The role of secretome in restoring ovarian function: A systematic review and meta-analysis of in vivo studies in mice with premature ovarian insufficiency.

To evaluate the efficacy of secretomes in restoring ovarian function in premature ovarian insufficiency (POI) in a mouse model, researchers emphasizing their potential as a novel, cell-free therapy. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and included studies from four databases through December 2023. The bias risk was assessed using the tool for animal studies, which is Systematic Review Centre for Laboratory Animal Experimentation risk-of-bias. Outcomes, including the hormonal levels of estradiol (E2), anti-müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were analyzed, with statistical comparisons made between the secretome-treated and control groups. Four studies encompassing sixty mice were included. The meta-analysis showed a significant increase in E2 levels in the secretome group [mean difference (MD)=37.45, 95% confidence interval (CI): 5.78 to 69.11; p=0.02]. No significant difference in AMH levels was observed; however, a sensitivity analysis resulted in the difference becoming statistically significant (MD=1.83, 95% CI: 0.95 to 2.71; p<0.0001). Moreover, the analysis revealed a significant reduction in FSH levels in the secretome group (MD=-36.80, 95% CI: -61.91 to -11.69; p=0.004) even after the sensitivity analysis. Our findings demonstrated enhanced outcomes with secretome therapy in the management of POI. Further research, particularly involving human subjects, is necessary to validate these findings.