Download PDF
Exp Clin Endocrinol Diabetes 2011; 119(6): 338-342
DOI: 10.1055/s-0030-1269883
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Early Onset and High Prevalence of Gestational Diabetes in PCOS and Insulin Resistant Women Before and After Assisted Reproduction

M. Bals-Pratsch1 , B. Großer2 , B. Seifert1 , O. Ortmann3 , C. Seifarth2
  • 1Center for Reproductive Medicine, Regensburg, Germany
  • 2Practice for Endocrinology, Regensburg, Germany
  • 3University Hospital Regensburg, Department of Gynecology and Obstetrics, Regensburg
Further Information

Publication History

received 18.08.2010 first decision 23.10.2010

accepted 23.11.2010

Publication Date:
03 March 2011 (online)

Also available at
    Permissions and Reprints

Abstract

Objectives: Polycystic ovary syndrome (PCOS) and/or insulin resistance (IR) are frequent conditions in women choosing assisted reproduction techniques (ART). However, infertility work-up has to include testing of insulin sensitivity to diagnose IR. It was the aim of the study to analyze the frequency of impaired glucose tolerance (IGT) or gestational diabetes (GD) in the first weeks of gestation after ART in women receiving metformin.

Design and Methods: This study included 107 women who were seeking ART under the pretreatment of metformin for PCOS, confirmed IR, recurrent spontaneous miscarriages (RSA) or other fertility disorders. They were examined for prepregnancy health parameters (weight, glucose tolerance). When pregnancy was confirmed a 75 g oral glucose tolerance test (OGTT) was conducted between the 5th and 7th week of gestation.

Results: A high rate of GD or IGT already was observed in the first weeks of pregnancy in our cohort under metformin treatment. The predominant risk factor for diagnosed early onset of IGT or GD (58 cases) was PCOS (p=0.014). The frequency of GD was the highest in the subgroup with prepregnancy confirmed IR not fulfilling the criteria of PCOS (55%); it was 40.6% in PCOS women and 26.1% in women neither exhibiting IR nor PCOS.

Conclusions: Women seeking ART and being treated with metformin still show a very high rate of GD or IGT after achieving pregnancy by ART. Therefore in women undergoing ART screening for GD should be performed as soon as pregnancy is confirmed to avoid miscarriages due to overlooked uncontrolled glucose metabolism.

