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Archives of Gynecology and Obstetrics

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01-11-2013 | Reproductive Medicine

Metformin treatment in different phenotypes of polycystic ovary syndrome

Authors: Marzieh Agha Hosseini, Ashraf Alleyassin, Fatemeh Sarvi, Leila Safdarian, Abas Kokab, Mehran Fanisalek

Published in: Archives of Gynecology and Obstetrics | Issue 5/2013

Abstract

Background

The aim of this study was to evaluate the effectiveness of Metformin on ovulation and eventual clinical pregnancy in different phenotypes of polycystic ovary syndrome (PCOS).

Materials and methods

A total of 359 subjects who had proven PCOS according to Rotterdam criteria were prospectively selected. Patients’ PCOS phenotypes were determined and recorded. All patients were younger than 35 years. Clinical and biochemical assays in all patients were initially obtained. Then patients were divided into two separate groups. One group received both 1,500 mg of Metformin and 1 mg of folic acid per day and the other group received only 1 mg of folic acid for a total of 2 months. Subsequently, all patients underwent ovulation stimulation with 5 mg of Letrozole per day for 5 days followed by an intra-uterine insemination. Finally, ovulation and pregnancy rates were evaluated for all four PCOS phenotypes. Effect of Metformin therapy was evaluated for each group and each phenotype.

Results

The pregnancy rate in Metformin and non-Metformin groups were, respectively, as follows: in phenotype A (39.2 vs. 33.7 %, p = 0.270), phenotype B (43.8 vs. 20 %, p = 0.210), phenotype C (44 vs. 20 %, p = 0.064), and phenotype D (36.5 vs. 28.6 %, p = 0.279).

Conclusion

Although there was a little improvement in ovulation and pregnancy rates among patients with B and C phenotypes, there was not a statistically significant difference between the two groups. Based on our study, Metformin therapy does not change the ovulation and pregnancy rate.

Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO (2004) The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745–2749PubMedCrossRef

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81:19–25

Guastella E, Longo RA, Carmina E (2010) Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes. Fertil Steril 94:2197–2201PubMedCrossRef

Wang Y, Qu J, Wu X, Hou L, Erkkola R, Wang Y (2010) Different phenotypes of polycystic ovary syndrome by Rotterdam criteria are differently steroidogenic but similarly insulin resistant. Fertil Steril 93:1362–1365PubMedCrossRef

Santana LF, de Sa MF, Ferriani RA, de Moura MD, Foss MC, dos Reis RM (2004) Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome. Gynecol Endocrinol 19:88–96PubMedCrossRef

Palomba S, Falbo A, Russo T, Orio F, Tolino A, Zullo F (2010) Systemic and local effect of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the Ovulatory response. Hum Reprod 25(1005–1013):23

Billa E, Kapolla N, Nicopoulou SC, Koukkou E, Veraki E et al (2009) Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome. Gynecol Endocrinol 25:427–434PubMedCrossRef

WHO (1999) WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press, Cambridge

Ferriman D, Gallwey JD (1961) Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 21:1440–1447PubMedCrossRef

10.

Knochenhauer ES, Key TL, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R (1998) Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 83:3078–3082PubMedCrossRef

11.

Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H (2007) Utility, limitation and pitfalls in measuring testosterone: an endocrine society position statement. J Clin Endocrinol Metab 92:405–413PubMedCrossRef

12.

Ghiringhello MT, Vieira JGH, Tachibana TT, Ferrer C, Maciel RMB, Amioka PHC, Hauache OM, de Oliveira CH, Khawali C, Reis AF (2006) Distribution of HOMA-IR in Brazilian subjects with different body mass index. Arg Bras Endocrinol Metab 50:573–574CrossRef

13.

Balen AH, Laven JSE, Tan SL, Dewailly D (2003) Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update 9:505–514PubMedCrossRef

14.

Velasquez E, Mendoza S, Hamer T et al (1994) Metformin therapy in polycystic ovarian syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia and systolic blood pressure, while facilitating normal menses and pregnancy. Metab Clin Exp 43:647–654CrossRef

15.

Moll E, van der Veen F, van Wely M (2007) The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update 13:527–537PubMedCrossRef

16.

Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH (2010) Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 1:CD003053

17.

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA et al (2007) Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 356:551–566PubMedCrossRef

18.

Creanga AA, Bradley HM, McCormick C, Witkop CT (2008) Use of metformin in polycystic ovary syndrome: a meta-analysis. Obstet Gynecol 111:959–968PubMedCrossRef

19.

Thessaloniki ESHRE/ASRM- Sponsored PCOS Consensus Workshop Group (2008) Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 89:505–522CrossRef

20.

Johnson NP, Stewart AW, Falkiner J, Farquhar CM, Milson S, Singh VP, Okonkwo QL, Buckingham KL (2010) PCOSMIC: a multi-centre randomized trial in women with polycystic ovary syndrome evaluating metformin for infertility with clomiphene. Hum Reprod 25:1675–1683PubMedCrossRef

21.

Gollay A (2008) Metformin and body weight. Int J Obes (Lond) 32:61–72CrossRef

22.

Harborne LR, Sattar N, Norman JE, Fleming R (2005) Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab 90:4593–4598PubMedCrossRef

23.

Barbieri RL (2007) Clomiphene versus metformin for ovulation induction in polycystic ovary syndrome: the winner is …. J Clin Endocrinol Metab 92:3399–3401PubMedCrossRef

24.

Lobo RA, Gysler M, March CM, Goebelsmann U, Mishell DR (1982) Clinical and laboratory predictors of clomiphene response. Fertil Steril 37:168–174PubMed

25.

Jungheim ES, Odibo AO (2010) Fertility treatment in women with polycystic ovary syndrome: a decision analysis of different oral ovulation induction agents. Fertil Steril 94(7):2659–2664PubMedCrossRef

26.

Nestler JE (2008) Metformin in the treatment of infertility in polycystic ovarian syndrome: an alternative perspective. Fertil Steril 90:14–16PubMedCrossRef

27.

Gonen Y, Casper RF (1990) Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod 5:670–674PubMed

28.

Samuel S, Elizabeth M, Jackson BS (2006) Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin. Fertil Steril 85:1002–1009CrossRef

29.

Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L (2002) Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod 17:46–52CrossRef

30.

Fruzzeti F, Perini D, Lazzarini V, Parrini D, Genazzani AR (2009) Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels. Fertil Steril 92:626–634CrossRef

31.

Badawy A, Abdel Aal A, Abulatta M (2009) Clomiphene citrate or Letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 92(3):849–852PubMedCrossRef

32.

Wu HH, Wang NM, Cheng ML, Hsieh JN (2007) A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility. Gynecol Endocrinol 23:76–81PubMedCrossRef

33.

Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R (1998) Effects of metformin on spontaneous and clomiphen induced ovulation in the polycystic ovary syndrome. N Engl J Med 338:1876–1880PubMedCrossRef

Title: Metformin treatment in different phenotypes of polycystic ovary syndrome
Authors: Marzieh Agha Hosseini
Ashraf Alleyassin
Fatemeh Sarvi
Leila Safdarian
Abas Kokab
Mehran Fanisalek
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 5/2013
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-013-2800-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Metformin treatment in different phenotypes of polycystic ovary syndrome

Abstract

Background

Materials and methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusion

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