School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Gynecology, Evangelisches Krankenhaus Herne ،Ruhr-Universität Bochum, Herne, Germany.
J Ovarian Res. 2024 Oct 14;17(1):200. doi: 10.1186/s13048-024-01513-1.
Primary ovarian insufficiency (POI) manifests with hormonal imbalances, menstrual irregularities, follicle loss, and infertility. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as a promising treatment for POI. This systematic review aims to assess the effects of MSC-EVs on follicle number, hormonal profile, and fertility in POI animal models.
A systematic search of PubMed, Scopus, and Web of Science databases up to December 14th, 2023 was conducted. Two reviewers independently conducted screening, risk of bias assessment, and data extraction. Meta-analysis was performed to analyze treatment versus control outcomes using a random effects model. Publication bias was assessed using Egger's regression test and sensitivity analysis was assessed using the leave-one-out method. Subgroup analyses and meta-regressions were conducted based on EV source, induction model, type of animal, study quality, administration route, administration frequency and route, and dose.
a total of 29 studies were included. MSC-EVs treatment significantly increased total follicle count (SMD, (95CI), p-value; 3.56, (0.91, 6.21), < 0.001), including primordial (SMD, (95CI), p-value; 2.86, (1.60, 4.12), < 0.001), primary (SMD, (95CI), p-value; 3.17, (2.28, 4.06), < 0.001), mature (SMD, (95CI), p-value; 2.26, (1.02, 3.50), < 0.001), and antral follicles (SMD, (95CI), p-value; 2.44, (1.21, 3.67), < 0.001). Administration frequency and route did not affect this outcome, but EV source affected primordial, primary, secondary and antral follicle count. Additionally, MSC-EVs treatment elevated anti-müllerian hormone (SMD, (95CI); 3.36, (2.14, 4.58)) and estradiol (SMD, (95CI); 3.19, (2.20, 4.17)) levels while reducing follicle stimulating hormone levels (SMD, (95CI); -2.68, (-4.42, -0.94)). Unlike EV source, which had a significant impact on all three hormones, administration frequency, route, and EV dose did not affect this outcome. Moreover, treatment increased offspring number (SMD, (95CI); 3.70, (2.17, 5.23)) and pregnancy odds (OR, (95CI); 10.25, (4.29, 24.46)) compared to controls. Publication bias and a high level of heterogeneity was evident in all analyses, except for the analysis of the pregnancy odds. However, sensitivity analysis indicated that all of the analyses were stable.
MSC-EVs therapy shows promise for POI treatment, potentially facilitating clinical translation. However, Further research is warranted to optimize methodology and assess side effects.
原发性卵巢功能不全（POI）表现为激素失衡、月经不规律、卵泡丢失和不孕。间充质干细胞衍生的细胞外囊泡（MSC-EVs）作为治疗 POI 的一种有前途的方法正在出现。本系统评价旨在评估 MSC-EVs 对 POI 动物模型中卵泡数量、激素谱和生育能力的影响。
对 PubMed、Scopus 和 Web of Science 数据库进行了系统搜索，截至 2023 年 12 月 14 日。两名审查员独立进行筛选、偏倚风险评估和数据提取。使用随机效应模型分析治疗与对照组的结果进行 meta 分析。使用 Egger 回归检验评估发表偏倚，使用逐个剔除法评估敏感性分析。根据 EV 来源、诱导模型、动物类型、研究质量、给药途径、给药频率和途径以及剂量进行亚组分析和荟萃回归。
共纳入 29 项研究。MSC-EVs 治疗可显著增加总卵泡数（SMD，（95CI），p 值；3.56，（0.91，6.21），<0.001），包括原始卵泡（SMD，（95CI），p 值；2.86，（1.60，4.12），<0.001）、初级卵泡（SMD，（95CI），p 值；3.17，（2.28，4.06），<0.001）、成熟卵泡（SMD，（95CI），p 值；2.26，（1.02，3.50），<0.001）和窦卵泡（SMD，（95CI），p 值；2.44，（1.21，3.67），<0.001）。给药频率和途径并不影响这一结果，但 EV 来源影响原始卵泡、初级卵泡、次级卵泡和窦卵泡计数。此外，MSC-EVs 治疗可提高抗苗勒管激素（SMD，（95CI）；3.36，（2.14，4.58））和雌二醇（SMD，（95CI）；3.19，（2.20，4.17））水平，同时降低卵泡刺激素水平（SMD，（95CI）；-2.68，（-4.42，-0.94））。与对所有三种激素都有显著影响的 EV 来源不同，给药频率、途径和 EV 剂量并不影响这一结果。此外，与对照组相比，治疗组的后代数量（SMD，（95CI）；3.70，（2.17，5.23））和妊娠几率（OR，（95CI）；10.25，（4.29，24.46））增加。除了妊娠几率分析外，所有分析均存在发表偏倚和高度异质性，但敏感性分析表明所有分析均稳定。
MSC-EVs 治疗 POI 有一定的疗效，可能促进临床转化。但是，需要进一步研究来优化方法和评估副作用。
