Comparison of stimulated versus modified natural cycles for endometrial preparation prior to frozen embryo transfer: a randomized controlled trial

Labrosse, Julie; Lobersztajn, Annina; Piétin-Vialle, Claire; Villette, Claire; Dessapt, Anne-Lucie; Jung, Camille; Brussieux, Maxime; Bry-Gauillard, Hélène; Pasquier, Maud; Massin, Nathalie

doi:10.1016/j.rbmo.2020.01.007

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…SC was used first line in two centers. In NC and SC, FET was performed according to hormonal monitoring and embryo stage (Day 2, Day 3 or blastocysts) ( Labrosse et al , 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles)

Vinsonneau

Labrosse

Porcu-Buisson

et al. 2022

Human Reproduction Open

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Study question Does the endometrial preparation protocol (artificial cycle (AC) vs. natural cycle (NC) vs. stimulated cycle (SC)) impact the risk of early pregnancy loss and live birth rate after frozen/thawed embryo transfer (FET)? Summary answer In FET, artificial cycles were significantly associated with a higher pregnancy loss rate and a lower live birth rate compared with stimulated cycle or natural cycle. What is known already To date, there is no consensus on the optimal endometrial preparation in terms of outcomes. Although some studies have reported a higher pregnancy loss rate using AC compared with NC or SC, no significant difference was found concerning the pregnancy rate or live birth rate. Furthermore, no study has compared the three protocols in a large population. Study design, size, and duration A multicenter retrospective cohort study was conducted in nine reproductive health units in France using the same software to record medical files between January 1st, 2012 and December 31st, 2016. FET using endometrial preparation by AC, modified NC or SC were included. The primary outcome was the pregnancy loss rate at 10 weeks of gestation. The sample size required was calculated to detect an increase of 5% in the pregnancy loss rate (21 to 26%), with an alpha risk of 0.5 and a power of 0.8. We calculated that 1126 pregnancies were needed in each group, i.e., 3378 in total. Participants/materials, setting, methods Data were collected by automatic extraction using the same protocol. All consecutive autologous FET cycles were included: 14,421 cycles (AC: n = 8,139; NC: n = 3,126; SC: n = 3,156) corresponding to 3,844 pregnancies (hCG > 100 IU/L) (AC: n = 2,214; NC: n = 812; SC: n = 818). Each center completed an online questionnaire describing its routine practice for FET, particularly the reason for choosing one protocol over another. Main results and the role of chance AC represented 56.5% of FET cycles. Mean age of women was 33.5 (SD ± 4.3) years. The mean number of embryos transferred was 1.5 (±0.5). Groups were comparable, except for history of ovulation disorders (P = 0.01) and prior delivery (P = 0.03), which were significantly higher with AC. Overall, the early pregnancy loss rate was 31.5% (AC: 36.5%; NC: 25.6%; SC: 23.6%). Univariable analysis showed a significant association between early pregnancy loss rate and age > 38 years, history of early pregnancy loss, ovulation disorders, and duration of cryopreservation > 6 months. After adjustment (multivariable regression), the early pregnancy loss rate remained significantly higher in AC vs. NC (odds ratio (OR) 1.63 (95% CI) [1.35-1.97]; P < 0.0001) and in AC vs. SC (OR 1.87 [1.55-2.26]; P < 0.0001). The biochemical pregnancy rate (hCG > 10 and lower than 100 IU/L) was comparable between the three protocols: 10.7% per transfer. Limitations, reasons for caution This study is limited by its retrospective design that generates missing data. Routine practice within centers was heterogeneous. However, luteal phase support and timing of embryo transfer were similar in AC. Univariable analysis showed no difference between centers. Moreover, a large number of parameters were included in the analysis. Wider implications of the findings Our study shows a significant increase in early pregnancy loss when using AC for endometrial preparation before FET. These results suggest either a larger use of NC or SC, or an improvement of AC by individualizing hormone replacement therapy for patients in order to avoid an excess of pregnancy losses. Study funding/competing interests The authors declare no conflicts of interest in relation to this work. G. P.-B. declares consulting fees from Ferring, Gedeon-Richter, Merck KGaA, Theramex, Teva; Speaker’s fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter, Theramex, Teva N.C. declares consulting fees from Ferring, Merck KGaA, Theramex, Teva; Speaker’s fees or equivalent from Merck KGaA, Ferring C.R. declares a research grant from Ferring, Gedeon-Richter; consulting fees from Gedeon-Richter, Merck KGaA; Speaker’s fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter E.M.A. declares Speaker’s fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Theramex, Teva I.C-D. declares Speaker’s fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, IBSA N.M. declares a research grant from Merck KGaA, MSD, IBSA; consulting fees from MSD, Ferring, Gedeon-Richter, Merck KGaA; Speaker’s fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Teva, Goodlife, General Electrics Trial registration number Not applicable

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“…SC was used first line in two centers. In NC and SC, FET was performed according to hormonal monitoring and embryo stage (Day 2, Day 3 or blastocysts) ( Labrosse et al , 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles)

