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

Fertil Steril. 2019 Sep;112(3):577-585.e3. doi: 10.1016/j.fertnstert.2019.05.003. Epub 2019 Jul 4.


Objective: 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.

Design: 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.

Setting: Academic hospitals and private clinics.

Patient(s): Women who experienced RPL spontaneously or after undergoing IVF.

Intervention(s): 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.

Result(s): 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).

Conclusion(s): Women of European countries with the HLA-G 14 bp insertion/insertion genotype have a significantly higher prevalence of RPL.

Keywords: HLA-G 14 bp polymorphism; meta-analysis; recurrent pregnancy loss.

Publication types

  • Meta-Analysis

MeSH terms

  • Abortion, Habitual / epidemiology*
  • Abortion, Habitual / genetics*
  • Case-Control Studies
  • Europe / epidemiology
  • Female
  • Genetic Association Studies / methods*
  • HLA-G Antigens / genetics*
  • Humans
  • Polymorphism, Genetic / genetics*
  • Pregnancy


  • HLA-G Antigens