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: An International Journal of Obstetrics and Gynaecology

Volumn 120, Issue 3, 2013, Pages 267-276

  Palomba, S ^a   Falbo, A ^a   La Sala, G B ^a  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

Gonadotrophins; in vitro fertilisation; intracytoplasmic sperm injection; meta analysis; metformin; polycystic ovary syndrome; randomised controlled trials

Indexed keywords

CHORIONIC GONADOTROPIN; ESTRADIOL; GONADORELIN AGONIST; GONADOTROPIN; METFORMIN; PLACEBO; PROGESTERONE;

DATA BASE; DRUG EFFECT; DRUG MEGADOSE; EMBRYO TRANSFER; ESTRADIOL BLOOD LEVEL; FEMALE INFERTILITY; FERTILIZATION IN VITRO; HUMAN; INTRACYTOPLASMIC SPERM INJECTION; LIVE BIRTH; LOW DRUG DOSE; LUTEAL PHASE; META ANALYSIS; NIDATION; OOCYTE RETRIEVAL; OVARY HYPERSTIMULATION; OVARY POLYCYSTIC DISEASE; PREGNANCY RATE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK REDUCTION; SPONTANEOUS ABORTION; SYSTEMATIC REVIEW; TREATMENT DURATION; TREATMENT OUTCOME;

ABORTION, SPONTANEOUS; DINOPROSTONE; EMBRYO IMPLANTATION; FEMALE; FERTILITY AGENTS, FEMALE; FERTILIZATION IN VITRO; GONADOTROPINS; HUMANS; INFERTILITY, FEMALE; LIVE BIRTH; METFORMIN; OOCYTE RETRIEVAL; OVARIAN HYPERSTIMULATION SYNDROME; POLYCYSTIC OVARY SYNDROME; PREGNANCY; PREGNANCY OUTCOME; PREGNANCY RATE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SPERM INJECTIONS, INTRACYTOPLASMIC;

EID: 84872387244     PISSN: 14700328     EISSN: 14710528     Source Type: Journal    
DOI: 10.1111/1471-0528.12070     Document Type: Review

References (45)

1. Palomba S, Falbo A, Zullo F, Orio F,. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev 2009; 30: 1-50.
2. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R,. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011; 7: 219-31.
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 2012; 16: CD003053.
4. Palomba S, Falbo A, Zullo F,. Management strategies for ovulation induction in women with polycystic ovary syndrome and known clomifene citrate resistance. Curr Opin Obstet Gynecol 2009; 21: 465-73.
5. www.ivf-worldwide.com/survey/survey-metformin-use-in-ivf-patients.html
6. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 2008; 89: 505-22.
7. Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Freitas V,. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2009; 2: CD006105.
8. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: 2535.
9. www.highlycited.com/
10. www.scopus.com/home.url
11. http://scholar.google.it/
12. www.who.int/ictrp/network/en/
13. http://controlled-trials.com/
14. http://clinicaltrials.gov/
15. www.umin.ac.jp/ctr/
16. Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2004159. Hum Reprod 2009; 24: 2683-7.
17. Higgins JPT, Green S, (Editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration 2011. Available from www.cochrane-handbook.org.
18. Mantel N, Haenszel W,. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 4: 719-48.
19. DerSimonian R, Laird N,. Meta-analysis in clinical trials. Control Clin Trials 1986; 3: 177-88.
20. Fedorcsák 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.
21. Visnová H, Ventruba P, Crha I, Záková J,. Importance of sensitization of insulin receptors in the prevention of ovarian hyperstimulation syndrome. Ceska Gynekol 2003; 68: 155-62.
22. Kjøtrød SB, von Düring 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.
23. Kjøtrød 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.
24. Onalan G, Pabuçcu 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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). Fertil Steril 2008; 89: 505-22.
31. Zawadzki JK, Dunaif A,. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In:, Dunaif A, Givens JR, Haseltine FP, Merriam GR, editors. Polycystic ovary syndrome. Boston: Blackwell; 1992. pp. 337-84.
32. Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS,. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006; 12: 673-83.
33. Palomba S, Falbo A, Russo T, Battista L, Tolino A, Orio F, et al. Uterine blood flow in pregnant patients with polycystic ovary syndrome: relationships with clinical outcomes. BJOG 2010; 117: 711-21.
34. Palomba S, Falbo A, Russo T, Tolino A, Orio F, Zullo F,. Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertil Steril 2010; 94: 1805-11.
35. Palomba S, Falbo A, Orio F, Zullo F,. 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: 1646-58.
36. Falbo A, Orio F, Venturella R, Rania E, Materazzo C, Tolino A, et al. Does metformin affect ovarian morphology in patients with polycystic ovary syndrome? A retrospective cross-sectional preliminary analysis. J Ovarian Res 2009; 31: 2-5.
37. Palomba S, Falbo A, Russo T, Orio F, Tolino A, Zullo F,. Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response. Hum Reprod 2010; 25: 1005-13.
38. Falbo A, Rocca M, Russo T, D'Ettore A, Tolino A, Zullo F, et al. Serum and follicular anti-Mullerian hormone levels in women with polycystic ovary syndrome (PCOS) under metformin. J Ovarian Res 2010; 3: 16.
39. Nestler JE, Jakubowicz DJ,. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996; 335: 617-23.
40. Nestler JE, Jakubowicz DJ,. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab 1997; 82: 4075-9.
41. Attia GR, Rainey WE, Carr BR,. Metformin directly inhibits androgen production in human thecal cells. Fertil Steril 2001; 76: 517-24.
42. Sonnatag B, Gotte M, Wiilfing P, Schuring AN, Kiesel L, Greb RR,. Metformin alters insulin signaling and viability of human granulosa cells. Fertil Steril 2005; 84: 1173-9.
43. Tosca L, Chabrolle C, Uzbekova S, Dupont J,. Effects of metformin on bovine granulosa cells steroidogenesis: possible involvement of adenosine 5′ monophosphate-activated protein kinase (AMPK). Biol Reprod 2007; 76: 368-78.
44. Tosca L, Solnais P, Ferrè P, Foufelle F, Dupont J,. Metformin-induced stimulation of adenosine 5′ monophosphate-activated protein kinase (PRKA) impairs progesterone secretion in rat granulosa cells. Biol Reprod 2006; 75: 342-51.
45. Coyral-Castel S, Tosca L, Ferreira G, Jeanpierre E, Rame C, Lomet D, et al. The effect of AMP-activated kinase activation on gonadotrophin-releasing hormone secretion in GT1-7 cells and its potential role in hypothalamic regulation of the oestrous cyclicity in rats. J Neuroendocrinol 2008; 20: 335-46.