Influencing ovarian aging in reproductive medicine: promise, evidence, and unresolved questions.

Abstract

Ovarian aging is a fundamental biological constraint on female fertility, driven by depletion of the primordial follicle pool and progressive alterations in the ovarian microenvironment. In recent years, a range of intraovarian interventions aimed at modifying ovarian aging, including platelet-rich plasma, autologous stem cell-based approaches, and mitochondrial transfer, have gained clinical and commercial attention. These strategies are supported by biologic hypotheses and early changes in surrogate markers such as antimüllerian hormone and antral follicle count, yet their clinical significance remains uncertain. This Views and Reviews critically evaluates the evidence supporting these interventions, emphasizing the distinction between transient follicular activation and true modification of reproductive aging. Clinical data are integrated with emerging mechanistic insights from aging biology, including nutrient-sensing pathways, partial epigenetic reprogramming, and ovarian fibrosis as a modifiable determinant of ovarian function. Across modalities, improvements in surrogate outcomes have not reliably translated into gains in embryo competence, euploidy, or live birth, and safety data remain limited, with procedural and infectious risks that warrant careful consideration. We conclude that routine clinical use of intraovarian aging-targeted interventions is premature. Future progress will require standardized protocols, adequately powered randomized trials with live birth endpoints, and rigorous assessment of both efficacy and risk.