Department of Reproductive Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province, 410008, China.
Clinical Medicine Eight-Year Program, Xiangya Hospital, Central South University, Changsha, China.
J Ovarian Res. 2024 Sep 9;17(1):182. doi: 10.1186/s13048-024-01489-y.
There has been a significant surge in animal studies of stem cell-derived extracellular vesicles (EVs) therapy for the treatment of premature ovarian failure (POF) but its efficacy remains unknown and a comprehensive and up-to-date meta-analysis is lacking. Before clinical translation, it is crucial to thoroughly understand the overall impact of stem cell-derived EVs on POF.
PubMed, EMBASE, Cochrane Library, Web of Science were searched up to February 18, 2024. The risk of bias was evaluated according to Cochrane Handbook criteria, while quality of evidence was assessed using the SYRCLE system. The PRISMA guidance was followed. Trial sequential analysis was conducted to assess outcomes, and sensitivity analysis and publication bias analysis were performed using Stata 14.
Data from 25 studies involving 339 animals were extracted and analyzed. The analysis revealed significant findings: stem cell-derived EVs increase ovary weight (SMD = 3.88; 95% CI: 2.50 ~ 5.25; P < 0.00001; I = 70%), pregnancy rate (RR = 3.88; 95% CI: 1.94 ~ 7.79; P = 0.0001; I = 0%), count of births (SMD = 2.17; 95% CI: 1.31 ~ 3.04; P < 0.00001; I = 69%) and counts of different types of follicles. In addition, it elevates the level of AMH (SMD = 4.15; 95% CI: 2.75 ~ 5.54; P < 0.00001; I = 88%) and E2 (SMD = 2.88; 95% CI: 2.02 ~ 3.73; P < 0.00001; I = 80%) expression, while reducing FSH expression (SMD = -5.05; 95% CI: -6.60 ~ -3.50; P < 0.00001; I = 90%). Subgroup analysis indicates that the source of EVs, animal species, modeling method, administration route, and test timepoint affected efficacy. Trial sequential analysis showed that there was sufficient evidence to confirm the effects of stem cell-derived EVs on birth counts, ovarian weights, and follicle counts. However, the impact of stem cell-derived EVs on pregnancy rates needs to be further demonstrated through more animal experimental evidence.
Stem cell-derived EVs demonstrate safety and efficacy in treating POF animal models, with potential improvements in fertility outcomes.
PROSPERO registration number: CRD42024509699.
干细胞衍生细胞外囊泡（EVs）治疗卵巢早衰（POF）的动物研究显著增加，但疗效仍不清楚，也缺乏全面的最新荟萃分析。在临床转化之前，彻底了解干细胞衍生 EVs 对 POF 的整体影响至关重要。
检索 PubMed、EMBASE、Cochrane 图书馆、Web of Science 至 2024 年 2 月 18 日。根据 Cochrane 手册标准评估偏倚风险，使用 SYRCLE 系统评估证据质量。遵循 PRISMA 指南。进行试验序贯分析以评估结局，使用 Stata 14 进行敏感性分析和发表偏倚分析。
提取并分析了 25 项涉及 339 只动物的研究的数据。分析结果表明：干细胞衍生 EVs 增加卵巢重量（SMD=3.88；95%CI：2.505.25；P<0.00001；I=70%）、妊娠率（RR=3.88；95%CI：1.947.79；P=0.0001；I=0%）、产仔数（SMD=2.17；95%CI：1.313.04；P<0.00001；I=69%）和不同类型卵泡数。此外，它还提高了 AMH（SMD=4.15；95%CI：2.755.54；P<0.00001；I=88%）和 E2（SMD=2.88；95%CI：2.023.73；P<0.00001；I=80%）的水平，同时降低了 FSH 的表达（SMD=-5.05；95%CI：-6.60-3.50；P<0.00001；I=90%）。亚组分析表明，EVs 的来源、动物种类、建模方法、给药途径和检测时间点影响疗效。试验序贯分析表明，有足够的证据证实干细胞衍生 EVs 对产仔数、卵巢重量和卵泡计数的影响。然而，需要更多的动物实验证据来进一步证实干细胞衍生 EVs 对妊娠率的影响。
干细胞衍生 EVs 在治疗 POF 动物模型中具有安全性和疗效，可能改善生育结局。
PROSPERO 注册号：CRD42024509699。
