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

BackgroundRecurrent pregnancy loss is defined as the loss of two or more pregnancies and is a distressing condition for couples. ObjectiveTo investigate the relationship between variants in the candidate susceptibility genes and epigenetic factors to identify risk factors for idiopathic recurrent pregnancy loss (iRPL). Search StrategyA systematic literature search was performed using PubMed, Google Scholar, ScienceDirect, and Scopus databases. Insilico analysis was carried out using ShinyGO and STRING software. Selection CriteriaResearch papers examining the association between variations in genetic and epigenetic factors and iRPL. Data Collection and AnalysisData were independently extracted by two authors. Main ResultsIn 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. ConclusionPolymorphisms 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 NumberProspero CRD42021287315.