Does adding vaginal oestradiol after oral oestradiol facilitate artificial autologous freeze-thaw embryo transfer cycles? A retrospective cohort study

Abstract

Abstract Research question This study investigates the difference in reproductive outcomes with the late addition of vaginal oestradiol to oral oestradiol in artificially cycled frozen embryo transfer (AC-FET) cycles. Design This retrospective cohort study was conducted at a university-affiliated tertiary care hospital. We divided 806 infertility patients who underwent programmed pre-FET endometrial preparation from January 2018 to July 2021 into two independent groups: Group A (591 with oral estradiol valerate only) and group B (215 with late oral estradiol valerate plus vaginal 17 β-estradiol). The primary outcome was the live birth rate (LBR), and the secondary outcome was other pregnancy-related outcomes. Propensity score matching (PSM) and multivariate logistic regression were applied to analyze all pregnancy outcomes, with a subgroup analysis based on vaginal oestradiol dose for group B. A subanalysis of cycles with endometrial thickness < 8 mm on the day prior to progesterone was also performed to assess the effect of adding vaginal oestradiol late in the thin endometrial transplantation cycle on reproductive outcomes. Results Before and after PSM analysis, the live birth rates in group A were 41.1% and 42.2%, significantly higher than 31.2% and 30.8% in group B (P = 0.015), respectively. Multiple logistic regression analysis demonstrates that group B was less likely to have a live birth than group A (OR 0.643, 95% Cl 0.453–0.913, P = 0.014). Subgroup analysis of group B according to vaginal oestradiol dose demonstrated an insignificant difference in live birth rates between the subgroups (42.6% vs. 26.8% vs. 34.6%, P = 0.118). In thin endometrial transplant cycles with an endometrial thickness < 8 mm on the day prior to progesterone, live birth rates were similar in both groups (36.9% vs. 26.8%, P = 0.234). Conclusion The addition of vaginal oestradiol as part of an artificial endometrial preparation (AEP) at a late stage of oral oestradiol significantly reduced LBR in autologous frozen-thawed embryo transfer, is independent of the dose of vaginal oestradiol, and does not improve the reproductive outcome in thin endometrial transfer cycles. However, more well-designed randomized clinical trials merit further investigation to confirm this conclusion.