The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis

The human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion polymorphism was implicated in recurrent implantation failure (RIF), but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of HLA-G 14-bp polymorphism on RIF risk.

A comprehensive search for relevant articles was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for HLA-G 14-bp polymorphism and RIF were calculated.

A total of five studies were included. In studies conducted in RIF patients and controls who had at least one spontaneous pregnancy, meta-analysis revealed no statistically significant association between the HLA-G 14-bp polymorphism and RIF in allele contrast and all genetic models in the overall population, but significant association was found in the population of Caucasian origin under allele contrast (OR = 1.73, 95% CI, 1.20, 2.50) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 3.09, 95% CI, 1.43, 6.65). In studies conducted in RIF patients and controls who had successful pregnancy following IVF-ET, the meta-analysis showed that there was statistically significant association between the HLA-G 14 bp polymorphism and RIF in allele contrast (OR = 1.74, 95% CI, 1.13, 2.67) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 10.20, 95% CI, 2.47, 42.14) and dominant model (OR = 4.34, 95% CI, 1.72, 10.92). No publication bias was found in the present studies.

This meta-analysis suggested that the HLA-G 14-bp insertion allele may increase the risk of RIF in Caucasians. Further studies with large sample size of different ethnic populations are necessary.