Addition of Estrogen for Luteal Phase Support in Women with Suboptimal or Poor Response After an Antagonist Protocol: A Cohort Study

Objective: To evaluate the potential benefits of estradiol (E 2 ) supplementation as luteal phase support (LPS) on reproductive outcomes in women who exhibited suboptimal or poor ovarian response after a gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and fresh embryo transfer. Methods: In this retrospective study, we assessed the potential benefits of E 2 supplementation as LPS on reproductive outcomes in 4,992 women who met the following criteria: 1) age <45 years; 2) use of the GnRH-ant protocol; 3) fewer than 10 collected oocytes; and 4) transfer of an embryo in a fresh cycle between January 2018 and April 2023 at Northwest Women’s and Children’s Hospital. Based on whether the women received E 2 supplementation (2 mg E 2 valerate tablets twice daily) as LPS after fresh embryo transfer, they were allocated to two groups: non-E 2 supplement and E 2 supplement. Propensity score matching (1:1 ratio) was applied using multiple covariates known to influence reproductive outcomes. Primary outcomes were the clinical pregnancy and live birth rates. Results: The clinical pregnancy rate did not significantly differ between the non-E 2 supplement and E 2 supplement groups (45.89% vs. 45.29%, adjusted odds ratio [aOR]: 0.97, 95% confidence interval [CI]: 0.84–1.11, P = 0.615). Similarly, the live birth rate did not significantly differ between groups (36.14% vs. 35.43%, aOR: 0.96, 95% CI: 0.83–1.10, P = 0.543). Conclusions: Our findings suggest that adding E 2 supplementation as LPS in women with a suboptimal or poor response undergoing the GnRH-ant protocol does not improve the clinical pregnancy rate or live birth rate.