Immunogenetic factors in recurrent pregnancy loss: The role of human leukocyte antigen polymorphisms and autoimmune mechanisms

Recurrent pregnancy loss, defined as two or more pregnancy losses before 20 weeks of gestation, remains unexplained in nearly 50% of cases despite comprehensive evaluation. It is a multifactorial condition that involves uterine, endocrine, thrombophilic, genetic, environmental, and immunological factors. Increasing evidence supports a role for immune dysregulation, particularly autoimmunity. Human leukocyte antigen polymorphisms have received growing attention as immunogenetic factors that may contribute to recurrent pregnancy loss through modulation of maternal–fetal immune tolerance. This review examines the immunogenetic landscape of recurrent pregnancy loss, with an emphasis on autoimmune disorders and associations between specific human leukocyte antigen polymorphisms and disease risk. These include classical class I human leukocyte antigen polymorphisms (A, B, C), non-classical class I polymorphisms (G, F, E), and class II polymorphisms (DQ, DP, DR). Clarification of these associations may provide insight into immune-mediated pregnancy complications and underscores the need for further research to define the underlying etiology of recurrent pregnancy loss. Such advances may support the development of personalized diagnostic and therapeutic strategies.