini/uni00A0AC, Hancock/uni00A0KL, Rosenwaks/uni00A0Z. Fresh or frozen\nembryo transfer in in vitro fertilization: an update. Clinical\nObstetrics and Gynecology 2019;62:293-9.\nPinborg 2014\nPinborg/uni00A0A, Henningsen/uni00A0AA, Lo/f_t/uni00A0A, Malchau/uni00A0SS, Forman/uni00A0J,\nAndersen/uni00A0AN. Large baby syndrome in singletons born a/f_ter\nfrozen embryo transfer (FET): is it due to maternal factors or the\ncryotechnique? Human Reproduction 2014;29:618-27.\nReview Manager 2020 [Computer program]\nThe Cochrane Collaboration Review Manager 5 (RevMan 5).\nVersion 5.4. Copenhagen: The Cochrane Collaboration, 2020.\nRevMan Web 2019 [Computer program]\nThe Cochrane Collaboration Review Manager Web (RevMan\nWeb). The Cochrane Collaboration, 2019. Available\nat/uni00A0revman.cochrane.org.\nRoque 2017\nRoque/uni00A0M, Valle/uni00A0M, Kostolias/uni00A0A, Sampaio/uni00A0M, Geber/uni00A0S. Freeze-all\ncycle in reproductive medicine: current perspectives. JBRA\nAssisted Reproduction 2017;21(1):49-53.\nRoque 2019\nRoque/uni00A0M, Valle/uni00A0M, Sampaio/uni00A0M, Geber/uni00A0S. Obstetric outcomes\na/f_ter fresh versus frozen-thawed embryo transfers: a systematic\nreview and meta-analysis. JBRA Assisted Reproduction\n2018;22:253-60.\nSaito 2019\nSaito/uni00A0K, Kuwahara/uni00A0A, Ishikawa/uni00A0T, Morisaki/uni00A0N, Miyado/uni00A0M,\nMiyado/uni00A0K, et al. Endometrial preparation methods for frozen-\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n32\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nthawed embryo transfer are associated with altered risks\nof hypertensive disorders of pregnancy, placenta accreta,\nand gestational diabetes mellitus. Human Reproduction\n2019;34(8):1567-75.\nSazonova 2012\nSazonova/uni00A0A, Kallen/uni00A0K, Thurin-Kjellberg/uni00A0A, Wennerholm/uni00A0UB,\nBergh/uni00A0C. Obstetric outcome in singletons a/f_ter in vitro\nfertilization with cryopreserved/thawed embryos. Human\nReproduction 2012;27:1343-50.\nSchatz 2016\nSchatz/uni00A0F, Guzeloglu-Kayisli/uni00A0O, Arlier/uni00A0S, Kayisli/uni00A0UA, Lockwood/uni00A0CJ.\nThe role of decidual cells in uterine hemostasis, menstruation,\ninflammation, adverse pregnancy outcomes and abnormal\nuterine bleeding. Human Reproduction Update 2016;4:497-515.\nSchünemann 2020\nSchünemann/uni00A0HJ, Higgins/uni00A0JP, Vist/uni00A0GE, Glasziou/uni00A0P, Akl/uni00A0EA,\nSkoetz/uni00A0N, et al. Chapter 14: Completing ‘Summary of findings’\ntables and grading the certainty of the evidence. In: Higgins\nJP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch\nVA, editor(s). Cochrane Handbook for Systematic Reviews of\nInterventions Version 6.1 (updated September 2020). Cochrane,\n2020. Available from www.training.cochrane.org/handbook.\nSingh 2020\nSingh/uni00A0B, Reschke/uni00A0L, Segars/uni00A0J, Baker/uni00A0VL. Frozen-thawed embryo\ntransfer: the potential importance of the corpus luteum in\npreventing obstetrical complications. Fertility and Sterility\n2020;113:252-7.\nSpijkers 2017\nSpijkers/uni00A0S, Lens/uni00A0JW, Schats/uni00A0R, Lambalk/uni00A0CB. Fresh and frozen-\nthawed embryo transfer compared to natural conception:\ndifferences in perinatal outcome. Gynecologic and Obstetric\nInvestigation 2017;82:538-46.\nTakeshima 2016\nTakeshima/uni00A0K, Jwa/uni00A0SC, Saito/uni00A0H, Nakaza/uni00A0A, Kuwahara/uni00A0A,\nIshihara/uni00A0O, et al. Impact of single embryo transfer policy on\nperinatal outcomes in fresh and frozen cycles-analysis of the\nJapanese assisted reproduction technology registry between\n2007 and 2012. Fertility and Sterility 2016;105:337-46.\nVail 2003\nVail/uni00A0A, Gardener/uni00A0E. Common statistical errors in the design\nand analysis of subfertility trials. Human Reproduction\n2003;18:1000-4.\nVan Vaerenbergh 2009\nVan Vaerenbergh/uni00A0I, Van Lommel/uni00A0L, Ghislain/uni00A0V, In't Veld/uni00A0P,\nSchuit/uni00A0F, Fatemi/uni00A0H, et al. In GnRH antagonist/rec-FSH stimulated\ncycles, advanced endometrial maturation on the day of oocyte\nretrieval correlates with altered gene expression. Human\nReproduction 2009;24:1085-91.\nVan Voorhis 2007\nVan Voorhis/uni00A0BJ. Clinical practice. In vitro fertilization. New\nEngland Journal of Medicine 2007;356:379-86.\nVenetis 2013\nVenetis/uni00A0CA, Kolibianakis/uni00A0EM, Bosdou/uni00A0JK, Tarlatzis/uni00A0BC.\nProgesterone elevation and probability of pregnancy a/f_ter IVF:\na systematic review and meta-analysis of over 60 000 cycles.\nHuman Reproduction Update 2013;19:433-57.\nVenetis 2015\nVenetis/uni00A0CA, Kolibianakis/uni00A0EM, Bosdou/uni00A0JK, Lainas/uni00A0GT,\nSfontouris/uni00A0IA, Tarlatzis/uni00A0BC, et al. Estimating the net effect\nof progesterone elevation on the day of hCG on live birth\nrates a/f_ter IVF: a cohort analysis of 3296 IVF cycles. Human\nReproduction 2015;30:684-91.\nVenetis 2016\nVenetis/uni00A0CA, Kolibianakis/uni00A0EM, Bosdou/uni00A0JK, Lainas/uni00A0GT,\nSfontouris/uni00A0IA, Tarlatzis/uni00A0BC, et al. Basal serum progesterone\nand history of elevated progesterone on the day of hCG\nadministration are significant predictors of late follicular\nprogesterone elevation in GnRH antagonist IVF cycles. Human\nReproduction 2016;31:1859-65.\nvon Versen-Höynck 2019a\nvon/uni00A0Versen-Höynck/uni00A0F, Schaub/uni00A0AM, Chi Y-Y, Chiu K-H, Liu/uni00A0J,\nLingis/uni00A0M, et al. Increased preeclampsia risk and reduced aortic\ncompliance with in vitro fertilization cycles in the absence of a\ncorpus luteum. Hypertension 2019;73:640-9.\nvon Versen-Höynck/uni00A02019b\nvon/uni00A0Versen-Höynck/uni00A0F, Strauch/uni00A0NK, Liu/uni00A0J, Chi/uni00A0YY, Keller-Woods/uni00A0M,\nConrad/uni00A0KP, et al. Effect of mode of conception on maternal\nserum relaxin, creatinine, and sodium concentrations in an\ninfertile population. Reproductive Sciences (Thousand Oaks,\nCalif.) 2019;26:412-19.\nWong 2014\nWong/uni00A0KM, Mastenbroek/uni00A0S, Repping/uni00A0S. Cryopreservation of\nhuman embryos and its contribution to IVF success rates.\nFertility and Sterility 2014;102(1):19-26.\nYoussef 2016\nYoussef/uni00A0MA, Mourad/uni00A0S. Volume expanders for the prevention\nof ovarian hyperstimulation syndrome. Cochrane Database\nof Systematic Reviews 2016, Issue 8. Art. No: CD001302. [DOI:\n10.1002/14651858.CD001302.pub3]\nZaat 2019\nZaat/uni00A0T, Mol/uni00A0F, Van Wely/uni00A0M, Wilkinson/uni00A0J, Mastenbroek/uni00A0S. Fresh\nversus frozen blastocyst transfer. Lancet 2019;394(10204):1227.\n[DOI: doi.org/10.1016/S0140-6736(19)31392-3]\nZegers-Hochschild 2017\nZegers-Hochschild/uni00A0F, Adamson/uni00A0GD, Dyer/uni00A0S, Racowsky/uni00A0C,\nde/uni00A0Mouzon/uni00A0J, Sokol/uni00A0R, et al. The international glossary on\ninfertility and fertility care, 2017. Human Reproduction\n2017;32:1786-801.\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n33\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nReferences to other published versions of this review\nWong 2017\nWong/uni00A0KM, Van Wely/uni00A0M, Mol/uni00A0F, Repping/uni00A0S, Mastenbroek/uni00A0S. Fresh\nversus frozen embryo transfers in assisted reproduction.\nCochrane Database of Systematic Reviews 2017, Issue 3. Art. No:\nCD011184. [DOI: 10.1002/14651858.CD011184.pub2]\n/uni00A0\n* Indicates the major publication for the study\n/uni00A0\nC H A R A C T E R I S T I C S /uni00A0 O F /uni00A0 S T U D I E S\nCharacteristics of included studies [ordered by study ID]\n/uni00A0\nStudy characteristics\nMethods Multicentre RCT\nConducted: in 3 fertility clinics throughout Iran\nEnrolment: January 2014-January 2017\nPower calculation: stated\nRandomisation: computer-generated random numbers in wrapped, unlabeled envelope each holding a\nunique number\nTiming randomisation: at day of oocyte retrieval\nNature of intervention: day-2 embryo cryopreservation by means of vitrification\nFollow-up: LBR after the first ET\nParticipants 240 women (121 freeze-all, 119 control)\nInclusion criteria:\n• women with OHSS risk\n• Age between 20-40 years\n• A number of 14- 25 follicles ≥ 12 mm on the day of trigger\n• BMI > 18 and < 35 kg/m2\nExclusion criteria were: women with < 14 and > 25 follicles ≥ 12 mm on the day of trigger, women with a\nprevious history of OHSS development, endocrine disorders and > 40 years of age\nInterventions In the fresh transfer group, 2 embryos of good or excellent quality were transferred 48-72 h after oocyte\nretrieval. In the fresh transfer group, 1500 IU hCG was administered on the day of ET. Moreover, proges-\nterone suppositories 400 mg twice daily were administered vaginally, from the day of oocyte retrieval\nuntil the observation of fetal heart activity by ultrasound in the 8th week.\nIn the freeze-all group embryos were vitrified on day 2 after oocyte collection. The subsequent cycle\nwas considered as a study cycle. The endometrium was artificially prepared prior to transfer in freeze-\nall group. ET was performed 3 days after the beginning of progesterone administration.\nOutcomes Primary outcome was clinical pregnancy, defined as observation of fetal heart activity by transvaginal\nultrasonography 2-3 weeks after positive β-hCG. Secondary outcomes included chemical pregnancy,\nLBR, OHSS development and perinatal data.\nNotes Funding: by Yazd Reproductive Sciences Institute. 2 of the authors reported conflicts of interest be-\ncause they received unrestricted research grants from MSD, Merck and Ferring, as well as honoraria for\nlectures.\nWe requested additional information regarding cumulative data from the study authors by email but\nwe did not receive a response.\nAflatoonian 2018/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n34\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Computer-generated random numbers\nAllocation concealment\n(selection bias)\nLow risk Wrapped, unlabeled envelope each holding a unique number\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nUnclear risk All registered outcomes were reported.\nStudy was registered in a prospective trials register with the trial number: IRC-\nT2016092224512N4. However, the study was registered while recruiting as it is\nstated in the trials register.\nOther bias Unclear risk (Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison\nof results after first transfer in frozen group vs results after first 2 transfers in\nfresh group).\nAflatoonian 2018/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Multicentre RCT\nConducted: in 2 fertility clinics in Teheran, Iran\nEnrolment: January 2016-April 2016\nPower calculation: stated\nRandomisation: computer-generated random numbers in wrapped, unlabeled envelope each holding a\nunique number\nTiming randomisation: at day of oocyte retrieval, after retrieval\nNature of intervention: blastocyst (day 5) cryopreservation by means of vitrification\nFollow-up: LBR after the first ET\nParticipants 72 women (36 freeze-all, 36 control)\nInclusion criteria:\nAghahosseini 2017/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n35\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n• Infertile women (information from manuscript)\n• Women undergoing IVF with their own eggs (information from trials register)\n• women with normal HSG and ultrasound of the uterine cavity (information from trials register)\nExclusion criteria were: uterine anomaly or previous uterine surgery, oocyte donation, azoospermia,\nsevere endometriosis, previous chemotherapy or radiotherapy, conditions affecting the reproductive\nstatus.\nInterventions In the conventional IVF strategy group, a total of 1 or 2 blastocysts (grade A) were transferred at 5th\nday. Luteal phase support was carried out for all participants. In the freeze-all strategy, all embryos\nwere cryopreserved by vitrification and after 2 menstrual cycles, artificial endometrial preparation was\nperformed. A total of 1 or 2 grade A thawed blastocysts were transferred.\nOutcomes Primary outcome was clinical pregnancy, defined as a gestational sac with a live fetus on ultrasound 5\nweeks after transfer. Secondary outcomes were not specified in the manuscript.\nNotes Funding was not reported.\nWe requested additional information regarding cumulative data from the authors by email but we did\nnot receive a response.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nUnclear risk Authors state that women were randomly allocated using random allocation\nsoftware, no further information provided.\nAllocation concealment\n(selection bias)\nUnclear risk Authors state that women were randomly allocated using random allocation\nsoftware, no further information provided.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nUnclear risk Study was registered in a prospective trials register with the trial number: IRC-\nT2016122131508N1. However, the study was registered while recruiting as it is\nstated in the trials register.\nOther bias Unclear risk (Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison\nof results after first transfer in frozen group vs results after first 2 transfers in\nfresh group).\nAghahosseini 2017/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nChen 2016/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n36\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nMethods Multicentre RCT\nConducted: in 14 reproductive medical centres throughout China\nEnrolment: June 2013-May 2014\nPower calculation: stated\nRandomisation: an online central randomisation system (www.medresman.org) was used\nTiming randomisation: at day of oocyte retrieval\nNature of intervention: day-3 embryo cryopreservation by means of vitrification. Local investigators\nhad the option to transfer day-2 embryos if there were < 3 embryos on day 2\nFollow-up: cumulative live birth (including all FETs performed within 12 months after the initial trans-\nfer)\nParticipants 1508 women (746 freeze-all, 762 control)\nInclusion criteria:\n• PCOS, using modified Rotterdam criteria (which included menstrual abnormalities (irregular uterine\nbleeding, oligomenorrhoea, or amenorrhoea) combined with either hyperandrogenism or polycystic\novaries)\n• first IVF cycle\nExclusion criteria: history of unilateral oophorectomy, recurrent spontaneous abortion (defined as ≥ 3\nprevious spontaneous pregnancy losses), congenital or acquired uterine malformations, abnormal re-\nsults on parental karyotyping, or medical conditions that contraindicated ART or pregnancy\nInterventions For women who were assigned to the fresh embryo group, on day 3, 2 high-quality embryos were\npicked out for fresh transfer and supernumerary embryos were transferred by means of vitrification.\nFor women who were assigned to the FET group, there was no fresh transfer as all day-3 embryos were\ncryopreserved for later transfer. Local investigators had the option to transfer day-2 embryos if there\nwere < 3 embryos on day 2. In cycles following the menstrual cycle with ovum pick-up, after artificial\nendometrial preparation, on day 4 of the progesterone regimen, 2 day-3 frozen embryos were thawed\nand transferred.\nOutcomes Primary outcome was a live birth, defined as delivery of any viable infant at ≥ 28 weeks of gestation\nduring the first ET. Prespecified secondary outcomes included biochemical pregnancy, clinical preg-\nnancy, ongoing pregnancy, singleton LBR, cLBR (including subsequent FET), pregnancy loss, moderate\nor severe OHSS, ectopic pregnancy, pregnancy and neonatal complications, and congenital anomalies.\nNotes Funding: supported by a grant from the National Basic Research Program of China, by grants from the\nNational Natural Science Foundation of China, and by grants from the Thousand Talents Program (to\nDrs. Legro and H. Zhang).\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk An online central randomisation system (www.medresman.org) was used to\nautomatically generate the assignment sequence\nAllocation concealment\n(selection bias)\nLow risk Assignment sequence was unknown to the clinical investigators\nChen 2016/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n37\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nHigh risk Some prespecified outcomes (e.g. time to pregnancy) were missing from the\nreport\nOther bias Unclear risk Not reported on blinding of doctors to interim analyses of outcomes of the\nstudy. Blinding of investigators was not reported (which is relevant for deter-\nmining end of study).\nChen 2016/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT\nConducted: Oregon Reproductive Medicine Center\nEnrolment: December 2013-August 2015\nPower calculation: stated\nRandomisation: stratified block randomisation sequence was prepared by a professional third party\n(sealedenvelope.com). The allocation sequence was stratified for female age (< 35, 35–37, 38–40, and\n41–42 years) and number of prior ART cycles (%2 or R3).