Evidence for intravenous immunoglobulin (IVIG) in recurrent pregnancy loss remains inconsistent. This individual patient data meta-analysis aimed to explore possible treatment-effect modification by the number of previous pregnancy losses across six randomized trials. One-stage logistic regression included treatment, number of previous losses, their interaction, maternal age, and study-specific intercepts. The estimated live birth odds ratio for each additional loss was 0.6 in the placebo group and significantly higher 0.9 in the IVIG group (ratio of odds ratios 1.50, 95% CI 1.06–2.18). These exploratory findings suggest that the effect of IVIG on live birth odds may increase with previous loss burden.
Anticentromere antibodies (ACAs) impair chromosome segregation of oocytes and embryos, contributing to repeated in vitro fertilization failure. We evaluated whether ex vivo γ-globulin supplementation of oocyte culture medium could improve reproductive outcomes without systemic administration of high-dose intravenous immunoglobulin. This prospective study enrolled women aged 30–46 years with infertility and ACA titres ≥ 1:640 undergoing intracytoplasmic sperm injection. In Phase I, 40 oocytes underwent parallel dose-ranging at 0%, 1.0%, 1.5%, and 2.0% γ-globulin. No concentration met the prespecified criterion for an unacceptable reduction in fertilization with ≥ 1 pronucleus, and 2.0% was selected for Phase II. The γ-globulin–treated cohort (n = 16) was compared with historical controls (n = 28) and age-matched ACA-negative controls. In the primary oocyte-based analysis, normal fertilization rates were similar between treatment and historical control groups, whereas treatment was associated with higher good-quality blastocyst (9.6% vs. 4.2%; risk ratio [RR], 2.28; 95% confidence interval [CI], 1.05–4.93) and live birth rates (4.0% vs. 0.4%; RR, 11.40; 95% CI, 1.35–96.58). A patient-based analysis similarly showed a higher cumulative live birth rate than in historical controls (31.3% vs. 3.6%; P = 0.018). A supplementary age-adjusted mixed-effects analysis accounting for clustering within patients and retrievals yielded a consistent but imprecise association with higher odds of live birth (adjusted OR, 12.02; 95% CI, 1.38–104.45; P = 0.024). Several oocyte-based developmental outcomes remained lower than in ACA-negative controls. These findings provide preliminary proof of concept, with potential benefit observed in isolated oocytes without immune cells. Further studies are required.
