Comparison of Letrozole Combined With Gonadotropins Versus Clomiphene Citrate Combined With Gonadotropins in Infertile Women Presenting With Polycystic Ovary Syndrome (PCOS)
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age and an important cause of anovulatory infertility. Although clomiphene citrate (CC) has traditionally been used for ovulation induction, letrozole is increasingly preferred because of its favorable effects on ovulation and its limited peripheral antiestrogenic activity. This randomized controlled trial compared clinical pregnancy outcomes following letrozole combined with gonadotropins and CC combined with gonadotropins among infertile women with PCOS. The study was conducted in the Department of Obstetrics and Gynecology, Sir Ganga Ram Hospital, Lahore, from November 2025 to April 2026. A total of 110 women aged 20–39 years were randomized into two groups of 55. Group L received letrozole 2.5 mg daily on cycle days 2–6, while Group CC received CC 50 mg daily on the same days. Both groups subsequently received gonadotropins at 75 IU daily from cycle day 7, with treatment offered for up to three consecutive cycles. Ovulation was triggered using 10,000 IU of human chorionic gonadotropin once the dominant follicle reached at least 18 mm. Clinical pregnancy was assessed using serum β-hCG testing and transvaginal ultrasonographic confirmation of an intrauterine gestational sac. Data were analyzed using SPSS version 26. Clinical pregnancy occurred in 17 of 55 women (30.9%) in Group L and 4 of 55 women (7.3%) in Group CC. The between-group difference was statistically significant (two-sided Fisher exact test, p = 0.0029). These findings indicate that, in this single-center sample, the letrozole–gonadotropin regimen was associated with a higher clinical pregnancy rate than the CC–gonadotropin regimen. The study did not provide sufficient adverse-event or live-birth data to establish comparative safety or longer-term reproductive outcomes. Further multicenter trials with transparent allocation procedures, complete safety reporting, and live-birth follow-up are warranted.