This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jakubowicz, D. J. Articles by Nestler, J. E. Search for Related Content PubMed PubMed Citation Articles by Jakubowicz, D. J. Articles by Nestler, J. E.

Effects of Metformin on Early Pregnancy Loss in the Polycystic Ovary Syndrome

Hospital de Clinicas Caracas and Central University of Venezuela (D.J.J., S.J.), Caracas 1040, Venezuela; and Departments of Medicine (M.J.I., K.A.R., J.E.N.) and Obstetrics and Gynecology (J.E.N.), Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0111

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

Abstract

Polycystic ovary syndrome is the most common form of female infertility in the United States. In addition to poor conception rates, pregnancy loss rates are high (30–50%) during the first trimester. We hypothesized that hyperinsulinemic insulin resistance contributes to early pregnancy loss in the syndrome, and that decreasing hyperinsulinemic insulin resistance with metformin during pregnancy would reduce the rate of early pregnancy loss.

We conducted a retrospective study of all women with polycystic ovary syndrome who were seen in an academic endocrinology clinic within the past 4.5 yr and who became pregnant during that time.

Sixty-five women received metformin during pregnancy (metformin group) and 31women did not (control group). The early pregnancy loss rate in the metformin group was 8.8% (6 of 68 pregnancies), as compared with 41.9% (13 of 31 pregnancies) in the control group (P < 0.001). In the subset of women in each group with a prior history of miscarriage, the early pregnancy loss rate was 11.1% (4 of 36 pregnancies) in the metformin group, as compared with 58.3% (7 of 12 pregnancies) in the control group (P = 0.002).

Metformin administration during pregnancy reduces first-trimester pregnancy loss in women with the polycystic ovary syndrome.

This article has been cited by other articles:

				Z. Veleva, A. Tiitinen, S. Vilska, C. Hyden-Granskog, C. Tomas, H. Martikainen, and J. S. Tapanainen High and low BMI increase the risk of miscarriage after IVF/ICSI and FET Hum. Reprod., April 1, 2008; 23(4): 878 - 884. [Abstract] [Full Text] [PDF]

				D. S Feig, G. G Briggs, and G. Koren Oral Antidiabetic Agents in Pregnancy and Lactation: A Paradigm Shift? Ann. Pharmacother., July 1, 2007; 41(7): 1174 - 1180. [Abstract] [Full Text] [PDF]

				J. A. Rowan and on behalf of the MiG Investigators A Trial in Progress: Gestational Diabetes: Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial) Diabetes Care, July 1, 2007; 30(Supplement_2): S214 - S219. [Full Text] [PDF]

				R. S. Legro, H. X. Barnhart, W. D. Schlaff, B. R. Carr, M. P. Diamond, S. A. Carson, M. P. Steinkampf, C. Coutifaris, P. G. McGovern, N. A. Cataldo, et al. Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome N. Engl. J. Med., February 8, 2007; 356(6): 551 - 566. [Abstract] [Full Text] [PDF]

				M. Manno, F. Tomei, and E. Marchesan Polycystic ovary-related miscarriage: should metformin be proposed to such frustrated women? Hum. Reprod., February 1, 2007; 22(2): 623 - 623. [Full Text] [PDF]

				E. Jauniaux, R. Farquharson, O. Christiansen, and N. Exalto Reply: Polycystic ovary-related miscarriage--should metformin be proposed to such frustrated women? Hum. Reprod., February 1, 2007; 22(2): 623 - 624. [Full Text] [PDF]

				E. Moll, P. M M Bossuyt, J. C Korevaar, C. B Lambalk, and F. van der Veen Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial BMJ, June 24, 2006; 332(7556): 1485. [Abstract] [Full Text] [PDF]

				R. Pasquali and A. Gambineri Insulin-sensitizing agents in polycystic ovary syndrome. Eur. J. Endocrinol., June 1, 2006; 154(6): 763 - 775. [Abstract] [Full Text] [PDF]

