Evaluating the efficacy of potential ovarian reserve markers from theca and granulosa cells: INSL3 & TNFR2

Accurate assessment of ovarian reserve remains challenging in clinical practice, particularly when conventional markers like anti-müllerian hormone (AMH) and antral follicle count show inconsistent results. Despite widespread use, AMH has limitations in predicting reproductive lifespan and oocyte quality. This study evaluated 2 emerging biomarkers, insulin-like peptide-3 (INSL3) and tumor necrosis factor receptor 2 (TNFR2), for ovarian reserve assessment. We included 179 women aged 20 to 40 years. Participants underwent ultrasound evaluation for antral follicle count and blood sampling for hormone measurements. Women were classified using decreased ovarian reserve (DOR) and premature ovarian insufficiency (POI) criteria. INSL3 showed moderate effectiveness in detecting both DOR (area under the curve [AUC]: 0.685) and POI (AUC: 0.711), though not as strong as AMH. TNFR2 was statistically significant in predicting DOR (AUC: 0.651) but ineffective for POI identification. While AMH remained the strongest marker, INSL3 may serve as a supportive indicator for evaluating ovarian reserve, especially in identifying women at risk of POI. TNFR2, despite its biological relevance, shows limited clinical usefulness. These findings indicate INSL3's potential as a complementary marker to improve individualized assessment of ovarian function.