Efficacy and Safety Profile of Natural Vaginal Progesterone vs. Oral Dydrogesterone in Fresh Embryo Transfer Cycles: A Retrospective Analysis

Objective: To compare the efficacy and neonatal safety profiles of natural vaginal progesterone (P4) and oral dydrogesterone (DYG) used for luteal phase support in fresh embryo transfer (ET) cycles. Material and Methods:This retrospective cohort study included fresh ET cycles performed at a single tertiary IVF center between January 2018 and October 2022.Cycles in which luteal phase support consisted of either vaginal P4 (capsules or vaginal gel) or oral DYG (30 mg/day) were analyzed.Only day-3 or day-5 fresh ET cycles with complete reproductive and neonatal follow-up data were included.Frozen ET cycles, cycles using additional or alternative luteal support regimens, and cases with incomplete follow-up were excluded.The primary outcome was live birth rate.Secondary outcomes included the prevalence of major and minor congenital malformations.Results: A total of 1,331 fresh ET cycles were analyzed, including 782 cycles in the oral DYG group and 549 cycles in the vaginal P4 group.Live birth rates were comparable between the oral DYG and vaginal P4 groups (39.7% vs. 38.8%;p=0.756).The incidence of minor congenital malformations was 2.0% in the DYG group and 3.5% in the vaginal P4 group (p=0.112),while major congenital malformations occurred in 0.8% and 1.5% of cases, respectively (p=0.225).In univariable logistic regression analysis, the type of P4 used for luteal phase support was not associated with the occurrence of congenital malformations.Conclusion: This large real-world retrospective analysis demonstrates that oral DYG provides comparable live birth outcomes and a similar neonatal safety profile to vaginal P4 when used for luteal phase support in fresh ET cycles.Oral DYG may therefore be considered an effective and safe alternative for luteal support in routine IVF practice.