Association of human leukocyte antigen-G 14 bp polymorphism with recurrent pregnancy loss in European countries: a meta-analysis of literature studies

Abstract

To study the controversial association between human leukocyte antigen-G (HLA-G) 14bp polymorphism and recurrent pregnancy loss (RPL). We performed a meta-analysis of studies in the literature that enrolled only women of European countries who experienced RPL spontaneously or after undergoing IVF. Systematic meta-analysis of articles published before January 2019 pertaining the association of HLA-G genotype and RPL. The search was performed in electronic databases (PubMed, Web of Science, Scopus, EMBASE), without any language or publication year restriction. Academic hospitals and private clinics. Women who experienced RPL spontaneously or after undergoing IVF. Genotyping of 14bp polymorphism (insertion/insertion, insertion/deletion, deletion/deletion) in exon 8 of the HLA-G gene. Meta-analyses of the association between HLA-G 14bp polymorphism in homozygosis (insertion/insertion) and heterozygosis (insertion/deletion) in women with RPL compared with pregnant controls with at least one live birth and no history of RPL. Ten studies were analyzed comprising 1,091 women with RPL and 808 controls without RPL. Women with RPL showed significantly higher prevalence of HLA-G 14bp insertion/insertion genotype compared with women without RPL (19.8% vs. 14.1%; odds ratio = 1.562; 95% confidence interval, 1.203-2.027), and this result was also confirmed when separately analyzing women with RPL during a spontaneous pregnancy (odds ratio, 1.562; 95% confidence interval, 1.203-2.027) and those undergoing IVF (odds ratio, 1.990; 95% confidence interval, 0.978-4.051). Women of European countries with the HLA-G 14bp insertion/insertion genotype have a significantly higher prevalence of RPL.