				G. S. Daftary and H. S. Taylor Endocrine Regulation of HOX Genes Endocr. Rev., June 1, 2006; 27(4): 331 - 355. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Aspects of type 2 diabetes and related insulin-resistant States. Diabetes Care, March 1, 2006; 29(3): 732 - 740. [Full Text] [PDF]

				R. Azziz, C. Marin, L. Hoq, E. Badamgarav, and P. Song Health Care-Related Economic Burden of the Polycystic Ovary Syndrome during the Reproductive Life Span J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4650 - 4658. [Abstract] [Full Text] [PDF]

				R. Homburg Clomiphene citrate--end of an era? a mini-review Hum. Reprod., August 1, 2005; 20(8): 2043 - 2051. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Second World Congress on the Insulin Resistance Syndrome: Mediators, pediatric insulin resistance, the polycystic ovary syndrome, and malignancy Diabetes Care, July 1, 2005; 28(7): 1821 - 1830. [Full Text] [PDF]

				S. Palomba, F. Orio Jr., A. Falbo, F. Manguso, T. Russo, T. Cascella, A. Tolino, E. Carmina, A. Colao, and F. Zullo Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4068 - 4074. [Abstract] [Full Text] [PDF]

				M.A. Checa, A. Requena, C. Salvador, R. Tur, J. Callejo, J.J. Espinos, F. Fabregues, J. Herrero, and (Reproductive Endocrinology Interest Group of the Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome Hum. Reprod. Update, July 1, 2005; 11(4): 375 - 390. [Abstract] [Full Text] [PDF]

				C. Ortega-Gonzalez, S. Luna, L. Hernandez, G. Crespo, P. Aguayo, G. Arteaga-Troncoso, and A. Parra Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1360 - 1365. [Abstract] [Full Text] [PDF]

				M. van Wely, N. Bayram, F. van der Veen, and P. Bossuyt Reply to: Are laparoscopic ovarian diathermy and gonadotropin administration the only therapeutic second-steps in clomiphene-citrate resistant women with polycystic ovary syndrome? Hum. Reprod., November 1, 2004; 19(11): 2683 - 2683. [Full Text] [PDF]

				P. Fedorcsak, P. O. Dale, R. Storeng, G. Ertzeid, S. Bjercke, N. Oldereid, A. K. Omland, T. Abyholm, and T. Tanbo Impact of overweight and underweight on assisted reproduction treatment Hum. Reprod., November 1, 2004; 19(11): 2523 - 2528. [Abstract] [Full Text] [PDF]

				S. Kashyap, G. A. Wells, and Z. Rosenwaks Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome Hum. Reprod., November 1, 2004; 19(11): 2474 - 2483. [Abstract] [Full Text] [PDF]

				C. J. Glueck, P. Wang, N. Goldenberg, and L. Sieve Pregnancy Loss, Polycystic Ovary Syndrome, Thrombophilia, Hypofibrinolysis, Enoxaparin, Metformin Clinical and Applied Thrombosis/Hemostasis, October 1, 2004; 10(4): 323 - 334. [Abstract] [PDF]

				S. Palomba, F. Orio Jr., L. G. Nardo, A. Falbo, T. Russo, D. Corea, P. Doldo, G. Lombardi, A. Tolino, A. Colao, et al. Metformin Administration Versus Laparoscopic Ovarian Diathermy in Clomiphene Citrate-Resistant Women with Polycystic Ovary Syndrome: A Prospective Parallel Randomized Double-Blind Placebo-Controlled Trial J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4801 - 4809. [Abstract] [Full Text] [PDF]

				N. Brettenthaler, C. De Geyter, P. R. Huber, and U. Keller Effect of the Insulin Sensitizer Pioglitazone on Insulin Resistance, Hyperandrogenism, and Ovulatory Dysfunction in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3835 - 3840. [Abstract] [Full Text] [PDF]

