Clomiphene citrate plus letrozole versus clomiphene citrate alone for ovulation induction in infertile women with chronic anovulation: A randomized controlled trial

Objective To compare the efficacy of combination clomiphene citrate (CC) plus letrozole with that of CC alone for ovulation induction in infertile women with chronic anovulation. Material and methods This randomized controlled trial was conducted at the Infertility and Reproductive Biology Unit of the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the August 2020-September 2021 study period. Anovulatory women aged 18-40 years were equally allocated into either the CC 50 mg plus letrozole 2.5 mg once daily group or the CC 50 mg once daily group. The study drugs were administered on days 3-7 of each study patient’s menstrual cycle. The primary outcome was the ovulation rate defined by serum progesterone >3 ng/mL at mid-luteal phase. The secondary outcomes were menstrual cycle characteristics, endometrial thickness, conception rate, and adverse events. Results One hundred women (50 per group) were enrolled. The mean age and prevalence of polycystic ovary syndrome were non-significantly different between groups. The ovulation rate according to intention-to-treat analysis was 78% and 70% in the combination and CC alone groups, respectively (p>0.05). There was no significant difference between groups for either mean endometrial thickness or number of dominant follicles. No serious adverse events were observed in either group. Conclusion There was no significant difference between combination CC plus letrozole and CC alone relative to their ability to induce ovulation in infertile women with chronic anovulation. The small number of live births (1 per group) was too low to be statistically analyzed.