\nTiming of randomisation: at time of hCG administration (trigger)\nNature of intervention: day-6 embryo cryopreservation by means of vitrification.\nFollow-up: LBR after the first ET\nParticipants 179 women (91 freeze-all, 88 control)\nInclusion criteria:\n• Age between 18 and 42 years\n• Undergoing IVF and PGS\n• Using own eggs\nExclusion criteria: the need to use surgically retrieved sperm (microsurgical epididymal sperm aspira-\ntion (MESA) or testicular sperm aspiration (TESA)), women using preimplantation genetic diagnosis for\na single-gene or chromosomal disorder, egg donor cycles, gender selection cycles, decreased ovarian\nreserve indicated by early follicular phase serum FSH level > 10 IU/L or random serum AMH level < 1 ng/\nmL, and any medical reasons occurring before recruitment that would not allow a participant to under-\ngo a fresh ET such as the need for uterine surgery before transfer.\nCoates 2017/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n38\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nInterventions Assisted hatching was performed on all embryos on day 3 after retrieval. The embryos were transferred\nback to culture media until day 5 or day 6 of development. Embryos were biopsied for PGS on day 5 or\n6, based on the development of the hatching process.\nwomen had either 1 or 2 embryos transferred depending on availability of euploid embryos and\nwoman's request. Women assigned to the conventional strategy received 1 or 2 fresh embryos on day\n6, any remaining embryos were frozen.\nIn the FET group, there was no fresh transfer and available embryos had been cryopreserved on day 6\nby means vitrification. In menstrual cycles following the ovum pick-up the endometrium was artificially\nprepared for transfer using estradiol and progesterone for transfer of a maximum of 2 embryos.\nOutcomes The primary outcomes were: implantation rates (number of gestational sacs divided by the number of\nembryos transferred per group), ongoing pregnancy rates (defined as a pregnancy beyond 8 weeks),\nand LBR after the first ET.\nNo prespecified secondary outcomes were stated in the manuscript. In the trial registration the follow-\ning secondary outcome was stated: determining retrospectively if mitochondrial DNA content is linked\nto implantation potential and if that is measurable by NGS.\nNotes Funding: supported by Life Technologies, Carlsbad, CA; Oregon Reproductive Medicine, Portland; and\nReprogenetics, NJ\nWe requested additional information regarding cumulative data from the authors by email but we did\nnot receive a response.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Stratified block randomisation sequence was prepared by a professional third\nparty (sealedenvelope.com).\nAllocation concealment\n(selection bias)\nUnclear risk No information provided\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nUnclear risk Not all registered outcomes were reported (correlation of mitochondrial DNA\nand implantation)\nNot all reported outcomes were registered (ongoing pregnancy rates, and LBR\nafter the first ET)\nStudy was registered in a prospective trials register with the trial number:\nNCT02000349.\nOther bias Unclear risk 3 of the authors disclosed to be co-owner of Oregon Reproductive Medicine. 2\nof the authors reported to be founding partner for Reprogenetics.\nCoates 2017/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n39\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n(Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup).\nCoates 2017/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT\nConducted: in Italy\nEnrolment: January 1996-July 1997\nPower calculation: not reported\nRandomisation: allocation was performed with sealed envelopes\nTiming of randomisation: not reported\nNature of intervention: slow freezing\nFollow-up: until no cryopreserved embryos were le/f_t or delivery of child\nParticipants 125 women (58 freeze-all, 67 control)\nInclusion criteria: all women with a high level of oestradiol the day of hCG administration (oestradiol ≥\n1500 pg/mL or ≥ 5.500 mmol/mL (conversion factor to SI unit 53.671)) and a high number of retrieved\neggs (≥ 15 oocytes)\nInterventions Intervention: zygotes were cryopreserved, 3 or 4 zygotes were thawed and cultured for 36-40 h before\nET. If ≥ 2 zygotes did not cleave 24 h after being cultured, 1 or 2 additional zygotes were thawed.\nControl: zygotes were cultured for a subsequent 48 h, 3 or 4 fresh embryos were transferred, surplus\nembryos were cryopreserved\nOutcomes Clinical pregnancies: gestational sac and fetal heartbeat by ultrasound\nNotes Funding was not reported.\nAdditional information was obtained from the study authors by email.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nUnclear risk No information about method of randomisation available. Randomisation was\nused, but it is unclear how.\nAllocation concealment\n(selection bias)\nUnclear risk No information about method of allocation concealment available.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nFerraretti 1999/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n40\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nUnclear risk No protocol available. This trial was not registered because these registries did\nnot exist at the time this study was performed.\nOther bias High risk No power calculation reported. Unclear what determined the end of study.\n(Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup).\nFerraretti 1999/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT\nConducted: in Belgium/uni00A0\nEnrolment: May 2014-2017\nPower calculation: stated\nRandomisation:/uni00A0performed using a computer-generated randomisation list (SPSS/uni00A0Version 20VR, IBM\nCorporation, New York, USA). Each entry of\nthe list was sealed in a sequentially numbered opaque envelope and/uni00A0allocated in that order to women.\nParticipating physicians did not have access to the randomisation list.\nTiming of randomisation: prior to oocyte retrieval\nNature of intervention: vitrification/uni00A0\nFollow-up: 24 months after randomisation/uni00A0\nParticipants 212 women (106/uni00A0freeze-all, 106/uni00A0control)\nInclusion criteria:/uni00A0women with an excessive response to ovarian stimulation (≥ 18 follicles/uni00A0measuring/uni00A0≥\n11 mm on the day of the GnRH triggering), GnRH antagonist suppression, age between 18-40 years,\nfirst/second ART cycle in the centre, planned placement of 1 or 2 blastocysts./uni00A0\nInterventions Intervention:/uni00A0all viable embryos were vitrified, preferably at blastocyst stage (Day 5 or 6), according\nto the/uni00A0threshold of good-quality embryos available on day/uni00A03. After thaw, 1 or 2/uni00A0frozen embryo(s) were\ntransferred, scheduled/uni00A0according to the developmental stage of the embryo.\nControl: fresh transfer of day 3 or 5 of/uni00A0development with preference to the latter whenever at least 4\ngood-quality embryos/uni00A0were available on day 3.\nIn women who were assigned to the fresh embryo group, luteal-phase support was started immediate-\nly after oocyte retrieval and was continued until the day of serum hCG testing. On day 2 or 3 of the em-\nbryo culture, up to 2 embryos were selected and transferred.\nIn women who were assigned to the FET group, all the embryos were vitrified. 2 good-quality embryos\nwere vitrified on day 2 or day 3, and the other embryos could be vitrified at the cleavage or blastocyst\nSantos-Ribeiro 2020/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n41\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nstage. At the second spontaneous menstrual cycle after oocyte retrieval, natural ovulation was moni-\ntored by means of ultrasonography. Luteal-phase support was started from the day of ovulation. Up to\ntwo day 2 or day 3 frozen embryos were thawed and transferred 2 or 3 days, after ovulation. If the nat-\nural ovulation cycle was cancelled owing to anovulation or poor endometrial development, an artificial\ncycle was used for endometrial preparation in the next menstrual cycle.\nOutcomes • Clinical pregnancy at 7 weeks of gestational age; defined/uni00A0as the visualisation of/uni00A0≥ 1 gestational sacs\n(including an ectopic pregnancy) during/uni00A0transvaginal ultrasound\n• hCG-positive (assessed in the serum/uni00A012–14 days after ET)\n• LBR (after/uni00A024 weeks)\n• Incidence of moderate to severe OHSS\n• Biochemical pregnancy\n• Clinical miscarriage\n• Ectopic pregnancy\nNotes Funding: this research received no specific grant from any funding agency in the/uni00A0public, commercial or\nnot-for-profit sectors.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk By means of a computer-generated randomisation list (SPSS/uni00A0Version 20VR, IBM\nCorporation, New York, USA)\nAllocation concealment\n(selection bias)\nLow risk Each entry of/uni00A0the list was sealed in a sequentially numbered opaque enve-\nlope and/uni00A0allocated in that order to women. Participating physicians did not\nhave/uni00A0access to the randomisation list.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women according to ITT./uni00A0\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes reported.\nStudy was registered in a prospective trials register with the trial number:/uni00A0NC-\nT02148393.\nOther bias Low risk The study appears to be free of other sources of bias.\nSantos-Ribeiro 2020/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT\nConducted: USA\nShapiro 2011a/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n42\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nEnrolment: October 2007-October 2010\nPower calculation: stated. However, study was prematurely terminated after interim analysis\nRandomisation: performed by random drawing among identical, opaque, unmarked sealed envelopes\nTiming of randomisation: after oocyte retrieval\nNature of intervention: slow freezing\nFollow-up: clinical pregnancy after first ET\nParticipants 137 women (70 freeze-all, 67 fresh transfer)\nInclusion criteria:\n• Women must be undergoing her first IVF cycle\n• Cycle day 3 FSH < 10 IU/L\n• 8-15 antral follicles observed on baseline ultrasound scan\nExclusion criteria: genetic testing of embryos was excluded.\nInterventions Intervention: 2pn oocytes were frozen, and entire cohorts of frozen 2pn oocytes were thawed and sub-\nsequently cultured to the blastocyst stage. The morphologically best 1 or 2 blastocysts were trans-\nferred on the first day on which at least 1 good expanded blastocyst appeared. Supernumerary expand-\ned blastocysts of high quality were cryopreserved.\nControl: fresh blastocysts transfer\nOutcomes • Pregnancy: serum hCG levels within 10 days after blastocyst transfer\n• Clinical pregnancy: fetal heart motion at 7 weeks' gestation\n• Ongoing pregnancy: fetal heart motion at 10 weeks' gestation\n• Implantation rate: proportion of transferred blastocysts that resulted in fetal heart motion (monozy-\ngotic twins with fetal heart motion counted as single implantations)\n• Early pregnancy losses: pregnancies that did not become ongoing pregnancies\nNotes Funding: research grant from the Investigator-Initatiated trial research grant from Ferring Pharmaceu-\nticals, Parsippany, NJ. Medications for this study were also provided by Ferring Pharmaceuticals.\nTime period was obtained from trials register\nAdditional information was obtained from study authors by email.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nUnclear risk Random sequence generation was not reported.\nAllocation concealment\n(selection bias)\nLow risk Drawing randomly among identical, opaque, unmarked, sealed envelopes.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nShapiro 2011a/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n43\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAll outcomes\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nUnclear risk Data were not reported for all women randomised, but per transfer. Dropouts\nand loss to follow-up were not accounted for in the analysis. No ITT analy-\nsis was performed. Sufficient data available for analysis per woman in meta-\nanalysis. Ongoing pregnancy was determined at 10 weeks' gestation instead of\n12 weeks' gestation.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes reported\nStudy was registered in a prospective trials register with the trial number:\nNCT00963625.\nOther bias Unclear risk Study was pre-terminated after interim analysis. Interim analysis was pre-\nplanned, but calculated per transfer (unit of analysis error) with a P value of\n0.03, overestimating possible effects.\n(Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup).\nShapiro 2011a/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT\nConducted: USA\nEnrolment: July 2007-July 2010\nPower calculation: stated (referred to Shapiro 2011a). However, study was terminated because of dif-\nfering embryo quality between the 2 groups.\nRandomisation: performed by random drawing among identical, opaque, unmarked, sealed envelopes\nTiming of randomisation: after oocyte retrieval\nNature of intervention: slow freezing\nFollow-up: clinical pregnancy after 1 ET\nParticipants 122 women (60 freeze-all, 62 control)\nInclusion criteria:\n• First cycle\n• Cycle day 3 FSH < 10 IU/L\n• > 15 antral follicles observed on baseline ultrasound examination\nExclusion criteria: genetic testing of embryos was excluded.\nInterventions Intervention: 2pn oocytes were frozen, and entire cohorts of frozen 2pn oocytes were thawed and sub-\nsequently cultured to the blastocyst stage. The morphologically best 1 or 2 blastocysts were trans-\nferred on the first day on which at least 1 good expanded blastocyst appeared. Supernumerary expand-\ned blastocysts of high quality were cryopreserved.\nControl: fresh blastocysts transfer\nShapiro 2011b/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n44\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nOutcomes • Pregnancy: serum hCG levels within 10 days after blastocyst transfer\n• Clinical pregnancy: fetal heart motion at 6-7 weeks' gestation\n• Ongoing pregnancy: fetal heart motion at 10 weeks' gestation\n• Implantation rate: ratio of the number of observed fetal hearts to the number of transferred blasto-\ncysts\n• Early pregnancy losses: pregnancies that did not become ongoing pregnancies\nNotes Funding: research grant from the Investigator-Initatiated Studies Program of Merck Sharp & Dohme\nTime period was obtained from trial register. Additional information was obtained from study authors\nby email.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nUnclear risk Random sequence generation was not reported.\nAllocation concealment\n(selection bias)\nLow risk Drawing randomly among identical, opaque, unmarked, sealed envelopes\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nUnclear risk Data were not reported for all women randomised, but per transfer. Dropouts\nand loss to follow-up were not accounted for in the analysis. No ITT analy-\nsis was performed. Sufficient data available for analysis per woman in meta-\nanalysis. Ongoing pregnancy was determined at 10 weeks' gestation instead of\n12 weeks' gestation.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes reported\nStudy was registered in a prospective trials register with the trial number:\nNCT00963079.\nOther bias Unclear risk Trial was pre-terminated after interim analysis. Interim analysis was pre-\nplanned, but calculated per transfer (unit of analysis error) with a P value of\n0.03, overestimating possible effects. Stopping rules for interim analysis (em-\nbryo quality) were unclear.\n(Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup).\nShapiro 2011b/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Post hoc analysis of the results of 2 single-centre RCTs (Shapiro 2011a and Shapiro 2011b)\nShapiro 2016/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n45\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nConducted: USA\nEnrolment: July 2007-July 2010\nPower calculation: stated (referred to Shapiro 2011a). However, study was terminated because of dif-\nfering embryo quality between the 2 groups.