{"paper_id":"9c913c9a-e5a3-4d6a-bda7-c4acbf949ee3","body_text":"Review began\n 03/09/2025 \nReview ended\n 03/20/2025 \nPublished\n 03/25/2025\n© Copyright \n2025\nNishio et al. This is an open access article\ndistributed under the terms of the Creative\nCommons Attribution License CC-BY 4.0.,\nwhich permits unrestricted use, distribution,\nand reproduction in any medium, provided\nthe original author and source are credited.\nDOI:\n 10.7759/cureus.81185\nPregnancy Rate Is High When the Length of the\nLuteal Phase During the In Vitro Fertilization\nHormone Replacement Cycle Is 144 Hours or\nMore Before Embryo Transfer\nEiji Nishio \n, \nShota Oikawa \n, \nEriko Sakakibara \n, \nMiho Ishikawa \n, \nKiriko Kotani \n, \nHikari Yoshizawa \n,\nHironori Miyamura \n, \nTakanori Hayashi \n, \nHaruki Nishizawa \n1.\n Obstetrics and Gynecology, Fujita Health University, Toyoake, JPN \n2.\n Clinical Laboratory, Fujita Health University,\nToyoake, JPN \n3.\n Anatomy and Medical Biology, Fujita Health University, Toyoake, JPN\nCorresponding author: \nEiji Nishio, \nenishio@fujita-hu.ac.jp\nAbstract\nBackground: When using assisted reproductive technology, there are cases where, despite the transfer of a\ngood embryo, sometimes pregnancy may not be the case. Thus, during hormone replacement cycle\nimplantation, it is important to synchronize the number of days of progesterone administration with the\ndegree of embryo maturity. This study aimed to compare the outcomes of the administration of oral\ndydrogesterone for the duration of progestin use during the hormone replacement cycle for frozen-thawed\nblastocyst transfer.\nMaterial and methods: The primary outcome of this study was the clinical pregnancy rate. We performed a\nretrospective cohort study of patients who underwent frozen-thawed blastocyst transfers between January\n2017 and December 2024. According to our standard protocol, a vitrified-warmed blastocyst transfer was\nperformed using dydrogesterone, which was administered orally at our center. A total of 554 cases were\nincluded in the study. Using the Gardner classification to evaluate the quality of blastocysts, grade AA was\nclassified as the best quality, the AB/BA group as good quality, and the BB group as fair quality. We classified\nthe 554 cases into 317 AA, 163 AB/BA, and 74 BB cases using the Gardner classification. Based on the\nduration of progestin administration, patients were divided into four groups: 120 hours (120 h), 132 hours\n(132 h), 144 hours (144 h), and 156 hours (156 h). We used the Shapiro-Wilk method and the Steel-Dwass\ntest to determine whether there were differences in patients' background age and BMI among the four\ngroups (120 h, 132 h, 144 h, and 156 h). We used Fisher's exact test and the Bonferroni method to determine\nwhether there were differences in the final outcome of pregnancy rate between the four groups of 120 h, 132\nh, 144 h, and 156 h.\nResults: In the analysis of all embryos, the pregnancy rate at each timepoint of the primary evaluation was\nsignificantly higher in the 144-h group than in the 132-h group. Next, on analyzing the results by embryo\ngrade, there was no difference in the pregnancy rate at each timepoint in the AA group. In the AB/BA group,\nthe pregnancy rate was higher in the 144-h group than in the 132-h group. In the BB group, the pregnancy\nrate was higher in the 144-h group than in the 132-h group.\nConclusion: This study clarified two aspects. First, the pregnancy rate in the 144-h group was significantly\nhigher than that in the 132-h group in the analysis of all embryos. Second, the window of implantation may\nbe more important for poor-quality embryos. This study showed that the oral administration of\ndydrogesterone requires a window of implantation of at least 144 hours.\nCategories:\n Obstetrics/Gynecology\nKeywords:\n assisted reproductive technology, dydrogesterone, endometrial receptivity, frozen-thawed embryo\ntransfer, hormone replacement cycle, pregnancy rate, window of implantation\nIntroduction\nWhen using assisted reproductive technology, there are cases in spite of the transfer of a good embryo,\nsometimes pregnancy may not be the case. In recent years, preimplantation genetic diagnosis has been\nintroduced, and endometrial factors have attracted attention as a cause of pregnancy failure, even when\neuploid embryos are transferred. The clinical pregnancy rate per embryo transfer in which a preimplantation\ngenetic diagnosis was performed was reported to be 54.4% \n[1]\n, suggesting that factors other than embryo\nquality are necessary for a successful pregnancy.