Evaluation of Th1‐Th2 Balance in Patients With Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta‐Analysis

ABSTRACT Objective Unexplained recurrent spontaneous abortion (URSA) poses a major challenge in reproductive medicine, with increasing evidence of maternal immune dysregulation. This systematic review and meta‐analysis assessed differences in T helper (Th) 1 and Th2 cell frequencies and their ratio between women with URSA and healthy fertile controls. Methods A comprehensive search of PubMed, Scopus, and Web of Science (WoS), up to October 2024, included studies evaluating peripheral blood Th subsets by flow cytometry. Results Meta‐analyses were performed for Th1(IFN‐γ), Th1(TNF‐α), Th2(IL‐4), Th2(IL‐10), and Th1/Th2 ratios. Th1(IFN‐γ) frequencies were significantly higher in URSA (mean difference [MD] = 2.31, 95% CI = 0.30–4.33, p = 0.02), while Th2(IL‐4) levels were lower (MD = −0.51, 95% CI = −0.91 to −0.11, p = 0.01). No significant differences were observed for Th1(TNF‐α) (SMD = 0.25, 95% CI = −0.06 to 0.55, p = 0.11) and Th2(IL‐10) (SMD = −0.28, 95% CI = −0.62 to 0.05, p = 0.10). The Th1(IFN‐γ)/Th2(IL‐4) ratio was significantly elevated (MD = 5.37, 95% CI = 1.47–9.27, p = 0.007), reflecting a shift toward a Th1‐dominant immune profile. Conclusions These findings support the role of Th1/Th2 imbalance in URSA and suggest its potential value as a diagnostic or prognostic marker.