\nRandomisation: performed by random drawing among identical, opaque, unmarked, sealed envelopes\nTiming of randomisation: after oocyte retrieval\nNature of intervention: slow freezing\nFollow-up: live birth, birth weight\nParticipants The 2 combined RCTs included 259 women (130 freeze-all, 129 control)\nInclusion criteria:\n• First cycle\n• Cycle day 3 FSH < 10 IU/L\n• > 15 antral follicles observed on baseline ultrasound examination\nExclusion criteria: genetic testing of embryos was excluded.\nInterventions Intervention: 2pn oocytes were frozen, and entire cohorts of frozen 2pn oocytes were thawed and sub-\nsequently cultured to the blastocyst stage. The morphologically best 1 or 2 blastocysts were trans-\nferred on the first day on which at least 1 good expanded blastocyst appeared. Supernumerary expand-\ned blastocysts of high quality were cryopreserved.\nControl: fresh blastocysts transfer\nOutcomes • Birth weight\nNotes Funding was not reported.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Drawing randomly among identical, opaque, unmarked, sealed envelopes.\nAllocation concealment\n(selection bias)\nLow risk Drawing randomly among identical, opaque, unmarked, sealed envelopes.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nUnclear risk Data were not reported for all women randomised, but per transfer. Dropouts\nand loss to follow-up were not accounted for in the analysis. No ITT analy-\nsis was performed. Sufficient data available for analysis per woman in meta-\nanalysis. Ongoing pregnancy was determined at 10 weeks' gestation instead of\n12 weeks' gestation.\nShapiro 2016/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n46\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes reported.\nBoth studies used for this follow-up study were registered in a prospective tri-\nals register with the trial numbers NCT00963625 and NCT00963079.\nOther bias Unclear risk Trial was pre-terminated after interim analysis. Interim analysis was pre-\nplanned, but calculated per transfer (unit of analysis error) with a P value of\n0.03, overestimating possible effects. Stopping rules for interim analysis (em-\nbryo quality) were unclear.\n(Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup).\nShapiro 2016/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Multicenter RCT\nConducted: 20 reproductive medical centres throughout China\nEnrolment: March 2015-March 2017\nPower calculation: stated\nRandomisation: by means of an online central randomisation system (www.medresman.org)\nTiming of randomisation: on the day of oocyte retrieval\nNature of intervention: day 2 or 3 embryo cryopreservation by means of vitrification\nFollow-up: LBR after the first ET\nParticipants 2157 women (1077 freeze-all, 1080 control)\nInclusion criteria:\n• Women who underwent their first cycle of IVF with or without ICSI\n• Women with regular menses (defined as a spontaneous cycle length of ≥ 21 days and ≤ 35 days)\n• Reason for IVF procedure: tubal factor, male factor, or both\n• Age between 20 and 35 years\n• Duration of infertility of > 1 year\nExclusion criteria: women with a history of unilateral oophorectomy, recurrent spontaneous abortion,\ndiagnosis of the PCOS, or uterine abnormality (e.g. Müllerian duct anomaly, adenomyosis, submucous\nmyoma, intra-uterine adhesion, or scarred uterus) were excluded. Women were also excluded if they\nhad a chronic medical condition that has been associated with adverse pregnancy outcomes, such as\nhypertension, symptomatic heart disease, diabetes mellitus, liver disease or dysfunction (according to\nthe results of serum liver-enzyme testing), renal disease or abnormal renal function, severe anaemia,\nhistory of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident. All the couples\nwere screened with the use of karyotyping, and those with an abnormal karyotype were excluded.\nInterventions In women who were assigned to the fresh embryo group, luteal-phase support with was started imme-\ndiately after oocyte retrieval and was continued until the day of serum hCG testing. On day 2 or 3 of the\nembryo culture, up to 2 embryos were selected and transferred.\nIn women who were assigned to the FET group, all the embryos were vitrified. 2 good-quality embryos\nwere vitrified on day 2 or day 3, and the other embryos could be vitrified at the cleavage or blastocyst\nShi 2018/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n47\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nstage. At the second spontaneous menstrual cycle after oocyte retrieval, natural ovulation was moni-\ntored by means of ultrasonography. Luteal-phase support was started from the day of ovulation. Up to\n2 day 2 or day 3 frozen embryos were thawed and transferred 2 or 3 days after ovulation. If the natural\novulation cycle was cancelled owing to anovulation or poor endometrial development, an artificial cy-\ncle was used for endometrial preparation in the next menstrual cycle.\nOutcomes The primary outcome was: a live birth after the first ET.\nPrespecified secondary efficacy outcomes included biochemical pregnancy, implantation, clinical\npregnancy, ongoing pregnancy, pregnancy loss, and birth weight. Safety outcomes included moderate\nor severe OHSS, ectopic pregnancy, congenital anomaly, and obstetric and perinatal complications\n(i.e. gestational diabetes, gestational hypertension, pre-eclampsia, placenta praevia, placental abrup-\ntion, preterm delivery, neonatal hospitalisation/uni00A0for > 3 days, and perinatal death).\nNotes Funded by the National Key Research and Development Program of China and the National Natural\nScience Foundation of China.\nWe requested additional information regarding cumulative data from the authors by email but we did\nnot receive a response.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk By means of an online central randomisation system (www.medresman.org).\nAllocation concealment\n(selection bias)\nLow risk By means of an online central randomisation system (www.medresman.org).\nThe randomisation sequence was generated and kept by the data-coordinat-\ning centre and was not accessible/uni00A0to the investigators who enrolled women.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes were reported.\nProtocol publication.\nStudy was registered in a prospective trials register with the trial number:\nChiCTR-IOR-14005406.\nOther bias Unclear risk (Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup).\nShi 2018/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n48\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nStudy characteristics\nMethods Multicenter RCT\nConducted: 8 clinical sites in Denmark, Sweden and Spain\nEnrolment: May 2016-September 2018\nPower calculation: stated\nRandomisation: by means of a computerised randomisation program running a minimisation algo-\nrithm performed by a study nurse or non-treating physician\nTiming of randomisation: on inclusion day (cycle/uni00A0day 2 or 3) before initiation of ovarian stimula-\ntion,/uni00A0and was blinded until the day of ovulation triggering/uni00A0so that ovarian stimulation was not influ-\nenced by/uni00A0the result\nNature of intervention: day 5/uni00A0or 6/uni00A0embryo blastocyst vitrification (depending/uni00A0on embryo development)\nFollow-up: LBR after the first ET, cumulative data will be accounted for in separate publications\nParticipants 460 women (230 freeze-all, 230 control)\nInclusion criteria: were present during ovarian stimulation\n• Women who underwent their first, second or third/uni00A0cycle of IVF with or without ICSI/uni00A0because of male,\ntubal, uterine, or/uni00A0unexplained infertility\n• Women with regular menses (defined as a spontaneous cycle length of ≥ 24/uni00A0days and ≤ 35 days)\n• Aged 18-39 years\n• Women with normal or high responds (defined/uni00A0by serum AMH levels >/uni00A06.28 pmol/L (Roche Elecsys\nassay), corresponding to/uni00A0the poor responder AMH threshold level in the Bologna criteria)\n• The randomisation result was disclosed when ≥ 3 follicles of at least 17 mm mean diameter\nExclusion criteria:/uni00A0women with a diagnosis of endometriosis (stage III or IV), uterine abnormalities and\nsubmucosal fibroids, or dysregulated thyroid/uni00A0disease./uni00A0Additionally,/uni00A0women with any severe comorbidi-\nty\npotentially associated with adverse pregnancy/uni00A0outcomes, such as insulin dependent or non-insulin/uni00A0de-\npendent diabetes mellitus, gastrointestinal, cardiovascular,/uni00A0pulmonary, liver, or kidney disease. Cou-\nples/uni00A0that required testicular sperm aspiration or oocyte/uni00A0donation were also excluded from participa-\ntion./uni00A0Women were only allowed to participate once.\nInterventions Final oocyte maturation was induced by administering 0.5 mg of a GnRH agonist (buserelin: Supref-\nact, Sanofi) in/uni00A0the FET group or 250 /uni03BCg of hCG (choriogonadotropin alpha: Ovitrelle, Merck) in the fresh\ntransfer group./uni00A0Women randomised to the fresh transfer group received GnRH/uni00A0agonist triggering if > 18\nfollicles with a mean diameter > 11 mm were present on/uni00A0the day of ovulation triggering to prevent ovar-\nian/uni00A0hyperstimulation syndrome as predefined in the/uni00A0protocol. Consequently, the first single blastocyst\ntransfer was postponed to a subsequent modified/uni00A0natural FET cycle.\nAll/uni00A0fertilised oocytes were cultured to the blastocyst stage/uni00A0and assessed according to the classification\nsystem by Gardner and Schoolcraft. Day-5 blastocysts with a/uni00A0Gardner score of ≥ 3BB were considered to\nbe/uni00A0good quality and suitable for transfer or vitrification./uni00A0Additionally, day-6 blastocysts with a Gardner\nscore of ≥ 4BB were considered suitable for vitrification./uni00A0If only suitable day-6 blastocysts were present\nin the fresh transfer group, the first single blastocyst/uni00A0transfer was postponed until a subsequent modi-\nfied\nnatural FET cycle.\nIn the fresh transfer group, the blastocyst/uni00A0with the highest ranking was transferred on day 5/uni00A0of embryo\nculture. Luteal phase support was administered from day 2 after oocyte retrieval with/uni00A0vaginal proges-\nterone /uni00A0and continued until a/uni00A0hCG test was performed 11 days after blastocyst transfer.\nIn the FET group, blastocyst vitrification/uni00A0was done on day 5 or 6, depending on embryo development.\nThe highest ranking blastocyst was/uni00A0graded and marked before vitrification using the same criteria as\nin the fresh transfer group. For FET, endometrial preparation was/uni00A0done in a modified natural cycle regi-\nStormlund 2020/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n49\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nmen, which meant/uni00A0that a single injection of 250 /uni03BCg of hCG was administered as soon as the leading/uni00A0folli-\ncle was > 17 mm in the natural cycle./uni00A0 No luteal phase support was given.\nOutcomes The primary outcome was ongoing pregnancy rate/uni00A0per randomised participant, which also included\nnatural/uni00A0conceptions (defined as a detectable fetal heart beat after 8 weeks of/uni00A0gestation)./uni00A0Ongoing preg-\nnancy rate was recorded per randomised participant, per started stimulation, per oocyte/uni00A0retrieval, and\nper ET.\nSecondary outcomes/uni00A0were positive hCG rates/uni00A0(biochemical pregnancies), LBRs, pregnancy-related\ncomplications, obstetric complications, and/uni00A0prevalence of OHSS, which included women who had as-\ncites puncture/uni00A0and those admitted to hospital with the condition.\nFor pregnancies that continued beyond 22 weeks,/uni00A0pregnancy-related, obstetrical, and neonatal out-\ncomes were recorded, including infants born small for/uni00A0gestational age or large for gestational age.\nSmall for/uni00A0gestational age and large for gestational age were/uni00A0calculated from growth curves for Scandi-\nnavian/uni00A0children adjusted for sex and gestational age.\nPost hoc analysis was performed for selected/uni00A0obstetric outcomes (pregnancy-induced hyperten-\nsion,/uni00A0gestational diabetes, chorioamnionitis, postpartum/uni00A0haemorrhage, induction of birth, mode of\nbirth/uni00A0(vaginal delivery or caesarean section), twin rates,/uni00A0and duration of hospital stay).\nNotes Funding: the study is part of the Reprounion collaborative study,/uni00A0co-financed by the European Union,\nInterreg V ÖKS.\nWe requested additional information regarding cumulative data from the authors, but we did not re-\nceive these data.\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Performed by a study nurse or non-treating physician. Randomisation by using\na computerised/uni00A0randomisation programme running a minimisation/uni00A0algorithm,\ninitially seeded using a random block/uni00A0sequence for the first women.\nAllocation concealment\n(selection bias)\nLow risk The random concealed/uni00A0allocation sequence was generated by statisticians-\n/uni00A0from Statistika Konsultgruppen (Gothenburg, Sweden)./uni00A0Randomisation was\ndone on inclusion day (cycle/uni00A0day 2 or 3) before initiation of ovarian stimula-\ntion,/uni00A0and was blinded until the day of ovulation triggering/uni00A0so that ovarian stim-\nulation was not influenced by/uni00A0the result.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes were reported.\nProtocol publication.\nStudy was registered in a prospective trials register with the trial number:/uni00A0Clin-\nicaltrials.gov NCT02746562.\nStormlund 2020/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n50\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nOther bias Unclear risk (Cumulative) data per subsequent menstrual or cryo-transfer cycle not report-\ned (relevant for time-to-pregnancy comparison and the related comparison of\nresults after first transfer in FET group vs results after first 2 transfers in fresh\ngroup). Cumulative LBRs including time to delivery/uni00A0in the cumulative cycles,\ndetailed embryo data, and/uni00A0evaluation of cost effectiveness will be accounted\nfor in/uni00A0separate publications.\nStormlund 2020/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT, My Duc Hospital, Ho Chi Minh City\nConducted: Vietnam\nEnrolment: June 2015-April 2016\nPower calculation: stated\nRandomisation: performed by an independent study co-ordinator by means of block randomisation us-\ning a computer-generated random list\nTiming of randomisation: on day 3 after retrieval\nNature of intervention: Cryotech vitrification method\nFollow-up: cumulative ongoing pregnancy rate and LBR (including all FETs performed within the 12\nmonths after the initial transfer)\nParticipants 782 women (391 freeze-all, 391 control)\nInclusion criteria:\n• First or second IVF cycle\n• Possibility to undergo ET on day 3\n• At least 1 grade 1 embryo on day 3 available\n• Agreement that a maximum of 2 embryos would be transferred\nExlusion criteria: history of PCOS (based on the Rotterdam criteria), in vitro maturation with polycystic\novaries visible on the ultrasonography or cycle with oocyte donation.\nInterventions For women who were assigned to the fresh-embryo group, a maximum of 2 grade 1 or 2 embryos were\ntransferred on day 3. Any remaining grade 1 or 2 embryos, along with grade 3 embryos (if requested by\nthe couple), were frozen and transferred in subsequent cycles if needed.\nIn the FET group, there was no fresh transfer and all grade 1 and 2 embryos had been cryopreserved on\nday 3 by means of the Cryotech vitrification method. In menstrual cycles following the ovum pick-up\nthe endometrium was artificially prepared for transfer using estradiol and progesterone for transfer of\na maximum of 2 embryos.\nOutcomes The primary outcome was ongoing pregnancy after the first ET. Prespecified secondary outcomes were\nthe rates of implantation, clinical pregnancy, ectopic pregnancy, miscarriage, live birth, multiple preg-\nnancy, vanishing-twin pregnancy, and OHSS. Pregnancy complications for pregnancies that continued\nbeyond 24 weeks, complications were recorded. Time to pregnancy was calculated in a post hoc analy-\nsis at 12 months after randomisation using the median to pregnancy.\nNotes Funding: by My Duc Hospital\nRisk of bias\nVuong 2018/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n51\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Performed by an independent study co-ordinator by means of block randomi-\nsation using a computer-generated random list\nAllocation concealment\n(selection bias)\nUnclear risk Randomised women by means of block randomisation by an independent\nstudy co-ordinator using a computer-generated random list, there was no fur-\nther explanation about allocation concealment.