Introduction: Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more abortion before 20^th week of gestation. The etiology of RPL is unknown in 50% of cases, which defines as idiopathic RPL (IRPL). Immune-related embryo injuries play an important role in the occurrence of RPL. Interferon regulatory factor-5 (IRF-5) is a member of IRF family of transcription factor, acts as upstream regulatory element of inflammatory cytokines (IL-6, and TNF-α). The aim of the present study was to investigate the relationship between IRF-5 gene rs10954213 polymorphism in the occurrence of IRPL.
 
Materials & Methods: In this case- control study, blood samples were collected from 176 IRPL women with a history of at least 2 miscarriages with mean age of 34.2±10.9 years as the patient group, and 173 healthy postmenopausal women with at least two live births, and without a history of previous miscarriage (mean age±SD; 56.5±7.7 years) as the control group. Genotyping was performed using T-ARMS PCR. The data were analyzed using SPSS v.16 software.
 
Findings: The frequency of G allele was lower in cases compared to control subjects. This difference was statistically significant and supported the protective effect of this allele against miscarriage (OR: 0.7, 95%CI: 0.5-0.9, p=0.04). The frequency of G carriage genotypes (GG+GA vs. AA) in women with IRPL was lower compared to the women of the control group and showed the protective role of this allele (OR:0.45, 95%CI:0.22-0.91, p-0.02).
 
Discussion & Conclusions: Regarding the results of the present study, the rs10954213G allele of the IRF-5 gene demonstrated a protective marker against idiopathic recurrent pregnancy losses in Iranian women.