Abstract
Introduction To re-evaluate Lymphocyte Immunization Therapy (LIT) efficacy for unexplained recurrent pregnancy loss (uRPL) to bridge the gap between restrictive international guidelines and clinical practice Methods Following PRISMA 2020, we searched databases through August 4, 2025. Six randomized controlled trials (RCTs) involving women with uRPL and confirmed alloimmune etiology (APCA or MLR-Bf deficiency) were included. Primary outcome was live birth rate (≥24 weeks), analyzed using a random-effects model (RR) and JBI quality assessment Results LIT (paternal cells, pre-conception) was associated with a significantly higher probability of live birth (RR 1.432; 95% CI: 1.037–1.978; p=0.029). Statistical heterogeneity was high ( = 78.5%). Sensitivity analysis revealed fragility; removing specific trials (Mowbray 1985, Pandey 2004, or Li 2021) eliminated statistical significance. Adverse events were primarily localized, and neonatal security was supported by reassuring birth outcomes Conclusion Empirical LIT application remains unjustified. However, a significant therapeutic signal exists for optimized protocols in biomarker-screened cohorts. We advocate for a "Precision Medicine Blueprint" prioritizing standardized protocols and strict immunologic screening.