Association of GPR30 Genetic Variants with Recurrent Implantation Failure: A Case-Control Study Comparing Fertile Women, ART Success and RIF Patients

GPR30 (G-protein coupled receptor 30) plays a key role in regulating reproductive processes, particularly through estrogen signaling. Previous studies have linked GPR30 polymorphisms to female reproductive disorders such as infertility, recurrent pregnancy loss, endometriosis, leiomyoma, and breast or ovarian cancers. This study investigated, for the first time, the association between two GPR30 polymorphisms (rs3808350 and rs3808351) and recurrent implantation failure (RIF) in infertile women referred to the Royan Institute. A total of 300 Iranian women were divided into three groups: 100 with RIF, 100 fertile controls, and 100 women with successful ART outcomes as a second control group. The frequencies of rs3808350 and rs3808351 polymorphisms were analyzed using ARMS-PCR, and confirmed by Sanger sequencing. Statistical analysis was performed using Chi-square and Fisher's exact tests (p ≤ 0.05). For rs3808350, genotype frequencies significantly differed across the three groups (p < 0.001), though allele frequencies did not (p = 0.107). Further comparison between the RIF and ART+ groups showed significant differences in both genotype (p = 0.005) and allele (p = 0.041) frequencies. For rs3808351, significant differences in both genotype and allele frequencies were observed among all groups (p < 0.001). These findings suggest that rs3808350 and rs3808351 polymorphisms in the GPR30 gene are significantly associated with increased risk of recurrent implantation failure.