Platelet-rich plasma in reproductive medicine: from ovarian follicles to the ovarian niche and emerging stem cell mobilization-based regenerative strategies.

Ovarian aging is a complex biological process traditionally attributed to the progressive depletion of the follicular reserve. However, accumulating evidence suggests that age-related reproductive decline is not solely determined by follicular loss but also by profound alterations in the ovarian microenvironment, including stromal fibrosis, vascular dysfunction, chronic low-grade inflammation, oxidative stress, and impaired intercellular communication. This evolving understanding has promoted a shift from a follicle-centered view of ovarian aging toward a broader ovarian niche-centered paradigm. Within this context, platelet-rich plasma (PRP) has emerged as one of the most extensively investigated regenerative approaches in reproductive medicine. PRP provides a concentrated source of growth factors, cytokines, and bioactive mediators capable of modulating angiogenesis, tissue remodeling, inflammation, and cellular signaling. Nevertheless, interpretation of the available clinical evidence remains challenging due to substantial heterogeneity in PRP preparation protocols, biological composition, patient selection, and outcome measures. This narrative review examines the biological basis of PRP, its potential effects on the ovarian niche, and the current clinical evidence supporting its use in women with diminished ovarian reserve, poor ovarian response, premature ovarian insufficiency, and advanced reproductive age. Particular attention is given to the emerging concept that restoration of ovarian niche functionality, rather than isolated activation of residual follicles, may represent the primary biological objective of contemporary ovarian rejuvenation strategies. The review also explores the rationale for combining local regenerative interventions with systemic regenerative approaches, including hematopoietic progenitor cell mobilization induced by granulocyte colony-stimulating factor (G-CSF). We discuss the hypothesis that mobilization-induced changes in circulating progenitor cells, chemotactic signaling pathways, and the systemic regenerative milieu may enhance the biological activity of autologous regenerative products and contribute to ovarian niche restoration. Current evidence does not yet support definitive conclusions regarding the efficacy of ovarian rejuvenation therapies. However, the integration of local and systemic regenerative signals represents a promising avenue for future investigation. Further progress will require standardized biological products, robust biomarkers, and well-designed clinical trials capable of clarifying the mechanisms, indications, and clinical value of regenerative interventions targeting the ovarian niche.