Thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) are associated with recurrent pregnancy loss (RPL) and spontaneous abortion (SAB) alone and concurrently. The efficacy and safety of combined enoxaparin-metformin was prospectively assessed in women with PCOS with one or more previous SAB, thrombophilia, and/or hypofibrinolysis. Twenty-four white women with PCOS were studied; 23 with previous pregnancies, seven with RPL of unknown etiology (≥ three consecutive pregnancy losses <20 weeks’ gestation), two with two consecutive SABs, 13 with one SAB, and one with one live birth (HELLP syndrome). Prospectively, metformin (1.5 to 2.55 g/day) was administered before and throughout gestation, with concurrent enoxaparin (60 mg/day) throughout gestation. The 24 cases differed from 93 normal white female controls for the factor V Leiden mutation, 17% vs. 2%, Fisher’s p [pf] = .016, and for the 4G4G mutation of the plasminogen activator inhibitor-1 (PAI-1) gene (46% vs. 24%, Chi-square 4.63, p =. 031). The patients also differed from 44 normal white female controls for high levels (> 21.1 U/mL) of the PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx) (33% vs. 8%, pf =. 018), and for high factor VIII (>150%) (22% vs. 0%, pf = .037). Of the 24 women, 23 had 65 previous pregnancies without metformin or enoxaparin, with 18 live births, 46 SAB (71%), and one elective abortion. On metforminenoxaparin, the same 23 women had 26 current pregnancies (28 fetuses), with 20 live births, two normal pregnancies 13 weeks or longer, and six SAB (21%), 3.4-fold lower than previous gestations (McNemar’s S = 33.6, p <. 0001). There were no adverse maternal or fetal therapy effects. Enoxaparin-metformin reduces pregnancy loss in women with PCOS with one or more previous SAB, who also have thrombophilia and/or hypofibrinolysis.
Recurrent Pregnancy Loss in Polycystic Ovary Syndrome: Role of Hyperhomocysteinemia and Insulin Resistance