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes were reported.\nProtocol publication.\nStudy was registered in a prospective trial register with the trial number:\nNCT02471573.\nOther bias Unclear risk Not reported on blinding of doctors to interim analyses of outcomes of the\nstudy. Blinding of investigators was not reported (which is relevant for deter-\nmining end of study).\nVuong 2018/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Multi-centre RCT\nConducted: in 21 academic fertility centres in China\nEnrolment: August 2016-June 2017\nPower calculation: stated\nRandomisation: performed by means of block randomisation using a computer-generated random list\nTiming of randomisation: on day 3 after retrieval\nNature of intervention: cryopreservation\nFollow-up: cumulative ongoing pregnancy rate and LBR (including all FETs performed within the 12\nmonths after the initial transfer)\nParticipants 1650 women (825 freeze-all, 825 control)\nInclusion criteria:\n• First cycle of IVF with or without ICSI with an indication of tubal, male, or unexplained infertility\nWei 2019/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n52\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n• Age between 20 and 35 years\n• Regular menses with length of 21-35 days\nExlusion criteria: women who were planning cycles of preimplantation genetic testing, women with di-\nagnosis of a congenital or acquired uterine abnormality (such as a uterine malformation, adenomyosis,\nsubmucous\nmyoma, or intrauterine adhesion), women also with medical conditions that are contraindications to\nIVF procedures or pregnancy (uncontrolled hypertension, known symptomatic heart disease, poorly\ncontrolled type 1 or type 2 diabetes, undiagnosed liver disease or dysfunction, renal disease, severe\nanaemia, history of deep venous thrombosis, history of pulmonary embolus, previous cerebrovascular\naccident, or history of cervical cancer, endometrial cancer, or breast cancer)\nInterventions For the fresh blastocyst transfer group, a single blastocyst was selected and transferred on day 5 of\nembryo culture (details of ET procedure are provided in the appendix). If ≥ 2 blastocysts were of equal\ngrade, their early scores at cleavage stage were referred for the selection of the single blastocyst. Su-\npernumerary embryos were frozen on day 5 or 6 according to embryo development. If pregnancy was\nachieved after fresh single blastocyst transfer, luteal phase support was continued until 10 weeks’ ges-\ntation.\nFor women who were assigned to the fresh-embryo group, a maximum of 2 grade 1 or 2 embryos were\ntransferred on day 3. Any remaining grade 1 or 2 embryos, along with grade 3 embryos (if requested by\nthe couple), were frozen and transferred in subsequent cycles if needed.\nFor the FET group, all blastocysts were vitrified on day 5 or day 6 according to embryo development.\nLuteal phase support was stopped after randomisation. At least 4 weeks later, the endometrium was\nprepared either with a natural cycle regimen or a programmed cycle regimen, at the discretion of local\ninvestigators. For the natural ovulatory cycle regimen, ovulation was determined by ultrasound moni-\ntoring.\nOutcomes The primary outcome was singleton live birth rate.\nPrespecified secondary outcomes were rates of conception, clinical pregnancy, ongoing pregnancy,\npregnancy loss, live birth, moderate and severe OHSS, ectopic pregnancy, pregnancy and perinatal\ncomplications, neonatal complication and other adverse events, and birth weight. A post-hoc analysis\nwas performed for the outcomes of small for gestational age (SGA), large for gestational age (LGA), the\nrate of cumulative live birth within 12 months after the first ET and the number of embryos remaining.\nThe time to live birth was defined as after ET and not after randomisation which is not a fair compari-\nson.\nNotes Funding: by The National Key Research and Development Program of China\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Perfomed by means of block randomisation using a computer-generated ran-\ndom list.\nAllocation concealment\n(selection bias)\nLow risk Used a sequence that was entered into the central online database, which was\nsecured by the username and password log-in.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nWei 2019/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n53\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes were reported.\nProtocol publication.\nStudy was registered in a prospective trial register with the trial number: ChiC-\nTR-IOR-14005405.\nOther bias Unclear risk Not reported on blinding of doctors to interim analyses of outcomes of the\nstudy. Blinding of investigators was not reported (which is relevant for deter-\nmining end of study).\nWei 2019/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Single-centre RCT\nConducted: in the Netherlands\nEnrolment: January 2013-July 2015\nPower calculation: stated\nRandomisation: performed by an independent study co-ordinator by means of block randomisation us-\ning a computer-generated random list\nTiming of randomisation: on day 3 after retrieval\nNature of intervention: cryopreservation\nFollow-up: cumulative ongoing pregnancy rate and LBR (including all FETs from 1 IVF cycle within 12\nmonths after randomisation)\nParticipants 204 (102 freeze-all, 102 control)\nInclusion criteria:\n• Women between 18 and 43 years old\n• Sceduled for first IVF cycle\nExlusion criteria: women undergoing a PGS cycle, women undergoing a modified natural cycle and\ncouples with an HIV, HBV or HCV infection since all these cycles required modified IVF protocols.\nInterventions For both groups a single ET policy was adhered to for women < 38 years of age and a double ET policy\nfor women of ≥ 38 years, if ≥ 2 embryos were available.\nFor women who were assigned to the conventional (fresh) group, embryos at day 5 of culture were\ntransferred. The morphologic best embryo(s) was transferred first. All surplus embryos were cryopre-\nserved on day 6 of culture and were transferred in subsequent artificial cycles if needed.\nIn the FET group, there was no fresh transfer and all embryos were cryopreserved on day 6 of culture.\nIn menstrual cycles following the ovum pick-up the endometrium was artificially prepared for transfer\nusing estradiol and progesterone for transfer of a maximum of 2 embryos.\nOutcomes The primary outcome was cumulative ongoing pregnancy resulting from 1 IVF cycle within 12 months\nafter randomisation. Prespecified secondary outcomes were time to pregnancy, defined as the time to\nWong 2021/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n54\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nongoing pregnancy, from the date of randomisation to the date of ET that led to an ongoing pregnancy,\nlive birth, defined as the delivery of a live fetus at ≥ 20 weeks of gestation, clinical pregnancy, defined as\nthe presence of at least 1 intra-uterine gestational sac at 7 weeks of gestation, biochemical pregnancy,\ndefined as serum hCG > 2 IU/L. Safety outcomes were OHSS, multiple pregnancy, premature birth and\ncongenital abnormalities. The study authors also reported on miscarriage rate, ectopic pregnancy rate\nand birth weight of the children born.\nNotes Funding: by The Netherlands Organization for Health Research and Development\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk Randomisation of women using an online randomisation program with block\nrandomisation.\nAllocation concealment\n(selection bias)\nLow risk Randomisation program generated a unique study number with allocation\ncode after entry of the patient’s date of birth and randomisation date\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes reported.\nStudy was registered in a prospective trials register with the trial number:\nNTR3187\nOther bias Unclear risk Not reported on blinding of doctors to interim analyses of outcomes of the\nstudy. Blinding of investigators was not reported (which is relevant for deter-\nmining end of study).\nWong 2021/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy characteristics\nMethods Secondary analysis of the results of a multicentre RCT (Chen 2016)\nConducted: in 14 reproductive medical centres throughout China\nEnrolment: June 2013-May 2014\nPower calculation: stated (Chen 2016)\nRandomisation: an online central randomisation system (www.medresman.org) was used.\nTiming of randomisation: after oocyte retrieval\nNature of intervention: day-3 embryo cryopreservation by means of vitrification. Local investigators\nhad the option to transfer day-2 embryos if there were < 3 embryos on day 2\nFollow-up: until delivery, cLBR, birth outcomes\nZhang 2018/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n55\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nParticipants 1508 women (746 freeze-all, 762 control)\nInclusion criteria:\n• PCOS, using modified Rotterdam criteria (which included menstrual abnormalities (irregular uterine\nbleeding, oligomenorrhoea, or amenorrhoea) combined with either hyperandrogenism or polycystic\novaries)\n• First IVF cycle\nExclusion criteria: history of unilateral oophorectomy, recurrent spontaneous abortion (defined as ≥ 3\nprevious spontaneous pregnancy losses), congenital or acquired uterine malformations, abnormal re-\nsults on parental karyotyping, or medical conditions that contraindicated assisted reproductive tech-\nnology or pregnancy\nInterventions For women who were assigned to the fresh embryo group, on day 3, 2 high-quality embryos were\npicked out for fresh transfer and supernumerary embryos were transferred by means of vitrification For\nwomen who were assigned to the FET group, there was no fresh transfer as all day-3 embryos were cry-\nopreserved for later transfer. Local investigators had the option to transfer day-2 embryos if there were\n< 3 embryos on day 2. In cycles following the menstrual cycle with ovum pick-up, on day 4 of the prog-\nesterone regimen, 2 day-3 frozen embryos were thawed and transferred.\nOutcomes Gestational diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and large for\ngestational age. All outcomes reported for first ET.\nNotes Funding: by the National Basic Research Program of China; the State Key Program of National Natural\nScience Foundation of China; the National Natural Science Foundation of China; and the Thousand Tal-\nents Program\nRisk of bias\nBias Authors' judgement Support for judgement\nRandom sequence genera-\ntion (selection bias)\nLow risk An online central randomisation system (www.medresman.org) was used to\nautomatically generate the assignment sequence.\nAllocation concealment\n(selection bias)\nLow risk Assignment sequence was unknown to the clinical investigators.\nBlinding of participants\nand personnel (perfor-\nmance bias)\nAll outcomes\nLow risk Blinding of doctors and participants was not possible due to the nature of the\nintervention.\nBlinding of outcome as-\nsessment (detection bias)\nAll outcomes\nLow risk Outcome assessor blinding was not reported, however primary outcome is not\nlikely to be influenced by lack of blinding.\nIncomplete outcome data\n(attrition bias)\nAll outcomes\nLow risk Data were analysed for all randomised women.\nSelective reporting (re-\nporting bias)\nLow risk All registered outcomes reported.\nThe study used for this follow-up study was registered in a prospective trials\nregister with the trial number: NCT01841528.\nOther bias Unclear risk (Cumulative) data regarding obstetric complications per subsequent menstru-\nal or cryo-transfer cycle not reported\nZhang 2018/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n56\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n2pn: 2 pro-nucleate; AMH: anti-Müllerian hormone; ART: assisted reproductive technology; BMI: body mass index; cLBR: cumulative live\nbirth rate; ET: embryo transfer; FET: frozen embryo transfer; FSH: follicle-stimulating hormone; GnRH: gonadotropin-releasing hormone;\nHBV: hepatitis B virus; hCG: human chorionic gonadotropin; HCV: hepatitis C virus; HSG: hysterosalpingogram; ICSI: intracytoplasmic\nsperm injection; ITT: intention-to-treat; IVF: in vitro fertilisation; LBR: live birth rate; NGS: next-generation sequencing; OHSS: ovarian\nhyperstimulation syndrome; PCOS: polycystic ovary syndrome; PGS: pre-implantation genetic screening; RCT: randomised controlled trial\n/uni00A0\nCharacteristics of excluded studies [ordered by study ID]\n/uni00A0\nStudy Reason for exclusion\nAbsalan 2013 Unclear from report whether study was a RCT, and the authors did not respond to our request for\nfurther information.\nAflatoonian 2010 This article has been retracted from the literature at the request of the Editor and the ASRM Publi-\ncations Committee.\nBeyer 2016 Wrong study design (retrospective cohort)\nBoostanfar 2016 Randomised a different intervention\nChandel 2016 Wrong study design (pseudo-RCT)\nMagdi 2017 Wrong study design (prospective cohort)\nSimon 2020 Wrong comparison\nYang 2015 One-third of participants chose to be in group 3 after randomisation. Not considered a properly\nrandomised RCT.\nASRM: American Society for Reproductive Medicine; RCT: randomised controlled trial\n/uni00A0\nCharacteristics of ongoing studies [ordered by study ID]\n/uni00A0\nStudy name A randomised study of IVF patients to assess whether freezing all of the embryos and transferring\nthem in a later natural, unstimulated cycle results in a higher pregnancy rate than transferring an\nembryo 5 days after egg collection\nMethods RCT\nTarget enrolment: 200\nParticipants Included:\n• Women of infertile couples for whom controlled ovarian stimulation and IVF with or without ICSI\nis indicated\n• Age 20-38 years at the time of screening, regular menstrual cycles with a range of 24-33 days, BMI\n18-28, AMH 5 to 20\nExcluded:\n• Previous IVF treatment cycle that resulted in < 6 follicles on day 8 ultrasound\n• > 2 previous unsuccessful stimulated cycles\n• History of or current endocrine abnormality such as PCOS or evidence of ovarian dysfunction\n• Any clinically significant abnormal laboratory value (TSH, PRL, SHBG test)\n• Any ovarian or abdominal abnormality, or both, that would interfere with adequate ultrasound\ninvestigation of at least 1 ovary\nACTRN12612000422820/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n57\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n• Only 1 ovary\n• Contraindications for the use of gonadotropins\n• Alcohol or drug abuse, or history thereof, within the 12 months preceding signing informed con-\nsent\n• Smokers\nInterventions Both study groups will undertake a stimulated IVF cycle.\nThe first (intervention) group will have all embryos cryostored electively for transfer in a later nat-\nural menstrual cycle.\nThe second group will have the best-quality embryo transferred to the endometrial cavity fresh and\nall remaining embryos cryostored.\nThe protocol for the second group is standard practice today.\nBoth groups will undertake the same drug regimen, therefore there is no difference in drug inter-\nvention.\nOutcomes • Live birth\n• Cumulative clinical pregnancy: a fetal heartbeat seen on ultrasound at 7 weeks\n• Perinatal complications\n• Blastulation anomalies\nStarting date 1 May 2012\nContact information Mark Livingstone: ecosse@ihug.com.au\nNotes www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362361\nACTRN12612000422820/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy name Comparison of the probability of live birth after elective freezing of all embryos versus standard\nfresh embryo transfer in patients undergoing in-vitro fertilisation (IVF)\nMethods RCT\nTarget enrolment: 400\nParticipants Women aged 18-39 with indication for COS and IVF or ICSI with autologous gametes\nKey inclusion criteria:\n• Age: 18-39 years\n• BMI: 18-32 kg/m2\n• Presence of both ovaries\n• Normal menstruating cycles: 21-35 days\n• Cycle where prevention of premature LH rise is achieved using a GnRH antagonist\n• 8-19 follicles ≥ 10 mm in mean diameter on the day of triggering\nKey exclusion criteria:\n• Endometriosis stage > II\n• Indication for PGD/PGS\n• History of OHSS\n• Previous participation in the RCT\n• > 3 previous unsuccessful stimulated cycles\n• History of hypothalamic dysfunction or history of inadequate pituitary response to GnRH agonist\ntriggering\nACTRN12616000643471/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n58\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nInterventions Interventional freeze-all group\n• Triggering of final oocyte maturation will be performed in the freeze-all arm with a bolus subcu-\ntaneous injection of 2 mg of leuprolide acetate when at least 3 follicles ≥ 17mm in mean diameter\nare present at ultrasound. Oocyte retrieval will be performed at 34-36 h after leuprolide adminis-\ntration.