Efficacy of Gonadotropin with Clomiphene versus Letrozole in Women with Ovulatory Dysfunction Undergoing Intrauterine Insemination: A Research Protocol for a Randomised Controlled Trial

Introduction: Globally, infertility poses a significant problem for young couples. In cases of mild male factor infertility, unexplained infertility, and ovulatory dysfunction, Intrauterine Insemination (IUI) is often used as a first-line treatment. Clomiphene Citrate (CC) is a selective oestrogen receptor modulator that is often used to help women ovulate. However, it can have antioestrogenic effects on the endometrium and cervical mucus, which could make pregnancy less likely to go well. Letrozole, a third-generation aromatase inhibitor, offers advantages such as mono-ovulation, a shorter half-life, and minimal anti-oestrogenic activity, making it a promising alternative. Need of the study: Women with ovulatory dysfunction commonly undergo IUI, but the optimal ovulation-induction agent remains unclear. CC may impair endometrial receptivity, while letrozole offers more favourable physiological effects. Comparative evidence is needed to determine which regimen improves pregnancy outcomes in this population. Aim: The present study aims to compare the efficacy of letrozole with Human Menopausal Gonadotropin (HMG) and CC with HMG in infertile women with ovulatory dysfunction undergoing IUI. Materials and Methods: The current study is a Randomised Controlled Trial (RCT) that will be conducted at Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra, India, from June 2024 to May 2026. A total of 142 women aged 20-38 years with ovulatory dysfunction will be enrolled and randomly assigned to two groups: Group A will receive CC 50 mg twice daily from Day 2 to 6; Group B will receive Letrozole 2.5 mg twice daily from Day 2 to 6. Both groups will receive IM HMG 75 IU from Day 6 to Day 10. Ovulation will be monitored by transvaginal ultrasonography and triggered with Human Chorionic Gonadotropin (hCG) once dominant follicles reach 18-20 mm, followed by IUI. The primary outcomes are the clinical pregnancy rate (confirmed by ultrasound) and biochemical pregnancy rate (positive β-hCG test). Secondary outcomes include endometrial thickness, number of dominant follicles, perifollicular blood flow, and incidence of Ovarian Hyperstimulation Syndrome (OHSS). Numerical data will be presented as mean±Standard Deviation (SD) or proportions. Continuous variables will be tested for normality using the Shapiro-Wilk test. Normally distributed data will be compared using the independent samples t-test; non-normally distributed data will be compared using the Mann-Whitney U test. A p-value of <0.05 will be considered statistically significant.