Recurrent Second‐Trimester Euploid Pregnancy Loss Associated With Maternal–Paternal HLA Compatibility: Review Based on a Case Report of Immune‐Mediated Failure

PROBLEM: Recurrent pregnancy loss (RPL) is often unexplained, and emerging evidence supports a potential alloimmune contribution in a subset of patients. Excessive maternal-paternal HLA compatibility has been proposed as a mechanism impairing maternal-fetal immune tolerance. This review, based on a representative clinical case, examines the role of HLA sharing in recurrent euploid pregnancy loss. METHOD OF STUDY: A narrative review of current literature on alloimmune mechanisms in RPL, including classical and non-classical HLA pathways and KIR-HLA interactions, was conducted. A clinical case involving recurrent second-trimester euploid losses despite multimodal immunotherapy was used to contextualize these mechanisms. RESULTS: The patient experienced multiple losses of chromosomally normal fetuses despite treatment with intravenous immunoglobulin, corticosteroids, hydroxychloroquine, progesterone, aspirin, and low-molecular-weight heparin. HLA typing demonstrated allele sharing across four of five loci, suggesting markedly reduced immunogenetic diversity at the maternal-fetal interface. This pattern aligned with proposed mechanisms of impaired trophoblast-immune signaling and inadequate tolerance induction. CONCLUSIONS: Excessive maternal-paternal HLA compatibility may contribute to recurrent euploid pregnancy loss through disruption of maternal-fetal immune tolerance. This case-based review underscores the need for individualized immunologic assessment and further research into targeted therapies for alloimmune-mediated reproductive failure.