Abstract: ObjectiveTo explore the association between polymorphisms of miRNA biogenesis related gene DICER, DROSHA, RAN and unexplained recurrent spontaneous abortion (URSA) in Chinese women. MethodsWe recruited 217 patients with URSA (URSA group) and 390 healthy controls who were fertile women with history of more than one successful pregnancy outcome (control group) from June 2013 to December 2015 in the West China Second University Hospital of Sichuan University. The control group was recruited from regular physical examination and prepregnancy check for women of childbearing age during the same period. A case-control study was performed to analyze polymorphism of miRNA machinery genes, including DICER rs3742330, DROSHA rs10719, RAN rs14035, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. ResultsThe frequencies of genotypes and alleles of DICER rs3742330, DROSHA rs10719, and RAN rs14035 showed no difference between URSA patients and control group (all P＞0.05). DICER rs3742330/DROSHA rs10719 GG/TC+TT combinations were synergistically associated with increased URSA risk 〔odds ratio (OR)=1.657, 95% confidence interval (CI)=1.006-2.731, P=0.047〕. Although DICER rs3742330/RAN rs14035 GG / TT+TC combinations was significantly higher in the URSA group than in the control group, there was no statistical significance (OR=1.977, 95%CI=0.956-4.087, P=0.066). However, DROSHA10719/RAN14035 TT+TC/TT+TC had no significant correlation with URSA (OR=0.958, 95%CI=0.679-1.353, P=0.808). ConclusionOur study demonstrated the relationship between URSA development and combined genotype.