\nDuring hormone replacement cycle implantation, it is important to synchronize the number of days of\nprogesterone administration with the degree of embryo maturity. The clinical translation of endometrial\ntranscriptomics has provided an objective definition of the limited period during which the maternal\n1\n2\n2\n2\n1\n1\n1\n3\n1\n \nOpen Access Original Article\nHow to cite this article\nNishio E, Oikawa S, Sakakibara E, et al. (March 25, 2025) Pregnancy Rate Is High When the Length of the Luteal Phase During the In Vitro\nFertilization Hormone Replacement Cycle Is 144 Hours or More Before Embryo Transfer. Cureus 17(3): e81185. \nDOI 10.7759/cureus.81185\n\nendometrium is receptive to an embryo, known as the window of implantation (WOI) \n[2]\n. Although there is\nlittle clear supportive evidence, the duration of progestin use during a hormone replacement cycle is often\n5-7 days.\nDydrogesterone has long been used to treat conditions associated with progesterone deficiency.\nDydrogesterone is a 6-dihydro-retroprogesterone characterized by high oral bioavailability, good\ntolerability, easy absorption, and high selectivity for progesterone receptors \n[3]\n. It was developed in\nthe 1960s and has been shown to be effective in relieving dysmenorrhea \n[4-6]\n. To date, only a few studies\nhave examined the use of oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles,\nwith variable results summarized in a recent review \n[7]\n. \nIn recent years, two randomized controlled clinical trials have demonstrated that oral dydrogesterone, an\nartificial progesterone derivative, is non-inferior in terms of pregnancy rate at 12 weeks of gestation and\ncould be an alternative option \n[8,9]\n. However, to the best of our knowledge, there are no reports on the most\nfavorable duration of dydrogesterone administration during the in vitro fertilization hormone replacement\ncycle before embryo transfer. Therefore, this study aimed to compare the outcomes of an administration\nprotocol of oral dydrogesterone for the duration of progestin use during a hormone replacement cycle for\nfrozen-thawed blastocyst transfer.\nMaterials And Methods\nWe performed a retrospective cohort study of patients who underwent frozen-thawed blastocyst transfers at\nFujita Health University Hospital between January 2017 and December 2024. Patient ages ranged from 18-43\nyears (at the time of embryo freezing). Per our standard protocol, vitrified-warmed blastocyst transfer was\nperformed, with dydrogesterone (Duphaston®) administered orally in our center. The exclusion criteria were\nas follows: fresh embryo transfer, early embryo transfer, in vitro matured blastocysts using endometrial\nreceptivity analysis (ERA), preimplantation genetic testing (PGT) cycles, and missing data regarding body\nmass index (BMI) and endometrial thickness on the day of frozen-thawed blastocyst transfer. In total, 554\ncases were included, excluding 206 of 760 cases from 298 patients. First, all embryos were analyzed, and no\nembryo classification was performed. Subsequently, for the subgroup analysis, the embryos were divided\ninto three groups. Using the Gardner classification to evaluate the quality of blastocysts, grade AA was\nclassified as the best quality, AB/BA group as good quality, and BB group as fair quality. We classified the 554\ncases into 317 AA, 163 AB/BA, and 74 BB cases using the Gardner classification (Figure \n1\n).\nFIGURE\n 1: Flow chart showing the inclusion and exclusion criteria for\nthis study\nUsing the Gardner classification to evaluate the quality of blastocysts, grade AA was classified as the best quality,\nAB/BA group as good quality, and BB group as fair quality.\nWe classified the 554 cases into 317 AA, 163 AB/BA, and 74 BB cases using the Gardner classification.\nHRT: hormone replacement therapy cycle, FET: frozen embryo transfer, IVM: in vitro maturation, PGT:\npreimplantation genetic testing, ERA: endometrial receptivity analysis.