OVARIAN AGING: EMERGING BIOMARKERS, BIOLOGICAL MECHANISMS, AND STRATEGIES FOR FERTILITY PRESERVATION

Abstract

Ovarian aging is recognized as one of the earliest and most consequential manifestations of the aging process in women, preceding by decades the decline observed in most other organ systems and directly conditioning both reproductive potential and long-term health outcomes. Although anti-Müllerian hormone, antral follicle count, and follicle-stimulating hormone have long served as the principal markers of ovarian reserve, growing evidence indicates that ovarian aging is driven by an interconnected network of biological hallmarks, including genomic instability, telomere attrition, epigenetic remodeling, mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation. These mechanisms progressively compromise oocyte quality and follicular reserve, accelerating the transition toward diminished fertility and, ultimately, menopause. This study aimed to critically review the current scientific evidence regarding novel biomarkers, the underlying biological mechanisms, and the therapeutic strategies available for fertility preservation in the context of ovarian aging. A narrative literature review was conducted through comprehensive searches of the PubMed, MEDLINE, ScienceDirect, SpringerLink, Web of Science, and Scopus databases, using descriptors related to ovarian aging, ovarian reserve, oocyte quality, fertility preservation, and reproductive senescence, combined with Boolean operators. The reviewed evidence indicates that multi-omic and single-cell approaches have substantially expanded the panel of biomarkers available beyond classical hormonal indices, while mitochondrial and epigenetic alterations emerge as central, potentially reversible drivers of oocyte decline. Furthermore, fertility preservation strategies, including oocyte, embryo, and ovarian tissue cryopreservation, have demonstrated encouraging clinical outcomes, although methodological heterogeneity and limited long-term follow-up continue to constrain broader clinical standardization. In conclusion, ovarian aging represents a systemic biological process with implications that extend well beyond fertility, and the identification of reliable biomarkers together with individualized preservation strategies constitutes a promising avenue for improving reproductive and overall health outcomes in women.