Endometrial preparation: effect of estrogen levels before the embryo transfer on the live birth rate from 14825 freezing-all cycles

Abstract Study question Is there a difference in live birth rate during discrepant estrogen levels before the embryo transfer following either hormone replacement therapy (HRT) or natural cycle(NC)? Summary answer The higher estrogen level on the day before embryo transfer may reduce the live birth rate in either HRT or NC. What is known already The endometrial preparation of frozen embryo transfer cycle is to synchronize of endometrium and embryo under the condition of exogenous estrogen and progesterone drugs in HRT or follicle monitoring in NC. Estrogen is crucial and different estrogen levels could imply variations on endometrial preparation. Information on the effect of discrepant estrogen levels before the embryo transfer on reproductive outcomes of women undergoing freezing-all cycles is scarce. Study design, size, duration Retrospective cohort study including 14825 first frozen embryo transfers following IVF/ICSI undergoing freezing-all cycles from January 2016 to December 2020. A total of 12305 (83.0%) patients received NC while 2520 (17.0%) received HRT. Participants/materials, setting, methods Effect of estrogen levels on live birth rates, stratifified by deciles and ROC to determine the cutoff values for estrogen level on the day before embryo transfer.Multivariable logistic regression analysis was performed to adjust for confounders. Main results and the role of chance The live birth rate was 44.7% and 52.4% in HRT and NC respectively. The live birth rate of HRT began to decline when the estrogen level was P60 in the deciles which the cut-off values of ROC was closed with the estrogen level was 891.6 pg/ml. The lower level of estrogen on the day before embryo transfer in HRT corresponds to a higher live birth rate（51.4% vs 32.9%）.The cut-off values of ROC in NC was statistically different with the estrogen level was 194.4 pg/ml. The lower level of estrogen on the day before embryo transfer in NC corresponds to a higher live rate（53.0% vs 48.6%）.After adjusting the possible confounding factors by multivariate logistic regression, it was found that the estrogen level on the day before embryo transfer in HRT and NC was the independent influencing factor of live birth rate with the OR of 0.57 (0.47,0.68) and 0.82 (0.74,0.90), respectively. Limitations, reasons for caution The greatest limitation of this study is its retrospective study. On the other hand, this study was performed using non-PGT cycle, although this is unlikely to affect the results,we cannot exclude the possibility that euploid embryo responds differently to endometrial state in comparison to aneuploid embryo. Wider implications of the findings In freezing-all cycles, the higher estrogen level on the day before embryo transfer may reduce the live birth rate in either HRT or NC. Clinicians should pay attention to the control of estrogen level in luteal phase. Trial registration number Nona