Decoding Genetic risk factors in Recurrent Pregnancy Loss: A comprehensive molecular and bioinformatics Investigation

Background Recurrent Pregnancy Loss (RPL) remains a multifactorial reproductive challenge involving anatomical, endocrine, immunological, and genetic anomalies. Among these, genetic abnormalities encompassing both aneuploidies and submicroscopic chromosomal alterations play a pivotal yet underutilized role in maternal, paternal, and fetal contributions. Methods DNA extracted from Product of conceptus and fetal tissue samples and Rapid aneuploidy screening with the help of QF-PCR, 30 specimens went under aCGH microarray. Bioinformatics tools were used for gene ontology and pathway enrichment analysis was used to identify potential gene-associated pathways contributing to RPL. Results An analysis of 118 specimens revealed diverse abnormalities in aneuploidy detection, including monosomy ( n  = 20) and trisomy ( n  = 16). A significant correlation was observed between advanced maternal age and aneuploidy ( p  < 0.05). In the aCGH cohort, pathogenic CNVs implicated genes such as CFHR3, TNFRSF4, UGT2B17, CD24, MSR1, and members of the pregnancy-specific glycoprotein (PSG) gene family. Functional annotation highlighted the involvement of these genes in immune regulation, endocrine function, and placental development pathways increasingly recognized as critical to pregnancy maintenance. Conclusions This study confirms association between advanced maternal age and fetal aneuploidy, candidate pathogenic CNVs contribute to RPL. Our integrative molecular approach with genetic testing and managing high-risk pregnancies and counseling affected couples. These findings Insights into molecular pathways may guide future early prenatal diagnostic and targets for future therapeutic or predictive interventions.