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Reduced Serum Glycodelin and Insulin-Like Growth Factor-Binding Protein-1 in Women with Polycystic Ovary Syndrome during First Trimester of Pregnancy

Hospital de Clinicas Caracas (D.J.J.) and Central University of Venezuela (D.J.J., S.J.), Caracas 1040, Venezuela; Departments of Medicine (P.A.E., J.E.N.) and Obstetrics and Gynecology (J.E.N.), Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298; Department of Clinical Chemistry (M.S.), Biomedicum, University Central Hospital, and Department of Obstetrics and Gynecology (R.K.), Biomedicum, Helsinki University Central Hospital, Helsinki SF-00290, Finland; and Department of Medicine (J.-P.B.), Université de Sherbrooke, Sherbrooke, Canada J1H 5N4

Address all correspondence and requests for reprints to: John E. Nestler, M.D., Medical College of Virginia, P.O. Box 980111, Virginia Commonwealth University, Richmond, Virginia 23298-0111. E-mail: nestler{at}hsc.vcu.edu.

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.

This work was supported in part by National Institutes of Health Grants K12DA 14041-03 (to P.A.E.) and K24HD40237 (to J.E.N.) and grants from the Finnish Cancer Center Foundation (to M.S.), the University of Helsinki (to R.K.), and the Helsinki University Central Hospital Research Fund (to R.K.).

Abbreviations: EPL, Early pregnancy loss; hCG, human chorionic gonadotropin; IGFBP-1, IGF binding protein-1; ISI, insulin sensitivity index; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome.

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