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Meta-Analysis
. 2020 Dec 21;12(12):CD006105.
doi: 10.1002/14651858.CD006105.pub4.

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome

Leopoldo O Tso  1 , Michael F Costello  2 , Luiz Eduardo T Albuquerque  3 , Regis B Andriolo  4 , Cristiane R Macedo  5
Affiliations
Meta-Analysis

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome

Leopoldo O Tso et al. Cochrane Database Syst Rev. .

Abstract

Background: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates.

Objectives: To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.

Search methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020).

Selection criteria: Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.

Types of participants: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment.

Primary outcome measures: live birth rate, incidence of ovarian hyperstimulation syndrome.

Data collection and analysis: Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach.

Main results: This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I2 = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I2 = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I2 = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I2 = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I2 = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I2 = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision.

Authors' conclusions: This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.

Trial registration: ClinicalTrials.gov NCT03086005 NCT00159575 NCT01233206.

PubMed Disclaimer

Conflict of interest statement

Leopoldo de Oliveira Tso: none known.

Dr Michael Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for scientific conference presentations. These relationships are declared in the interests of transparency and do not constitute a conflict of interest in this review.

Luiz Eduardo T Albuquerque: none known.

Regis B Andriolo: none known.

Cristiane R Macedo: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.1 Live birth rate per woman.
5
5
Sensitivity analysis by excluding Palomba 2011 due to a data discrepancy (suspected risk of bias).
6
6
Forest plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.2 Incidence of OHSS per woman.
7
7
Sensitivity analysis including only studies with low risk of bias (An 2014; Jacob 2016; Kjotrod 2004; Kjotrod 2011; Palomba 2011; Tang 2006).
8
8
Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.2 Incidence of OHSS per woman.
9
9
Forest plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.3 Clinical pregnancy rate per woman.
10
10
Funnel plot of comparison: 1 Metformin versus placebo or no treatment, outcome: 1.3 Clinical pregnancy rate per woman.
1.1
1.1. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 1: Live birth rate per woman
1.2
1.2. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 2: Incidence of OHSS per woman
1.3
1.3. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 3: Clinical pregnancy rate per woman
1.4
1.4. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 4: Miscarriage rate per woman
1.5
1.5. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 5: Miscarriage rate per pregnant woman
1.6
1.6. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 6: Side effects per woman
1.7
1.7. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 7: Number of oocytes retrieved per woman
1.8
1.8. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 8: Mean total dose of FSH (IU) per woman
1.9
1.9. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 9: Mean days of gonadotrophin per woman
1.10
1.10. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 10: Cycle cancellation rate (after ovulation induction)
1.11
1.11. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 11: Serum oestradiol level (nmol/L) per woman
1.14
1.14. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 14: Fertilisation rate
1.15
1.15. Analysis
Comparison 1: Metformin versus placebo or no treatment, Outcome 15: Sensitivity analysis live birth by excluding Palomba 2011 due to a data discrepancy (suspected risk of bias)
See this image and copyright information in PMC

