Abstract
Background: Recurrent implantation failure (RIF) is the failure of embryos to implant more than two times in a
given individual. There is debate about a precise definition for RIF, but we consider more than two implantation
failures for individuals who undergo in vitro fertilization-embryo transfer (IVF-ET) to constitute RIF. There are many
potential reasons for RIF, including embryonic factors, immunological factors, uterine factors, coagulate factors, and
genetic factors. Genetic variation has been suggested as one of the contributing factors leading to RIF, and a
number of single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF. The recent
elucidation of miRNA functions has provided new insight into the regulation of gene expression.
Methods: We investigated associations between polymorphisms in four miRNAs and RIF in 346 Korean women:
118 patients with RIF and 228 controls. We determined the genotypes of the miRNAs in the study participants by
polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. We analyzed the effects of
genotypes, allele combinations, and environmental and clinical factors on the risk of RIF.
Results: The miR-25 T/miR-125aT/miR-222G (odds ratio (OR), 0.528; 95% confidence interval (CI), 0.282–0.990; P =
0.044) and miR-25 T/miR-125aT allele combinations were associated with a reduced risk of RIF. The miR-25 T/miR-
32C/miR-125aC/miR-222 T allele combination was associated with an increased risk of RIF. The miR-222GT+TT
genotypes interacted with high prothrombin time (≥ 12 s) to increase the risk of RIF.
Conclusions: MicroRNA polymorphisms are significantly different between patients that experience RIF and healthy
controls. Combinations of microRNA polymorphisms were associated with the risk of RIF. Interactions between
environmental factors and genotypes increased the risk of RIF in Korean women