Abstract
BACKGROUND: In assisted reproductive technology, preventing premature ovulation is crucial for achieving successful pregnancy outcomes. The traditional GnRH antagonist protocol is commonly used to suppress the luteinizing hormone (LH) surge, while the progesterone-primed ovarian stimulation (PPOS) protocol has gained attention due to its simplicity, lower cost, and fewer side effects. This study compared the PPOS and GnRH antagonist protocols in frozen embryo transfer (FET) cycles, focusing on evaluating the safety of the PPOS protocol and its impact on neonatal birth outcomes. METHODS: This prospective cohort study was conducted at the Assisted Reproductive Medicine Department of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2020 to December 2023. The study included infertile patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, followed by frozen embryo transfer. To balance baseline characteristics and ensure a fair comparison, a combination of propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) was employed. PSM and IPTW were used to match patients based on baseline characteristics, including age, body mass index (BMI), infertility duration, hormone levels (FSH, LH, E2), pregnancy history, and other factors. RESULTS: The study compared the outcomes of IVF/ICSI using PPOS and GnRH antagonist protocols. After propensity score matching, 1,950 patients were included in each group. No significant differences were observed between the PPOS and GnRH antagonist groups in clinical pregnancy rate (46.26% vs. 46.21%, P = 0.979), live birth rate (36.26% vs. 35.49%, P = 0.550), miscarriage rate (10.05% vs. 10.72%, P = 0.375), or ectopic pregnancy rate (0.82% vs. 0.82%, P = 0.880). There were no significant differences were found between the two protocols in neonatal outcomes, including sex distribution and incidence of congenital anomalies. Further analysis of singleton live births showed no significant differences in the risk of low birth weight between groups (4.86% vs. 3.16%, adjusted OR = 1.62, 95% CI: 0.97-2.71, P = 0.063) or congenital anomalies (2.35% vs. 1.58%, adjusted OR = 0.67, 95% CI: 0.32-1.39, P = 0.278). In IVF/ICSI treatment, the PPOS protocol showed similar live birth rates and neonatal health outcomes compared to the GnRH antagonist protocol. INNOVATION AND CONTRIBUTION: This prospective cohort study observed patients undergoing IVF/ICSI treatment with either the PPOS or GnRH antagonist protocols, ensuring a fair comparison. PSM and IPTW were used to balance baseline characteristics and adjust for remaining differences, thereby improving the reliability of the results. A key strength lies in the large matched sample, which enhances statistical power. Additionally, unlike previous studies, this research included neonatal outcomes, offering a more comprehensive evaluation of both pregnancy success and infant health. The combination of advanced statistical methods and a focus on long-term outcomes renders this study a significant contribution to the field of infertility treatment.