Extended versus conventional letrozole regimen in patients with polycystic ovary syndrome undergoing their first ovulation induction cycle: a prospective randomized controlled trial.

study questionCan an extended letrozole (LE) regimen result in a higher ovulatory rate than a conventional regimen in patients with polycystic ovary syndrome (PCOS) undergoing their first ovulation induction cycle? SUMMARY ANSWER: There was no statistical difference in ovulation rate between patients with PCOS using the extended LE regimen and those using the conventional LE regimen. WHAT IS KNOWN ALREADY: LE has become the first-line agent for ovulation induction. However, there is still a proportion of non-responsive cycles in patients with PCOS undergoing ovulation induction therapy with LE alone, and the extended LE regimen has been demonstrated to be a feasible method for inducing ovulation in these non-responders. Nevertheless, whether the extended regimen could be applied to all patients with PCOS as a first choice for the induction of ovulation remains to be explored. STUDY DESIGN SIZE DURATION: This was a prospective randomized controlled trial that included 148 female patients with PCOS who underwent their first ovulation induction cycle with LE from January 2021 to October 2022. PARTICIPANTS/MATERIALS SETTING

methodsParticipants were randomly assigned to receive an extended (5 mg LE daily for 7 days) or conventional regimen (5 mg LE daily for 5 days) for one treatment cycle. The ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, and the rate of multiple pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: The ovulation rate among patients receiving an extended LE regimen was slightly higher than the rate with a conventional LE regimen, but the difference did not reach statistical significance in either the intention-to-treat analysis (90.54% [67/74] vs 79.73% [59/74], LIMITATIONS REASONS FOR CAUTION: The major concerns regarding this study are its single-center and open-label nature. Additionally, the limited number of lean patients with PCOS with a mean body mass index of 23-25 kg/m WIDER IMPLICATION OF THE

findingsA change from the standard strategy of ovulation induction in patients with PCOS is not advisable, because a statistically superior effect of the extended LE regimen over a conventional regimen was not detected. The extended LE regimen could be applied with caution in a specific population who failed to respond to a conventional regimen rather than all the patients with PCOS during ovulation induction. Additional prospective trials with larger sample sizes and different PCOS subgroups are needed to assess the ovulatory effects of various LE treatment durations. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Shanghai First Maternity and Infant Hospital, affiliated with Tongji University School of Medicine (grant numbers: 2023B03 to Y.F., 2023B18 to X.Z., and 2020RC02 to Y.F.). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2100042082). TRIAL REGISTRATION DATE: 13 January 2021. DATE OF FIRST PATIENT’S ENROLMENT: 21 January 2021.