Skip to main content
Log in

Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey

  • Assisted Reproduction Technologies
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To identify trends regarding therapeutic approaches to metformin administration in patients undergoing in vitro fertilization (IVF) treatment worldwide.

Methods

A retrospective evaluation utilizing the results of a web-based survey, IVFWorldwide (www.IVF-worldwide.com/), was performed.

Results

Responses from 101 centers performing a total of 50,800 annual IVF cycles was performed. Of these cycles, 10.4 % (n = 5,260) reported metformin use during IVF cycles. Indications for metformin use in IVF cycles included polycystic ovary syndrome (PCOS) patients who were habitual abortions (67 %), had prior poor egg quality (61 %), had high serum insulin levels (56 %). Less reported was PCOS with obesity/anvoulation (29 %), PCOS with multiple manifestations (23 %) and glucose intolerance and insulin resistance (23 %). Over half of cycles (54 %) treated patients with metformin up to 3 months prior to starting IVF. A majority (82 %) of IVF cycles utilized 1500–2000 mg/day of metformin. A nearly equal percentage of centers continued metformin up to a positive β-HCG test (35 %) or to 12 weeks gestation (33 %). 70 % of IVF cycles reported increased pregnancy rates and decreased miscarriage rates due to the use of metformin. 75 % reported the data in the literature is not sufficient for reaching a definitive conclusion concerning metformin treatment in patients undergoing IVF.

Conclusions

While metformin is used worldwide as an adjunct to standard IVF protocols, there is much variation in its use and the majority of centers report lack of evidence supporting its use.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sivalingam VN, Myers J, Nicholas S, Balen AH, Crosbie EJ. Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications. Hum Reprod Update. 2014;20:853–68.

    Article  PubMed  Google Scholar 

  2. Barbieri RL. Metformin for the treatment of polycystic ovary syndrome. Obstet Gynecol. 2003;101:785–93.

    Article  CAS  PubMed  Google Scholar 

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

  4. Creanga AA, Bradley HM, McCormick C, Witkop CT. Use of metformin in polycystic ovary syndrome: a meta-analysis. Obstet Gynecol. 2008;111:959–68.

    Article  CAS  PubMed  Google Scholar 

  5. Moll E, van der Veen F, van Wely M. The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update. 2007;13:527–37.

    Article  CAS  PubMed  Google Scholar 

  6. Palomba S, Pasquali R, Orio Jr F, Nestler JE. Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis. Clin Endocrinol. 2009;70:311–21.

    Article  CAS  Google Scholar 

  7. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23:462–77.

  8. Kumbak B, Kahraman S. Efficacy of metformin supplementation during ovarian stimulation of lean PCOS patients undergoing in vitro fertilization. Acta Obstet Gynecol Scand. 2009;88:563–8.

    Article  CAS  PubMed  Google Scholar 

  9. Shibahara H, Kikuchi K, Hirano Y, Suzuki T, Takamizawa S, Suzuki M. Increase of multiple pregnancies caused by ovulation induction with gonadotropin in combination with metformin in infertile women with polycystic ovary syndrome. Fertil Steril. 2007;87:1487–90.

    Article  CAS  PubMed  Google Scholar 

  10. 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;75:505–9.

    Article  CAS  PubMed  Google Scholar 

  11. Fedorcsak P, Dale PO, Storeng R, Abyholm T, Tanbo T. The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial. Gynecol Endocrinol. 2003;17:207–14.

    Article  CAS  PubMed  Google Scholar 

  12. Visnova H, Ventruba P, Crha I. Zakova J [Importance of sensitization of insulin receptors in the prevention of ovarian hyperstimulation syndrome]. Ceska Gynekol. 2003;68:155–62.

    CAS  PubMed  Google Scholar 

  13. Kjotrod SB, Carlsen SM, Rasmussen PE, Holst-Larsen T, Mellembakken J, Thurin-Kjellberg A, et al. Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study. Hum Reprod. 2011;26:2045–53.

    Article  CAS  PubMed  Google Scholar 

  14. 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;19:1315–22.

    Article  CAS  PubMed  Google Scholar 

  15. Onalan G, Pabuccu R, Goktolga U, Ceyhan T, Bagis T, Cincik M. Metformin treatment in patients with polycystic ovary syndrome undergoing in vitro fertilization: a prospective randomized trial. Fertil Steril. 2005;84:798–801.

    Article  CAS  PubMed  Google Scholar 

  16. Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006;21:1416–25.

    Article  CAS  PubMed  Google Scholar 

  17. Qublan HS, Al-Khaderei S, Abu-Salem AN, Al-Zpoon A, Al-Khateeb M, Al-Ibrahim N, et al. Metformin in the treatment of clomiphene citrate-resistant women with polycystic ovary syndrome undergoing in vitro fertilisation treatment: a randomised controlled trial. J Obstet Gynaecol. 2009;29:651–5.

    Article  CAS  PubMed  Google Scholar 

  18. Palomba S, Falbo A, Carrillo L, Villani MT, Orio F, Russo T, 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;96:1384–90. e4.

    Article  CAS  PubMed  Google Scholar 

  19. 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;96:1128–33.

    Article  CAS  PubMed  Google Scholar 

  20. Doldi N, Persico P, Di Sebastiano F, Marsiglio E, Ferrari A. Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2006;22:235–8.

    Article  PubMed  Google Scholar 

  21. 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;120:267–76.

    Article  CAS  PubMed  Google Scholar 

  22. Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014;11, CD006105.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mindy S. Christianson.

Additional information

Capsule There is much variation in use of metformin in IVF cycles worldwide.

Appendix A

Appendix A

Table 2 Question stems used in the survey “Metformin use in IVF patients”

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Christianson, M.S., Wu, H., Zhao, Y. et al. Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey. J Assist Reprod Genet 32, 401–406 (2015). https://doi.org/10.1007/s10815-014-0414-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-014-0414-x

Keyword

Navigation