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

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.