Evidence check: FOXO3 in the context of fertility

FOXO3 is a transcription factor associated with longevity in multiple studies. In the context of fertility, GWAS have linked certain variants (e.g., rs2802292) to later age at menopause and longer reproductive lifespan. Effect sizes are modest (OR ~1.1–1.3) and not deterministic. Mechanisms may involve regulation of oxidative stress and apoptosis in oocytes. However, most evidence comes from population-based association studies, not prospective clinical trials. Direct causal evidence for improved fertility in humans is lacking. Consumer DNA tests that report FOXO3 variants often overstate clinical utility. Results should not be used alone for reproductive decisions. In summary, FOXO3 is a promising but not established biomarker for ovarian reserve. Evidence is moderate and primarily GWAS-based.