The Efficacy of Letrozole vs. Clomiphene Citrate in Ovulation Induction for Women with Polycystic Ovary Syndrome (PCOS)

Abstract

Introduction: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder that significantly impairs female fertility. Clomiphene Citrate (CC) has long been considered the first-line agent for ovulation induction, while Letrozole (LTZ), a selective aromatase inhibitor, has emerged as a promising alternative. This study aimed to compare the clinical efficacy of LTZ and CC in women with PCOS attending tertiary care centers in Peshawar, Pakistan.

Materials and Methods: A prospective randomized controlled trial was conducted over a 12-month period involving 158 women diagnosed with PCOS based on the Rotterdam Criteria. Participants were randomly assigned to receive either LTZ (2.5–7.5 mg/day) or CC (50–150 mg/day) from cycle days 3 to 7. The primary outcomes were ovulation rate, clinical pregnancy rate, and endometrial thickness. Data were analyzed using the chi-square test, independent t-test, and binary logistic regression to evaluate treatment efficacy and predictors of response.

Results: Ovulation was confirmed in 86.1% of women treated with Letrozole versus 67.1% in the Clomiphene Citrate group (p = 0.002), indicating a statistically significant difference in ovulatory response. The clinical pregnancy rate was higher in the LTZ group (39.2%) than in the CC group (30.4%), although this difference did not reach statistical significance (p = 0.141). Endometrial thickness was significantly improved in the LTZ group (mean 9.4 mm) compared to the CC group (mean 8.1 mm) (p = 0.003). Both medications were well tolerated, with a slightly lower incidence of adverse effects such as hot flashes and abdominal discomfort in the LTZ group.

Conclusion: Letrozole demonstrated superior efficacy over Clomiphene Citrate in promoting ovulation and enhancing endometrial development among women with PCOS. Although the improvement in pregnancy rate did not achieve statistical significance, the observed trend may have clinical relevance. Further large-scale, multi-center studies are warranted to confirm these findings and evaluate live birth rates and long-term safety.