Skip to main content

Advertisement

SpringerLink
Log in

Impact of Metformin on IVF Outcomes in Overweight and Obese Women With Polycystic Ovary Syndrome: A Randomized Double-Blind Controlled Trial

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Objectives: To evaluate the impact of metformin on in vitro fertilization (IVF) outcomes in overweight and obese women with polycystic ovary syndrome (PCOS). Methods: This was a randomized double-blind placebo-controlled study (ClinicalTrials.gov: NCT 02910817) carried out in a University IVF Center. The study included 102 overweight and obese women (body mass index [BMI] >24 kg/m2) with PCOS who underwent their first fresh autologous IVF-embryo transfer cycle and agreed to participate in the study. The study participants were randomized into 2 groups: metformin group received metformin (1000 mg per day) at the start of controlled ovarian stimulation (COH) until the day of the pregnancy check, and placebo group received placebo tablets in the same duration. The primary outcome measure was the total number of retrieved oocytes. Results: Both groups were homogenous in baseline demographic characteristics. Metformin group versus the placebo group demonstrated decrease in the mean number of the retrieved oocytes (9.06 ± 4.23 vs 16.86 ± 8.3, P <.01) and similar live birth rate (LBR; 25.5% vs 17.6%, P =.34). The number of fertilized oocytes was lower in the metformin group (5.65 ± 2.66 vs 9 ± 4.55, P <.01). However, the fertilization rate was similar in both groups (62.3% vs 53.4%, P =.10). There was no difference in the implantation rate (15.7% vs 11.8%, P =.32), multiple pregnancy rate (13.4% vs 3.9%, P =.08), or miscarriage rate (23.5% vs 35.7%, P =.46). No cases of ovarian hyperstimulation syndrome (OHSS) were observed in both groups. Conclusion: Short-term administration of metformin to overweight or obese women with PCOS undergoing IVF decreased number of the retrieved oocytes but did not improve the LBR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dunaif A. Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Med. 1995;98(1A): 33S–39S.

    Article  CAS  Google Scholar 

  2. Franks S. Polycystic ovary syndrome. New Eng J Med. 1995;333(13):853–861.

    Article  CAS  Google Scholar 

  3. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reprod. 2004;19(1):41–47.

  4. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008;89(3):505–522.

  5. Gorry A, White DM, Franks S. Infertility in polycystic ovary syndrome. Endocrine. 2006;30(1):27–33.

    Article  CAS  Google Scholar 

  6. Sam S. Obesity and polycystic ovary syndrome. Obes Manag. 2007;3(2):69–73.

    Article  Google Scholar 

  7. Venkatesan AM, Dunaif A, Corbould A. Insulin resistance in polycystic ovary syndrome: progress and paradoxes. Recent Prog Horm Res. 2001;56:295–308.

    Article  CAS  Google Scholar 

  8. Lashen H. Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2010;1(3):117–128.

    Article  CAS  Google Scholar 

  9. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774–800.

    CAS  PubMed  Google Scholar 

  10. Murakawa H, Hasegawa I, Kurabayashi T, et al. Polycystic ovary syndrome. Insulin resistance and ovulatory responses to clomiphene citrate. J Reprod Med. 1999;44(1):23–27.

    CAS  PubMed  Google Scholar 

  11. Diamanti-Kandarakis E, Kouli C, Tsianateli T, et al. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol. 1998;138(3):269–274.

    Article  CAS  Google Scholar 

  12. Nestler JE, Stovall D, Akhter N, Iuorno MJ, Jakubowicz DJ. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril. 2002;77(2):209–215.

    Article  Google Scholar 

  13. Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(3):CD002966.

    Google Scholar 

  14. DeFronzo RA, Barzilai N, Simonson DC. Mechanism of metfor-min action in obese and lean noninsulin-dependent diabetic subjects. J Clin Endocrinol Metabo. 1991;73(6):1294–1301.

    Article  CAS  Google Scholar 

  15. Moll E, van der Veen F, van Wely M. The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update. 2007;13(6):527–537.

