Comparing efficacy and safety of stair step protocols for clomiphene citrate and letrozole in ovulation induction for women with polycystic ovary syndrome (PCOS): a randomized controlled clinical trial

Polycystic ovary syndrome (PCOS) is characterized by menstrual irregularities, high androgen levels, and ovarian cysts. Clomiphene citrate (Clomid) and letrozole have both been investigated as ovulation induction therapies for PCOS. This interventional study aimed to compare the efficacy and safety of a stairstep practice of letrozole versus clomiphene citrate in women with PCOS. A total of 100 women diagnosed with PCOS and infertility participated in the study, which took place from March 2021 to July 2022 at the Maternity and Children Teaching Hospital in Adiwaniyah Province, Iraq. Participants were randomly assigned to one of two groups (each with 50 women): the first group received clomiphene citrate in a stair step pattern (single dose of 50 mg, 100 mg, and 150 mg) for five days, for a maximum of three cycles; the second group received letrozole in a stair step pattern (single dose of 2.5, 5, and 7.5 mg) for five days, for a maximum of three cycles. Follicle size was monitored using ultrasound to achieve a follicle size >18 mm. The ovulation rate was higher in the letrozole group (86.0%) compared to the clomiphene citrate group (72.0%), although the difference was not statistically significant (p=0.086). The pregnancy rate was slightly higher in the letrozole group (22.0% vs 18.0%), but also not statistically significant (p=0.617). However, the mean time from menstruation to ovulation was significantly shorter in the letrozole group (17.20±1.32 days) compared to the clomiphene citrate group (24.08 ± 1.56 days, p<0.001). There were no significant differences in common side effects between the two groups. Overall, letrozole was found to be as safe as clomiphene citrate but demonstrated a shorter time to ovulation. Further studies with larger sample sizes are necessary to validate these findings and determine their clinical implications.