Hu Xianyang, Huang Xixi, Yin Tingxuan, Yu Hailin, Liu Lu, Du Meirong
Laboratory of Reproduction Immunology, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, 200032, China.
Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
EClinicalMedicine. 2025 Aug 21;87:103442. doi: 10.1016/j.eclinm.2025.103442. eCollection 2025 Sep.
Recurrent spontaneous abortion (RSA) poses a significant clinical challenge for childbearing women. Cyclosporine A (CsA), first introduced by our group for RSA treatment, has gained wide clinical application in China, yet remains underutilized internationally. With this systematic review, we aimed to systematically evaluate the efficacy and safety of CsA based therapy in the management of RSA.
PubMed, Embase, Web of Science, Cochrane library, CNKI, VIP, and Wanfang databases were searched from inception to July 12, 2025. Eligible studies in English and Chinese language, involved patients with RSA and assessed CsA's effects on pregnancy outcomes were included. Risk of bias was evaluated using appropriate tools based on study design. Pooled odds ratios (ORs) were calculated via meta-analysis. Publication bias was evaluated with funnel plots. Subgroup and network meta-analysis (NMA) were conducted to assess robustness and compare relative efficacy. Primary outcomes included miscarriage rate and live birth rate as reported in clinical pregnancy outcomes. This study was registered with PROSPERO (CRD42024541367).
A total of 29 clinical studies (n = 3556 RSA patients) were included, with 22 comparing CsA-treated vs non-CsA-treated groups. The majority of studies were conducted in a Chinese population (28 = China, and 1 = Iran) as CsA therapy for RSA has not received approval outside of China. CsA therapy was associated with a lower miscarriage rate (OR, 0.37 [95% CI, 0.25-0.56]), higher live birth rate (OR, 37 2.44 [95% CI, 1.59-3.74]), and higher ongoing pregnancy rate (OR, 2.59 [95% CI, 1.54-38 4.37]). NMA revealed that CsA combined with conventional treatment, and immunotherapy (P-score: 0.147-0.275) had superior effects on miscarriage reduction compared to monotherapy (P41 score: 0.619-0.792). CsA-based combinations also remained superior to monotherapies (P-score: 0.704-0.791 vs 0.27-0.305). However, for live birth rate, the combination of conventional treatment and immunotherapy showed the greatest efficacy (P-score: 0.892).
This meta-analysis demonstrates the potential benefits of CsA therapy for pregnancy outcomes in RSA patients, particularly when combined with other therapeutic interventions. These findings require further multi-center prospective testing at an international level.
This study was supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, the Shanghai Municipal Health and Family Planning Commission, and the Shanghai Sailing Program.
复发性自然流产（RSA）给育龄妇女带来了重大的临床挑战。环孢素A（CsA）由本团队首次引入用于RSA治疗，在中国已得到广泛临床应用，但在国际上仍未得到充分利用。通过本系统评价，我们旨在系统评估基于CsA的疗法在RSA管理中的疗效和安全性。
检索了PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、维普和万方数据库，检索时间从建库至2025年7月12日。纳入英文和中文的符合条件的研究，这些研究涉及RSA患者并评估了CsA对妊娠结局的影响。根据研究设计使用适当工具评估偏倚风险。通过荟萃分析计算合并比值比（OR）。用漏斗图评估发表偏倚。进行亚组和网状荟萃分析（NMA）以评估稳健性并比较相对疗效。主要结局包括临床妊娠结局中报告的流产率和活产率。本研究已在PROSPERO（CRD42024541367）注册。
共纳入29项临床研究（n = 3556例RSA患者），其中22项比较了CsA治疗组与非CsA治疗组。由于CsA治疗RSA在中国境外未获批准，大多数研究在中国人群中进行（28项在中国，1项在伊朗）。CsA治疗与较低的流产率（OR，0.37 [95% CI，0.25 - 0.56]）、较高的活产率（OR，2.44 [95% CI，1.59 - 3.74]）和较高的持续妊娠率（OR，2.59 [95% CI，1.54 - 4.37]）相关。NMA显示，与单一疗法（P评分：0.619 - 0.792）相比，CsA联合传统治疗和免疫疗法（P评分：0.147 - 0.275）在减少流产方面具有更好的效果。基于CsA的联合疗法也仍然优于单一疗法（P评分：0.
