Thrombophilia and Recurrent Pregnancy Loss

Abstract

Recurrent pregnancy loss (RPL) is usually defined as the loss of three or more consecutive pregnancies before 20 weeks of gestation. Within this definition is a large and heterogeneous group of patients with many different causes of miscarriage. RPL is a common clinical problem that occurs in approximately 1 % of reproductive-aged women. However, this frequency increases up to 5% when clinicians define RPL as two or more losses of pregnancy. In addition, epidemiological investigations have demonstrated that the frequency of subsequent pregnancy loss is 24% after two pregnancy losses, 30% after three and 40% after four successive pregnancy losses. In many cases, the etiology is unknown, but several hypotheses have been proposed, including chromosomal and uterine anatomic abnormalities, endometrial infections, endocrine abnormalities, antiphospholipid syndrome, inherited thrombophilias, alloimmune causes, genetic factors, exposure to environmental factors and unexplained causes. Recently, it has become clear that prothrombotic changes are associated with a substantial proportion of these fetal losses. Therefore, the role of thrombophilias in RPL has generated a great deal of interest. This heterogeneous group of disorders results in increased venous and arterial thrombosis. Although some thrombophilic states in RPL may be acquired such as antiphospholipid antibody syndrome (APAS), most are heritable such as hyperhomocyteinemia, activated protein C resistance, deficiencies in proteins C and S, mutations in prothrombin, and mutations in antithrombin III. Data suggest that women with thrombophilia have an increased risk of pregnancy loss and other serious obstetric complications, including placental abruption, pre-eclampsia, intrauterine growth restriction and intrauterine fetal death. Recent attention has focused on thrombophilic factors that might be associated with pregnancy complications, including early pregnancy loss. Additionally pregnancy complications including idiopathic fetal loss are thought to result from placental under perfusion due to occlusive events, including thrombosis of placental vessels. Thrombosis of placental vessels is multicausal in nature and may involve both acquired and inherited risk factors, leading to RPL. It has been reported that genetic tendencies to thrombosis may also be associated with recurrent pregnancy loss. The three most common genetic markers for thrombophilia which are known to predispose to venous thrombosis are; factor V Leiden (FVL), methylenetetrahydrofolate reductase mutation (MTHFR, C677T) and prothrombin gene mutation (FII, G20210). In this chapter, we discuss the association of thrombophilia and RPL; these include important roles in management and treatment that appear to be required for normal pregnancy.