Hostname: page-component-745bb68f8f-hvd4g Total loading time: 0 Render date: 2025-01-15T18:49:51.782Z Has data issue: false hasContentIssue false
  • English
  • Français

COMPLICATIONS OF PREGNANCY IN WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

Published online by Cambridge University Press:  23 June 2011

MALLIKA AZIZIA  and
PAUL HARDIMAN
MALLIKA AZIZIA
Affiliation:
Department of Obstetrics and Gynaecology, The Royal Free Hospital, Pond Street, London NW3 2PF
PAUL HARDIMAN*
Affiliation:
Institute for Women's Health, University College London (Royal Free Campus), Rowland Hill Street London NE3 2PF
*
Institute for Women's Health, University College London (Royal Free Campus), Rowland Hill Street, London NW3 2PF, United Kingdom E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Extract

Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting around 5–8% of women of reproductive age. It has a variable clinical spectrum including hyperandrogenism, menstrual abnormalities, polycystic ovaries and metabolic features like diabetes mellitus, obesity and dyslipidaemia. The manifestation of PCOS and its impact especially on reproductive function and pregnancy are profoundly affected by associated features of obesity/raised body mass index and metabolic syndrome.

Type
Research Article
Information
Fetal and Maternal Medicine Review , Volume 22 , Issue 3 , August 2011 , pp. 188 - 206
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1Azziz, R, Woods, KS, Reyna, R, Key, TJ, Knochenhauer, ES, Yildiz, BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89: 2745–749.Google Scholar
2Franks, S.Polycystic ovary syndrome. N Engl J Med 1995; 333: 853–61.CrossRefGoogle ScholarPubMed
3Escobar-Morreale, HF, San Millan, JL. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 2007; 18: 266–72.Google Scholar
4Sam, S, Dunaif, A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab 2003; 14: 365–70.Google Scholar
5Moran, LJ, Misso, ML, Wild, RA, Norman, RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010; 16: 347–63.Google Scholar
6Zawadzki, J, Dunaif, A. In: Dunaif, A, Givens, J, Haseltine, F, Merriam, G, (eds) Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Boston, Blackwell Scientific 1992; 377.Google Scholar
7Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.Google Scholar
8Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41–47.Google Scholar
9Azziz, R, Carmina, E, Dewailly, D, Diamanti-Kandarakis, E, Escobar-Morreale, HF, Futterweit, W, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91: 4237–45.Google Scholar
10Diamanti-Kandarakis, E, Panidis, D. Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS. Clin Endocrinol (Oxf). 2007; 67: 735–42.Google Scholar
11Pehlivanov, B, Orbetzova, M. Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population. Gynecol Endocrinol 2007; 23: 604–609.Google Scholar
12Shroff, R, Syrop, CH, Davis, W, Van Voorhis, BJ, Dokras, A. Risk of metabolic complications in the new PCOS phenotypes based on the Rotterdam criteria. Fertil Steril 2007; 88: 1389–395.CrossRefGoogle ScholarPubMed
13Welt, CK, Gudmundsson, JA, Arason, G, Adams, J, Palsdottir, H, Gudlaugsdottir, G, et al. Characterizing discrete subsets of polycystic ovary syndrome as defined by the Rotterdam criteria: the impact of weight on phenotype and metabolic features. J Clin Endocrinol Metab 2006; 91: 4842–848.Google Scholar
14Dewailly, D, Catteau-Jonard, S, Reyss, AC, Leroy, M, Pigny, P. Oligoanovulation with polycystic ovaries but not overt hyperandrogenism. J Clin Endocrinol Metab 2006; 91: 3922–927.CrossRefGoogle Scholar
15Barber, TM, Wass, JA, McCarthy, MI, Franks, S. Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007; 66: 513–17.CrossRefGoogle ScholarPubMed
