Maternal candidate gene variants, epigenetic factors, and susceptibility to idiopathic recurrent pregnancy loss: A systematic review

Background Recurrent pregnancy loss is defined as the loss of two or more pregnancies and is a distressing condition for couples. Objective To investigate the relationship between variants in the candidate susceptibility genes and epigenetic factors to identify risk factors for idiopathic recurrent pregnancy loss (iRPL). Search Strategy A systematic literature search was performed using PubMed, Google Scholar, ScienceDirect, and Scopus databases. Insilico analysis was carried out using ShinyGO and STRING software. Selection Criteria Research papers examining the association between variations in genetic and epigenetic factors and iRPL. Data Collection and Analysis Data were independently extracted by two authors. Main Results In total, 83 research papers were finally selected for the present study. Among all the genes involved in the pathogenesis of recurrent pregnancy loss, polymorphisms in IL superfamily genes, VEGF, ESR, and MTHFR were the most investigated. Conclusion Polymorphisms in angiogenesis, immune tolerance, and thrombophilia pathway genes, which occur independently or synergistically, may lead to various complications during fetal development. Identification of multi‐allele risk variants and epigenetic factors in women will be helpful in the identification of high‐risk pregnancies. Prospero Registration Number Prospero CRD42021287315. Synopsis Investigation of maternal genetic/epigenetic risk factors for idiopathic recurrent pregnancy loss could help to identify high‐risk pregnancies, and couples could be counseled and managed accordingly.