Received April 07, 2026
Accepted April 07, 2026

Objective: Genetic factors may influence variability in ovarian response to gonadotropin stimulation. However, evidence in women with PCOS, particularly in Southeast Asian populations, is limited. This pilot study aimed to identify genetic variations associated with ovarian response to gonadotropin stimulation in Indonesian women with PCOS undergoing IVF. Methods: A subset GWAS dataset of 172 PCOS women was evaluated. All participants fulfilled at least 2 of the 3 Rotterdam criteria. Women retrieving fewer than 8 mature oocytes after stimulation were categorized as hypo-responder (n=50), while those retrieving 8 or more were categorized as normo-hyporesponder (n=122). Association between SNPs and ovarian response was analyzed using additive logistic regression with Bonferroni correction for multiple testing. Result: Clinical characteristics of hyporesponder and hyperresponder PCOS women recruited in the study differed in basal FSH (6.72 vs. 5.80 mIU/mL, respectively, p = 0.001), basal LH (4.80 vs. 6.24 mIU/mL, respectively, p = 0.040), AMH (3.15 vs. 5.23 ng/mL, respectively, p < 0.001), and AFC (14 vs. 19, respectively, p < 0.001). Pilot GWAS 19 SNPs significantly associated with ovarian hypo-response, showing large effect sizes and higher minor allele frequencies in hypo-responders. Key loci included PXDNL, LRP1B, and ENOX1, with most variants being intronic and enriched in women with reduced ovarian responsiveness. Conclusion: This pilot GWAS identifies novel genetic variants associated with gonadotropin hypo-response in Indonesian women with PCOS, implicating mitochondrial, immune, extracellular matrix, oxidative, and intracellular signaling pathways that warrant validation in larger cohorts and may inform personalized stimulation strategies.