16Belosi, C, Selvaggi, L, Apa, R, Guido, M, Romualdi, D, Fulghesu, AM, et al. Is the PCOS diagnosis solved by ESHRE/ASRM 2003 consensus or could it include ultrasound examination of the ovarian stroma? Hum Reprod 2006; 21: 3108–115.CrossRefGoogle ScholarPubMed
17Hsu, MI, Liou, TH, Chou, SY, Chang, CY, Hsu, CS. Diagnostic criteria for polycystic ovary syndrome in Taiwanese Chinese women: comparison between Rotterdam 2003 and NIH 1990. Fertil Steril. 2007; 88: 727–29.Google Scholar
18Chae, SJ, Kim, JJ, Choi, YM, Hwang, KR, Jee, BC, Ku, SY, et al. Clinical and biochemical characteristics of polycystic ovary syndrome in Korean women. Hum Reprod 2008; 23: 1924–931.Google Scholar
19Dunaif, A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18: 774–800.Google ScholarPubMed
20Bremer, AA, Miller, WL. The serine phosphorylation hypothesis of polycystic ovary syndrome: a unifying mechanism for hyperandrogenemia and insulin resistance. Fertil Steril 2008; 89: 1039–48.CrossRefGoogle ScholarPubMed
21Poretsky, L, Cataldo, NA, Rosenwaks, Z, Giudice, LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999; 20: 535–82.CrossRefGoogle ScholarPubMed
22Dunaif, A, Wu, X, Lee, A, Diamanti-Kandarakis, E. Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS). Am J Physiol Endocrinol Metab 2001; 281: E392–99.Google Scholar
23Ehrmann, DA, Sturis, J, Byrne, MM, Karrison, T, Rosenfield, RL, Polonsky, KS. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 96: 520–27.CrossRefGoogle ScholarPubMed
24Ioannidis, A, Ikonomi, E, Dimou, NL, Douma, L, Bagos, PG. Polymorphisms of the insulin receptor and the insulin receptor substrates genes in polycystic ovary syndrome: a Mendelian randomization meta-analysis. Mol Genet Metab 2010; 99: 174–83.CrossRefGoogle ScholarPubMed
25Nestler, JE, Jakubowicz, DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996; 335: 617–23.Google Scholar
26Dunaif, A, Scott, D, Finegood, D, Quintana, B, Whitcomb, R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81: 3299–306.Google ScholarPubMed
27Ek, I, Arner, P, Ryden, M, Holm, C, Thorne, A, Hoffstedt, J, et al. A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes 2002; 51: 484–92.CrossRefGoogle ScholarPubMed
28Zang, H, Carlstrom, K, Arner, P, Hirschberg, AL. Effects of treatment with testosterone alone or in combination with estrogen on insulin sensitivity in postmenopausal women. Fertil Steril 2006; 86: 136–44.Google Scholar
29Webber, LJ, Stubbs, S, Stark, J, Trew, GH, Margara, R, Hardy, K, et al. Formation and early development of follicles in the polycystic ovary. Lancet 2003; 362: 1017–21.Google Scholar
30Kenigsberg, S, Bentov, Y, Chalifa-Caspi, V, Potashnik, G, Ofir, R, Birk, OS. Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients. Mol Hum Reprod 2009; 15: 89–103.CrossRefGoogle ScholarPubMed
31Cresswell, JL, Barker, DJ, Osmond, C, Egger, P, Phillips, DI, Fraser, RB. Fetal growth, length of gestation, and polycystic ovaries in adult life. Lancet 1997; 350: 1131–55.CrossRefGoogle ScholarPubMed
32Amato, P, Simpson, JL. The genetics of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004; 18: 707–18.CrossRefGoogle ScholarPubMed
33Legro, RS, Driscoll, D, Strauss, JF 3rd, Fox, J, Dunaif, A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A 1998; 95: 14956–960.Google Scholar
34Franks, S, McCarthy, MI, Hardy, K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl 2006; 29: 278–85.Google Scholar
35Escobar-Morreale, HF, Luque-Ramirez, M, San Millan, JL. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev 2005; 26: 251–82.Google Scholar
36Goodarzi, MO. Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med 2008; 26: 5–13.Google Scholar
37Stewart, DR, Dombroski, BA, Urbanek, M, Ankener, W, Ewens, KG, Wood, JR, et al. Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J Clin Endocrinol Metab 2006; 91: 4112–117.Google Scholar
