Genomic Profile of Asian Women with Recurrent Implantation Failure: A Systematic Review

Recurrent implantation failure is a major challenge in assisted reproductive technology, affecting up to 15% of women undergoing in vitro fertilization. Although several hypotheses for the pathogenesis of the condition have been proposed, many RIF cases remain unexplained. Studies have suggested potential genomic contributions to RIF. However, most studies have focused on non-Asian or mixed populations, leaving gaps in understanding population-specific genetic risks. This systematic review aimed to characterize the genomic profile of Asian women with RIF and identify candidate genetic variants associated with increased susceptibility. A comprehensive search of PubMed, Scopus, OVID, and ScienceDirect up to June 2025 for case-control studies analyzing genetic polymorphisms in Asian women diagnosed with RIF. Five eligible studies were identified, comprising 566 women with RIF and 732 fertile controls from East and West Asia. Variants in genes related to angiogenesis (VEGF), RNA interference (AGO2), lipid transport (APOE), folate metabolism (MTHFR, TYMS/TS), and DNA repair (MDM2) were identified. Consistent associations were observed for VEGF polymorphisms (rs833061, rs25648, rs1570360) and AGO2 rs4961280, reported up to two-fold higher risk of RIF, while APOE ε4 carriage was linked to a similar increase. Combined MTHFR and TYMS genotypes also showed additive effects on RIF susceptibility. Genetic variants affecting angiogenesis, RNA processing, and lipid metabolism may contribute to RIF pathogenesis in Asian women. VEGF emerged as the most consistently associated gene, highlighting the importance of endometrial vascular remodeling in implantation success. Larger, multi-ethnic genomic studies with functional validation, together with a standardized definition of RIF, are warranted to clarify these associations and advance personalized reproductive medicine in ART.