Genetic markers for inherited thrombophilia related pregnancy loss and implantation failure in Indian population – implications for diagnosis and clinical management

Aim The biology of recurrent pregnancy loss and recurrent implantation failure (RPL-RIF) is complex with multi-factorial etiology, with defective thrombosis being one of the most important and highly prevalent causes. The role of several thrombophilia related genes and variants associated with RPL-RIF is widely reported, and this study aimed to identify the risk associated with these genes in the Indian population.Methods Next generation sequencing (NGS) was employed for the current study. NGS enables sequencing of multiple genes, identification of new variants, and establishment of genetic correlations with reproductive failure in diverse population groups. The present NGS based study evaluates association of twenty-nine genotypes of ten coagulation pathway genes (F2, F5, F13, MTR, MTRR, MTHFR, ANXA5, PROZ, SERPINE1 and VEGFA) with RPL-RIF in 540 female subjects − 474 patients with early recurrent pregnancy loss, late pregnancy loss, pregnancy complications in late gestation and recurrent implantation failure, with 66 controls.Results The results emphasize inclusion of genotypes of seven thrombophilia genes (MTHFR, MTRR, MTR, ANXA5, PROZ, SERPINE1, VEGFA) for diagnosis of inherited thrombophilia risk for RPL-RIF in Indian population, as against the common practice of testing limited to F2, F5 and MTHFR genes.Conclusion Deriving risk magnitude from Combined Risk Analysis and interpretation of high-risk haplotypes are crucial components for evidence based personalized management such as selection of drugs and dosage, and prenatal or pre-implantation recommendations, for high-risk patients in fertility and obstetric clinics.