The protective role of BMP-15 in infertility development with NLRP3 and IL-18 in infertility development in obese patients with PCOS: clinical and mouse model investigations.

Background: Obesity-related polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility and metabolic dysfunction. While bone morphogenetic protein-15 (BMP-15) plays a recognized role in ovarian function, its specific impact on infertility in obese PCOS patients remains unclear Objective: This study aimed to investigate the influence of BMP-15, NOD-like receptor protein 3 (NLRP3), and interleukin-18 (IL-18) on infertility in this population and to evaluate their predictive clinical value. Methods: Clinical data from 185 obese PCOS patients were retrospectively analyzed. Univariate and logistic regression analyses identified infertility-related factors. Results: Results showed an infertility rate of 34.43%, with significant differences in BMP-15, NLRP3, IL-18, Morisky Medication Adherence Scale (MMAS-8), and Connor-Davidson Resilience Scale (CD-RISC) scores between infertility and non-infertility groups. NLRP3, IL-18, and MMAS-8 emerged as risk factors, while BMP-15 and CD-RISC were protective.In an obese PCOS mouse model, BMP-15 administration improved metabolic parameters, restored hormonal balance, reduced ovarian inflammation, and preserved fertility. Conclusion: These findings suggest that BMP-15 plays a protective role in PCOS-related infertility by modulating metabolic and inflammatory pathways. BMP-15 may serve as a valuable biomarker and therapeutic target for early identification and intervention in obese PCOS patients at risk of infertility.