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

The human leukocyte antigen-G (HLA-G) circulate in maternal blood and persist throughout pregnancy. Our meta-analysis reported a significantly higher prevalence of recurrent pregnancy loss (RPL) in European women carrying HLA-G 14 bp insertion polymorphism in homozygosis.

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Volume 112, Issue 3, Pages 577–585.e3


Marcello Monti, M.Sc., Ph.D., Roberta Lupoli, M.D., Ph.D., Loredana Maria Sosa Fernandez, M.D., Ph.D., Ferdinando Cirillo, M.Sc., Matteo Nicola Dario Di Minno, M.D., Ph.D.



To study the controversial association between human leukocyte antigen-G (HLA-G) 14 bp 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 14 bp polymorphism (insertion/insertion, insertion/deletion, deletion/deletion) in exon 8 of the HLA-G gene.

Main Outcome Measure(s)

Meta-analyses of the association between HLA-G 14 bp 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 14 bp 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 14 bp insertion/insertion genotype have a significantly higher prevalence of RPL.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.