Ovarian ageing: from biological constraint to emerging therapeutic frontier

Ovarian ageing is a central determinant of female reproductive potential, defined by a progressive and largely irreversible decline in both the quantity and the quality of oocytes. Although the process is universal, its onset and pace vary widely, and early ovarian ageing (EOA) affects a substantial minority of women, contributing to subfertility, miscarriage and earlier menopause. This narrative review synthesises current understanding of the biology, diagnosis and management of ovarian ageing. Two interrelated but partly independent processes drive the decline: exhaustion of the primordial follicle pool and deterioration of oocyte developmental competence. Beneath them lies an interconnected molecular network encompassing mitochondrial and metabolic dysfunction, genomic and meiotic instability, cellular senescence and inflammation and progressive ageing of the ovarian microenvironment. In clinical practice, assessment still depends on surrogate markers-anti-Müllerian hormone (AMH), antral follicle count (AFC) and follicle-stimulating hormone (FSH)-that quantify reserve but cannot measure oocyte quality; importantly, these markers predict ovarian response rather than natural fertility, and improvements in AMH, AFC, oocyte yield or menstrual function do not necessarily translate into better oocyte competence, euploid embryo formation or live birth. Management remains centred on fertility preservation and optimisation of assisted reproductive technology, with pharmacological adjuvants offering, at best, modest and inconsistent benefit and none currently endorsed by guidelines for improving live birth. A new generation of experimental strategies-in vitro activation, platelet-rich plasma, stem-cell and exosome therapies, mitochondrial replacement and in vitro gametogenesis-signals a conceptual shift from managing decline towards restoring ovarian function, but the supporting evidence remains preliminary. Despite remarkable progress, no intervention currently reverses ovarian ageing or reliably improves age-related oocyte competence, and bridging this gap will require rigorous translational research and careful, evidence-based clinical integration.