Maad Rayan Publishing Company Biomedical Research Bulletin 2980-9924 3 4 2025 12 29 Lymphocyte Immunization Therapy for Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis 158 167 10.34172/biomedrb.9093 EN Shahla Danaei Mehrabad https://orcid.org/0000-0002-2800-1975 Zahra Attarilar Nasim Mahdavi Ali Pourmohammad Faezeh Mohseni Mohammadreza Behvarz Morteza Atayi https://orcid.org/0000-0001-5128-7185 Journal Article 10.34172/biomedrb.9093 2025 05 19 2025 06 23 Introduction: This study aimed to re-evaluate lymphocyte immunization therapy (LIT) efficacy for unexplained recurrent pregnancy loss (uRPL) to bridge the gap between restrictive international guidelines and clinical practices. Methods: Following PRISMA 2020, PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus databases were searched through August 4, 2025. Six randomized controlled trials involving women with uRPL and confirmed alloimmune etiology (anti-paternal cytotoxic antibodies or mixed lymphocyte reaction–blocking factor deficiency) underwent investigation. The primary outcome was the live birth rate (≥24 weeks) that was analyzed using a random-effects model (risk ratio) and the Joanna Briggs Institute quality assessment. Results: LIT (paternal cells, pre-conception) was associated with a significantly higher probability of live birth (RR: 1.432; 95% confidence interval: 1.037–1.978; P=0.029). Statistical heterogeneity was high (78.5%). Sensitivity analysis revealed fragility, and removing three specific trials eliminated statistical significance. Finally, 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. Overall, we advocate for a "Precision Medicine Blueprint" that prioritizes standardized protocols and strict immunologic screening.