Key words

insulin resistance - polycystic ovary syndrome - gestational diabetes

References

  • 1 Anttila L, Karjala K, Penttilä RA. et al . Polycystic ovaries in women with gestational diabetes.  Obstet Gynecol. 1998;  92 13-16
    Google Scholar
  • 2 Balen AH, Tan SL, MacDougall J. et al . Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin.  Hum Reprod. 1993;  8 959-964
    Google Scholar
  • 3 Craig LB, Ke RW, Kutteh WH. Increased prevalence of insulin resistance in women with a history of recurrent pregnancy loss.  Fertil Steril. 2002;  78 487-490
    Google Scholar
  • 4 Ehrmann DA. Polycystic ovary syndrome.  N Engl J Med. 2005;  352 1223-1236
    Google Scholar
  • 5 Ewens KG, Stewart DR, Ankener W. et al . Family-based analysis of candidate genes for polycystic ovary syndrome.  J Clin Endocrinol Metab. 2010;  95 2306-2315
    Google Scholar
  • 6 Glueck CJ, Phillips H, Cameron D. et al . 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
  • 7 Glueck CJ, Wang P, Kobayashi S. et al . Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome.  Fertil Steril. 2002;  77 520-525
    Google Scholar
  • 8 Glueck CJ, Pranikoff J, Aregawi D. et al . Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome.  Fertil Steril. 2008;  89 625-634
    Google Scholar
  • 9 Jakubowicz DJ, Iuorno MJ, Jakubowicz S. et al . Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 2002;  87 524-529
    Google Scholar
  • 10 Jinno M, Kondou K, Watanabe A. et al . Improvement of pregnancy rates by low-dose metformin in IVF repeaters without polycystic ovary syndrome: its mechanism and indication.  Fertil Steril. 2008;  90 S480
    Google Scholar
  • 11 Khattab S, Mohsen IA, Foutouh IA. et al . Metformin reduces abortion in pregnant women with polycystic ovary syndrome.  Gynecol Endocrinol. 2006;  22 680-684
    Google Scholar
  • 12 Kim H, Toyofuku Y, Lynn FC. et al . Serotonin regulates pancreatic beta cell mass during pregnancy.  Nat Med. 2010;  16 804-808
    Google Scholar
  • 13 Legro RS, Kunselman AR, Dodson WC. et al . 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.  Clin Endocrinol Metab. 1999;  84 165-169
    Google Scholar
  • 14 Levran D, Shoham Z, Habib D. et al . Glucose tolerance in pregnant women following treatment for sterility.  Int J Fertil. 1990;  35 157-159
    Google Scholar
  • 15 Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis.  BMJ. 2003;  327 951-953
    Google Scholar
  • 16 Maman E, Lunenfeld E, Levy A. et al . Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously.  Fertil Steril. 1998;  70 240 –245
    Google Scholar
  • 17 McIntyre HD, Chang AM, Callaway LK. et al . Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group. Hormonal and metabolic factors associated with variations in insulin sensitivity in human pregnancy.  Diabetes Care. 2010;  33 356-360
    Google Scholar
  • 18 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing.  Diabetes Care. 1999;  22 1463-1470
    Google Scholar
  • 19 Matthews D, Hosker J, Rudenski A. et al . Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
    Google Scholar
  • 20 Mayer A, Lunenfeld E, Wiznitzer A. et al . Increased prevalence of gestational diabetes mellitus in in vitro fertilization pregnancies inadvertently conceived during treatment with long-acting triptorelin acetate.  Fertil Steril. 2005;  84 789-792
    Google Scholar
  • 21 Mikola M, Hiilesmaa V, Halttunen M. et al . Obstetric outcome in women with polycystic ovarian syndrome.  Hum Reprod. 2001;  16 226-229
    Google Scholar
  • 22 Moghetti P, Castello R, Negri C. et al . Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.  J Clin Endocrinol Metab. 2000;  85 39-146
    Google Scholar
  • 23 Nadal A, Alonso-Magdalena P, Soriano S. et al . The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes.  Mol Cell Endocrinol. 2009;  304 63-68
    Google Scholar
  • 24 Nestler JE, Jakubowicz DJ, Evans WS. et al . Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.  N Engl J Med. 1998;  338 1876-1880
    Google Scholar
  • 25 Palomba S, Falbo A, Orio Jr F. et al . Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.  Fertil Steril. 2009;  92 1646-1658
    Google Scholar
  • 26 Radon PA, McMahon MJ, Meyer WR. Impaired glucose tolerance in pregnant women with polycystic ovary syndrome.  Obstet Gynecol. 1999;  94 194-197
    Google Scholar
  • 27 Rodriguez-Pinilla E, Weber-Schöndorfer C. 2007 Oral antidiabetics. In: Schaefer C, Peters P, Miller RK (eds). Drugs during pregnancy and lactation. 1st edn. Amsterdam: Elsevier Academic Press; 2007: 401-403
    Google Scholar
  • 28 Stadtmauer LA, Wong BC, Oehninger S. Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome – beyond ovulation induction.  Hum Reprod. 2002;  17 3016-3026
    Google Scholar
  • 29 The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.  Fertil Steril. 2004a; 81: 19–25/Hum Reprod 2004;  19 41-47
    Google Scholar
  • 30 The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. . Consensus on infertility treatment related to polycystic ovary syndrome.  Fertil Steril. 2008a; 89: 505–522/Hum Reprod 2008b;  23 462-477
    Google Scholar
  • 31 Toulis KA, Goulis DG, Kolibianakis EM. et al . Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and a meta-analysis.  Fertil Steril. 2009;  92 667-677
    Google Scholar
  • 32 Urman B, Sarac E, Dogan L. et al . Pregnancy in infertile PCOD patients. Complications and outcome.  J Reprod Med. 1997;  42 501-505
    Google Scholar
  • 33 Villarroel AC, Echiburú B, Riesco V. et al . Síndrome de ovario poliquístico (SOP)y embarazo: Experiencia clínica.  Rev Med Chil. 2007;  135 1530-1538
    Google Scholar
  • 34 Wei Z, Cao Y, Cong L. et al . Effect of metformin pretreatment on pregnancy outcome of in vitro matured oocytes retrieved from women with polycystic ovary syndrome.  Fertil Steril. 2008;  90 1149-1154
    Google Scholar
  • 35 Yemini M. Metformin use in IVF patients.  http://www.ivf-worldwide.com/survey/survey-metformin-use-in-ivf-patients.html 2010; 
    Google Scholar

Correspondence

PD Dr. med. M. Bals-Pratsch

Center for Reproductive

Medicine

Hemauerstraße 1

93049 Regensburg

Germany

Phone: + 49/0941/592 060

Fax: + 49/0941/568 1091

Email: pdbalspratsch@t-online.de

      >