\nThis study was approved by the Institutional Review Board of Fujita Health University, Japan. All patients\ninvolved in this study consented to the use of their medical records for research in an unidentifiable\nmanner.\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n2\n of \n12\n\nOvarian stimulation was performed using recombinant or urinary follicle-stimulating hormones. Once the\nfollicles reached 18 mm in size, human chorionic gonadotropin was administered. Oocyte retrieval was\nperformed 36 hours later. All blastocysts were cryopreserved on days five or six. Frozen-thawed embryo\ntransfer was performed under hormone replacement therapy. Transdermal estrogen was administered for 21\ndays from day two or three following the onset of menses to the day of the pregnancy test. Once serum\nestradiol concentrations reached ≥ 300 pg/mL and ultrasonic endometrial stripe thickness reached ≥ 8 mm\nwith a proliferative pattern, progesterone was administered, usually via oral dydrogesterone tablets\n(Duphaston®). Dydrogesterone was administered orally (15 mg three times daily).\nBased on the duration of progestin administration, patients were divided into four groups: 120 hours (120 h),\n132 hours (132 h), 144 hours (144 h), and 156 hours (156 h). The duration of progestin administration varied\ndepending on the time of year.\nWe used the Shapiro-Wilk method and the Steel-Dwass test to determine whether there were differences in\npatients' background age and BMI among the four groups (120 h, 132 h, 144 h, and 156 h). We used Fisher's\nexact test and the Bonferroni method to determine whether there were differences in the final outcome of\npregnancy rate between the four groups (120 h, 132 h, 144 h, and 156 h).\nResults\nIn the analysis of all embryos, there were no differences in patient background, including age or BMI, at each\ntime point, as determined by the Shapiro-Wilk and Steel-Dwass tests (Table \n1\n).\nTime (hour)\nAge, years (mean ± SD)\nBMI, kg/m2 (mean ± SD)\n120\n36.9 ± 4.4\n20.8 ± 3.5\n132\n36.3 ± 4.9\n21.8 ± 4.3\n144\n36.4 ± 4.9\n21.6 ± 4.2\n156\n37.4 ± 4.2\n21.2 ± 3.8\nTABLE\n 1: Baseline characteristics of the women who underwent frozen-thawed blastocyst\ntransfer at Fujita Health University Hospital between January 2017 and December 2024 in the\nanalysis of all embryos (n=504)\nThe Shapiro-Wilk and Steel-Dwass tests revealed no differences in the patients' background characteristics including age or BMI at any time point.\nSD: standard deviation, BMI: body mass index\nIn the AA group, there were no differences in age at each time point, as determined by the Shapiro-Wilk and\nSteel-Dwass tests (Table \n2\n). The 132-h group had a higher BMI than the 120-h group (P<0.0329) (Table \n2\n).\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n3\n of \n12\n\nTime (hour)\nAge, years (mean ± SD)\nBMI, kg/m2 (mean ± SD)\n120\n36.4 ± 4.9\n20.1 ± 3.6\n132\n35.9 ± 4.7\n21.6 ± 3.9\n144\n35.4 ± 5.1\n21.8 ± 4.5\n156\n36.8 ± 4.5\n21.1 ± 3.5\nTABLE\n 2: Baseline characteristics of the women who underwent frozen-thawed blastocyst\ntransfer at Fujita Health University Hospital between January 2017 and December 2024 in the\nanalysis of embryos in the AA group (n=317)\nThe Shapiro-Wilk and Steel-Dwass tests revealed no difference in the patient age at each timepoint. The 132-h group had a higher BMI than the 120-h\ngroup (p<0.0329).\nSD: standard deviation, BMI: body mass index\nIn the AB/BA group, there were no differences in age or BMI at each time point, as determined by the\nShapiro-Wilk and Steel-Dwass tests (Table \n3\n).\nTime (hour)\nAge, years (mean ± SD)\nBMI, kg/m2 (mean ± SD)\n120\n37.8 ± 3.6\n22.0 ± 3.1\n132\n35.9 ± 5.0\n21.5 ± 4.4\n144\n37.6 ± 4.3\n20.9 ± 3.2\n156\n37.8 ± 3.5\n20.7 ± 1.8\nTABLE\n 3: Baseline characteristics of the women who underwent frozen-thawed blastocyst\ntransfer at Fujita Health University Hospital between January 2017 and December 2024 in the\nanalysis of embryos in the AB/BA group (n=163)\nThe Shapiro-Wilk and Steel-Dwass tests revealed no difference in the patients' background characteristics including age or BMI at each timepoint.\nSD: standard deviation, BMI: body mass index\nIn the BB group, there were no differences in age and BMI at each time point, as determined by the Shapiro-\nWilk and Steel-Dwass tests (Table \n4\n).