Vinsonneau

Labrosse

Porcu-Buisson

et al. 2022

Human Reproduction Open

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“…A retrospective cohort study analysed 214 NC cycles and 276 HRT cycles, with similar live birth rates (NC = 33.6% HRT = 29.3%, P = 0.47) and clinical pregnancy rates (NC = 40.2% HRT = 36.6%, P = 0.35) in the two groups (22). In addition, a prospective randomized controlled trial comparing clinical data from the NC group (n = 59) and the OC group (n = 60) showed no signi cant differences between the two groups in terms of positive biochemical pregnancy rate (NC = 34.0% OC = 23.1%, P = 0.22), clinical pregnancy rate (OC: 13/53 = 24.5%; NC: 12/52 = 23.1%; P = 0.86) and live birth rate (OC = 24.5% and NC = 23.1%, P = 0.86) (23). In this study also, there were no signi cant differences in ectopic pregnancy rates and miscarriage rates between the four groups in our study.…”

Section: Discussionmentioning

confidence: 87%

Effect of different endometrial preparation protocols on pregnancy outcomes in frozen- embryo transfer cycles: a retrospective cohort study

Qian

Wan

et al. 2021

Preprint

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Background Owing to the crucial role the endometrium plays in embryo implantation, the four main endometrial preparation protocols have become important factors in the study of pregnancy outcomes in the FET cycles. Previous studies have shown that the best of these four protocols remains controversial for women undergoing FET. Methods A total of 10333 FET cycles from January 2018 to December 2018 were analyzed in this study. They were categorized into four groups according to endometrial preparation regimen: natural cycles (Group NC,n = 815), hormone replacement therapy cycles (Group HRT ,n = 6434), GnRH agonist artificial cycles (Group GAC,n = 1392) and ovarian stimulation cycles (Group OC, n = 1692). All patients were followed up for at least 1 year. Pregnancy outcomes were compared between the four groups and multiple logistic regression models were used to adjust for the effects of confounding factors. Results The ectopic pregnancy rate (P = 0.627) and miscarriage rate (P = 0.164) were not statistically significant between the four groups. Moreover, biochemical pregnancy rate, clinical pregnancy rate and live birth rate in the NC group were not statistically significant compared to the other three groups. After adjusting for covariates, multiple logistic regression analysis showed no statistical significance in pregnancy outcomes in the HRT, GAC and OC groups compared to the NC group.And the adjusted OR for live births was 0.988 (95 % CI0.847-1.152) for the HRT group, 0.955 (95 % CI0.795-1.146) for the GAC group,0.898 (95 % CI0.754-1.070) for the OC group. Conclusions Our study showed that natural cycles have similar pregnancy outcomes in terms of clinical pregnancy and live birth to the other three endometrial preparation options. As it has other advantages, the natural cycle protocol can therefore be the recommended option for endometrial preparation in the FET population.

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“…When comparing pregnancy outcomes between the NC and the OC groups in our entire population, our study found that although the NC group was associated with higher biochemical pregnancy, clinical pregnancy, and live birth rates, the differences were not statistically significant. Several other published manuscripts also do not have conclusive evidence to indicate which protocol, NC or OC is superior [28–30] . Successful pregnancy is the result of the synchronization between embryo maturation and endometrial development, yet the above studies lacked precise information on transplanted embryo types, which might have biased the results.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy outcomes of four different cycle protocols for frozen embryo transfer: a large retrospective cohort study

Qian

Wan

et al. 2022

Reproductive and Developmental Medicine

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Objective: To evaluate the pregnancy outcomes of the four endometrial preparation protocols for people undergoing frozenthawed embryo transfer (FET), including natural cycle (NC), hormone replacement therapy cycle (HRT), gonadotropin-releasing hormone agonist artificial cycle (GAC), and ovarian stimulation cycle (OC).Methods: This retrospective cohort study enrolled 10,333 cycles of frozen embryo transfer performed at Xinan Gynecological Hospital in Sichuan, China, from January 2018 to December 2018. The patient's baseline characteristics and pregnancy outcomes were extracted from the medical record system. Pregnancy outcomes were compared among the four groups and multiple logistic regression models were used to adjust for the confounding factors.Results: After adjusting for covariates, multiple logistic regression analysis showed no statistical significance in pregnancy outcomes in the HRT group, GAC group, and OC group compared to the NC group in the entire population. The adjusted odds ratio of live birth was 0.976 (95% confidence interval [CI] 0.837-1.138) for the HRT group, 0.959 (95% confidence interval 0.797-1.152) for the GAC group, and 0.909 (95% confidence interval 0.763-1.083) for the OC group.Conclusions: The natural protocol had comparable pregnancy outcomes compared to the other three endometrial preparation protocols in the overall FET population. More high-quality prospective randomized controlled trials are required to assess the efficacy of the four protocols and explore the optimal one.

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Comparison of stimulated versus modified natural cycles for endometrial preparation prior to frozen embryo transfer: a randomized controlled trial

Cited by 8 publications

References 25 publications

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles)

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles)

Effect of different endometrial preparation protocols on pregnancy outcomes in frozen- embryo transfer cycles: a retrospective cohort study

Pregnancy outcomes of four different cycle protocols for frozen embryo transfer: a large retrospective cohort study

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