{"paper_id":"c3dc07d8-5b64-4a3d-92df-66ccb9e5cd18","body_text":"Abstract\nIn order to inform patients undergoing ART regarding their chances for motherhood, it seems useful to describe “freeze all” outcomes according to the different potential indications. The goal of this study was to examine the impact of a “freeze-all approach” on the cumulative live birth rate (cLBR) according to the indication. It is a cohort study including women who had undergone ovarian stimulation (OS) using an antagonist protocol with GnRH agonist triggering between 09.2016 and 09.2018 followed by a freeze-all cycle of blastocyst embryos. The ART outcomes were compared between the two main indications of the freeze-all strategy which were in our cohort: risk of ovarian hyperstimulation syndrome (OHSS) and endometriosis. The ART outcomes were also described for the others indications (inadequate endometrium and/or premature progesterone elevation at trigger day, two or more previous ART failures, and autoimmune disease and/or a high risk of thromboembolic disease (AI and/or TE risk)). In total, 658 women were included. The cLBR in the total population was 37.7% (248/658). The cLBR was significantly higher in the “OHSS risk” group (133/281, 47.3%) than in the “endometriosis” group (69/190, 36.3%) (p = 0.017). No significant differences were noted regarding perinatal outcomes, except a significantly higher risk of placenta praevia (PP) observed in the “endometriosis” group (10.1%) (p = 0.002). The “freeze-all approach” yielded good results in terms of the cLBR and especially in case of OHSS risk. These data should be taken into account when informing patients about the ART strategy and their chances of motherhood.\nSimilar content being viewed by others\nData Availability\nThe data underlying this article will be shared on reasonable request to the corresponding author.\nReferences\nEuropean IVF-monitoring Consortium (EIM)‡ for the European Society of Human Reproduction and Embryology (ESHRE), Wyns C, Bergh C, Calhaz-Jorge C, De Geyter C, Kupka MS, et al. ART in Europe, 2016: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020:hoaa032. https://doi.org/10.1093/hropen/hoaa032.\nVan Landuyt L, Stoop D, Verheyen G, Verpoest W, Camus M, Van de Velde H, et al. Outcome of closed blastocyst vitrification in relation to blastocyst quality: evaluation of 759 warming cycles in a single-embryo transfer policy. Hum Reprod. 2011;26:527–34. https://doi.org/10.1093/humrep/deq374.\nBodri D, Guillén JJ, Trullenque M, Schwenn K, Esteve C, Coll O. Early ovarian hyperstimulation syndrome is completely prevented by gonadotropin releasing-hormone agonist triggering in high-risk oocyte donor cycles: a prospective, luteal-phase follow-up study. Fertil Steril. 2010;93:2418–20. https://doi.org/10.1016/j.fertnstert.2009.08.036.\nBourdon M, Maignien C, Pocate-Cheriet K, Plu Bureau G, Marcellin L, Patrat C, et al. The freeze-all strategy after IVF: which indications? Reprod Biomed Online. 2021;42(3):529–45. https://doi.org/10.1016/j.rbmo.2020.11.013.\nShi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med. 2018;378:126–36. https://doi.org/10.1056/NEJMoa1705334.\nWei D, Liu J-Y, Sun Y, Shi Y, Zhang B, Liu J-Q, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019. https://doi.org/10.1016/S0140-6736(18)32843-5.\nChen Z-J, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375:523–33. https://doi.org/10.1056/NEJMoa1513873.\nRoque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2019;25:2–14. https://doi.org/10.1093/humupd/dmy033.\nVuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, et al. IVF transfer of fresh or frozen embryos in women without polycystic ovaries. N Engl J Med. 2018;378:137–47. https://doi.org/10.1056/NEJMoa1703768.\nWong KM, van Wely M, Mol F, Repping S, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2017;3:CD011184. https://doi.org/10.1002/14651858.CD011184.pub2.