\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n4\n of \n12\n\nTime (hour)\nAge, years (mean ± SD)\nBMI, kg/m2 (mean ± SD)\n120\n(-)\n(-)\n132\n37.9 ± 5.4\n23.1 ± 5.0\n144\n36.4 ± 5.4\n23.1 ± 5.2\n156\n39.3± 3.4\n21.9 ± 5.5\nTABLE\n 4: Baseline characteristics of the women who underwent frozen-thawed blastocyst\ntransfer at Fujita Health University Hospital between January 2017 and December 2024 in the\nanalysis of embryos in the BB group (n=74)\nThe Shapiro-Wilk and Steel-Dwass tests revealed no differences in the patients' background characteristics, including age and BMI at each timepoint.\nSD: standard deviation, BMI: body mass index\nIn the analysis of all embryos using Fisher's exact test and the Bonferroni method, the pregnancy rate at\neach time point of the primary evaluation was significantly higher in the 144-h group than in the 132-h\ngroup (p<0.0001) (Figure \n2\n).\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n5\n of \n12\n\nFIGURE\n 2: Pregnancy rate in the analysis of all embryos(n=504)\nFirst, to determine whether there was a difference in the pregnancy rate at all timepoints, we performed Fisher's\nexact test and found a significant difference (p=0.0001) at each timepoint. Second, using the Bonferroni method,\nthe pregnancy rate at 144-h group was significantly higher than that at 132-h group (p<0.0001).\n* Significant difference.\nNext, on analyzing the results by embryo grade in the AA group, Fisher's exact test showed that there was no\ndifference in the pregnancy rate at each time point (Figure \n3\n).\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n6\n of \n12\n\nFIGURE\n 3: Pregnancy rate in the analysis of embryos in the AA group\n(n=317)\nOn performing Fisher's exact test to determine whether there was a difference in the pregnancy rate at all\ntimepoints, the p-value for the AA group was 0.059, and no significant difference was found.\nn.s. = not significant\nIn the AB/BA group, Fisher's exact test and the Bonferroni method revealed that the pregnancy rate was\nhigher in the 144-h group than in the 132-h group (p = 0.0002) (Figure \n4\n).\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n7\n of \n12\n\nFIGURE\n 4: Pregnancy rate in the analysis of embryos in the AB/BA\ngroup (n=163)\nFirst, we performed Fisher’s exact test to determine whether there was a difference in the pregnancy rate at all\ntime points and found a significant difference (p<0.001) at each timepoint in the AB/BA group. Second, on using\nthe Bonferroni method, we found that the pregnancy rate at 144-h group was significantly higher than that at 132-h\ngroup (p=0.0002).\n* Significant difference.\nIn the BB group, Fisher's exact test and the Bonferroni method revealed that the pregnancy rate was higher\nin the 144-h group than in the 132-h group (p=0.02) (Figure \n5\n).\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n8\n of \n12\n\nFIGURE\n 5: Pregnancy rate in the analysis of embryos in the BB group\n(n=74)\nFirst, we performed Fisher's exact test to determine whether there was a difference in the pregnancy rate at all\ntimepoints, and the result was significant at p=0.0249 in the BB group. Second, on using the Bonferroni method,\nthe pregnancy rate at 144-h group was found to be significantly higher than that at 132-h group (p=0.02).\nDiscussion\nThe results of this study clarify two aspects. First, the pregnancy rates in the 144-h group were significantly\nhigher than those in the 132-h group in the analysis of all embryos. Second, WOI may be more important for\npoor-quality embryos.\nThis study showed that the oral administration of dydrogesterone requires a WOI of at least 144 hours. The\nendometrium undergoes dynamic morphological and functional changes in response to estrogen and\nprogesterone that affect implantation. The concept of the WOI was proposed in the 1950s and has since\nbeen supported by various studies in the fields of clinical medicine, epidemiology, and morphology \n[10-13]\n.