Comparison of Letrozole and Clomiphene Citrate Success Rate in Ovulation Induction

Background: Clomiphene citrate has traditionally been the first-line agent for ovulation induction; however, increasing evidence suggests that letrozole may offer superior efficacy with a more favorable endometrial profile. Comparative data examining treatment response across demographic and socioeconomic variables remain limited, especially within South Asian populations. Objective: To compare the efficacy of letrozole and clomiphene citrate for ovulation induction in subfertile women with ovulatory dysfunction presenting to a tertiary care hospital in Khyber Pakhtunkhwa, Pakistan. Methodology: This pilot randomized controlled trial was conducted from January to July 2024 in the Department of Gynecology and Obstetrics at Saidu Group of Teaching Hospital, Swat. A total of 64 subfertile women aged 18–30 years with anovulatory infertility were randomized in equal numbers to receive either letrozole 5 mg/day or clomiphene citrate 100 mg/day for five consecutive days, initiated between cycle days 3 and 5. Ovulation was monitored over three cycles using transvaginal ultrasonography, with biochemical confirmation using mid-luteal serum progesterone where applicable. The primary outcome was ovulation induction success. Results: Baseline demographic and clinical characteristics were comparable between groups. Ovulation was achieved in 65.6% of women receiving letrozole compared with 37.5% of those receiving clomiphene citrate, representing a statistically significant difference (p = 0.024). Exploratory subgroup analyses suggested higher efficacy of letrozole among women with higher body mass index and selected socioeconomic subgroups. Conclusion: In this pilot randomized controlled trial, letrozole demonstrated significantly higher ovulation induction efficacy compared with clomiphene citrate in subfertile women with ovulatory dysfunction. These findings support the growing evidence favoring letrozole as a first-line ovulation induction agent, while underscoring the need for larger multicenter trials evaluating pregnancy and live birth outcomes. Keywords: Clomiphene citrate, Letrozole, Ovulation induction, Polycystic ovarian syndrome, Subfertility.