38Wood, JR, Ho, CK, Nelson-Degrave, VL, McAllister, JM, Strauss, JF 3rd. The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling. J Reprod Immunol 2004; 63: 51–60.CrossRefGoogle ScholarPubMed
39Jansen, E, Laven, JS, Dommerholt, HB, Polman, J, van Rijt, C, Van Den Hurk, C, et al. Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients. Mol Endocrinol 2004; 18: 3050–63.Google Scholar
40Oksjoki, S, Soderstrom, M, Inki, P, Vuorio, E, Anttila, L. Molecular profiling of polycystic ovaries for markers of cell invasion and matrix turnover. Fertil Steril 2005; 83: 937–44.Google Scholar
41Wood, JR, Dumesic, DA, Abbott, DH, Strauss, JF 3rd. Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis. J Clin Endocrinol Metab 2007; 92: 705–13.Google Scholar
42Palmert, MR, Gordon, CM, Kartashov, AI, Legro, RS, Emans, SJ, Dunaif, A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 1017–23.Google Scholar
43Ehrmann, DA, Barnes, RB, Rosenfield, RL, Cavaghan, MK, Imperial, J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999; 22: 141–46.Google Scholar
44Legro, RS, Kunselman, AR, Dodson, WC, Dunaif, A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84: 165–69.Google Scholar
45Carmina, E, Orio, F, Palomba, S, Cascella, T, Longo, RA, Colao, AM, et al. Evidence for altered adipocyte function in polycystic ovary syndrome. Eur J Endocrinol 2005; 152: 389–94.Google Scholar
46Toulis, KA, Goulis, DG, Farmakiotis, D, Georgopoulos, NA, Katsikis, I, Tarlatzis, BC, et al. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update 2009; 15: 297–307.Google Scholar
47Kirchengast, S, Huber, J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 2001; 16: 1255–260.Google Scholar
48Vrbikova, J, Cibula, D, Dvorakova, K, Stanicka, S, Sindelka, G, Hill, M, et al. Insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89: 2942–945.Google Scholar
49Dunaif, A, Segal, KR, Futterweit, W, Dobrjansky, A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38: 1165–674.Google Scholar
50Diamanti-Kandarakis, E, Papavassiliou, AG, Kandarakis, SA, Chrousos, GP. Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 2007; 18: 280–85.Google Scholar
51Koh, KK, Han, SH, Quon, MJ. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol 2005; 46: 1978–85.Google Scholar
52Hu, FB, Meigs, JB, Li, TY, Rifai, N, Manson, JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 2004; 53: 693–700.Google Scholar
53Bhattacharya, SM. Prevalence of metabolic syndrome in women with polycystic ovary syndrome, using two proposed definitions. Gynecol Endocrinol 2010; 26: 516–20.Google Scholar
54Ehrmann, DA, Liljenquist, DR, Kasza, K, Azziz, R, Legro, RS, Ghazzi, MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 48–53.Google Scholar
55Weerakiet, S, Bunnag, P, Phakdeekitcharoen, B, Wansumrith, S, Chanprasertyothin, S, Jultanmas, R, et al. Prevalence of the metabolic syndrome in Asian women with polycystic ovary syndrome: using the International Diabetes Federation criteria. Gynecol Endocrinol 2007; 23: 153–60.Google Scholar
56Veltman-Verhulst, SM, van Rijn, BB, Westerveld, HE, Franx, A, Bruinse, HW, Fauser, BC, et al. Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk. Menopause 2010; 17: 990–96.Google Scholar
57Paradisi, G, Steinberg, HO, Hempfling, A, Cronin, J, Hook, G, Shepard, MK, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 2001; 103: 1410–415.Google Scholar
58Talbott, EO, Guzick, DS, Sutton-Tyrrell, K, McHugh-Pemu, KP, Zborowski, JV, Remsberg, KE, et al. Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 2000; 20: 2414–421.Google Scholar
59Christian, RC, Dumesic, DA, Behrenbeck, T, Oberg, AL, Sheedy, PF 2nd, Fitzpatrick, LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 2562–568.CrossRefGoogle ScholarPubMed
60Wild, S, Pierpoint, T, McKeigue, P, Jacobs, H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000; 52: 595–600.CrossRefGoogle ScholarPubMed
