Effect of Total Gonadotropin-Releasing Hormone Antagonists Dose on Assisted Reproductive Outcomes in Women With Normal Ovarian Reserve: A Retrospective Cohort Study

Background: Gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) have been demonstrated to exert adverse effects on endometrial receptivity; however, the association between their cumulative dose and pregnancy outcomes in fresh embryo transfer cycles remains inconclusive. This study aimed to evaluate the effect of the cumulative dose of GnRH-ant on pregnancy outcomes in fresh embryo transfer cycles. Methods: This retrospective cohort study evaluated 1795 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles conducted between January 1, 2023 and March 31, 2024, at Sichuan Jin’xin Xi’nan Women’s and Children’s Hospital using flexible GnRH-ant protocols. The initial dose of antagonist (0.125–0.25 mg/day) was individualized according to age, body mass index (BMI), estradiol (E2), and basal luteinizing hormone (LH) levels. Antagonist doses were increased to 0.25 mg/day if LH levels exceeded 10 mIU/mL during stimulation. Participants were stratified by median total GnRH-ant dose into group A (≤0.75 mg, n = 909) and group B (>0.75 mg, n = 886). Propensity score matching (PSM) (1:1 nearest-neighbor method) was performed to balance baseline characteristics, yielding 719 matched pairs. Embryological parameters, including oocyte yield, fertilization rate, and embryo quality, and clinical outcomes, such as implantation, pregnancy, and live birth, were compared between the two groups. Results: Compared with group A, group B exhibited significantly higher levels of progesterone, E2, oocyte yield, 2-pronuclear (2PN) fertilization, and quality embryo counts (cleavage-stage and blastocyst) (p < 0.001). The embryo implantation rate was significantly lower in group B than in group A (adjusted odds ratio [OR] = 0.74, 95% CI: 0.55–0.99, p = 0.048). No differences in clinical pregnancy, miscarriage rates, or live birth were observed between the two groups (all p > 0.05). The total dose of GnRH-ant was positively correlated with oocyte and embryo parameters (r = 0.171–0.102, p < 0.001). Conclusions: In women under 35 years of age with normal ovarian reserve, reduced GnRH-ant doses did not significantly improve the clinical pregnancy rate during fresh cycles.