Plasminogen activator inhibitor activity: An independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome

In 41 women with at least one pregnancy drawn from a group of 149 (108 neve r-pregnant) women with polycystic ovary syndrome (PCOS), our specific aim w as to determine whether hypofibrinolysis mediated by high plasminogen activ ator inhibitor activity (PAI-Fx) is an independent risk factor for miscarri age. The 41 women had 77 total pregnancies with 34 miscarriages (44%) and 4 2 live births (55%). There were 12 women with at least one pregnancy, at le ast one miscarriage, and no live births (16 pregnancies and 16 miscarriages ). There were 15 women with at least one pregnancy, no miscarriages, and at least one live birth (25 pregnancies and 28 live births). Of 12 women with only miscarriages and no live births, 67% had PAI-Fx greater than 16.4 U/m L (normals' 95th percentile), versus 29% of 15 women with no miscarriages a nd all live births (chi(2) = 3.8, P =.052). By stepwise logistic regression , the number of pregnancies (P =.0001) and PAI-Fx (P =.016) were significan t positive explanatory variables for the number of miscarriages. Age, 4G/5G polymorphisms of the PAI gene, factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) gene mutations, androstenedione, testosterone, sex hormon e-binding globulin, the Quetelet index, and fasting serum insulin and gluco se were not significant variables in the logistic regression model. In a se parate stepwise logistic regression, three nonoverlapping groups of women ( 12 with greater than or equal to 1 pregnancy, greater than or equal to 1 mi scarriage, and 0 live births, 10 with greater than or equal to 1 pregnancy, greater than or equal to 1 miscarriage, and greater than or equal to 1 liv e births, and 15 with greater than or equal to 1 pregnancy, 0 miscarriages, and greater than or equal to 1 live births) were the dependent variables. PAI-Fx was positively associated (P =.05) with the group with the worst pre gnancy outcome (greater than or equal to 1 pregnancy, greater than or equal to 1 miscarriage, and 0 live births). The 41 women with PCOS and at least one pregnancy were more likely than healthy normal controls to have heteroz ygosity and homozygosity for the 4G/5G polymorphism of the PAI-1 gene (P =. 028), but did not differ from normals for factor V Leiden (P >.10) or MTHFR (P >.09) mutations. PAI-Fx is a predominant independent significant positi ve reversible risk factor for miscarriage in women with PCOS. Copyright (C) 1999 by W.B. Saunders Company.