Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) patients typically undergo either an ovulation induction regimen or a programmed regimen for endometrial preparation before frozen embryo transfer (FET). However, the superiority of one approach over the other remains controversial. While previous studies suggest that the letrozole regimen may improve pregnancy outcomes, prospective studies are insufficient. Therefore, we designed a multi-center randomized controlled trial to compare the pregnancy outcomes between these two regimens in PCOS patients undergoing FET. METHODS: This multicentre, randomised controlled, open-label trial included 155 PCOS patients from six hospitals in China between September 2022 and February 2024. Patients were randomised into either the letrozole ovulation regimen group (n = 81) or the programmed regimen group (n = 74) during FET cycles. Subgroup analysis was used among patients with single blastocyst transfer. The primary outcome was clinical pregnancy rate, with secondary outcomes including abortion rate, live birth rate, and other pregnancy and neonatal outcomes. RESULTS: Analysis of 155 FET women showed no significant difference in clinical pregnancy rates between the letrozole group (62.96%) and the programmed group (60.81%, P > 0.05). Similarly, no differences were observed in abortion rate, live birth rate, hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm birth, or neonatal birth weight. However, more patients in the letrozole group received single-drug luteal support (53.16% vs. 16.67%, P < 0.05). A subgroup analysis of 108 women involving patients who underwent single blastocyst transfer revealed no significant differences in clinical pregnancy rates (66.67% vs. 73.33%, P > 0.05) or live birth rates (58.73% vs. 55.56%, P > 0.05) between the two groups. A higher proportion of women in the letrozole ovulation regimen group received single-drug luteal support compared to those in the programmed regimen group (58.73% vs. 22.22%, P < 0.05). No statistically significant differences were observed between the groups in terms of fertilization method, abortion rate, or obstetric and neonatal outcomes. CONCLUSIONS: The letrozole ovulation regimen demonstrated comparable clinical pregnancy rates to the programmed regimen in PCOS patients undergoing FET, while requiring only simple luteal support. These findings suggest that the letrozole regimen may be a favourable alternative for endometrial preparation in this population. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062244 ( https://www.chictr.org.cn ). Registered on 31 July 2022.