\nBlockeel C, Drakopoulos P, Santos-Ribeiro S, Polyzos NP, Tournaye H. A fresh look at the freeze-all protocol: a SWOT analysis. Hum Reprod. 2016. https://doi.org/10.1093/humrep/dev339.\nCoates A, Kung A, Mounts E, Hesla J, Bankowski B, Barbieri E, et al. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial. Fertil Steril. 2017;107:723-730.e3. https://doi.org/10.1016/j.fertnstert.2016.12.022.\nDe Ziegler D, Pirtea P, Galliano D, Cicinelli E, Meldrum D. Optimal uterine anatomy and physiology necessary for normal implantation and placentation. Fertil Steril. 2016;105:844–54. https://doi.org/10.1016/j.fertnstert.2016.02.023.\nVuong LN, Pham TD, Dang VQ, Ho TM, Ho VNA, Norman RJ, et al. Live birth rates with a freeze-only strategy versus fresh embryo transfer: secondary analysis of a randomized clinical trial. Reprod Biomed Online. 2019;38:387–96. https://doi.org/10.1016/j.rbmo.2018.12.012.\nBourdon M, Santulli P, Maignien C, Gayet V, Pocate-Cheriet K, Marcellin L, et al. The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: a retrospective matched cohort study. PLoS One. 2018;13:e0194800. https://doi.org/10.1371/journal.pone.0194800.\nJi Wu, Yang X, Huang J, Kuang Y, Wang Y. Fertility and neonatal outcomes of freeze-all vs. fresh embryo transfer in women with advanced endometriosis. Front Endocrinol (Lausanne). 2019;10:770. https://doi.org/10.3389/fendo.2019.00770.\nShapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Freeze-all can be a superior therapy to another fresh cycle in patients with prior fresh blastocyst implantation failure. Reprod Biomed Online. 2014;29:286–90. https://doi.org/10.1016/j.rbmo.2014.04.009.\nOlausson N, Discacciati A, Nyman AI, Lundberg F, Hovatta O, Westerlund E, et al. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilization with fresh respectively frozen-thawed embryo transfer: nationwide cohort study. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14840.\nPapanikolaou EG, Humaidan P, Polyzos N, Kalantaridou S, Kol S, Benadiva C, et al. New algorithm for OHSS prevention. Reprod Biol Endocrinol. 2011;9:147. https://doi.org/10.1186/1477-7827-9-147.\nBourdon M, Santulli P, Gayet V, Maignien C, Marcellin L, Chapron C. Deferred frozen embryo transfer: what benefits can be expected from this strategy in patients with and without endometriosis? J Endometriosis Pelvic Pain Disorders. 2017;9:87–97. https://doi.org/10.5301/jeppd.5000281.\nHuang Y, Wang E-Y, Du Q-Y, Xiong Y-J, Guo X-Y, Yu Y-P, et al. Progesterone elevation on the day of human chorionic gonadotropin administration adversely affects the outcome of IVF with transferred embryos at different developmental stages. Reprod Biol Endocrinol. 2015;13:82. https://doi.org/10.1186/s12958-015-0075-3.\nBourdon M, Santulli P, Chen Y, Patrat C, Pocate-Cheriet K, Maignien C, et al. The deferred embryo transfer strategy seems not to be a good option after repeated IVF/ICSI cycle failures. Reprod Sci. 2019;26:1210–7. https://doi.org/10.1177/1933719118811648.\nde Ziegler D, Gayet V, Aubriot FX, Fauque P, Streuli I, Wolf JP, et al. Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes. Fertil Steril. 2010;94:2796–9. https://doi.org/10.1016/j.fertnstert.2010.05.056.\nBourdon M, Ferreux L, Maignien C, et al. Tobacco consumption is associated with slow-growing day-6 blastocysts. F S Rep. 2020;1:30–6. https://doi.org/10.1016/j.xfre.2020.04.006.\nGardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J. A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum Reprod. 1998;13:3434–40. https://doi.org/10.1093/humrep/13.12.3434.\nFerreux L, Bourdon M, Sallem A, Santulli P, Barraud-Lange V, Le Foll N, et al. Live birth rate following frozen-thawed blastocyst transfer is higher with blastocysts expanded on day 5 than on day 6. Hum Reprod. 2018. https://doi.org/10.1093/humrep/dey004.\nBourdon M, Santulli P, Kefelian F, Vienet-Legue L, Maignien C, Pocate-Cheriet K, et al. Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate. Hum Reprod. 2018;33:905–13. https://doi.org/10.1093/humrep/dey041.\nZegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009;92:1520–4. https://doi.org/10.1016/j.fertnstert.2009.09.009.\nKolte AM, Bernardi LA, Christiansen OB, Quenby S, Farquharson RG, Goddijn M, et al. Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod. 2015;30:495–8. https://doi.org/10.1093/humrep/deu299.\nMaheshwari A, McLernon D, Bhattacharya S. Cumulative live birth rate: time for a consensus? Hum Reprod. 2015;30:2703–7. https://doi.org/10.1093/humrep/dev263.\nFarquhar C, Rombauts L, Kremer JA, Lethaby A, Ayeleke RO. Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2017;5:CD006109. https://doi.org/10.1002/14651858.CD006109.pub3.\nWei D, Shi Y, Li J, Wang Z, Zhang L, Sun Y, et al. Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome. Hum Reprod. 2017;32:354–61. https://doi.org/10.1093/humrep/dew325.\nMontoya-Botero P, Martinez F, Rodríguez-Purata J, Rodríguez I, Coroleu B, Polyzos NP. The effect of type of oral contraceptive pill and duration of use on fresh and cumulative live birth rates in IVF/ICSI cycles. Hum Reprod. 2020;35:826–36. https://doi.org/10.1093/humrep/dez299.\nImudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, et al. Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization. Fertil Steril. 2012;97:1374–9. https://doi.org/10.1016/j.fertnstert.2012.03.028.\nPereira N, Elias RT, Christos PJ, Petrini AC, Hancock K, Lekovich JP, et al. Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. Hum Reprod. 2017;32:1410–7. https://doi.org/10.1093/humrep/dex095.\nBourdon M, Ouazana M, Maignien C, Pocate-Cheriet K, Patrat C, Marcellin L, et al. Impact of supraphysiological estradiol serum levels on birth weight in singletons born after fresh embryo transfer. Reprod Sci. 2020. https://doi.org/10.1007/s43032-020-00174-x.\nMaheshwari A, Pandey S, Amalraj Raja E, Shetty A, Hamilton M, Bhattacharya S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update. 2018;24:35–58. https://doi.org/10.1093/humupd/dmx031.\nRoque M, Bedoschi G, Cecchino GN, Esteves SC. Fresh versus frozen blastocyst transfer. The Lancet. 2019;394:1227–8. https://doi.org/10.1016/S0140-6736(19)31393-5.\nBenaglia L, Candotti G, Papaleo E, Pagliardini L, Leonardi M, Reschini M, et al. Pregnancy outcome in women with endometriosis achieving pregnancy with IVF. Hum Reprod. 2016;31:2730–6. https://doi.org/10.1093/humrep/dew210.\nBourdon M, Santulli P, Sebbag L, Maignien C, Goffinet F, Marcellin L, et al. Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis. Reprod Biomed Online. 2020. https://doi.org/10.1016/j.rbmo.2020.08.009.\nAcknowledgements\nThe authors wish to thank staff members of our department for their expert assistance with data collection, particularly Valerie Blanchet, Julia Gonnot, Emmanuelle Laviron and Célie Cervantes.\nFunding\nThis study was partially supported by a Finox Forward Research Grant.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nEthics Approval\nThis study was approved by the Ethics Review Committee of Cochin University Hospital (CLEP)(n°AAA-2022–08012).\nConflict of Interest\nThe authors declare no competing interests.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nThe authors consider that the first two authors (Mathilde Bourdon and Asim Alwohaibi) should be regarded as joint first author.\nThe authors consider that the last two authors (Charles Chapron and Pietro Santulli) should be regarded as joint last author.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nBourdon, M., Alwohaibi, A., Maignien, C. et al. IVF/ICSI Outcomes After a Freeze-All Strategy: an Observational Cohort Study. Reprod. Sci. 30, 2283–2291 (2023). https://doi.org/10.1007/s43032-023-01173-4\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-023-01173-4","source_license":"CC0","license_restricted":false}