\n• Embryos will be cultured for 5 days using the standard protocol of each clinic. All day-5 embryos\nof top and good quality (at least at early blastocyst stage and of ICM/trophectoderm: AA, AB, BA,\nBB) will be cryopreserved using the method of vitrification. Delayed embryos will be allowed to\nbe vitrified on day 6 as long as they fulfil the quality criteria (at least at early blastocyst stage and\nof ICM/trophectoderm: AA, AB, BA, BB). Based on the pre-vitrification morphological quality, the\nbest blastocyst will be thawed for the next ET. If the blastocyst does not survive, the next best blas-\ntocyst (based again on the pre-vitrification morphological criteria) will be thawed. The maximum\nperiod of embryo cryopreservation is theoretically indefinite, however it rarely exceeds 5 years.\nFor the primary outcome of this study, the embryo cryopreservation period is estimated between\n20 days-3 months. Hence, thawing and ET is expected to occur within this timeframe.\nFresh transfer group\n• Triggering of final oocyte maturation will be performed in the fresh transfer arm with a bolus sub-\ncutaneous injection of 250 mcg of r-hCG when at least three follicles of equal to or greater than\n17mm in mean diameter are present at ultrasound. Oocyte retrieval will be performed at 34-36h\nafter r-hCG administration. Embryos will be cultured for 5 days using the standard protocol of\neach clinic. On day 5 of embryo culture the developmental stage and quality of the blastocysts will\nbe recorded including ICM and trophectoderm grading. The morphologically best day-5 embryo\n(according to the judgement of the embryologist) will be transferred. All remaining day-5 embryos\nof top and good quality (at least at early blastocyst stage and of ICM/trophectoderm: AA, AB, BA,\nBB) will be cryopreserved using the method of vitrification. Delayed embryos will be allowed to\nbe vitrified on day 6 as long as they fulfil the quality criteria (at least at early blastocyst stage and\nof ICM/trophectoderm: AA, AB, BA, BB).\nOutcomes • Live birth after the transfer of the first embryo: delivery of a live baby after the 20th week of ges-\ntation\n• Ongoing pregnancy diagnosed by ultrasonography as presence of fetal heart activity at 10-12\nweeks of gestation\n• Clinical pregnancy diagnosed by ultrasound as presence of fetal heart activity at 6-8 weeks of\ngestation\n• First trimester miscarriage, defined as a biochemical pregnancy (assessed by serum hCG) at 11-16\ndays after ET but no fetal heart activity at 10-12 weeks of gestation as assessed by ultrasonography\n• Occurrence of severe OHSS\n• Preterm labour (defined as delivery < 37 weeks of gestation)\n• Mode of delivery (normal vaginal delivery, assisted vaginal delivery, caesarean section)\n• Neonatal birth weight\n• Stillbirth\n• Neonatal mortality\n• Death within the first 28 days of life\n• Intrauterine growth restriction\n• Hypertensive disorders of pregnancy (including gestational hypertension, pre-eclampsia,\neclampsia)\n• Gestational diabetes mellitus\nStarting date May 2016\nContact information Christos Venetis: c.venetis@unsw.edu.au\nNotes www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000643471\nACTRN12616000643471/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n59\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n/uni00A0\n/uni00A0\nStudy name Freezing of embryos in assisted conception: a randomised controlled trial evaluating the clinical\nand cost-effectiveness of a policy of freezing embryos followed by thawed frozen embryo transfer,\ncompared with a policy of fresh embryo transfer in women undergoing in-vitro fertilization\nMethods RCT\nEstimated enrolment: 1086\nParticipants Inclusion criteria\n• Female partner is between 18 and 42 years of age at the start of treatment (i.e. start of ovarian\nstimulation)\n• Couples who are undergoing their first cycle of IVF/ICSI treatment\n• Both partners are resident in the UK\n• Both partners are able to provide written informed consent\nExclusion criteria\nCouples in whom:\n• donor gametes are used;\n• pre-implantation genetic diagnosis is performed;\n• elective freezing of all embryos is preferred or clinically indicated (e.g. severe risk of OHSS).\nInterventions Intervention arm: all good-quality embryos will be frozen and couples will undergo frozen-thawed\nET within 3 months of the egg collection process. Couples will attend a clinic visit and additional\nmonitoring visits before FET is performed.\nStandard-care arm: women will undergo fresh ET on day 3 or 5 (after egg collection).\nOutcomes • Live birth\n• Clinical pregnancy: ultrasonic visualisation of ≥ 1 gestational sacs or definitive clinical signs of\npregnancy; ectopic counts as clinical pregnancy; multiple gestational sacs count as 1 clinical preg-\nnancy\n• Ongoing pregnancy (pregnancy with presence of fetal heartbeat)\n• OHSS\n• Miscarriage rate\n• Gestational diabetes mellitus\n• Multiple pregnancy\n• Hypertensive disorders of pregnancy (comprising pregnancy-induced hypertension, pre-eclamp-\nsia and eclampsia)\n• Antepartum haemorrhage\n• Preterm delivery (defined as delivery at < 37 completed weeks)\n• Very preterm delivery (defined as delivery at < 32 completed weeks)\n• Low birth weight (defined as weight < 2500 g at birth)\n• Very low birth weight (defined as < 1500 g at birth)\n• Large for gestational age (defined as birth weight > 90th centile for gestation, based on standard-\nised charts)\n• Small for gestational age (defined as < 10th centile for gestational age at delivery)\n• Congenital anomaly (all congenital anomalies identified will be included)\n• Perinatal mortality (late as well as early neonatal deaths, up to 28 days after birth)\nStarting date 1 March 2015\nISRCTN61225414/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n60\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nContact information Christina Cole: christina.cole@npeu.oxa.c.uk\nNotes www.isrctn.com/ISRCTN61225414\nISRCTN61225414/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy name Efficacy study of segmentation of PGD treatment\nMethods RCT\nEstimated enrolment: 240\nParticipants Women aged 20-40\nInclusion criteria:\n• 1st, 2nd, or 3rd cycle of PGD in which ET was performed\n• Indications for PGD: monogenic indications and X-linked disorders with a 25%-50% risk of trans-\nmission and that are not associated with reduced ovarian response\n• Normal ultrasound scan, i.e. presence of both ovaries, without evidence of abnormality within 6\nmonths prior to randomisation\n• Regular menstrual cycles of 21-35 days, presumed to be ovulatory\nExclusion criteria:\n• PCOS (Rotterdam criteria)\n• Poor responders (Bologna criteria)\n• Endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver, or kidney)\n• Anticipated high response: AMH > 5.0 ng/mL or AFC > 20\n• Endometriosis ≥ grade 3\n• Age > 40 years and 364 days\nInterventions Elective cryopreservation of available embryos after PGD\nPGD and elective fresh ET plus cryopreservation of supernumerary available embryos after PGD\nOutcomes cLBR of a single PGD treatment\nStarting date May 2014\nContact information Willem Verpoest, Centre for Reproductive Medicine UZ Brussel\nNotes /uni00A0\nNCT02133950/uni00A0\n/uni00A0\n/uni00A0\nStudy name Clinical effectiveness of frozen thawed embryo transfer compared to fresh embryo transfer\nMethods RCT\nEstimated enrolment: 800\nParticipants Women aged 18-42\nInclusion criteria:\nNCT02570386/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n61\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n• Women < 42 years of age\n• Presence of at least 3 embryos suitable to freeze on day 2 or 3 following fertilisation based on the\ncentre's criteria\n• Written informed consent\nExclusion criteria:\n• Women using donor eggs/donor sperm\n• Women undergoing pre-implantation genetic diagnosis\n• Women with abnormal uterine cavity shown on HSG or saline infusion sonogram\n• Women with hydrosalpinges shown on scanning and not treated\n• Women with excessive ovarian response at risk of OHSS where elective freeze is already planned\n• Women with serum progesterone level on day of hCG > 1.5 ng/mL or 5 nmol/L\n• Women whose embryos have previously not survived freeze-thawing\n• Fresh transfer is planned, e.g. women with endometriosis or adenomyosis who have received pro-\nlonged down-regulation\n• Only FET is planned, e.g. women receiving ovarian stimulation regimens that may adversely im-\npact the endometrium\nInterventions Intervention: fresh ET will not be undertaken in this group. Embryos will be frozen by vitrification or\nslow freezing at cleavage or blastocyst stage according to standard agreed local protocols. Women\nwill be contacted after 4 weeks and arrangements made for FET.\nControl: women allocated to the control arm will either undergo fresh ET at cleavage stage or ex-\ntended culture and transfer at blastocyst stage according to local policy. A maximum of 2 embryos\nor blastocysts will be replaced according to the standard protocol under transabdominal ultra-\nsound guidance. Luteal-phase support is given according to local protocols.\nOutcomes • cLBR: within 6 months of ovarian stimulation from the fresh and frozen-thawed ET\n• Live birth: a baby born alive after 20 weeks' gestation\n• Miscarriage: miscarriage before 20 weeks' gestation\n• Clinical pregnancy: presence of at least 1 gestational sac on ultrasound at 6 weeks\n• Ovarian hyperstimulation: classified according to Royal College of Obstetrics and Gynaecology in\nthe United Kingdom\n• Complications of pregnancy\nStarting date October 2015\nContact information Ernest HY Ng: nghye@hku.hk\nNotes clinicaltrials.gov/ct2/show/record/NCT02570386\nNCT02570386/uni00A0/uni00A0(Continued)\n/uni00A0\n/uni00A0\nStudy name Deferred versus fresh embryo transfers (DEFETOSE)\nMethods RCT\nEstimated enrolment: 2294\nParticipants Women aged 18-40\nInclusion criteria:\n• Women eligible for ovarian stimulation and ART treatment, including ICSI\nNCT03349905/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n62\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n• Absence of anatomical abnormalities of the reproductive tract that would interfere with implan-\ntation or pregnancy\n• Absence of any medical condition in which pregnancy is contraindicated\n• Motile, ejaculatory sperm must be available (donated and/or cryopreserved sperm is allowed)\n• ICSI will be allowed during this trial\n• BMI 18-35 kg/m2, inclusive\n• Able to understand the study\n• Affiliation with a social security scheme\n• Dated and signed inform consent\nExclusion criteria:\n• Altered ovarian reserve (day 3: FSH > 12 UI/L; AMH < 1.0 ng/mL; AFC < 8)\n• History or presence of tumours of the hypothalamus or pituitary gland\n• Presence of non isolated uni- or bilateral hydrosalpinx\n• Abnormal gynaecological bleeding of undetermined origin\n• Contraindication to being pregnant and/or carrying a pregnancy to term\n• Known infection with HIV, active HBV or HCV in the female or male partner\n• History or presence of ovarian, uterine or mammary cancer\n• Known allergy or hypersensitivity to human gonadotropin preparations or to compounds that are\nstructurally similar to any of the other medications administered during the trial\n• Substance abuse that would interfere with trial conduct, as determined by the investigator\n• Use of testicular or epididymal sperm\n• Pregnant patient, nursing patient\n• Participation in another ART clinical trial within the past 30 days\n• Women who have risk to develop severe OHSS during COS defined as ≥ 18 follicles measuring\n10-14 mm on the day of triggering\n• Women with < 3 follicles ≥ 15 mm on the triggering day or the day before the triggering\n• Women with premature progesterone elevation during COS ( ≥ 1.5 ng/mL)\n• Women with uterine polyps diagnosed during COS\n• Participation with another interventional study involving human participants\nInterventions Fresh transfer\n• Antagonist stimulation protocol\n• Ovarian triggering using a single injection of r-hCG (Ovitrelle®; Serono, France)\n• All of their embryos kept in prolonged culture\n• A fresh single ET at blastocyst stage (on day 5 or 6 according to blastocyst stage)\n• Supernumerary blastocysts cryopreserved\nDeferred-frozen ET\n• Antagonist stimulation protocol\n• Ovarian triggering using a single injection of 0.2 mg of GnRH agonist triptorelin (Decapeptyl® Ipsen\nFrance)\n• All of their embryos cryopreserved at the blastocyst stage after prolonged embryo culture\n• A frozen-thawed single ET at blastocyst stage, is planned 4-5 weeks after cryopreservation\nOutcomes • LBRs: cut-off of 35 weeks postmenstrual age is to ensure the health and well-being of the newborn\nbabies\n• Miscarriage: intrauterine clinical pregnancy that occurs before 20 completed weeks postmenstru-\nal age (18 weeks post fertilisation)\n• Clinical pregnancy: defined as a pregnancy diagnosed by ultrasonographic visualisation of ≥ 1\ngestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy\nNCT03349905/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n63\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n• Preterm birth: defined as a live birth or stillbirth that takes place after at least 20 but before 37\ncompleted weeks of postmenstrual age\n• Preterm rupture of membranes\n• Pre-eclampsia\n• Placenta praevia\n• LBRs in endometriosis-related infertility\n• Number of oocytes retrieved\n• Number of MII oocytes\n• Number of embryos\n• Number of blastocysts\n• Number of transferred blastocysts\n• The cancellation rate\n• The rate of started pregnancy\n• The rate of pregnancy confirmed by the echography (cardiac activity)\n• Started pregnancy defined by a rate of hCG > 100\n• Rate of multiple pregnancy\n• Implantation rate: defined as the number of gestational sacs seen via transvaginal ultrasonogra-\nphy 4-5 weeks after ET, per number of embryos transferred\n• Cryopreservation thaw rate: defined as percentage of vitrified blastocysts that survive warming\n• The incremental cost effectiveness ratio using LBR as the effectiveness endpoint, after 35 weeks\nStarting date September 2018\nContact information Pietro SANTULLI, MD, PhD: pietro.santulli@aphp.fr\nChristelle AUGER: christelle.auger@aphp.fr\nNotes https://clinicaltrials.gov/ct2/show/NCT03349905\nNCT03349905/uni00A0/uni00A0(Continued)\nAFC: antral follicle count; AMH: anti-Müllerian hormone; ART: assisted reproductive technology; BMI: body mass index; COS: controlled\novarian stimulation; ET: embryo transfer; FET: frozen embryo transfer; FSH: follicle-stimulating hormone; GnRH: gonadotropin-releasing\nhormone; HBV: hepatitis B virus; hCG: human chorionic gonadotropin; HCV: hepatitis C virus; ICM: inner cell mass; ICSI: intracytoplasmic\nsperm injection; HSG: hysterosalpingogram; IVF: in vitro fertilisation; LH: luteinising hormone; OHSS: ovarian hyperstimulation syndrome;\nPCOS: polycystic ovary syndrome; PGD: pre-implantation genetic diagnosis; PGS: pre-implantation genetic screening; PRL: prolactin; r-\nhCG: recombinant human chorionic gonadotropin; RCT: randomised controlled trial; SHBG: sex hormone-binding globulin; TSH: thyroid-\nstimulating hormone\n/uni00A0\n/uni00A0\nD A T A /uni00A0 A N D /uni00A0 A N A L Y S E S\n/uni00A0\nComparison 1. /uni00A0 Freeze-all versus conventional IVF, outcomes per woman\nOutcome or subgroup title No. of studies No. of partici-\npants\nStatistical method Effect size\n1.1 Cumulative live birth rate 8 4712 Odds Ratio (M-H, Fixed,\n95% CI)\n1.08 [0.95, 1.22]\n1.1.1 Live birth rate: cumulatively for\ncleavage stage transfer\n3 2415 Odds Ratio (M-H, Fixed,\n95% CI)\n1.09 [0.93, 1.29]\n1.1.2 Live birth rate: cumulatively for blas-\ntocyst stage transfer\n5 2297 Odds Ratio (M-H, Fixed,\n95% CI)\n1.06 [0.88, 1.27]\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n64\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nOutcome or subgroup title No. of studies No. of partici-\npants\nStatistical method Effect size\n1.2 Ovarian hyperstimulation syndrome\n(OHSS)\n6 /uni00A0 Peto Odds Ratio (Peto,\nFixed, 95% CI)\nSubtotals only\n1.2.1 Per cycle with ovarian hyperstimula-\ntion\n6 4478 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.26 [0.17, 0.39]\n1.3 Cumulative ongoing pregnancy rate 4 1245 Odds Ratio (M-H, Fixed,\n95% CI)\n0.95 [0.75, 1.19]\n1.3.1 Ongoing pregnancy rate: cumula-\ntively for cleavage stage transfer\n1 782 Odds Ratio (M-H, Fixed,\n95% CI)\n1.03 [0.78, 1.37]\n1.3.2 Ongoing pregnancy rate: cumula-\ntively for blastocyst stage transfer\n3 463 Odds Ratio (M-H, Fixed,\n95% CI)\n0.80 [0.54, 1.18]\n1.4 Cumulative clinical pregnancy rate 4 1320 Odds Ratio (M-H, Fixed,\n95% CI)\n0.92 [0.72, 1.16]\n1.4.1 Clinical pregnancy rate: cumulative-\nly for cleavage stage transfer\n2 907 Odds Ratio (M-H, Fixed,\n95% CI)\n1.00 [0.76, 1.32]\n1.4.2 Clinical pregnancy rate: cumulative-\nly for blastocyst stage transfer\n2 413 Odds Ratio (M-H, Fixed,\n95% CI)\n0.70 [0.44, 1.13]\n1.5 Ectopic pregnancy 6 /uni00A0 Peto Odds Ratio (Peto,\nFixed, 95% CI)\nSubtotals only\n1.5.1 Ectopic pregnancy: cumulatively 2 986 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.61 [0.31, 1.22]\n1.5.2 Ectopic pregnancy: after first em-\nbryo transfer\n5 4274 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.64 [0.39, 1.06]\n1.6 Miscarriage 8 /uni00A0 Peto Odds Ratio (Peto,\nFixed, 95% CI)\nSubtotals only\n1.6.1 Miscarriage rate: cumulatively 2 986 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.06 [0.72, 1.55]\n1.6.2 Miscarriage rate: after first embryo\ntransfer\n8 4569 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.90 [0.76, 1.07]\n1.7 Multiple pregnancy 5 5252 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.10 [0.92, 1.31]\n1.7.1 Multiple pregnancy rate: cumula-\ntively\n2 986 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.88 [0.61, 1.25]\n1.7.2 Multiple pregnancy rate: after first\nembryo transfer\n5 4266 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.18 [0.96, 1.45]\n1.8 Gestational diabetes mellitus 3 4722 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.26 [0.92, 1.71]\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n65\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nOutcome or subgroup title No. of studies No. of partici-\npants\nStatistical method Effect size\n1.8.1 Gestational diabetes mellitus: cu-\nmulatively\n1 782 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.83 [0.36, 1.94]\n1.8.2 Gestational diabetes mellitus: after\nfirst embryo transfer\n3 3940 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.34 [0.96, 1.86]\n1.9 Hypertensive disorders of pregnancy 3 4722 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.80 [1.23, 2.64]\n1.9.1 Hypertensive disorders of pregnan-\ncy: cumulatively\n1 782 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.70 [0.27, 1.82]\n1.9.2 Hypertensive disorders of pregnan-\ncy: after first embryo transfer\n3 3940 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n2.15 [1.42, 3.25]\n1.10 Preterm delivery (< 37 weeks of ges-\ntational age)\n4 4926 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.00 [0.80, 1.25]\n1.10.1 Preterm delivery (< 37 weeks of\ngestational age): cumulatively\n2 986 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.62 [0.39, 0.99]\n1.10.2 Preterm delivery (< 37 weeks of\ngestational age): after first embryo trans-\nfer\n3 3940 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.15 [0.89, 1.50]\n1.11 Perinatal and neonatal death 2 3072 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.18 [0.40, 3.51]\n1.11.1 Perinatal and neonatal death: cu-\nmulatively\n1 782 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.13 [0.01, 1.30]\n1.11.2 Perinatal and neonatal death: after\nfirst embryo transfer\n2 2290 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n2.27 [0.65, 7.84]\n1.12 Neonatal hospitalisation (> 3 days or\nneonatal intensive care unit admission)\n3 4722 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.35 [1.06, 1.72]\n1.12.1 Neonatal hospitalisation (> 3 days\nor neonatal intensive care unit admis-\nsion): cumulatively\n1 782 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.00 [0.29, 3.48]\n1.12.2 Neonatal hospitalisation (> 3 days\nor neonatal intensive care unit admis-\nsion): after first embryo transfer\n3 3940 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.37 [1.07, 1.75]\n1.13 Large for gestational age (birth\nweight > 90th percentile)\n3 4722 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.96 [1.52, 2.53]\n1.13.1 Large for gestational age (birth\nweight > 90th percentile): cumulatively\n1 782 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.97 [0.63, 6.15]\n1.13.2 Large for gestational age (birth\nweight > 90th percentile): after first em-\nbryo transfer\n3 3940 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.96 [1.51, 2.55]\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n66\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nOutcome or subgroup title No. of studies No. of partici-\npants\nStatistical method Effect size\n1.14 Small for gestational age (birth\nweight < 10th percentile)\n3 4722 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.77 [0.61, 0.97]\n1.14.1 Small for gestational age (birth\nweight < 10th percentile): cumulatively\n1 782 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.36 [0.16, 0.80]\n1.14.2 Small for gestational age (birth\nweight < 10th percentile): after first em-\nbryo transfer\n3 3940 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n0.82 [0.65, 1.05]\n1.15 Congenital abnormalities per live-\nborn children\n3 1789 Peto Odds Ratio (Peto,\nFixed, 95% CI)\n1.08 [0.65, 1.78]\n1.16 Birth weight of babies born 5 /uni00A0 Mean Difference (IV, Fixed,\n95% CI)\nSubtotals only\n1.16.1 Birth weight of singletons 5 1607 Mean Difference (IV, Fixed,\n95% CI)\n127.44 [77.08,\n177.80]\n1.16.2 Birth weight of multiples 4 804 Mean Difference (IV, Fixed,\n95% CI)\n49.46 [-21.15,\n120.08]\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n67\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.1. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 1: Cumulative live birth rate\nStudy or Subgroup\n1.1.1 Live birth rate: cumulatively for cleavage stage transferChen 2016Ferraretti 1999\nVuong 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.10, df = 2 (P = 0.95); I² = 0%\nTest for overall effect: Z = 1.09 (P = 0.28)\n1.1.2 Live birth rate: cumulatively for blastocyst stage transferSantos-Ribeiro 2020\nShapiro 2011a\nShapiro 2011b\nWei 2019\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.66, df = 4 (P = 0.32); I² = 14%\nTest for overall effect: Z = 0.59 (P = 0.55)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.83, df = 7 (P = 0.68); I² = 0%\nTest for overall effect: Z = 1.21 (P = 0.23)\nTest for subgroup differences: Chi² = 0.07, df = 1 (P = 0.78), I² = 0%\nFreeze all IVFEvents\n46523191\n679\n65373762718\n784\n1463\nTotal\n74658391\n1195\n907060825102\n1147\n2342\nConventional IVFEvents\n45526185\n666\n67353960429\n774\n1440\nTotal\n762673911220\n946762825102\n1150\n2370\nWeight\n34.1%2.9%19.0%56.0%\n3.7%3.4%3.0%29.1%4.8%44.0%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n1.12 [0.91 , 1.37]1.04 [0.50 , 2.13]1.06 [0.80 , 1.41]1.09 [0.93 , 1.29]\n1.05 [0.55 , 1.99]1.03 [0.52 , 2.00]0.95 [0.46 , 1.97]1.16 [0.93 , 1.45]0.54 [0.28 , 1.05]1.06 [0.88 , 1.27]\n1.08 [0.95 , 1.22]\nOdds RatioM-H, Fixed, 95% CI\n0.2 0.5 1 2 5Favours conventionalFavours freeze-all\n/uni00A0\n/uni00A0\nAnalysis 1.2. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes\nper woman, Outcome 2: Ovarian hyperstimulation syndrome (OHSS)\nStudy or Subgroup\n1.2.1 Per cycle with ovarian hyperstimulationChen 2016Ferraretti 1999Santos-Ribeiro 2020\nVuong 2018\nWei 2019\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.85, df = 5 (P = 0.43); I² = 0%\nTest for overall effect: Z = 6.61 (P < 0.00001)\nFreeze all IVFEvents\n1000340\n17\nTotal\n746581043918251022226\nConventional IVFEvents\n5449493\n83\nTotal\n762671053918251022252\nWeight\n63.4%4.0%9.0%7.2%13.3%3.1%100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.24 [0.15 , 0.40]0.15 [0.02 , 1.08]0.13 [0.03 , 0.48]0.75 [0.17 , 3.32]0.46 [0.15 , 1.37]0.13 [0.01 , 1.29]0.26 [0.17 , 0.39]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours freeze-allFavours conventional\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n68\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.3. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 3: Cumulative ongoing pregnancy rate\nStudy or Subgroup\n1.3.1 Ongoing pregnancy rate: cumulatively for cleavage stage transfer\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 0.22 (P = 0.83)\n1.3.2 Ongoing pregnancy rate: cumulatively for blastocyst stage transfer\nShapiro 2011a\nShapiro 2011b\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 3.32, df = 2 (P = 0.19); I² = 40%\nTest for overall effect: Z = 1.13 (P = 0.26)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.36, df = 3 (P = 0.23); I² = 31%\nTest for overall effect: Z = 0.49 (P = 0.63)\nTest for subgroup differences: Chi² = 1.08, df = 1 (P = 0.30), I² = 7.7%\nFreeze all IVFEvents\n212\n212\n393819\n96\n308\nTotal\n391391\n7060102232\n623\nConventional IVFEvents\n209\n209\n354032\n107\n316\nTotal\n391391\n6762102231\n622\nWeight\n63.0%63.0%\n10.4%9.5%17.1%37.0%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n1.03 [0.78 , 1.37]1.03 [0.78 , 1.37]\n1.15 [0.59 , 2.25]0.95 [0.45 , 1.99]0.50 [0.26 , 0.96]0.80 [0.54 , 1.18]\n0.95 [0.75 , 1.19]\nOdds RatioM-H, Fixed, 95% CI\n0.01 0.1 1 10 100Favours conventionalFavours freeze-all\n/uni00A0\n/uni00A0\nAnalysis 1.4. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 4: Cumulative clinical pregnancy rate\nStudy or Subgroup\n1.4.1 Clinical pregnancy rate: cumulatively for cleavage stage transferFerraretti 1999\nVuong 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.06, df = 1 (P = 0.81); I² = 0%\nTest for overall effect: Z = 0.02 (P = 0.99)\n1.4.2 Clinical pregnancy rate: cumulatively for blastocyst stage transferSantos-Ribeiro 2020\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 3.03, df = 1 (P = 0.08); I² = 67%\nTest for overall effect: Z = 1.46 (P = 0.14)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.65, df = 3 (P = 0.20); I² = 35%\nTest for overall effect: Z = 0.72 (P = 0.47)\nTest for subgroup differences: Chi² = 1.62, df = 1 (P = 0.20), I² = 38.4%\nFreeze all IVFEvents\n28260\n288\n8719\n106\n394\nTotal\n58391449\n104102206\n655\nConventional IVFEvents\n31261\n292\n8633\n119\n411\nTotal\n67391458\n105102207\n665\nWeight\n10.4%61.1%71.5%\n9.8%18.8%28.5%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n1.08 [0.54 , 2.19]0.99 [0.73 , 1.33]1.00 [0.76 , 1.32]\n1.13 [0.55 , 2.32]0.48 [0.25 , 0.92]0.70 [0.44 , 1.13]\n0.92 [0.72 , 1.16]\nOdds RatioM-H, Fixed, 95% CI\n0.10.2 0.51 2 5 10Favours conventionalFavours freeze-all\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n69\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.5. /uni00A0 Comparison 1: Freeze-all versus conventional\nIVF, outcomes per woman, Outcome 5: Ectopic pregnancy\nStudy or Subgroup\n1.5.1 Ectopic pregnancy: cumulatively\nVuong 2018\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.59, df = 1 (P = 0.44); I² = 0%\nTest for overall effect: Z = 1.40 (P = 0.16)\n1.5.2 Ectopic pregnancy: after first embryo transferChen 2016Ferraretti 1999Santos-Ribeiro 2020\nVuong 2018\nWei 2019Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 3.71, df = 4 (P = 0.45); I² = 0%\nTest for overall effect: Z = 1.74 (P = 0.08)\nFreeze all IVFEvents\n130\n13\n100266\n24\nTotal\n391102493\n746581043918252124\nConventional IVFEvents\n201\n21\n10211312\n38\nTotal\n391102493\n762671053918252150\nWeight\n96.9%3.1%100.0%\n32.3%3.2%4.9%30.4%29.2%100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.64 [0.32 , 1.29]0.14 [0.00 , 6.82]0.61 [0.31 , 1.22]\n1.02 [0.42 , 2.47]0.15 [0.01 , 2.48]1.98 [0.20 , 19.24]0.47 [0.19 , 1.17]0.51 [0.20 , 1.29]0.64 [0.39 , 1.06]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.005 0.1 1 10 200Favours freeze-allFavours conventional\n/uni00A0\n/uni00A0\nAnalysis 1.6. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes per woman, Outcome 6: Miscarriage\nStudy or Subgroup\n1.6.1 Miscarriage rate: cumulatively\nWong 2021\nVuong 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 2.25, df = 1 (P = 0.13); I² = 55%\nTest for overall effect: Z = 0.29 (P = 0.77)\n1.6.2 Miscarriage rate: after first embryo transfer\nWong 2021Ferraretti 1999\nShapiro 2011b\nShapiro 2011aSantos-Ribeiro 2020\nVuong 2018\nWei 2019Chen 2016Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 19.60, df = 7 (P = 0.007); I² = 64%\nTest for overall effect: Z = 1.15 (P = 0.25)\nTest for subgroup differences: Chi² = 0.55, df = 1 (P = 0.46), I² = 0%\nFreeze all IVFEvents\n1447\n61\n105461225\n119108\n289\nTotal\n102391493\n105860701043918257462264\nConventional IVFEvents\n2038\n58\n16357915\n114161\n330\nTotal\n102391493\n266762671053918257622305\nWeight\n27.3%72.7%100.0%\n1.2%1.5%1.6%2.3%3.7%7.4%39.1%43.2%100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.66 [0.31 , 1.37]1.27 [0.81 , 1.99]1.06 [0.72 , 1.55]\n6.45 [1.29 , 32.12]1.99 [0.48 , 8.30]0.82 [0.21 , 3.16]0.81 [0.26 , 2.51]1.39 [0.56 , 3.41]1.69 [0.90 , 3.20]1.05 [0.80 , 1.39]0.64 [0.49 , 0.83]0.90 [0.76 , 1.07]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.850.9 1 1.1 1.2Favours Freeze all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n70\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.7. /uni00A0 Comparison 1: Freeze-all versus conventional\nIVF, outcomes per woman, Outcome 7: Multiple pregnancy\nStudy or Subgroup\n1.7.1 Multiple pregnancy rate: cumulatively\nVuong 2018\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 2.71, df = 1 (P = 0.10); I² = 63%\nTest for overall effect: Z = 0.73 (P = 0.47)\n1.7.2 Multiple pregnancy rate: after first embryo transferChen 2016\nShapiro 2011b\nVuong 2018\nWei 2019\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 7.27, df = 4 (P = 0.12); I² = 45%\nTest for overall effect: Z = 1.59 (P = 0.11)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 12.01, df = 6 (P = 0.06); I² = 50%\nTest for overall effect: Z = 1.01 (P = 0.31)\nTest for subgroup differences: Chi² = 2.03, df = 1 (P = 0.15), I² = 50.7%\nFreeze all IVFEvents\n690\n69\n1182346400\n227\n296\nTotal\n391102493\n746603918251022124\n2617\nConventional IVFEvents\n743\n77\n1082545202\n200\n277\nTotal\n391102493\n762623918251022142\n2635\nWeight\n24.3%0.6%24.9%\n39.9%6.1%16.7%12.0%0.4%75.1%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.92 [0.64 , 1.32]0.13 [0.01 , 1.29]0.88 [0.61 , 1.25]\n1.14 [0.86 , 1.51]0.92 [0.45 , 1.90]1.03 [0.66 , 1.59]2.00 [1.19 , 3.34]0.13 [0.01 , 2.16]1.18 [0.96 , 1.45]\n1.10 [0.92 , 1.31]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nAnalysis 1.8. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 8: Gestational diabetes mellitus\nStudy or Subgroup\n1.8.1 Gestational diabetes mellitus: cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 0.43 (P = 0.67)\n1.8.2 Gestational diabetes mellitus: after first embryo transfer\nVuong 2018\nWei 2019Zhang 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 2.50, df = 2 (P = 0.29); I² = 20%\nTest for overall effect: Z = 1.73 (P = 0.08)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 3.56, df = 3 (P = 0.31); I² = 16%\nTest for overall effect: Z = 1.45 (P = 0.15)\nTest for subgroup differences: Chi² = 1.06, df = 1 (P = 0.30), I² = 5.3%\nFreeze all IVFEvents\n10\n10\n55227\n84\n94\nTotal\n391391\n3918257461962\n2353\nConventional IVFEvents\n12\n12\n73225\n64\n76\nTotal\n391391\n3918257621978\n2369\nWeight\n13.1%13.1%\n7.2%48.9%30.8%86.9%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.83 [0.36 , 1.94]0.83 [0.36 , 1.94]\n0.71 [0.23 , 2.23]1.65 [1.06 , 2.56]\n1.11 [0.64 , 1.92]1.34 [0.96 , 1.86]\n1.26 [0.92 , 1.71]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze-all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n71\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.9. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 9: Hypertensive disorders of pregnancy\nStudy or Subgroup\n1.9.1 Hypertensive disorders of pregnancy: cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 0.74 (P = 0.46)\n1.9.2 Hypertensive disorders of pregnancy: after first embryo transferChen 2016\nVuong 2018\nWei 2019Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 2.84, df = 2 (P = 0.24); I² = 29%\nTest for overall effect: Z = 3.63 (P = 0.0003)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 7.30, df = 3 (P = 0.06); I² = 59%\nTest for overall effect: Z = 3.05 (P = 0.002)\nTest for subgroup differences: Chi² = 4.46, df = 1 (P = 0.03), I² = 77.6%\nFreeze-all IVFEvents\n7\n7\n29529\n63\n70\nTotal\n391391\n7463918251962\n2353\nConventional IVFEvents\n10\n10\n11612\n29\n39\nTotal\n391391\n7623918251978\n2369\nWeight\n15.6%15.6%\n36.6%10.2%37.6%84.4%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.70 [0.27 , 1.82]0.70 [0.27 , 1.82]\n2.57 [1.37 , 4.82]0.83 [0.25 , 2.73]2.34 [1.26 , 4.35]2.15 [1.42 , 3.25]\n1.80 [1.23 , 2.64]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze-all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nAnalysis 1.10. