Background: Letrozole is widely used for ovulation induction in infertile women with normo-gonadotropic anovulation and polycystic ovarian syndrome (PCOS). Pretreatment with combined oral contraceptive pills (OCPs) may suppress the hypothalamic–pituitary–ovarian axis and potentially optimize follicular response, but the data on randomized controlled trials is limited in this regard.
Aim: To compare follicular growth and reproductive outcomes in infertile women receiving a prior cycle of OCPs followed by letrozole versus infertile women receiving letrozole alone.
Materials and Methods: This prospective, randomized, double-blind controlled trial was conducted over 24 months (August 2022–July 2024) in the Department of Obstetrics and Gynaecology at a tertiary care teaching hospital in western India. Adult infertile women (>18 years) with primary or secondary infertility and WHO Group II anovulation, including PCOS, with normo-gonadotropic normo-gonadism and patent tubes were enrolled. Women with male factor, endometriosis, genital Koch’s, pelvic inflammatory disease, anatomical abnormalities, prior IVF/IUI or prior ovulation induction were excluded. A total of 180 women were randomized; 17 withdrew before treatment, leaving 82 in Group A (letrozole only: 5 mg once daily for 5 days from day 2) and 81 in Group B (one cycle of OCPs [Mala-D] followed by the same letrozole regimen). Baseline demographics, BMI, and day-2 FSH, LH, and TSH were recorded along with baseline TVS on Day 2 followed by follicular growth monitoring from day 9 onwards.
Results: Both groups were comparable in age, BMI, type of infertility, comorbidities, and basal hormonal profile (p>0.05). AFC did not differ significantly between groups. Group B had a higher mean number of follicles >18 mm (3.02±1.28 vs 2.20±1.1; p<0.05) and greater mean endometrial thickness (8.06±2.19 vs 7.4±2.20 mm; p<0.05). Time to LH surge was significantly shorter in the OCP+letrozole group (p<0.05). UPT positivity (12.5% vs 17.28%) and clinical pregnancy rates (10.97% vs 14.81%) were higher in Group B. Rates of ectopic pregnancy, multiple gestation, and weight gain were low and comparable between groups (p>0.05).
Conclusion: A prior cycle of OCPs followed by letrozole results in improved follicular maturity, better endometrial development, shorter time to LH surge, and higher pregnancy rates compared with letrozole alone, without increasing adverse outcomes. OCP pretreatment appears to be a useful strategy to enhance ovulation induction outcomes in infertile women with WHO Group II anovulation and PCOS.
International Journal of Clinical Obstetrics and Gynaecology
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