Bone Marrow Mesenchymal Stem Cells Therapy for Premature Ovarian Insufficiency: A Systematic Review and Meta-analysis of Preclinical Studies

Background

Premature ovarian insufficiency (POI) affects approximately 1% of women under 40 and is characterized by elevated levels of gonadotropins, reduced estradiol, impaired folliculogenesis, and infertility. Bone marrow–derived mesenchymal stem cell (BM-MSC)-based therapy has emerged as a promising regenerative strategy in preclinical POI models. This systematic review and meta-analysis evaluated BM-MSC-based interventions, including cell transplantation and secretome/extracellular vesicle administration, in animal models of POI.

Methods

A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched from inception to February 19, 2025. Preclinical studies assessing BM-MSC-based interventions in animal models of POI were included.

Results

Thirty-four studies comprising 1,357 animals were included. Compared with controls, BM-MSC-based therapy increased serum estradiol (standardized mean difference [SMD] 3.11; 95% confidence interval [CI] 2.38–3.84) and anti-Müllerian hormone (SMD 1.86; 95% CI 1.03–2.69), while reducing follicle-stimulating hormone (SMD −3.54; 95% CI −4.37 to −2.71) and luteinizing hormone (SMD −3.44; 95% CI −5.17 to −1.70). Follicular counts increased across developmental stages, with fewer atretic follicles. Reproductive outcomes improved, including normal estrous cycles (risk ratio [RR] 7.80; 95% CI 3.15–19.34), pregnancy occurrence (RR 3.72; 95% CI 2.14–6.44), and offspring number (SMD 1.57; 95% CI 1.04–2.09).

Conclusion

BM-MSC-based therapy consistently improved hormonal, follicular, and reproductive outcomes in preclinical POI models. More well-designed, standardized, and adequately controlled studies to confirm these findings are warranted.

Systematic review registration: CRD42023449053