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Successful pregnancy requires trophoblast invasion into the maternal uterine spiral arteries converting them into large dilated vessels. Microthrombi are frequently found in the vessels of the placentas from women who have experienced pregnancy loss and placental infarction has been described in the placentas of some, but not all, women who have a pregnancy loss and who have thrombophilia. Published meta-analyses suggest that factor V Leiden, prothrombin G20210A, and protein S deficiency are associated with an increased risk of recurrent early pregnancy loss and non-recurrent late pregnancy loss. Women with a history of pregnancy loss merit increased surveillance in subsequent pregnancies and should be given folic acid during pregnancy. Despite the lack of evidence from randomized, double-blind, placebo-controlled trials, many clinicians are offering women with a history of pregnancy loss found to have a heritable thrombophilia self-administered prophylactic doses of low molecular weight heparin daily low dose aspirin in subsequent pregnancies.