\nThe period during which the human endometrium is receptive to implantation is defined as the WOI and is\nthought to approximately comprise days 19-22 of the mid-secretory phase of the menstrual cycle. The\nduration of progestin use during a hormone replacement cycle is often 5-7 days. WOI is induced by the\npresence of exogenous and/or endogenous progesterone following adequate estradiol stimulation. The\nwindow is within 30-36 hours during the hormone replacement cycle and varies from patient to patient \n[1]\n. It\nhas been reported that WOI is delayed in more than 30% of patients who have undergone embryo transfer\n[14-16]\n. There are reports that no differences were observed in the clinical pregnancy rate between 5 and 7\ndays when vaginal micronized progesterone tablets were administered for warmed blastocyst transfer \n[17]\n.\nHowever, it has been reported that warmed blastocyst transfer on the sixth and seventh day of progesterone\nadministration during a hormone replacement cycle results in a similar live birth rate. Subgroup analysis\nrevealed a significantly higher miscarriage rate for day six blastocysts transferred on the sixth day of\nprogesterone supplementation than those transferred on the seventh day of progesterone supplementation\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n9\n of \n12\n\n[18]\n.\nIn terms of the administration route, the question arises whether oral dydrogesterone is equivalent in\nefficacy to vaginal micronized progesterone for luteal phase support. One study stated that there was no\ndifference in pregnancy rates between vaginal and oral progesterone preparations \n[19]\n. Since vaginal\nadministration can cause implantation failure due to bacterial infection of the uterus, we used oral\nprogesterone instead of vaginal administration until embryo transfer. This study found that the highest\npregnancy rate was achieved when progestin was administered for 144 hours or more and that\nadministration for 132 hours was insufficient to achieve pregnancy.\nWe investigated whether there were differences in pregnancy rates according to grade. There was no\nsignificant difference in the pregnancy rate at the four-time points during the luteal hormone administration\nperiod in the AA group. However, there was a difference in the pregnancy rates at the four-time points\nduring the luteal hormone administration period in the AB/BA and BB groups. This indicates that the luteal\nhormone administration period is important for transferring poor-quality embryos. In this study, the\npregnancy rate was higher when progesterone was administered for 144 hours or more, but in all studies,\nthere was no difference in the pregnancy rate between 144-h group and 156-h group; therefore, it is not the\ncase that the longer the administration time, the better the results. ERA is a test used to determine the\noptimal WOI for each embryo. When ERA is performed in patients with recurrent implantation failure, it is\nbelieved that approximately 70% of women are receptive, and the remaining 30% are nonreceptive. For\nnonreceptive women, the implantation rate can be improved by modifying the timing of the transfer \n[20]\n.\nSimon et al. conducted a prospective study in which embryos were divided into three groups: fresh embryo\ntransfer, blastocyst transfer, and blastocyst transfer after ERA. The cumulative pregnancy rate for blastocyst\ntransfer after ERA was significantly higher than that for the other methods \n[21]\n. In 2018, Tan et al. reported\nindividualized embryo transfer of euploid embryos after ERA. Among the patients who did not become\npregnant after ERA, 62.5% were receptive and 37.5% were non-receptive. The pre-receptive and post-\nreceptive cases accounted for 83.3% and 5.6% of the non-receptive cases, respectively. Next, when single\nembryo transfer was performed in 17 women who had undergone ERA, there was no significant difference in\nthe implantation rate or pregnancy continuation rate between the ERA and non-ERA groups; however, this\nwas a retrospective study with a small number of cases, and therefore, it would be desirable to increase the\nnumber of cases in future studies \n[22]\n. Recently, an ER Map, a molecular tool for assessing human\nendometrial receptivity, was developed based on the transcriptome analysis of genes related to endometrial\nproliferation and implantation. Accordingly, it was reported that most patients became receptive by the fifth\nor sixth day of progesterone administration, but some patients became receptive as early as on the 2.5th day\nof progesterone administration, and others became receptive on the eighth day of progesterone\nadministration \n[23]\n. However, because gene transcriptome analysis is expensive and invasive, it is not\nconsidered beneficial in all cases. Therefore, the administration period before embryo transfer should be at\nleast 144 hours during hormone replacement cycles when using dydrogesterone for the first embryo transfer.