The effectiveness of stem cell‑derived extracellular vesicles therapy for intrauterine adhesions: a meta-analysis of preclinical studies.

BACKGROUND: The therapeutic potential of stem cell-derived extracellular vesicles (EVs) for intrauterine adhesions (IUA) has attracted increasing preclinical investigation, yet a comprehensive and up-to-date meta-analysis is currently lacking. Before moving forward with clinical applications, it is essential to fully understand the impact of stem cell-derived EVs on IUA. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science were searched up to May 19th 2025. Trial sequential analysis was conducted to evaluate outcomes, while sensitivity analysis and publication bias assessment were conducted using Stata 14. RESULTS: Across 26 studies (899 animals), our analyses have uncovered several important findings as the following: stem cell-derived EVs significantly improved the number of endometrial glands (SMD = 3.78; 95% CI: 2.62 ~ 4.93; P < 0.00001); endometrial thickness (SMD = 2.65; 95% CI: 1.90 ~ 3.40; P < 0.00001) and the number of embryos (SMD = 2.00; 95% CI: 1.02 ~ 2.97; P = 0.0004); fibrosis reduction (SMD = -3.25; 95% CI: -4.24~ -2.26; P < 0.00001) in IUA animal models. EVs downregulated fibrosis markers (TGF-β1, α-SMA, Col-1) and upregulated vascularization (VEGF) and proliferation (Ki67) genes. CONCLUSIONS: Stem cell-derived EVs demonstrate safety and efficacy in treating IUA animal models, with potential improvements in fertility outcomes.