61Dahlgren, E, Janson, PO, Johansson, S, Lapidus, L, Oden, A. Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992; 71: 599–604.Google Scholar
62Catalano, PM, Tyzbir, ED, Wolfe, RR, Calles, J, Roman, NM, Amini, SB, et al. Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol 1993; 264: E60–67.Google Scholar
63Catalano, PM, Huston, L, Amini, SB, Kalhan, SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol 1999; 180: 903–16.Google Scholar
64Homko, CJ, Sivan, E, Reece, EA, Boden, G. Fuel metabolism during pregnancy. Semin Reprod Endocrinol 1999; 17: 119–25.CrossRefGoogle ScholarPubMed
65Radon, PA, McMahon, MJ, Meyer, WR. Impaired glucose tolerance in pregnant women with polycystic ovary syndrome. Obstet Gynecol 1999; 94: 194–97.Google Scholar
66Toulis, KA, Goulis, DG, Kolibianakis, EM, Venetis, CA, Tarlatzis, BC, Papadimas, I. Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Fertil Steril 2009; 92: 667–77.Google Scholar
67Barbieri, RL, Hornstein, MD. Hyperinsulinemia and ovarian hyperandrogenism. Cause and effect. Endocrinol Metab Clin North Am 1988; 17: 685–703.Google Scholar
68Vanky, E, Stridsklev, S, Skogoy, K, Kleggetveit, O, Hjelle, S, Brandis, PV, et al. PCOS – what matters in early pregnancy?– data from a cross-sectional, multicenter study. Acta Obstet Gynecol Scand 2010; 90: 398–404.CrossRefGoogle Scholar
69Spaanderman, ME, Meertens, M, van Bussel, M, Ekhart, TH, Peeters, LL. Cardiac output increases independently of basal metabolic rate in early human pregnancy. Am J Physiol Heart Circ Physiol 2000; 278: H1585–588.Google Scholar
70Spaanderman, ME, Van Beek, E, Ekhart, TH, Van Eyck, J, Cheriex, EC, De Leeuw, PW, et al. Changes in hemodynamic parameters and volume homeostasis with the menstrual cycle among women with a history of preeclampsia. Am J Obstet Gynecol 2000; 182: 1127–34.Google Scholar
71Lakhani, K, Seifalian, AM, Hardiman, P. Impaired carotid viscoelastic properties in women with polycystic ovaries. Circulation 2002; 106: 81–85.Google Scholar
72Hu, S, Leonard, A, Seifalian, A, Hardiman, P. Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum Reprod 2007; 22: 1532–539.Google Scholar
73Rivarola, MA, Forest, MG, Migeon, CJ. Testosterone, androstenedione and dehydroepiandrosterone in plasma during pregnancy and at delivery: concentration and protein binding. J Clin Endocrinol Metab 1968; 28: 34–40.Google Scholar
74Mizuno, M, Lobotsky, J, Lloyd, CW, Kobayashi, T, Murasawa, Y. Plasma androstenedione and testerone during pregnancy and in the newborn. J Clin Endocrinol Metab 1968; 28: 1133–142.CrossRefGoogle ScholarPubMed
75McClamrock, HD, Adashi, EY. Gestational hyperandrogenism. Fertil Steril 1992; 57: 257–74.Google ScholarPubMed
76Sir-Petermann, T, Maliqueo, M, Angel, B, Lara, HE, Perez-Bravo, F, Recabarren, SE. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod 2002; 17: 2573–579.CrossRefGoogle ScholarPubMed
77Serin, IS, Kula, M, Basbug, M, Unluhizarci, K, Gucer, S, Tayyar, M. Androgen levels of preeclamptic patients in the third trimester of pregnancy and six weeks after delivery. Acta Obstet Gynecol Scand 2001; 80: 1009–13.Google Scholar
78Veltman-Verhulst, SM, van Haeften, TW, Eijkemans, MJ, de Valk, HW, Fauser, BC, Goverde, AJ. Sex hormone-binding globulin concentrations before conception as a predictor for gestational diabetes in women with polycystic ovary syndrome. Hum Reprod 2010; 25: 3123–128.Google Scholar
79Kauffman, RP, Baker, TE, Baker, VM, DiMarino, P, Castracane, VD. Endocrine and metabolic differences among phenotypic expressions of polycystic ovary syndrome according to the 2003 Rotterdam consensus criteria. Am J Obstet Gynecol 2008; 198: 670 e1–7.CrossRefGoogle Scholar
