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DOI: 10.1055/s-0030-1269883
© 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
Publication History
received 18.08.2010
first decision 23.10.2010
accepted 23.11.2010
Publication Date:
03 March 2011 (online)
![](https://www.thieme-connect.de/media/eced/201106/lookinside/thumbnails/10.1055-s-0030-1269883-1.jpg)
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
- 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
- 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
- 4 Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005; 352 1223-1236
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 12 Kim H, Toyofuku Y, Lynn FC. et al . Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med. 2010; 16 804-808
- 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
- 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
- 15 Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003; 327 951-953
- 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
- 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
- 18 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care. 1999; 22 1463-1470
- 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
- 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
- 21 Mikola M, Hiilesmaa V, Halttunen M. et al . Obstetric outcome in women with polycystic ovarian syndrome. Hum Reprod. 2001; 16 226-229
- 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
- 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
- 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
- 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
- 26 Radon PA, McMahon MJ, Meyer WR. Impaired glucose tolerance in pregnant women with polycystic ovary syndrome. Obstet Gynecol. 1999; 94 194-197
- 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
- 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
- 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
- 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
- 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
- 32 Urman B, Sarac E, Dogan L. et al . Pregnancy in infertile PCOD patients. Complications and outcome. J Reprod Med. 1997; 42 501-505
- 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
- 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
- 35 Yemini M. Metformin use in IVF patients. http://www.ivf-worldwide.com/survey/survey-metformin-use-in-ivf-patients.html 2010;
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