Efficacy and safety of tumour necrosis factor inhibitors in unexplained recurrent spontaneous abortion: A systematic review and meta-analysis.

Whether tumour necrosis factor inhibitors (TNFi) provide a safe and effective adjunctive therapy for enhancing pregnancy outcomes in women with unexplained recurrent spontaneous abortion (URSA) remains unclear. To resolve this ambiguity, we performed a meta-analysis. We systematically searched Web of Science, PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database (last search was performed on January 8, 2026). Eligible studies included randomized controlled trials (RCTs) and retrospective cohort studies (RCS) assessing TNFi in URSA patients. A random-effects model was applied. Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. A total of 529 patients from four studies were included. The results showed that adjunctive TNFi therapy significantly improved the live birth rate (OR = 2.50, 95% CI: 1.66-3.78; P < 0.0001) and reduced the miscarriage rate (OR = 0.37, 95% CI: 0.24-0.59; P < 0.0001). TNFi was associated with a slightly higher neonatal Apgar score without increasing the risk of adverse maternal or other neonatal outcomes. Exploratory subgroup analysis suggested that the benefit of TNFi on live birth rates appeared consistent regardless of concomitant intravenous immunoglobulin (IVIG) use; however, this finding requires further validation. Adding TNFi to conventional treatment may represent a promising strategy to improve live birth rates in women with URSA, with no major safety concerns identified. Nevertheless, the small number of included studies provides insufficient evidence for definitive conclusions and precludes a robust assessment of publication bias, thereby compromising the reliability of our findings. (PROSPERO: CRD420261305573).