Effect of a luteal phase rescue protocol on live birth rates in frozen embryo transfer cycles

Introduction Frozen embryo transfer (FET) is a standard procedure that improves live birth rates and reduces ovarian hyperstimulation risks. Optimizing luteal phase support with hormone replacement therapy (HRT), particularly by progesterone supplementation, enhances endometrial receptivity and embryo implantation success. Despite advances in cryopreservation techniques, optimal protocols for progesterone supplementation in HRT-FET cycles remain uncertain. This study aims to evaluate the effects of an individualized luteal phase protocol using subcutaneous progesterone on live birth rates in HRT-FET cycles. Methods In this retrospective cohort study, we analyzed data from 433 autologous FET cycles prepared with HRT. Serum progesterone levels were measured the day before FET. Two groups were compared according to serum progesterone measurement the day before FET. The control group (≥ 11 ng/ml), received standard luteal support (800 mg vaginal progesterone daily); and the rescue group (11 ng/ml), received an additional 25 mg subcutaneous progesterone daily. Pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, miscarriage, and live birth rates, were assessed across both groups. Results Despite overall similar pregnancy rates, the rescue group, receiving combined subcutaneous and vaginal progesterone, demonstrated a higher live birth rate compared to the control group (36.9% vs. 24.7%, p = 0.006). By Day 12 after FET, progesterone levels in the rescue group were comparable to those in the control group. Conclusion Our findings suggest that adding subcutaneous progesterone to standard vaginal support in HRT-FET cycles may improve reproductive outcomes in patients with low serum progesterone levels the day before transfer. These results support tailoring progesterone supplementation to optimize luteal phase support. Further controlled trials are needed to establish standardized protocols for HRT-FET cycles.