Therapeutic efficacy of Cyclosporine A in recurrent spontaneous abortion: a meta-analysis and network meta-analysis incorporating Chinese and English language studies.

Background: 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. Methods: 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). Findings: 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). Interpretation: 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. Funding: 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.