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

Abstract

In 41 women with at least one pregnancy drawn from a group of 149 (108 never-pregnant) women with polycystic ovary syndrome (PCOS), our specific aim was to determine whether hypofibrinolysis mediated by high plasminogen activator inhibitor activity (PAI-Fx) is an independent risk factor for miscarriage. The 41 women had 77 total pregnancies with 34 miscarriages (44%) and 42 live births (55%). There were 12 women with at least one pregnancy, at least 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/mL (normals' 95th percentile), versus 29% of 15 women with no miscarriages and all live births (chi2 = 3.8, P = .052). By stepwise logistic regression, the number of pregnancies (P = .0001) and PAI-Fx (P = .016) were significant 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 hormone-binding globulin, the Quetelet index, and fasting serum insulin and glucose were not significant variables in the logistic regression model. In a separate stepwise logistic regression, three nonoverlapping groups of women (12 with > or = 1 pregnancy, > or = 1 miscarriage, and 0 live births, 10 with > or = 1 pregnancy, > or = 1 miscarriage, and > or = 1 live births, and 15 with > or = 1 pregnancy, 0 miscarriages, and > or = 1 live births) were the dependent variables. PAI-Fx was positively associated (P = .05) with the group with the worst pregnancy outcome (> or = 1 pregnancy, > or = 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 heterozygosity 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 positive reversible risk factor for miscarriage in women with PCOS.