Comparative efficacy of immunomodulatory therapy with intravenous immunoglobulin versus placebo in idiopathic recurrent pregnancy loss

Background: Idiopathic recurrent pregnancy loss (RPL) is a clinical problem that affects a large number of women of reproductive age, with immunological dysfunction proposed as one of the underlying mechanisms. Intravenous immunoglobulin (IVIG) has been studied as an immunomodulatory therapy for idiopathic RPL, but its clinical efficacy remains uncertain. This study aims to assess the efficacy of intravenous immunoglobulin compared to placebo in improving reproductive outcomes in women with idiopathic RPL. Methods: A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. Randomized clinical trials comparing IVIG with placebo in women with idiopathic RPL were identified through a PubMed database search from January 2000 to December 2024. The primary outcomes analyzed included live birth rates, miscarriage rates, and ongoing pregnancies. Combined effect estimates were calculated using risk difference for live birth rates and odds ratio for miscarriage and ongoing pregnancies, each with 95% confidence intervals. Results: Four randomized clinical trials met the inclusion criteria. A meta-analysis showed that IVIG was associated with a small but statistically insignificant increase in live births compared with the placebo (risk difference, 0.11; 95% CI, −0.01 to 0.22; I² = 0%). IVIG therapy also showed a non-significant reduction in the risk of miscarriage (odds ratio 0.65; 95% CI 0.41–1.05; I² = 0%). No significant difference was found between groups in terms of pregnancy continuation beyond 20 weeks of gestation (odds ratio 1.26; 95% CI 0.62–2.56; I² = 0%). Conclusion: Current evidence from randomized clinical trials has not demonstrated a significant benefit of intravenous immunoglobulin compared to placebo in improving live birth rates, reducing miscarriage, or improving pregnancy continuation in women with idiopathic RPL. Although there is a trend toward favorable outcomes, the currently available data are insufficient to support the routine use of IVIG in this population. Large-scale clinical trials with robust methodological designs are needed to clarify the role of IVIG more definitively.