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.