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes\nper woman, Outcome 10: Preterm delivery (< 37 weeks of gestational age)\nStudy or Subgroup\n1.10.1 Preterm delivery (< 37 weeks of gestational age): cumulatively\nVuong 2018\nWong 2021Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.30, df = 1 (P = 0.58); I² = 0%\nTest for overall effect: Z = 2.02 (P = 0.04)\n1.10.2 Preterm delivery (< 37 weeks of gestational age): after first embryo transferChen 2016\nVuong 2018\nWei 2019Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 1.43, df = 2 (P = 0.49); I² = 0%\nTest for overall effect: Z = 1.09 (P = 0.27)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 7.02, df = 4 (P = 0.13); I² = 43%\nTest for overall effect: Z = 0.02 (P = 0.98)\nTest for subgroup differences: Chi² = 5.29, df = 1 (P = 0.02), I² = 81.1%\nFreeze all IVFEvents\n282\n30\n811932\n132\n162\nTotal\n391102493\n7463918251962\n2455\nConventional IVFEvents\n425\n47\n682326\n117\n164\nTotal\n391102493\n7623918251978\n2471\nWeight\n21.2%2.3%23.5%\n44.7%13.2%18.6%76.5%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.64 [0.39 , 1.05]0.41 [0.09 , 1.86]0.62 [0.39 , 0.99]\n1.24 [0.89 , 1.74]0.82 [0.44 , 1.52]1.24 [0.73 , 2.09]1.15 [0.89 , 1.50]\n1.00 [0.80 , 1.25]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze-all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n72\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.11. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 11: Perinatal and neonatal death\nStudy or Subgroup\n1.11.1 Perinatal and neonatal death: cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 1.73 (P = 0.08)\n1.11.2 Perinatal and neonatal death: after first embryo transferChen 2016\nVuong 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 8.52, df = 1 (P = 0.004); I² = 88%\nTest for overall effect: Z = 1.29 (P = 0.20)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 13.11, df = 2 (P = 0.001); I² = 85%\nTest for overall effect: Z = 0.30 (P = 0.77)\nTest for subgroup differences: Chi² = 4.58, df = 1 (P = 0.03), I² = 78.2%\nFreeze all IVFEvents\n0\n0\n70\n7\n7\nTotal\n391391\n746391\n1137\n1528\nConventional IVFEvents\n3\n3\n03\n3\n6\nTotal\n391391\n762391\n1153\n1544\nWeight\n23.1%23.1%\n53.8%23.1%76.9%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.13 [0.01 , 1.30]0.13 [0.01 , 1.30]\n7.61 [1.72 , 33.59]0.13 [0.01 , 1.30]2.27 [0.65 , 7.84]\n1.18 [0.40 , 3.51]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nAnalysis 1.12. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes per woman,\nOutcome 12: Neonatal hospitalisation (> 3 days or neonatal intensive care unit admission)\nStudy or Subgroup\n1.12.1 Neonatal hospitalisation (> 3 days or neonatal intensive care unit admission): cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 0.00 (P = 1.00)\n1.12.2 Neonatal hospitalisation (> 3 days or neonatal intensive care unit admission): after first embryo transfer\nVuong 2018\nWei 2019Zhang 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 1.37, df = 2 (P = 0.50); I² = 0%\nTest for overall effect: Z = 2.47 (P = 0.01)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 1.60, df = 3 (P = 0.66); I² = 0%\nTest for overall effect: Z = 2.42 (P = 0.02)\nTest for subgroup differences: Chi² = 0.23, df = 1 (P = 0.63), I² = 0%\nFreeze all IVFEvents\n5\n5\n550102\n157\n162\nTotal\n391391\n3918257461962\n2353\nConventional IVFEvents\n5\n5\n53085\n120\n125\nTotal\n391391\n3918257621978\n2369\nWeight\n3.8%3.8%\n3.8%29.3%63.1%96.2%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n1.00 [0.29 , 3.48]1.00 [0.29 , 3.48]\n1.00 [0.29 , 3.48]1.69 [1.08 , 2.65]1.26 [0.93 , 1.71]1.37 [1.07 , 1.75]\n1.35 [1.06 , 1.72]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n73\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.13. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes per\nwoman, Outcome 13: Large for gestational age (birth weight > 90th percentile)\nStudy or Subgroup\n1.13.1 Large for gestational age (birth weight > 90th percentile): cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 1.16 (P = 0.24)\n1.13.2 Large for gestational age (birth weight > 90th percentile): after first embryo transfer\nVuong 2018\nWei 2019Zhang 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.42, df = 2 (P = 0.81); I² = 0%\nTest for overall effect: Z = 5.03 (P < 0.00001)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.42, df = 3 (P = 0.94); I² = 0%\nTest for overall effect: Z = 5.16 (P < 0.00001)\nTest for subgroup differences: Chi² = 0.00, df = 1 (P = 1.00), I² = 0%\nFreeze all IVFEvents\n8\n8\n78466\n157\n165\nTotal\n391391\n3918257461962\n2353\nConventional IVFEvents\n4\n4\n34139\n83\n87\nTotal\n391391\n3918257621978\n2369\nWeight\n5.0%5.0%\n4.2%49.2%41.6%95.0%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n1.97 [0.63 , 6.15]1.97 [0.63 , 6.15]\n2.25 [0.65 , 7.82]2.10 [1.46 , 3.03]1.78 [1.20 , 2.64]1.96 [1.51 , 2.55]\n1.96 [1.52 , 2.53]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nAnalysis 1.14. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes per\nwoman, Outcome 14: Small for gestational age (birth weight < 10th percentile)\nStudy or Subgroup\n1.14.1 Small for gestational age (birth weight < 10th percentile): cumulatively\nVuong 2018Subtotal (95% CI)\nTotal events:Heterogeneity: Not applicable\nTest for overall effect: Z = 2.49 (P = 0.01)\n1.14.2 Small for gestational age (birth weight < 10th percentile): after first embryo transfer\nVuong 2018\nWei 2019Zhang 2018Subtotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 5.63, df = 2 (P = 0.06); I² = 64%\nTest for overall effect: Z = 1.59 (P = 0.11)\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 9.36, df = 3 (P = 0.02); I² = 68%\nTest for overall effect: Z = 2.23 (P = 0.03)\nTest for subgroup differences: Chi² = 3.72, df = 1 (P = 0.05), I² = 73.1%\nFreeze-all IVFEvents\n6\n6\n329102\n134\n140\nTotal\n391391\n3918257461962\n2353\nConventional IVFEvents\n18\n18\n1433\n115\n162\n180\nTotal\n391391\n3918257621978\n2369\nWeight\n8.2%8.2%\n5.8%20.9%65.1%91.8%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n0.36 [0.16 , 0.80]0.36 [0.16 , 0.80]\n0.27 [0.10 , 0.70]0.87 [0.53 , 1.45]0.89 [0.67 , 1.19]0.82 [0.65 , 1.05]\n0.77 [0.61 , 0.97]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze-all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n74\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 1.15. /uni00A0 Comparison 1: Freeze-all versus conventional IVF, outcomes\nper woman, Outcome 15: Congenital abnormalities per live-born children\nStudy or Subgroup\nChen 2016\nWei 2019\nWong 2021\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 0.60, df = 1 (P = 0.44); I² = 0%\nTest for overall effect: Z = 0.30 (P = 0.77)\nTest for subgroup differences: Not applicable\nFreeze all IVFEvents\n24120\n36\nTotal\n49146418\n973\nConventional IVFEvents\n17\n110\n28\nTotal\n43235529\n816\nWeight\n64.0%36.0%\n100.0%\nPeto Odds RatioPeto, Fixed, 95% CI\n1.25 [0.67 , 2.34]0.83 [0.36 , 1.91]Not estimable\n1.08 [0.65 , 1.78]\nPeto Odds RatioPeto, Fixed, 95% CI\n0.01 0.1 1 10 100Favours Freeze all IVFFavours Conventional IVF\n/uni00A0\n/uni00A0\nAnalysis 1.16. /uni00A0 Comparison 1: Freeze-all versus conventional IVF,\noutcomes per woman, Outcome 16: Birth weight of babies born\nStudy or Subgroup\n1.16.1 Birth weight of singletons\nWong 2021Shapiro 2016\nVuong 2018Chen 2016\nWei 2019Subtotal (95% CI)\nHeterogeneity: Chi² = 1.25, df = 4 (P = 0.87); I² = 0%\nTest for overall effect: Z = 4.96 (P < 0.00001)\n1.16.2 Birth weight of multiples\nWei 2019Shapiro 2016\nVuong 2018Chen 2016Subtotal (95% CI)\nHeterogeneity: Chi² = 3.63, df = 3 (P = 0.30); I² = 17%\nTest for overall effect: Z = 1.37 (P = 0.17)\nTest for subgroup differences: Chi² = 3.10, df = 1 (P = 0.08), I² = 67.8%\nFreeze all IVFMean\n352832423151.3\n3511.23407.9\n2544.824102501.52479.7\nSD\n518701434.5593.6476.2\n468.9\n611502.6503.2\nTotal\n1841142250416867\n236798237425\nConventional IVFMean\n328330763048.53349.43293.1\n2523.822272388.22481.7\nSD\n704\n511466.8553.2513.5\n472.7516520.8496\nTotal\n2936134212329740\n1249102216379\nWeight\n2.1%3.4%22.3%23.1%49.0%100.0%\n4.6%\n11.8%24.8%58.8%100.0%\nMean Difference\nIV, Fixed, 95% CI\n245.00 [-105.59 , 595.59]166.00 [-105.85 , 437.85]102.80 [-3.76 , 209.36]\n161.80 [57.11 , 266.49]\n114.80 [42.88 , 186.72]127.44 [77.08 , 177.80]\n21.00 [-308.02 , 350.02]183.00 [-22.62 , 388.62]\n113.30 [-28.53 , 255.13]-2.00 [-94.08 , 90.08]49.46 [-21.15 , 120.08]\nMean Difference\nIV, Fixed, 95% CI\n-200-1000 100200Higher with ConventionalHigher with Freeze-all\n/uni00A0\n/uni00A0\nComparison 2. /uni00A0 Freeze-all versus conventional IVF, adverse events per clinical pregnancy\nOutcome or subgroup title No. of studies No. of partici-\npants\nStatistical method Effect size\n2.1 Multiple pregnancy: after first em-\nbryo transfer\n5 2223 Odds Ratio (M-H, Fixed, 95%\nCI)\n1.09 [0.87, 1.36]\n2.2 Miscarriage: after first embryo trans-\nfer\n8 2451 Odds Ratio (M-H, Fixed, 95%\nCI)\n0.82 [0.66, 1.02]\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n75\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 2.1. /uni00A0 Comparison 2: Freeze-all versus conventional IVF, adverse events\nper clinical pregnancy, Outcome 1: Multiple pregnancy: a/f_ter first embryo transfer\nStudy or Subgroup\nChen 2016\nShapiro 2011b\nVuong 2018\nWei 2019\nWong 2021\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 4.63, df = 4 (P = 0.33); I² = 14%\nTest for overall effect: Z = 0.71 (P = 0.48)\nTest for subgroup differences: Not applicable\nFreeze-allEvents\n1182346400\n227\nTotal\n438391735129\n1171\nConventional IVFEvents\n1082545202\n200\nTotal\n4283416340126\n1052\nWeight\n54.4%7.5%23.2%14.1%0.9%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n1.09 [0.81 , 1.48]0.52 [0.19 , 1.40]0.95 [0.59 , 1.54]1.61 [0.93 , 2.81]\n0.52 [0.02 , 11.77]\n1.09 [0.87 , 1.36]\nOdds RatioM-H, Fixed, 95% CI\n0.01 0.1 1 10 100Favours freeze-allFavours conventional IVF\n/uni00A0\n/uni00A0\nAnalysis 2.2. /uni00A0 Comparison 2: Freeze-all versus conventional IVF, adverse events\nper clinical pregnancy, Outcome 2: Miscarriage: a/f_ter first embryo transfer\nStudy or Subgroup\nWong 2021Ferraretti 1999\nShapiro 2011b\nShapiro 2011aSantos-Ribeiro 2020\nVuong 2018\nWei 2019Chen 2016\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 19.09, df = 7 (P = 0.008); I² = 63%\nTest for overall effect: Z = 1.81 (P = 0.07)\nTest for subgroup differences: Not applicable\nFreeze-allEvents\n1054612256964\n195\nTotal\n1020394257173512438\n1291\nConventional IVFEvents\n1635791556107\n218\nTotal\n2628342951163401428\n1160\nWeight\n0.2%1.0%2.6%3.9%4.1%7.3%29.9%50.9%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n13.36 [0.71 , 252.95]2.78 [0.58 , 13.32]0.66 [0.16 , 2.70]0.52 [0.16 , 1.76]1.24 [0.48 , 3.25]1.67 [0.84 , 3.29]0.96 [0.66 , 1.40]0.51 [0.36 , 0.72]\n0.82 [0.66 , 1.02]\nOdds RatioM-H, Fixed, 95% CI\n0.01 0.1 1 10 100Favours freeze-allFavours conventional IVF\n/uni00A0\n/uni00A0\nComparison 3. /uni00A0 Additional analysis: freeze-all versus conventional IVF, live birth rate a/f_ter first transfer\nOutcome or subgroup title No. of studies No. of partici-\npants\nStatistical method Effect size\n3.1 Additional analysis: live birth rate after\nfirst transfer per randomised woman/uni00A0\n13 7766 Odds Ratio (M-H,\nFixed, 95% CI)\n1.17 [1.06, 1.28]\n/uni00A0\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n76\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nAnalysis 3.1. /uni00A0 Comparison 3: Additional analysis: freeze-all versus conventional IVF, live birth rate a/f_ter\nfirst transfer, Outcome 1: Additional analysis: live birth rate a/f_ter first transfer per randomised woman/uni00A0\nStudy or Subgroup\nAflatoonian 2018Aghahosseini 2017Chen 2016Coates 2017Ferraretti 1999Santos-Ribeiro 2020\nShapiro 2011a\nShapiro 2011bShi 2018Stormlund 2020\nVuong 2018\nWei 2019\nWong 2021\nTotal (95% CI)\nTotal events:\nHeterogeneity: Chi² = 46.47, df = 12 (P < 0.00001); I² = 74%\nTest for overall effect: Z = 3.27 (P = 0.001)\nTest for subgroup differences: Not applicable\nFreeze-all Events\n3315368472342231525611324397\n1716\nTotal\n12136746615810470621077223391825102\n3876\nConventional IVF Events\n311532027264110155426612334122\n1579\nTotal\n11936762466710567601080230391825102\n3890\nWeight\n2.7%1.0%19.0%0.8%1.7%2.9%0.8%1.8%32.8%5.6%9.6%18.9%2.4%\n100.0%\nOdds RatioM-H, Fixed, 95% CI\n1.06 [0.60 , 1.89]1.00 [0.39 , 2.55]1.34 [1.10 , 1.65]2.36 [1.02 , 5.46]1.04 [0.50 , 2.13]1.06 [0.61 , 1.84]2.79 [1.21 , 6.44]0.05 [0.01 , 0.39]0.94 [0.80 , 1.12]0.94 [0.62 , 1.41]\n1.11 [0.82 , 1.50]1.61 [1.33 , 1.96]\n0.27 [0.11 , 0.66]\n1.17 [1.06 , 1.28]\nOdds RatioM-H, Fixed, 95% CI\n0.01 0.1 1 10 100Favours conventional IVFFavours freeze-all\n/uni00A0\n/uni00A0\nA D D I T I O N A L /uni00A0 T A B L E S\n/uni00A0\nOutcome Number of stud-\nies\nNumber of par-\nticipants\nAnalysis method OR\nLive birth ratea after first embryo\ntransfer for all embryo stages of\ntransfer\n13 7766 Odds ratio (Mantel-Haenszel,\nfixed-effect, 95% confidence in-\nterval)\n1.17/uni00A0(95% CI 1.06\nto 1.28)\nTable 1. /uni00A0 Live birth rate a/f_ter first transfer/uni00A0\naLive birth rate calculated a/f_ter first transfer is added for illustrative purposes as this comparison is o/f_ten reported in the literature. It\npossibly shows differences in outcome for a stimulated and an unstimulated uterus, although this does not take into account the number\nof embryos that were thawed for transfer. This outcome is less relevant for women undergoing treatment since at the same time of first\ntransfer in a freeze-all strategy, they would already have received the second transfer (as long as there was a sufficient number of embryos)\nin a conventional strategy that includes fresh transfer. Here, one could consider the result of the first embryo transfer in the frozen group\nagainst the combined outcomes of the fresh transfer and the first frozen-thawed-transfer in the fresh group. Therefore cumulative live birth\nrate is the relevant outcome for women.\nFor the calculated live birth rate a/f_ter the first embryo transfer, we included the eight studies included for the primary outcome (Chen\n2016; Ferraretti 1999; Santos-Ribeiro 2020; Shapiro 2011a; Shapiro 2011b; Vuong 2018; Wei 2019; Wong 2021) and five additional RCTs:\nAflatoonian 2018; Aghahosseini 2017 ; Coates 2017; Shi 2018 ; Stormlund 2020. We contacted the authors for additional information\nregarding cumulative data by email but we did not receive a response.\nAflatoonian 2018 compared live birth rate a/f_ter the first embryo transfer between a freeze-all strategy and a conventional strategy in high\nresponders at risk for developing OHSS. Aghahosseini 2017 included infertile women who were candidates for an in vitro fertilisation (IVF)\ntreatment with no further specification of age or type of responder. Coates 2017 excluded women with a suspected decreased ovarian\nreserve (based on serum follicle-stimulating hormone and anti-Müllerian hormone. Women in both groups underwent IVF with assisted\nhatching and pre-implantation genetic screening. Shi 2018 compared live birth rate a/f_ter the first embryo transfer between a freeze-all\nstrategy and a conventional strategy in young women with a regular menses and the reason for IVF procedure: tubal factor, male factor, or\nboth./uni00A0Stormlund 2020/uni00A0compared live birth rate a/f_ter the first embryo transfer between a freeze-all strategy and a conventional strategy in\nyoung women with a regular menses and the reason for IVF procedure: male, tubal, uterine, or unexplained infertility.\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n77\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n/uni00A0\n/uni00A0\nStudy (number of participants) OR (95% CI)\nFixed-effect\nOR (95% CI) \nRandom-effects\nRR (95% CI)\nFixed-effect\nRR (95% CI) \nRandom-effects\nCumulative live birth rate\nChen 2016 (1508)\nFerraretti 1999 (125)\nSantos-Ribeiro 2020 (184)\nShapiro 2011a (103)\nShapiro 2011b (122)\nVuong 2018 (782)\nWei 2019 (1650)\nWong 2021 (204)\n1.08/uni00A0(0.95 to\n1.22)\n1.08 (0.95 to\n1.22)\n1.03 (0.98 to\n1.07)\n1.03 (0.99 to\n1.08)\nOHSS\nChen 2016 (1508)\nFerraretti 1999 (125)\nSantos-Ribeiro 2020 (184)\nVuong 2018 (782)\nWei 2019 (1650)\nWong 2021 (204)\n0.26/uni00A0(0.17 to\n0.39)\n0.25/uni00A0(0.13 to\n0.46)\n0.22/uni00A0(0.14 to\n0.37)\n0.25/uni00A0(0.14 to\n0.44)\nCI: confidence interval; OHSS: ovarian hyperstimulation syndrome; OR: odds ratio;RR: risk ratio\nTable 2. /uni00A0 Sensitivity analysis for primary outcomes/uni00A0\nIn the studies of Santos-Ribeiro 2020; Shapiro 2011a/uni00A0there was lost to follow up for the primary outcome and therefore numbers of\nparticipants differ with the Characteristics tables.