				E. Vanky, K.A. Salvesen, R. Heimstad, K.J. Fougner, P. Romundstad, and S.M. Carlsen Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study Hum. Reprod., August 1, 2004; 19(8): 1734 - 1740. [Abstract] [Full Text] [PDF]

				S. Ten and N. Maclaren Insulin Resistance Syndrome in Children J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2526 - 2539. [Abstract] [Full Text] [PDF]

				C.J. Glueck, N. Goldenberg, J. Pranikoff, M. Loftspring, L. Sieve, and P. Wang Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy Hum. Reprod., June 1, 2004; 19(6): 1323 - 1330. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Definitions of the Insulin Resistance Syndrome: The 1st World Congress on the Insulin Resistance Syndrome Diabetes Care, March 1, 2004; 27(3): 824 - 830. [Full Text] [PDF]

				C.J. Glueck, N. Goldenberg, P. Wang, M. Loftspring, and A. Sherman Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy Hum. Reprod., March 1, 2004; 19(3): 510 - 521. [Abstract] [Full Text] [PDF]

				D. J. Jakubowicz, P. A. Essah, M. Seppala, S. Jakubowicz, J.-P. Baillargeon, R. Koistinen, and J. E. Nestler Reduced Serum Glycodelin and Insulin-Like Growth Factor-Binding Protein-1 in Women with Polycystic Ovary Syndrome during First Trimester of Pregnancy J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 833 - 839. [Abstract] [Full Text] [PDF]

				M. T. Sheehan Polycystic Ovarian Syndrome: Diagnosis and Management Clin. Med. Res., February 1, 2004; 2(1): 13 - 27. [Abstract] [Full Text] [PDF]

				V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]

				C. J. Glueck, A. Moreira, N. Goldenberg, L. Sieve, and P. Wang Pioglitazone and metformin in obese women with polycystic ovary syndrome not optimally responsive to metformin Hum. Reprod., August 1, 2003; 18(8): 1618 - 1625. [Abstract] [Full Text] [PDF]

				M. Filicori, G. E. Cognigni, and W. Ciampaglia Effects of LH on oocyte yield and developmental competence Hum. Reprod., June 1, 2003; 18(6): 1357 - 1358. [Full Text] [PDF]

				R. L. Barbieri Metformin for the Treatment of Polycystic Ovary Syndrome Obstet. Gynecol., April 1, 2003; 101(4): 785 - 793. [Abstract] [Full Text] [PDF]

				D. Cermik, B. Selam, and H. S. Taylor Regulation of HOXA-10 Expression by Testosterone in Vitro and in the Endometrium of Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 238 - 243. [Abstract] [Full Text] [PDF]

				L. Ibanez and F. de Zegher Low-dose combination of flutamide, metformin and an oral contraceptive for non-obese, young women with polycystic ovary syndrome Hum. Reprod., January 1, 2003; 18(1): 57 - 60. [Abstract] [Full Text] [PDF]

				L. A. Stadtmauer, B. C. Wong, and S. Oehninger Should patients with polycystic ovary syndrome be treated with metformin?: Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction Hum. Reprod., December 1, 2002; 17(12): 3016 - 3026. [Abstract] [Full Text] [PDF]

				C. J. Glueck, P. Wang, N. Goldenberg, and L. Sieve-Smith Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin Hum. Reprod., November 1, 2002; 17(11): 2858 - 2864. [Abstract] [Full Text] [PDF]

				E. Seli and A. J. Duleba Should patients with polycystic ovarian syndrome be treated with metformin? Hum. Reprod., September 1, 2002; 17(9): 2230 - 2236. [Abstract] [Full Text] [PDF]

				J. E. Nestler Should patients with polycystic ovarian syndrome be treated with metformin?: An enthusiastic endorsement Hum. Reprod., August 1, 2002; 17(8): 1950 - 1953. [Abstract] [Full Text] [PDF]