\nThis study has several limitations that should be considered when interpreting these results. The\nretrospective, single-center design limits the assessment of causality and introduces selection bias, which\nlimits generalizability. As there is a report that says \"When endometrial thickness was ≥ 8 mm, patients were\ninjected intramuscularly with progesterone (80 mg/day) for 3 to 7 days, three days of progesterone regimen\nprior to day three embryo transfer may be more beneficial\", the optimal duration of progesterone\nadministration may differ depending on the type of progesterone hormone and the route of administration\n[24]\n. In this study, dydrogesterone was administered orally, but the optimal duration of administration may\ndiffer depending on the administration route and type of progesterone; therefore, further research is\nneeded.\nConclusions\nThe results of this study clarify two aspects. First, the pregnancy rate in the 144-h group was significantly\nhigher than that in the 132-h group in the analysis of all embryos. Second, WOI may be more important for\npoor-quality embryos. This study showed that the oral administration of dydrogesterone requires a WOI of\nat least 144 hours.\nAdditional Information\nAuthor Contributions\nAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the\nwork.\nConcept and design:\n  \nEiji Nishio\nAcquisition, analysis, or interpretation of data:\n  \nEiji Nishio, Haruki Nishizawa, Takanori Hayashi,\nHironori Miyamura, Kiriko Kotani, Shota Oikawa, Eriko Sakakibara, Miho Ishikawa, Hikari Yoshizawa\nDrafting of the manuscript:\n  \nEiji Nishio\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n10\n of \n12\n\nCritical review of the manuscript for important intellectual content:\n  \nEiji Nishio, Haruki Nishizawa,\nTakanori Hayashi, Hironori Miyamura, Kiriko Kotani, Shota Oikawa, Eriko Sakakibara, Miho Ishikawa, Hikari\nYoshizawa\nSupervision:\n  \nEiji Nishio, Haruki Nishizawa, Takanori Hayashi\nDisclosures\nHuman subjects:\n Consent for treatment and open access publication was obtained or waived by all\nparticipants in this study. The Institutional Review Board of Fujita Health university issued approval HM20-\n114. \nAnimal subjects:\n All authors have confirmed that this study did not involve animal subjects or tissue.\nConflicts of interest:\n In compliance with the ICMJE uniform disclosure form, all authors declare the\nfollowing: \nPayment/services info:\n All authors have declared that no financial support was received from\nany organization for the submitted work. \nFinancial relationships:\n All authors have declared that they have\nno financial relationships at present or within the previous three years with any organizations that might\nhave an interest in the submitted work. \nOther relationships:\n All authors have declared that there are no\nother relationships or activities that could appear to have influenced the submitted work.\nReferences\n1\n. \nRubio C, Bellver J, Rodrigo L, et al.: \nIn vitro fertilization with preimplantation genetic diagnosis for\naneuploidies in advanced maternal age: a randomized, controlled study\n. Fertil Steril. 2017, 107:1122-9.\n10.1016/j.fertnstert.2017.03.011\n2\n. \nRuiz-Alonso M, Valbuena D, Gomez C, et al.: \nEndometrial receptivity analysis (ERA): data versus opinions\n.\nHum Reprod Open. 2021, 2021:hoab011. \n10.1093/hropen/hoab011\n3\n. \nGriesinger G, Tournaye H, Macklon N, et al.: \nDydrogesterone: pharmacological profile and mechanism of\naction as luteal phase support in assisted reproduction\n. Reprod Biomed Online. 2019, 38:249-59.\n10.1016/j.rbmo.2018.11.017\n4\n. \nVercellini P, Viganò P, Somigliana E, Fedele L: \nEndometriosis: pathogenesis and treatment\n. Nat Rev\nEndocrinol. 2014, 10:261-75. \n10.1038/nrendo.2013.255\n5\n. \nA4] Bell ET, Loraine JA: \nEffect of dydrogesterone on hormone excretion in patients with dysmenorrhoea\n.\nLancet. 