\n/uni00A0\n/uni00A0\nA P P E N D I C E S\nAppendix 1. Cochrane Gynaecology and Fertility Group (CGFG) specialised register search strategy\nSearched 23 September 2020\nProcite platform\nKeywords CONTAINS \"cryopreservation\" or \"frozen embryo transfer\" or \"frozen embryos\" or \"frozen-thawed cycle\" or \"frozen-thawed\nembryo transfer\" or \"frozen-thawed embryos\" or \"FET\" or \"cryopreserved embryos\" or \"cryopreserved-thawed embryos\" or \"vitrified\"\nor \"vitrification\" or \"fresh v cryopreserved\" or \"freeze all\" or \"embryo vitrification\" or \"fresh versus frozen\" or Title CONTAINS\n\"cryopreservation\" or \"frozen embryo transfer\" or \"frozen embryos\" or \"frozen-thawed cycle\" or \"frozen-thawed embryo transfer\" or\n\"frozen-thawed embryos\" or \"FET\" or \"cryopreserved embryos\" or \"cryopreserved-thawed embryos\" or \"vitrified\" or \"vitrification\" or\n\"fresh v cryopreserved\" or \"freeze all\" or \"embryo vitrification\" or \"fresh versus frozen\"\nAND\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n78\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nKeywords CONTAINS \"fresh\" or \"fresh blastocyst transfer\" or \"fresh cycle\" or \"fresh embryos\" or \"fresh v cryopreserved\" or \"fresh versus\nfrozen\" or Title CONTAINS \"fresh\" or \"fresh blastocyst transfer\" or \"fresh cycle\" or \"fresh embryos\" or \"fresh v cryopreserved\" or \"fresh\nversus frozen\"\n117 records\nAppendix 2. CENTRAL Register of Studies Online (CRSO) search strategy\nSearched 23 September 2020\nWeb platform\n#1/uni00A0/uni00A0 /uni00A0MESH DESCRIPTOR Embryo Transfer EXPLODE ALL TREES/uni00A0/uni00A0 /uni00A01095\n#2/uni00A0/uni00A0 /uni00A0MESH DESCRIPTOR Fertilization in Vitro EXPLODE ALL TREES/uni00A0/uni00A0 /uni00A02060\n#3/uni00A0/uni00A0 /uni00A0MESH DESCRIPTOR Sperm Injections, Intracytoplasmic EXPLODE ALL TREES/uni00A0/uni00A0 /uni00A0538\n#4/uni00A0/uni00A0 /uni00A0embryo*: TI,AB,KY/uni00A0/uni00A0 /uni00A07483\n#5/uni00A0/uni00A0 /uni00A0(vitro fertili?ation):TI,AB,KY/uni00A0/uni00A0 /uni00A03433\n#6/uni00A0/uni00A0 /uni00A0ivf:TI,AB,KY/uni00A0/uni00A0 /uni00A05639\n#7/uni00A0/uni00A0 /uni00A0icsi:TI,AB,KY/uni00A0/uni00A0 /uni00A02736\n#8/uni00A0/uni00A0 /uni00A0(intracytoplasmic sperm injection*):TI,AB,KY/uni00A0/uni00A0 /uni00A01925\n#9/uni00A0/uni00A0 /uni00A0blastocyst*:TI,AB,KY/uni00A0/uni00A0 /uni00A01284\n#10/uni00A0/uni00A0 /uni00A0#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9/uni00A0/uni00A0 /uni00A010823\n#11/uni00A0/uni00A0 /uni00A0MESH DESCRIPTOR Cryopreservation EXPLODE ALL TREES/uni00A0/uni00A0 /uni00A0552\n#12/uni00A0/uni00A0 /uni00A0MESH DESCRIPTOR Vitrification EXPLODE ALL TREES/uni00A0/uni00A0 /uni00A042\n#13/uni00A0/uni00A0 /uni00A0((cryopreservat* or cryofixation or cryonic suspension)):TI,AB,KY/uni00A0/uni00A0 /uni00A01011\n#14/uni00A0/uni00A0 /uni00A0(freez* or frozen):TI,AB,KY/uni00A0/uni00A0 /uni00A05794\n#15/uni00A0/uni00A0 /uni00A0Vitrif*:TI,AB,KY/uni00A0/uni00A0 /uni00A0503\n#16/uni00A0/uni00A0 /uni00A0Thaw*:TI,AB,KY/uni00A0/uni00A0 /uni00A01117\n#17/uni00A0/uni00A0 /uni00A0#11 OR #12 OR #13 OR #14 OR #15 OR #16/uni00A0/uni00A0 /uni00A06782\n#18/uni00A0/uni00A0 /uni00A0#10 AND #17/uni00A0/uni00A0 /uni00A01692\nAppendix 3. MEDLINE search strategy\nSearched from 1946 until 23 September 2020\nOvid platform\n1 /uni00A0 /uni00A0 exp Cryopreservation/ (37259)\n2 /uni00A0 /uni00A0 exp Freezing/ (24066)\n3 /uni00A0 /uni00A0 (cryopreservat$ or cryofixation or cryonic suspension).tw. (16154)\n4 /uni00A0 /uni00A0 freez$.tw. (69378)\n5 /uni00A0 /uni00A0 thaw$.tw. (26106)\n6 /uni00A0 /uni00A0 exp Vitrification/ (1687)\n7 /uni00A0 /uni00A0 Vitrif$.tw. (5311)\n8 /uni00A0 /uni00A0 froze$.tw. (79302)\n9 /uni00A0 /uni00A0 disengage$.tw. (5314)\n10 /uni00A0 /uni00A0 or/1-9 (178214)\n11 /uni00A0 /uni00A0 exp embryo transfer/ or exp fertilization in vitro/ or exp sperm injections, intracytoplasmic/ or exp ovulation induction/ (49216)\n12 /uni00A0 /uni00A0 embryo$.tw. (354686)\n13 /uni00A0 /uni00A0 blastocyst$.tw. (22650)\n14 /uni00A0 /uni00A0 vitro fertili?ation.tw. (23551)\n15 /uni00A0 /uni00A0 ivf.tw. (24044)\n16 /uni00A0 /uni00A0 icsi.tw. (8560)\n17 /uni00A0 /uni00A0 intracytoplasmic sperm injection$.tw. (7331)\n18 /uni00A0 /uni00A0 ovulation induc$.tw. (4181)\n19 /uni00A0 /uni00A0 (ovar$ adj3 hyperstim$).tw. (5235)\n20 /uni00A0 /uni00A0 (ovar$ adj3 stimulat$).tw. (8195)\n21 /uni00A0 /uni00A0 exp Superovulation/ or Superovulat$.tw. (3960)\n22 /uni00A0 /uni00A0 or/11-21 (396906)\n23 /uni00A0 /uni00A0 10 and 22 (14532)\n24 /uni00A0 /uni00A0 randomized controlled trial.pt. (513703)\n25 /uni00A0 /uni00A0 controlled clinical trial.pt. (93853)\n26 /uni00A0 /uni00A0 randomized.ab. (493637)\n27 /uni00A0 /uni00A0 placebo.tw. (217021)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n79\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n28 /uni00A0 /uni00A0 clinical trials as topic.sh. (193027)\n29 /uni00A0 /uni00A0 randomly.ab. (341750)\n30 /uni00A0 /uni00A0 trial.ti. (225713)\n31 /uni00A0 /uni00A0 (crossover or cross-over or cross over).tw. (86227)\n32 /uni00A0 /uni00A0 or/24-31 (1346965)\n33 /uni00A0 /uni00A0 exp animals/ not humans.sh. (4736958)\n34 /uni00A0 /uni00A0 32 not 33 (1238835)\n35 /uni00A0 /uni00A0 23 and 34 (793)\nAppendix 4. Embase search strategy\nSearched from 1980 until 23 September 2020\nOvid platform\n1 /uni00A0 /uni00A0 exp Cryopreservation/ (41662)\n2 /uni00A0 /uni00A0 exp Freezing/ (28402)\n3 /uni00A0 /uni00A0 (cryopreservat$ or cryofixation or cryonic suspension).tw. (22526)\n4 /uni00A0 /uni00A0 freez$.tw. (75296)\n5 /uni00A0 /uni00A0 thaw$.tw. (33430)\n6 /uni00A0 /uni00A0 exp Vitrification/ (6065)\n7 /uni00A0 /uni00A0 Vitrif$.tw. (8400)\n8 /uni00A0 /uni00A0 froze$.tw. (107125)\n9 /uni00A0 /uni00A0 disengage$.tw. (6376)\n10 /uni00A0 /uni00A0 or/1-9 (216960)\n11 /uni00A0 /uni00A0 exp embryo transfer/ or exp fertilization in vitro/ or exp intracytoplasmic sperm injection/ (70627)\n12 /uni00A0 /uni00A0 in vitro fertili?ation.tw. (30829)\n13 /uni00A0 /uni00A0 icsi.tw. (16299)\n14 /uni00A0 /uni00A0 intracytoplasmic sperm injection$.tw. (9790)\n15 /uni00A0 /uni00A0 (blastocyst adj2 transfer$).tw. (2451)\n16 /uni00A0 /uni00A0 ivf.tw. (41016)\n17 /uni00A0 /uni00A0 exp superovulation/ (2881)\n18 /uni00A0 /uni00A0 superovulat$.tw. (3912)\n19 /uni00A0 /uni00A0 exp ovulation induction/ (14554)\n20 /uni00A0 /uni00A0 blastocyst$.tw. (30017)\n21 /uni00A0 /uni00A0 embryo$.tw. (392171)\n22 /uni00A0 /uni00A0 vitro fertili?ation.tw. (30870)\n23 /uni00A0 /uni00A0 ovulation induc$.tw. (5650)\n24 /uni00A0 /uni00A0 (ovar$ adj3 stimulat$).tw. (12319)\n25 /uni00A0 /uni00A0 (ovar$ adj3 hyperstim$).tw. (7688)\n26 /uni00A0 /uni00A0 or/11-25 (449099)\n27 /uni00A0 /uni00A0 10 and 26 (23805)\n28 /uni00A0 /uni00A0 Clinical Trial/ (974756)\n29 /uni00A0 /uni00A0 Randomized Controlled Trial/ (616533)\n30 /uni00A0 /uni00A0 exp randomization/ (88043)\n31 /uni00A0 /uni00A0 Single Blind Procedure/ (40177)\n32 /uni00A0 /uni00A0 Double Blind Procedure/ (173052)\n33 /uni00A0 /uni00A0 Crossover Procedure/ (64313)\n34 /uni00A0 /uni00A0 Placebo/ (341414)\n35 /uni00A0 /uni00A0 Randomi?ed controlled trial$.tw. (237064)\n36 /uni00A0 /uni00A0 Rct.tw. (38374)\n37 /uni00A0 /uni00A0 random allocation.tw. (2055)\n38 /uni00A0 /uni00A0 randomly allocated.tw. (35997)\n39 /uni00A0 /uni00A0 allocated randomly.tw. (2571)\n40 /uni00A0 /uni00A0 (allocated adj2 random).tw. (826)\n41 /uni00A0 /uni00A0 Single blind$.tw. (25257)\n42 /uni00A0 /uni00A0 Double blind$.tw. (205370)\n43 /uni00A0 /uni00A0 ((treble or triple) adj blind$).tw. (1191)\n44 /uni00A0 /uni00A0 placebo$.tw. (307127)\n45 /uni00A0 /uni00A0 prospective study/ (625354)\n46 /uni00A0 /uni00A0 or/28-45 (2232203)\n47 /uni00A0 /uni00A0 case study/ (71852)\n48 /uni00A0 /uni00A0 case report.tw. (411819)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n80\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\n49 /uni00A0 /uni00A0 abstract report/ or letter/ (1118194)\n50 /uni00A0 /uni00A0 or/47-49 (1590932)\n51 /uni00A0 /uni00A0 46 not 50 (2177816)\n52 /uni00A0 /uni00A0 27 and 51 (2370)\nAppendix 5. PsycINFO search strategy\nSearched from 1806 until 23 September 2020\nOvid platform\n1 /uni00A0 /uni00A0 (cryopreservat$ or cryofixation or cryonic suspension).tw. (97)\n2 /uni00A0 /uni00A0 freez$.tw. (4662)\n3 /uni00A0 /uni00A0 thaw$.tw. (155)\n4 /uni00A0 /uni00A0 Vitrif$.tw. (14)\n5 /uni00A0 /uni00A0 froze$.tw. (1606)\n6 /uni00A0 /uni00A0 disengage$.tw. (7954)\n7 /uni00A0 /uni00A0 or/1-6 (14202)\n8 /uni00A0 /uni00A0 exp reproductive technology/ (1863)\n9 /uni00A0 /uni00A0 icsi.tw. (74)\n10 /uni00A0 /uni00A0 intracytoplasmic sperm injection$.tw. (57)\n11 /uni00A0 /uni00A0 (blastocyst adj2 transfer$).tw. (4)\n12 /uni00A0 /uni00A0 assisted reproduct$.tw. (998)\n13 /uni00A0 /uni00A0 ovulation induc$.tw. (31)\n14 /uni00A0 /uni00A0 (ovari$ adj2 stimulat$).tw. (58)\n15 /uni00A0 /uni00A0 COH.tw. (132)\n16 /uni00A0 /uni00A0 superovulat$.tw. (7)\n17 /uni00A0 /uni00A0 infertil$.tw. (3600)\n18 /uni00A0 /uni00A0 subfertil$.tw. (95)\n19 /uni00A0 /uni00A0 (ovari$ adj2 induction).tw. (8)\n20 /uni00A0 /uni00A0 ivf.tw. (576)\n21 /uni00A0 /uni00A0 vitro fertili?ation.tw. (768)\n22 /uni00A0 /uni00A0 (ovar$ adj3 hyperstimulat$).tw. (14)\n23 /uni00A0 /uni00A0 or/8-22 (5473)\n24 /uni00A0 /uni00A0 7 and 23 (148)\n25 /uni00A0 /uni00A0 random.tw. (59350)\n26 /uni00A0 /uni00A0 control.tw. (450545)\n27 /uni00A0 /uni00A0 double-blind.tw. (23110)\n28 /uni00A0 /uni00A0 clinical trials/ (11762)\n29 /uni00A0 /uni00A0 placebo/ (5720)\n30 /uni00A0 /uni00A0 exp Treatment/ (1056217)\n31 /uni00A0 /uni00A0 or/25-30 (1458404)\n32 /uni00A0 /uni00A0 24 and 31 (66)\nAppendix 6. CINAHL search strategy\nSearched from 1961 to 23 September 2020\nEbsco platform\n/uni00A0\n# Query Results\nS32 S19 AND S31 310\nS31 S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR\nS30\n1,355,174\nS30 TX allocat* random* 11,049\nS29 (MH \"Quantitative Studies\") 23,579\n/uni00A0\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n81\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nS28 (MH \"Placebos\") 11,474\nS27 TX placebo* 59,611\nS26 TX random* allocat* 11,049\nS25 (MH \"Random Assignment\") 55,964\nS24 TX randomi* control* trial* 177,249\nS23 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (dou-\nbl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1\nblind*) or (trebl* n1 mask*) )\n1,033,075\nS22 TX clinic* n1 trial* 252,733\nS21 PT Clinical trial 86,291\nS20 (MH \"Clinical Trials+\") 268,471\nS19 S17 AND S18 1867\nS18 S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 29,812\nS17 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 16,748\nS16 TX ovulation induc* 1732\nS15 TX icsi 1137\nS14 TX ivf 4531\nS13 TX vitro fertili?ation 6874\nS12 TX blastocyst* 2176\nS11 TX embryo* 22,594\nS10 TX intracytoplasmic sperm injection* 884\nS9 (MM \"Fertilization in Vitro\") 3392\nS8 (MM \"Embryo Transfer\") 1088\nS7 TX disengage* 2122\nS6 TX frozen 8196\nS5 TX Vitrif* 448\nS4 TX thaw* 1733\nS3 TX freez* 4646\nS2 TX (cryopreservat* or cryofixation or cryonic suspension) 2630\n/uni00A0/uni00A0(Continued)\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n82\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nS1 (MH \"Cryopreservation+\") 2443\n/uni00A0/uni00A0(Continued)\n/uni00A0\nAppendix 7. ClinicalTrials.gov search string\nWeb platform\nhttps://clinicaltrials.gov/\nSearched 23 September 2020\nsearch terms\n(IVF OR ICSI OR embryo transfer) AND (freeze-all OR frozen thawed embryo transfer OR cryopreservation OR disengage)\nAppendix 8. WHO ICTRP search string\nWeb platform\napps.who.int/trialsearch\nSearched 23 September 2020\nsearch terms\n(IVF OR ICSI OR embryo transfer) AND (freeze-all OR frozen thawed embryo transfer OR cryopreservation OR disengage)\nW H A T ' S /uni00A0 N E W\n/uni00A0\nDate Event Description\n23 September 2020 New citation required but conclusions\nhave not changed\nThe addition of the new studies has not led to change in conclu-\nsions\n23 September 2020 New search has been performed We updated the review.\n/uni00A0\nH I S T O R Y\nProtocol first published: Issue 7, 2014\nReview first published: Issue 3, 2017\nC O N T R I B U T I O N S /uni00A0 O F /uni00A0 A U T H O R S\nTjitske Zaat, Miriam Zagers, Femke Mol, Madelon van Wely and Sebastiaan Mastenbroek updated the search and adjusted the review.\nPreviously, Kai Mee Wong, Sjoerd Repping, and Sebastiaan Mastenbroek developed the concept of the review. Mariëtte Goddijn provided\nfeedback on the review.\nD E C L A R A T I O N S /uni00A0 O F /uni00A0 I N T E R E S T\nTjitske Zaat: none known\nMiriam Zagers: none known\nMadelon van Wely: is author of the previous version of this review (Wong 2017), and is author of one of the included studies (Wong 2021).\nFemke Mol: is author of the previous version of this review (Wong 2017), and is author of one of the included studies (Wong 2021).\nMariëtte Goddijn: none known\nSebastiaan Mastenbroek is author of the previous version of this review (Wong 2017), and is author of one of the included studies (Wong\n2021).\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n83\n\nCochrane\nLibrary\nTrusted evidence.\nInformed decisions.\nBetter health.\n/uni00A0\n/uni00A0\nCochrane Database of Systematic Reviews\nS O U R C E S /uni00A0 O F /uni00A0 S U P P O R T\nInternal sources\n• None, Other\nExternal sources\n• None, Other\nD I F F E R E N C E S /uni00A0 B E T W E E N /uni00A0 P R O T O C O L /uni00A0 A N D /uni00A0 R E V I E W\nFor the primary version of the review we added a method of analysing time to pregnancy (by hazard ratios), as this was not reported in the\nprotocol; in the event, no data/uni00A0were available for this outcome.\nFor the primary version of the review we performed a subgroup analysis by timing of embryo transfer for the primary outcome of\ncumulative live birth.\nFor the primary version of the review we changed the unit of analysis for birth weight (from per woman to per baby).\nFor the primary version of the review we added some details to the section specifying our plans for the summary of findings table.\nFor the primary version of the review congenital disorders, defined as the number of congenital abnormalities at birth, were reported per\nlive-born children plus number of/uni00A0foetuses therapeutically terminated in stead of per all clinical pregnancies.\nFor the 2021 update we added a method of analysing time to pregnancy, eventually this method was not possible given the difference in\nthe studies included in this outcome.\nFor the 2021 update we extended the secondary outcomes regarding pregnancy outcomes and obstetric, perinatal and neonatal outcomes\nper woman.\nFor the 2021 update we added a second table with Summary of Findings concerning obstetric en neonatal safety outcomes.\nAll studies reported sufficient detail to calculate mean differences and standard deviations (SDs) and therefore we did not have to impute\ndata on basis of the assumption that the outcome had a SD equal to the highest SD from other studies within the same analysis as\nmentioned in the methods section.\nI N D E X /uni00A0 T E R M S\nMedical Subject Headings (MeSH)\nAbortion, Spontaneous /uni00A0[epidemiology];/uni00A0 Bias;/uni00A0 *Cryopreservation;/uni00A0 Embryo Transfer /uni00A0[adverse effects] /uni00A0[*methods];/uni00A0 *Embryo,\nMammalian;/uni00A0 Fertilization in Vitro;/uni00A0 Live Birth /uni00A0[epidemiology];/uni00A0 Ovarian Hyperstimulation Syndrome /uni00A0[epidemiology] /uni00A0[prevention &\ncontrol];/uni00A0 Pregnancy Complications /uni00A0[epidemiology];/uni00A0 Pregnancy Rate;/uni00A0 Pregnancy, Multiple /uni00A0[statistics & numerical data];/uni00A0 Randomized\nControlled Trials as Topic;/uni00A0 Sperm Injections, Intracytoplasmic;/uni00A0 Time-to-Pregnancy\nMeSH check words\nFemale; Humans; Pregnancy\nFresh versus frozen embryo transfers in assisted reproduction (Review)\nCopyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n84","source_license":"CC-BY-4.0","license_restricted":false}