P-604 A novel ovulation induction regimen in women with polycystic ovary syndrome resistant to letrozole: letrozole stair-step duration regimen

Abstract Study question Whether the letrozole stair-step duration regimen is effective and time-saving for ovulation induction in women with polycystic ovarian syndrome (PCOS) and letrozole resistance. Summary answer Letrozole stair-step duration regimen is effective for inducing ovulation in women with PCOS and letrozole resistance, and it is more time-saving. What is known already Letrozole has been considered as the primary choice for women with PCOS during ovulation induction. However, a proportion of women fail to ovulate using the conventional letrozole regimen, referred to as “letrozole resistance”. For those women, we proposed a method of extending letrozole treatment duration, firstly 7 days and then 10 days after progestin-induced bleeding if unresponsive in the subsequent cycles, which named as ‘‘2-step extended letrozole regimen’’. To further shorten the time required for ovulation, we proposed a novel letrozole stair-step duration protocol that skipped routine progestins withdrawal bleeding after anovulatory cycles and proceeded immediately to letrozole duration increase. Study design, size, duration This was a retrospective study performed at two university-affiliated reproductive medicine centers. A total of 158 women with PCOS and letrozole resistance for ovulation induction between March 2018 and September 2024 were included. Participants/materials, setting, methods Follicular growth, hormone profile, ovulation and pregnancy outcomes were compared between the letrozole stair-step duration regimen (n = 62) and the 2-step extended letrozole regimen (n = 96). The primary outcome was the ovulation rate. Secondary outcomes included the clinical pregnancy rate, live birth rate and the time to ovulation. Main results and the role of chance The ovulation rate using the letrozole stair-step duration regimen reached 95.16% (59/62), comparable with the 2-step extended letrozole regimen [94.79% (91/96)]. The rates of clinical pregnancy [(23.73% (14/59) vs. 20.88% (19/91), P = 0.681), and live birth [16.95% (11/59) vs. 18.68% (17/91), P = 0.824] did not differ significantly between the treatment groups. More importantly, the time required for ovulation was much less in the letrozole stair-step duration regimen group [36 (32-54) days] compared to the 2-step extended letrozole regimen group [47 (45-51) days]. Limitations, reasons for caution This is a retrospective cohort study with a relatively small sample size. It would be beneficial to conduct additional prospective trials with larger sample sizes. Further studies focusing on cumulative pregnancy outcomes and follow-up of newborns are needed to verify the long-term safety and effectiveness of this regimen. Wider implications of the findings Our study confirms that it is feasible to skip routine progestins withdrawal in between the unresponsive cycles for PCOS women with LE resistance. In other words, it is not necessary to induce menses before increasing LE treatment duration during ovulation induction. Trial registration number No