80Brassard, M, AinMelk, Y, Baillargeon, JP. Basic infertility including polycystic ovary syndrome. Med Clin North Am 2008; 92: 1163–92, xi.Google Scholar
81Palomba, S, Falbo, A, Russo, T, Tolino, A, Orio, F, Zullo, F. Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertil Steril Oct; 94: 1805–811.CrossRefGoogle Scholar
82Boomsma, CM, Eijkemans, MJ, Hughes, EG, Visser, GH, Fauser, BC, Macklon, NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006: 12: 673–83.Google Scholar
83Boomsma, CM, Fauser, BC, Macklon, NS. Pregnancy complications in women with polycystic ovary syndrome. Semin Reprod Med 2008; 26: 72–84.CrossRefGoogle ScholarPubMed
84Sagle, M, Bishop, K, Ridley, N, Alexander, FM, Michel, M, Bonney, RC, et al. Recurrent early miscarriage and polycystic ovaries. BMJ 1988; 297: 1027–1028.Google Scholar
85Fedorcsak, P, Storeng, R, Dale, PO, Tanbo, T, Abyholm, T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. Acta Obstet Gynecol Scand 2000; 79: 43–48.Google Scholar
86Van Der Spuy, ZM, Dyer, SJ. The pathogenesis of infertility and early pregnancy loss in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004; 18: 755–71.Google Scholar
87Bohrer, M, Kemmann, E. Risk factors for spontaneous abortion in menotropin-treated women. Fertil Steril 1987; 48: 571–75.Google Scholar
88Hamilton-Fairley, D, Kiddy, D, Watson, H, Paterson, C, Franks, S. Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. Br J Obstet Gynaecol 1992; 99: 128–31.Google Scholar
89Glueck, CJ, Wang, P, Fontaine, RN, Sieve-Smith, L, Tracy, T, Moore, SK. Plasminogen activator inhibitor activity: an independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism 1999; 48: 1589–95.Google Scholar
90Repaci, A, Gambineri, A, Pasquali, R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 2011; 335: 30–41.Google Scholar
91Repaci, A, Gambineri, A, Pasquali, R. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol Endocrinol 2010; 26: 281–96.Google Scholar
92Moradi, S, Mollabashi, M, Jafarian Kerman, SR. Relation between C-reactive protein and body mass index in patients with polycystic ovarian syndrome. Gynecol Endocrinol 2011; 27: 480–85.Google Scholar
93OrioF, Jr. F, Jr., Palomba, S, Cascella, T, Di Biase, S, Manguso, F, Tauchmanova, L, et al. The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 2–5.Google Scholar
94Diamanti-Kandarakis, E, Paterakis, T, Alexandraki, K, Piperi, C, Aessopos, A, Katsikis, I, et al. Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 2006; 21: 1426–431.Google Scholar
95Jakubowicz, DJ, Iuorno, MJ, Jakubowicz, S, Roberts, KA, Nestler, JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 524–29.CrossRefGoogle ScholarPubMed
96Glueck, CJ, Wang, P, Goldenberg, N, Sieve-Smith, L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod 2002; 17: 2858–864.Google Scholar
97Vanky, E, Stridsklev, S, Heimstad, R, Romundstad, P, Skogoy, K, Kleggetveit, O, et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab 2010; 95: E448–55.Google Scholar
98Altieri, P, Gambineri, A, Prontera, O, Cionci, G, Franchina, M, Pasquali, R. Maternal polycystic ovary syndrome may be associated with adverse pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol 2010; 149: 31–36.Google Scholar
99Legro, RS, Castracane, VD, Kauffman, RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv 2004; 59: 141–54.Google Scholar
100Holte, J, Gennarelli, G, Wide, L, Lithell, H, Berne, C. High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus. J Clin Endocrinol Metab 1998; 83: 1143–50.Google Scholar
101Diamant, YZ, Rimon, E, Evron, S. High incidence of preeclamptic toxemia in patients with polycystic ovarian disease. Eur J Obstet Gynecol Reprod Biol 1982; 14: 199–204.Google Scholar
102de Vries, MJ, Dekker, GA, Schoemaker, J. Higher risk of preeclampsia in the polycystic ovary syndrome. A case control study. Eur J Obstet Gynecol Reprod Biol. 1998; 76: 91–95.Google Scholar