1965, 1:403-6. \n10.1016/s0140-6736(65)90003-6\n6\n. \nFA DV: \nDuphaston in dysmenorrhoea; the results of a double blind clinical trial\n. J Obstet Gynaecol Br\nCommonw. 1965, 72:193-5. \n10.1111/j.1471-0528.1965.tb01416.x\n7\n. \nPatki A: \nRole of dydrogesterone for luteal phase support in assisted reproduction\n. Reprod Sci. 2024, 31:17-\n29. \n10.1007/s43032-023-01302-z\n8\n. \nTournaye H, Sukhikh GT, Kahler E, Griesinger G: \nA Phase III randomized controlled trial comparing the\nefficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal\nsupport in in vitro fertilization\n. Hum Reprod. 2017, 32:1019-27. \n10.1093/humrep/dex023\n9\n. \nGriesinger G, Blockeel C, Sukhikh GT, et al.: \nOral dydrogesterone versus intravaginal micronized\nprogesterone gel for luteal phase support in IVF: a randomized clinical trial\n. Hum Reprod. 2018, 33:2212-21.\n10.1093/humrep/dey306\n10\n. \nHE AT, RO J, AD EC: \nA description of 34 human ova within the first 17 days of development\n. Am J Anat.\n1956, 98:435-93. \n10.1002/aja.1000980306\n11\n. \nNavot D, Scott RT, Droesch K, et al.: \nThe window of embryo transfer and the efficiency of human\nconception in vitro\n. Fertil Steril. 1991, 55:114-8. \n10.1016/s0015-0282(16)54069-2\n12\n. \nWilcox AJ, Baird DD, Weinberg CR: \nTime of implantation of the conceptus and loss of pregnancy\n. N Engl J\nMed. 1999, 340:1796-9. \n10.1056/NEJM199906103402304\n13\n. \nMurphy CR: \nUterine receptivity and the plasma membrane transformation\n. Cell Res. 2004, 14:259-67.\n10.1038/sj.cr.7290227\n14\n. \nMahajan N: \nEndometrial receptivity array: Clinical application\n. J Hum Reprod Sci. 2015, 8:121-9.\n15\n. \nPatel JA, Patel AJ, Banker JM, et al.: \nPersonalized embryo transfer helps in improving in vitro\nfertilization/ICSI outcomes in patients with recurrent implantation failure\n. J Hum Reprod Sci. 2019, 12:59-\n66. \n10.4103/jhrs.JHRS_74_18\n16\n. \nRuiz-Alonso M, Blesa D, Díaz-Gimeno P, et al.: \nThe endometrial receptivity array for diagnosis and\npersonalized embryo transfer as a treatment for patients with repeated implantation failure\n. Fertil Steril.\n2013, 100:818-24. \n10.1016/j.fertnstert.2013.05.004\n17\n. \nvan de Vijver A, Drakopoulos P, Polyzos NP, et al.: \nVitrified-warmed blastocyst transfer on the 5th or 7th day\nof progesterone supplementation in an artificial cycle: a randomised controlled trial\n. Gynecol Endocrinol.\n2017, 33:783-6. \n10.1080/09513590.2017.1318376\n18\n. \nRoelens C, Santos-Ribeiro S, Becu L, et al.: \nFrozen-warmed blastocyst transfer after 6 or 7 days of\nprogesterone administration: impact on live birth rate in hormone replacement therapy cycles\n. Fertil Steril.\n2020, 114:125-32. \n10.1016/j.fertnstert.2020.03.017\n19\n. \nLorillon M, Robin G, Keller L, et al.: \nIs oral dydrogesterone equivalent to vaginal micronized progesterone\nfor luteal phase support in women receiving oocyte donation?\n. Reprod Biol Endocrinol. 2024, 22:154.\n10.1186/s12958-024-01322-7\n20\n. \nHashimoto T, Koizumi M, Doshida M, et al.: \nEfficacy of the endometrial receptivity array for repeated\nimplantation failure in Japan: A retrospective, two-centers study\n. Reprod Med Biol. 2017, 16:290-6.\n10.1002/rmb2.12041\n21\n. \nSimón C, Gómez C, Cabanillas S, et al.: \nA 5-year multicentre randomized controlled trial comparing\npersonalized, frozen and fresh blastocyst transfer in IVF\n. Reprod Biomed Online. 2020, 41:402-15.\n10.1016/j.rbmo.2020.06.002\n22\n. \nTan J, Kan A, Hitkari J, et al.: \nThe role of the endometrial receptivity array (ERA) in patients who have failed\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n11\n of \n12\n\neuploid embryo transfers\n. J Assist Reprod Genet. 2018, 35:683-92. \n10.1007/s10815-017-1112-2\n23\n. \nEnciso M, Aizpurua J, Rodríguez-Estrada B, et al.: \nThe precise determination of the window of implantation\nsignificantly improves ART outcomes\n. Sci Rep. 2021, 11:13420. \n10.1038/s41598-021-92955-w\n24\n. \nZhao L, Liu L, Dai Y, et al.: \nOptimal duration of progesterone before cryopreserved embryo transfer in\nhormone replacement therapy cycles: A prospective pilot study\n. Medicine (Baltimore). 2024, 103:e40864.\n10.1097/MD.0000000000040864\n \n2025 Nishio et al. Cureus 17(3): e81185. DOI 10.7759/cureus.81185\n12\n of \n12","source_license":"CC0","license_restricted":false}