Interaction between embryo transfer timing (D3/D4) and duration of progesterone exposure (P3/P4) on live birth rate in hormone replacement therapy cycles of frozen embryo transfer.

Abstract

Objective: In hormone replacement therapy (HRT) cycles of frozen embryo transfer (FET), progesterone-induced endometrial transformation is critical to clinical outcomes. This study aimed to evaluate the interactive impact of the extent of progesterone exposure and the timing of embryo transfer on live birth outcomes.

Methods: This study retrospectively reviewed 3,381 infertile individuals from June 2013 to June 2024. Participants were stratified into four categories based on the number of days of progesterone exposure (P) and embryo developmental stage at transfer (D): P3-D3 group, P3-D4 group, P4-D3 group, and P4-D4 group.

Results: Analysis showed comparable baseline characteristics among all groups, with no significant variation. When progesterone exposure duration was synchronized with embryo developmental day, the P4-D4 group exhibited significantly higher live birth rate (47.58% vs 30.41%), clinical pregnancy rate (58.89% vs 44.33%), and implantation rate (41.17% vs 25.07%) in contrast to the P3-D3 cohort (P < 0.001), along with a significantly lower miscarriage rate (17.2% vs 26.7%, P = 0.025). When progesterone exposure duration was held constant, D4 embryo transfer significantly improved live birth rate over D3 embryo transfer (P3-D4 group vs P3-D3 group: 44.72% vs 30.41%, P = 0.005; P4-D4 group vs P4-D3 group: 47.58% vs 30.80%, P < 0.001). When embryo developmental stage at transfer was fixed, outcomes related to pregnancy showed no variation between the three-day and four-day exposure schedules. progesterone exposure (P > 0.05). To systematically examine and identify the independent clinical factors that significantly influence live birth outcomes in a target population, a logistic regression approach was employed to provide a comprehensive understanding of the underlying relationships. Consistent results were observed.

Conclusion: Frozen embryo transfer cycles prepared with hormone replacement demonstrate higher live birth rates when embryos are transferred on day 4 rather than day 3, regardless of whether progesterone exposure is 3 or 4 days. When embryo developmental stage is fixed (D3 or D4), varying the duration of progesterone exposure (3 vs 4 days) does not significantly influence clinical or perinatal outcomes.