    Article  CAS  Google Scholar 

  16. Stadtmauer LA, Toma SK, Riehl RM, Talbert LM. Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors. Fertil Steril. 2001;75(3):505–509.

    Article  CAS  Google Scholar 

  17. Christianson MS, Wu H, Zhao Y, Yemini M, Leong M, Shoham Z. Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey. J Assist Reprod Genet. 2015;32(3):401–406.

    Article  Google Scholar 

  18. Refuerzo JS, Viteri OA, Hutchinson M, et al. The effects ofmetformin on weight loss in women with gestational diabetes: a pilot randomized, placebo-controlled trial. Am JObstet Gynecol. 2015; 212(3):389.e1–389.e9.

    Article  CAS  Google Scholar 

  19. Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685–697.

    Article  CAS  Google Scholar 

  20. De Leo V, la Marca A, Ditto A, Morgante G, Cianci A. Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome. Fertil Steril. 1999;72(2):282–285.

    Article  Google Scholar 

  21. Palomba S, Falbo A, Carrillo L, et al. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011; 96(6):1384–1390.e4.

    Article  CAS  Google Scholar 

  22. Palomba S, Falbo A, Di Cello A, Cappiello F, Tolino A, Zullo F. Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial. Fertil Steril. 2011;96(5):1128–1133.

    Article  CAS  Google Scholar 

  23. Cooper TG, Noonan E, Von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–245.

    Article  Google Scholar 

  24. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002;26(7):883–896.

    Article  CAS  Google Scholar 

  25. Costello MF, Chapman M, Conway U. A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome. Hum Reprod. 2006; 21(6):1387–1399.

    Article  CAS  Google Scholar 

  26. Conway G, Dewailly D, Diamanti-Kandarakis E, et al. European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire. Eur J Endocrinol. 2014;171(4):489–498.

    Article  CAS  Google Scholar 

  27. De Leo V, Musacchio MC, Morgante G, Piomboni P, Petraglia F. Metformin treatment is effective in obese teenage girls with PCOS. Hum Reprod. 2006;21(9):2252–2256.

    Article  Google Scholar 

  28. Kjotrod SB, von During V, Carlsen SM. Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Hum Reprod. 2004;19(6):1315–1322.

    Article  CAS  Google Scholar 

  29. Tso LO, Costello MF, Albuquerque LE, et al. Metformin treatment before and during in vitro fertilization or intracytoplasmic sperm injection in women with polycystic ovary syndrome: summary of a Cochrane review. Fertil Steril. 2015;104(3):542–544.

    Article  CAS  Google Scholar 

  30. Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006;21(6):1416–1425.

    Article  CAS  Google Scholar 

  31. Kumbak B, Kahraman S. Efficacy of metformin supplementation during ovarian stimulation of lean PCOS patients undergoing in vitro fertilization. Acta Obstet Gynecol Scand. 2009;88(5):563–568.

    Article  CAS  Google Scholar 

  32. Palomba S, Falbo A, La Sala GB. Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of randomised controlled trials. BJOG. 2013;120(3):267–276.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the clinical and laboratory team in Assiut University IVF Center.

Author information

Authors and Affiliations

  1. Assiut IVF center, Assiut University, Assiut, Egypt

    Osama S. Abdalmageed, Tarek A. Farghaly, Ahmed A. Abdelaleem & Ahmed E. Abdelmagied

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt

    Mohammed K. Ali & Ahmed M. Abbas

Authors
  1. Osama S. Abdalmageed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tarek A. Farghaly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed A. Abdelaleem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmed E. Abdelmagied
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammed K. Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmed M. Abbas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed M. Abbas.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdalmageed, O.S., Farghaly, T.A., Abdelaleem, A.A. et al. Impact of Metformin on IVF Outcomes in Overweight and Obese Women With Polycystic Ovary Syndrome: A Randomized Double-Blind Controlled Trial. Reprod. Sci. 26, 1336–1342 (2019). https://doi.org/10.1177/1933719118765985

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719118765985

Keywords

Search

Navigation