Evaluation of Letrozole versus Clomiphene Citrate for Ovulation Induction in Anovulatory Patients with Hypogonadotropic Hypogonadism

International Journal of Obstetrics and Gynecology | Vol. 14, No. 8, August 2026 | pp. 519–530

DOI: 10.46882/2026/IJOG/000524

Original Research Article

Title: Evaluation of Letrozole versus Clomiphene Citrate for Ovulation Induction in Anovulatory Patients with Hypogonadotropic Hypogonadism

Names of Authors: Anita P. Nwosu¹, Samuel T. Kudoyin²

Authors’ Affiliations:
¹ Reproductive Endocrinology and Infertility Unit, Department of Obstetrics and Gynecology, Lagos State University Teaching Hospital, Ikeja, Nigeria
² Department of Radiology, College of Medicine, University of Lagos, Lagos, Nigeria

Abstract:
While aromatase inhibitors are widely accepted as a first-line ovulation induction choice in polycystic ovary syndrome, comparative evaluations in patients presenting with WHO Group I anovulation remain sparse. This prospective randomized clinical trial evaluated the ovulation, endometrial thickness, and clinical pregnancy rates achieved by letrozole versus clomiphene citrate (CC) in women with idiopathic hypogonadotropic hypogonadism. Eighy infertile anovulatory women with confirmed low baseline gonadotropins and estradiol were randomized to receive either letrozole (5 mg daily for 5 days, n = 40) or CC (100 mg daily for 5 days, n = 40) for up to three consecutive treatment cycles. Human chorionic gonadotropin was administered when a dominant follicle reached ≥ 18 mm. Spontaneous ovulation occurred in 55.0% of letrozole-treated cycles compared to 52.5% of CC-treated cycles, showing no significant difference between the arms (p = 0.68). However, the mean endometrial thickness on the day of hCG administration was significantly greater in the letrozole cohort (8.8 ± 0.6 mm vs. 7.1 ± 0.8 mm, p < 0.001), secondary to the avoidance of anti-estrogenic mucosal depletion. Consequently, the cumulative clinical pregnancy rate was significantly higher in the letrozole group compared to the clomiphene citrate group (37.5% vs. 17.5%, p = 0.043). Letrozole provides ovulation rates equivalent to clomiphene citrate in hypogonadotropic hypogonadism but achieves significantly better endometrial proliferation and superior pregnancy outcomes.

Keywords: Ovulation Induction; Letrozole; Clomiphene Citrate; Hypogonadotropic Hypogonadism; Endometrial Thickness; Clinical Pregnancy Rate.

Manuscript Timeline: Received: June 05, 2026; Revised: July 22, 2026; Accepted: August 05, 2026; Published: August 29, 2026.

Citation: Nwosu AP, Kudoyin ST. Evaluation of Letrozole versus Clomiphene Citrate for Ovulation Induction in Anovulatory Patients with Hypogonadotropic Hypogonadism. International Journal of Obstetrics and Gynecology. 2026; 14(8): 519–530.

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