103Fridstrom, M, Nisell, H, Sjoblom, P, Hillensjo, T. Are women with polycystic ovary syndrome at an increased risk of pregnancy-induced hypertension and/or preeclampsia? Hypertens Pregnancy 1999; 18: 73–80.Google Scholar
104Kashyap, S, Claman, P. Polycystic ovary disease and the risk of pregnancy-induced hypertension. J Reprod Med 2000; 45: 991–94.Google Scholar
105Redman, CW, Sargent, IL. Immunology of pre-eclampsia. Am J Reprod Immunol 2010; 63: 534–43.Google Scholar
106Pawelczyk, L, Spaczynski, RZ, Banaszewska, B, Duleba, AJ. Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2004; 113: 209–13.Google Scholar
107Mikola, M, Hiilesmaa, V, Halttunen, M, Suhonen, L, Tiitinen, A. Obstetric outcome in women with polycystic ovarian syndrome. Hum Reprod 2001; 16: 226–29.Google Scholar
108Weerakiet, S, Srisombut, C, Rojanasakul, A, Panburana, P, Thakkinstian, A, Herabutya, Y. Prevalence of gestational diabetes mellitus and pregnancy outcomes in Asian women with polycystic ovary syndrome. Gynecol Endocrinol 2004; 19: 134–40.Google Scholar
109Alshammari, A, Hanley, A, Ni, A, Tomlinson, G, Feig, DS. Does the presence of polycystic ovary syndrome increase the risk of obstetrical complications in women with gestational diabetes? J Matern Fetal Neonatal Med 2010; 23: 545–49.Google Scholar
110Finnstrom, O, Kallen, B, Lindam, A, Nilsson, E, Nygren, KG, Olausson, PO. Maternal and child outcome after in-vitro fertilization-a review of 25 years population based data from Sweden. Acta Obstet Gynecol Scand 2011; 90: 494–500.CrossRefGoogle ScholarPubMed
111Thatcher, SS, Jackson, EM. Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin. Fertil Steril 2006; 85: 1002–1009.Google Scholar
112Gilbert, C, Valois, M, Koren, G. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril 2006; 86: 658–63.Google Scholar
113Allen, VM, Armson, BA, Wilson, RD, Blight, C, Gagnon, A, Johnson, JA, et al. Teratogenicity associated with pre-existing and gestational diabetes. J Obstet Gynaecol Can 2007; 29: 927–44.CrossRefGoogle ScholarPubMed
114Heard, MJ, Pierce, A, Carson, SA, Buster, JE. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril 2002; 77: 669–73.Google Scholar
115Glueck, CJ, Phillips, H, Cameron, D, Sieve-Smith, L, Wang, P. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril 2001; 75: 46–52.Google Scholar
116Melo, AS, Vieira, CS, Barbieri, MA, Rosa, ESAC, Silva, AA, Cardoso, VC, et al. High prevalence of polycystic ovary syndrome in women born small for gestational age. Hum Reprod 2010; 25: 2124–131.Google Scholar
117Sir-Petermann, T, Hitchsfeld, C, Maliqueo, M, Codner, E, Echiburu, B, Gazitua, R, et al. Birth weight in offspring of mothers with polycystic ovarian syndrome. Hum Reprod 2005; 20: 2122–126.CrossRefGoogle ScholarPubMed
118Barker, DJ, Osmond, C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986; 1: 1077–1081.Google Scholar
119Hattersley, AT, Tooke, JE. The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. Lancet 1999; 353: 1789–792.Google Scholar
120Palomba, S, Falbo, A, Russo, T, Battista, L, Tolino, A, Orio, F, et al. Uterine blood flow in pregnant patients with polycystic ovary syndrome: relationships with clinical outcomes. BJOG 2010; 117: 711–21.Google Scholar
121Salvesen, KA, Vanky, E, Carlsen, SM. Metformin treatment in pregnant women with polycystic ovary syndrome–is reduced complication rate mediated by changes in the uteroplacental circulation? Ultrasound Obstet Gynecol 2007; 29: 433–37.Google Scholar
122Xita, N, Tsatsoulis, A. Fetal origins of the metabolic syndrome. Ann N Y Acad Sci 2010; 1205: 148–55.Google Scholar
123Barry, JA, Kay, AR, Navaratnarajah, R, Iqbal, S, Bamfo, JE, David, AL, et al. Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. J Obstet Gynaecol 2010; 30: 444–46.Google Scholar
