Recurrent Miscarriage and the Role of Genetic Thrombophilic Mutations

Recurrent miscarriage (RM), defined as the loss of ≥3 pregnancies affects 1% of the population. Maternal age and previous reproductive history are independent risk factors for this condition. Traditionally, the aetiology of RM has been divided into chromosomal, anatomical, endocrinological, infective, environmental and immunological causes. Approximately 40% of couples investigated will have unexplained RM as no putative cause will be found after routine investigation. In the last decade, thrombophilia has emerged as aetiology of RM. The evidence for a thrombotic basis for RM comes from (i) histological evidence of placental infarction and intervillus thrombosis in products of conception from women with RM; (ii) the primary antiphospholipid syndrome - an acquired thrombophilia and (iii) the discovery of genetic thrombophilic mutations in the last decade and their variable association with RM. Factor V Leiden, Prothrombin G20210A and Methylenetetrahydrofolate reductase (MTHFR) C677T are the most common genetic thrombophilic mutations known. More recently, the concept of fetal thrombophilia in the aetiology of adverse pregnancy outcome has emerged. This review addresses the evidence pointing towards thrombophilia as an aetiological factor in RM, available prospective data and the emerging concept of the role of fetal thrombophilia and its association with adverse pregnancy outcome.