Factors Influencing Letrozole Response in Ovulation Induction among Polycystic Ovary Syndrome Women

Background: Letrozole is the first-line ovulation induction agent in PCOS, but some women do not respond. This study aimed to evaluate ovulatory response to Letrozole and identify predictors of non-response to individualise treatment. Methods: This retrospective observational study included women with PCOS (Rotterdam criteria) undergoing their first Letrozole ovulation induction cycle between January 2019 and December 2020. Exclusions were severe male factor infertility, pelvic pathologies, or repeat cycles. Baseline assessments included clinical evaluation, day 3 hormonal profiling (LH, FSH, TSH, Prolactin), and transvaginal ultrasound for antral follicle count (AFC). Letrozole (5 mg/day) was given from day 3 to 7, with follicular monitoring from day 9 to 27. Responders developed ≥1 dominant follicle (≥18 mm), non-responders did not. Data were analysed with Jamovi; logistic regression identified non-response predictors. ROC analysis determined optimal cut-offs (p<0.05 significant). Results: Of 327 women, 186 met criteria. The response rate was 83.3% (155 responders, 31 non-responders). Non-responders had higher BMI, AFC, LH, and LH/FSH ratios. Multivariable regression showed AFC as the only independent predictor of non-response (OR 1.039, 95% CI: 1.003–1.076, p=0.033). ROC analysis identified AFC ≥35 as the optimal cut-off with 61.3% sensitivity, 83.9% specificity, 43.2% PPV, and 91.5% NPV. This indicates women with AFC <35 are more likely to respond to Letrozole. Conclusion: Letrozole induces ovulation in 83.3% of PCOS women. AFC is a key predictor, with <35 indicating better response. Using AFC can reduce failed cycles and guide timely alternative treatments like gonadotropins or IVF.