124Anderson, H, Fogel, N, Grebe, SK, Singh, RJ, Taylor, RL, Dunaif, A. Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J Clin Endocrinol Metab 2010; 95: 2180–186.Google Scholar
125van de Beek, C, Thijssen, JH, Cohen-Kettenis, PT, van Goozen, SH, Buitelaar, JK. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure? Horm Behav 2004; 46: 663–69.Google Scholar
126Roland, AV, Nunemaker, CS, Keller, SR, Moenter, SM. Prenatal androgen exposure programs metabolic dysfunction in female mice. J Endocrinol 2010; 207: 213–23.Google Scholar
127King, AJ, Olivier, NB, Mohankumar, PS, Lee, JS, Padmanabhan, V, Fink, GD. Hypertension caused by prenatal testosterone excess in female sheep. Am J Physiol Endocrinol Metab 2007; 292: E1837–41.Google Scholar
128Eisner, JR, Barnett, MA, Dumesic, DA, Abbott, DH. Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess. Fertil Steril 2002; 77: 167–72.CrossRefGoogle ScholarPubMed
129Hickey, M, Sloboda, DM, Atkinson, HC, Doherty, DA, Franks, S, Norman, RJ, et al. The relationship between maternal and umbilical cord androgen levels and polycystic ovary syndrome in adolescence: a prospective cohort study. J Clin Endocrinol Metab 2009; 94: 3714–20.Google Scholar
130Whitehouse, AJ, Maybery, MT, Hart, R, Sloboda, DM, Stanley, FJ, Newnham, JP, et al. Free testosterone levels in umbilical-cord blood predict infant head circumference in females. Dev Med Child Neurol 2010; 52: e73–77.Google Scholar
131Whitehouse, AJ, Maybery, MT, Hart, R, Mattes, E, Newnham, JP, Sloboda, DM, et al. Fetal androgen exposure and pragmatic language ability of girls in middle childhood: implications for the extreme male-brain theory of autism. Psychoneuroendocrinology 2010; 35: 1259–264.Google Scholar
132Auyeung, B, Baron-Cohen, S, Ashwin, E, Knickmeyer, R, Taylor, K, Hackett, G. Fetal testosterone and autistic traits. Br J Psychol 2009; 100: 1–22.CrossRefGoogle ScholarPubMed
133Ingudomnukul, E, Baron-Cohen, S, Wheelwright, S, Knickmeyer, R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav 2007; 51: 597–604.Google Scholar
134Roos, N, Sahlin, L, Ekman-Ordeberg, G, Falconer, H, Kieler, H, Stephansson, O. Women with polycystic ovary syndrome (PCOS) are more likely to experience adverse pregnancy outcomes. A population-based study [Abstract]; http://humrep.oxfordjournals.org/content/25/suppl_1/i53.abstractGoogle Scholar
135Bals-Pratsch, M, Grosser, B, Seifert, B, Ortmann, O, Seifarth, C. Early onset and high prevalence of gestational diabetes in PCOS and insulin resistant women before and after assisted reproduction. Exp Clin Endocrinol Diabetes 2011 Mar 3, Epub ahead of print.Google Scholar
136Tang, T, Lord, JM, Norman, RJ, Yasmin, E, Balen, AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2009 (4):CD003053.Google Scholar
137McGovern, PG, Carson, SA, Barnhart, HX, Myers, ER, Legro, RS, Diamond, MP, et al. Medication adherence and treatment success in the National Institute of Child Health and Human Development-Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome Trial. Fertil Steril 2008; 90: 1283–286.Google Scholar
138Wassell, J, Michail, M, Soliman, N, Wardle, PG. The value of sex hormone binding globulin (SHBG) in predicting treatment response in polycystic ovary syndrome (PCOS). Clin Lab 2011; 57: 95–98.Google ScholarPubMed
139Moran, LJ, Hutchison, SK, Norman, RJ, Teede, HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2: CD007506.Google Scholar
140Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 2008; 89: 505–22.Google Scholar
141Diamanti-Kandarakis, E, Economou, F, Palimeri, S, Christakou, C. Metformin in polycystic ovary syndrome. Ann N Y Acad Sci 2010; 1205: 192–98.Google Scholar
142Clark, AM, Thornley, B, Tomlinson, L, Galletley, C, Norman, RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502–505.Google Scholar