Intravenous immunoglobulin versus placebo in recurrent pregnancy loss: A systematic review and meta-analysis of randomized trials

Recurrent pregnancy loss (RPL) affects 1–2 % of fertile couples, with immunological factors increasingly implicated in unexplained cases. Currently, no convincing treatment exists. Intravenous immunoglobulin (IVIg) has been explored as a potential treatment, but results have been inconsistent. This study evaluates whether IVIg affects live birth rates in women with RPL in subsequent pregnancies. We searched PubMed, Embase, and Cochrane libraries for relevant randomized controlled trials up to March 20, 2023, and contacted authors for individual patient data. Trials involving women with two or more consecutive pregnancy losses who received IVIg or placebo before or during the first trimester were included. Primary outcomes were live birth and clinical pregnancy rates, with secondary outcomes including pregnancy loss rate, side effects, adverse events, and perinatal outcomes. Risk of bias and certainty of evidence (GRADE) were evaluated. Ten studies involving 662 women were included. The intention-to-treat analysis showed no significant difference in live birth rates between IVIg and placebo groups (RR: 1.02, 95 % CI: 0.86–1.22, p = 0.78, GRADE: moderate). However, per-protocol analysis indicated an increased live birth rate with IVIg (RR: 1.23, 95 % CI: 1.00–1.50, GRADE: low). Live birth rates after IVIg improved with the number of previous losses, especially in patients with ≥ 6 losses (RR: 5.26 (1.58–17.53)). While IVIg therapy did not show a significant improvement in live birth rates overall, future research should focus on identifying specific patient subgroups, such as those with multiple prior losses, who may benefit most from this treatment.