Jakubowicz Daniela J, Essah Paulina A, Seppälä Markku, Jakubowicz Salomon, Baillargeon Jean-Patrice, Koistinen Riitta, Nestler John E
Hospital de Clinicas Caracas, and Central University of Venezuela, Caracas 1040, Venezuela.
J Clin Endocrinol Metab. 2004 Feb;89(2):833-9. doi: 10.1210/jc.2003-030975.
The polycystic ovary syndrome (PCOS) is associated with an increased rate of early pregnancy loss (EPL). Hyperinsulinemia is an independent risk factor for EPL and has been found to decrease levels of glycodelin and IGF binding protein-1 (IGFBP-1), two major endometrial proteins. We hypothesized that serum glycodelin IGFBP-1 concentrations would be reduced in women with PCOS during the first trimester of pregnancy. Fasting serum insulin, glycodelin, and IGFBP-1 were measured, and oral glucose tolerance tests were performed in 72 women with PCOS and 62 normal women. Each woman was seen once and assigned to one of three gestational groups: wk 3-5, 6-8, and 9-11. The insulin sensitivity index during oral glucose tolerance test was lower in women with PCOS compared with normal women throughout the first trimester (P < 0.0001). Both serum glycodelin and IGFBP-1 were markedly lower in women with PCOS (for glycodelin: wk 3-5, P < 0.0001; wk 6-8, P = 0.03; wk 9-11, P = 0.19; and for IGFBP-1: wk 3-5 and 6-8, P < 0.0001; wk 9-11, P = 0.0003). Comparing women with PCOS who experienced EPL with those who did not, serum glycodelin was significantly lower during wk 3-8 (P < 0.02) and serum IGFBP-1 during wk 9-11 (P = 0.003). During the first trimester, serum glycodelin and IGFBP-1 concentrations are markedly decreased in PCOS, implicating endometrial epithelial and stromal dysfunction during periimplantation and early pregnancy as a possible mechanism for EPL in PCOS. These decreases are likely to be secondary to hyperinsulinemia and reduced insulin sensitivity.
多囊卵巢综合征(PCOS)与早期妊娠丢失(EPL)率增加有关。高胰岛素血症是EPL的一个独立危险因素,并且已发现其会降低两种主要的子宫内膜蛋白——糖蛋白1和胰岛素样生长因子结合蛋白-1(IGFBP-1)的水平。我们假设,在妊娠的前三个月,PCOS女性血清中的糖蛋白1和IGFBP-1浓度会降低。对72名PCOS女性和62名正常女性测量了空腹血清胰岛素、糖蛋白1和IGFBP-1,并进行了口服葡萄糖耐量试验。每位女性只接受一次检查,并被分配到三个妊娠组之一:第3 - 5周、第6 - 8周和第9 - 11周。在整个妊娠早期,PCOS女性在口服葡萄糖耐量试验期间的胰岛素敏感性指数低于正常女性(P < 0.0001)。PCOS女性的血清糖蛋白1和IGFBP-1均显著较低(糖蛋白1:第3 - 5周,P < 0.0001;第6 - 8周,P = 0.03;第9 - 11周,P = 0.19;IGFBP-1:第3 - 5周和第6 - 8周,P < 0.0001;第9 - 11周,P = 0.0003)。将经历EPL的PCOS女性与未经历EPL的女性进行比较,在第3 - 8周期间血清糖蛋白1显著较低(P < 0.02),在第9 - 11周期间血清IGFBP-1较低(P = 0.003)。在妊娠早期,PCOS患者血清糖蛋白1和IGFBP-1浓度显著降低,这表明着床期和妊娠早期子宫内膜上皮和间质功能障碍可能是PCOS患者发生EPL的一种机制。这些降低可能继发于高胰岛素血症和胰岛素敏感性降低。