Update of

References

References to studies included in this review

An 2014 {published data only}
    1. An Y, Sun Z, Zhang Y, Liu B, Guan Y, Lu M. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clinical Endocrinology 2014;80(3):425-31. [PMID: ] - PubMed
Cheraghi 2018 {published data only}
    1. Cheraghi E, Mehranjani MS, Shariatzadeh MA, Esfahani MH, Ebrahimi Z. N-Acetylcysteine improves oocyte and embryo quality in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection: an alternative to metformin. Reproduction, Fertility, and Development 2016;28(6):723-31. [PMID: ] - PubMed
    1. Cheraghi E, Soleimani Mehranjani M, Shariatzadeh MA, Nasr Esfahani MH, Ebrahimi Z. Co-Administration of metformin and N-Acetyl cysteine fails to improve clinical manifestations in PCOS individual undergoing ICSI. International Journal of Fertility & Sterility 2014;8(2):119-28. [PMID: ] - PMC - PubMed
    1. Cheraghi E, Soleimani Mehranjani M, Shariatzadeh SMA, Nasr Esfahani MH, Alani B. N-Acetylcysteine compared to metformin, improves the expression profile of growth differentiation factor-9 and receptor tyrosine kinase c-Kit in the oocytes of patients with polycystic ovarian syndrome. International Journal of Fertility & Sterility 2018;11(4):270-8. [PMID: ] - PMC - PubMed
Doldi 2006 {published and unpublished data}
    1. 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. Gynecological Endocrinology 2006;22(5):235-8. - PubMed
Fedorcsak 2003 {published data only}
    1. 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. Gynecological Endocrinology 2003;17:207-14. - PubMed
Jacob 2016 {published data only}
    1. Jacob SL, Brewer C, Tang T, Picton HM, Barth JH, Balen AH. A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial. Human reproduction (Oxford, England) 2016;31(12):2756-64. [ISRCTN21199799] [PMID: ] - PubMed
Kim 2016 {published data only}
    1. Kim C, Jeung Y, Moon J, Kang B. Effect of metformin treatment on intrafollicular cytokines, ovarian response to gonadotropin and in vitro fertilization outcome in patients with polycystic ovary syndrome. Fertility and Sterility 2016;106(3 Suppl):e259-60. [CTG: ] [CN-01200008]
Kjotrod 2004 {published data only}
    1. Kjøtrød SB, Romundstad P, Düring V, Sunde A, Carlsen SM. Prospective, randomized trial of metformin and vitamins for the reduction of plasma homocysteine in insulin-resistant polycystic ovary syndrome. Fertility and Sterility 2008;89(3):635-41.
    1. Kjotrod S, Düring V, Sunde A, Carlsen SM. Metformin treatment before IVF/ICSI in polycystic ovary syndrome women: a prospective, randomized, double-blind study. Human Reproduction 2003;18 Suppl 1:42-3. - PubMed
    1. Kjotrod SB, Düring V, Carlsen SM. Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Human Reproduction 2004;19(6):1315-22. - PubMed
Kjotrod 2011 {published data only}
    1. Kjotrod S, Carlsen SM, Rasmussen PE, Holst-Larsen T, Mellembakken J, Thurin-Kjellberg A, et al. Metformin treatment before and during IVF or ICSI in PCOS women with BMI < 28 kg/m2. Human Reproduction 2010;25(Suppl 1):i286-7.
    1. 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. Human Reproduction 2011;26(8):2045-53. [CTG: ] [PMID: ] - PubMed
Onalan 2005 {published data only}
    1. 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. Fertility and Sterility 2005;84(3):798-801. - PubMed
Palomba 2011 {published data only}
    1. 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. Fertility and Sterility 2011;96:1384-90. [CTG: ] - PubMed
Qublan 2009 {published data only}
    1. 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. Journal of Obstetrics and Gynecology 2009;29(7):651-5. - PubMed
Tang 2006 {published data only}
    1. Tang T, Barth JH, Balen AH. Effect of metformin on follicular anti-Mullerian hormone concentrations in women with PCOS undergoing IVF treatment. Human Reproduction 2010;25(Suppl 1):i68.
    1. Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Human Reproduction 2006;21(6):1416-25. - PubMed
Visnova 2003 {published data only}
    1. Visnova H, Ventruba P, Crha I, Zakova J. Importance of sensitization of insulin receptors in the prevention of ovarian hyperstimulation syndrome [Význam senzitizace inzulinových receptoru pro prevenci ovariálního hyperstimulacního syndromu]. Ceská Gynekologie 2003;68(3):155-62. - PubMed
    1. Visnova H, Ventruba P, Crha I, Zakova J. The impact of insulin receptor sensitization on prevention of ovarian hyperstimulation syndrome. Human Reproduction 2002;17 Suppl:180.

References to studies excluded from this review

Abdalmageed 2019 {published data only}
    1. Abdalmageed OS, Farghaly TA, Abdelaleem AA, Abdelmagied AE, Ali MK, Abbas AM. Impact of Metformin on IVF Outcomes in Overweight and Obese Women With Polycystic Ovary Syndrome: a Randomized Double-Blind Controlled Trial. Reproductive Sciences (Thousand Oaks, Calif.) 2019;26(10):1336-42.. [PMID: ] - PubMed
    1. Abdalmageed OS, Farghaly TA, Ismail AM, Hurd WW. Impact of metformin on in vitro fertilization outcomes in overweight and obese polycystic ovary syndrome women: a prospective cohort Study. Fertility and Sterility 2016;106(3 Suppl):e262.
Akbari 2010 {published data only}
    1. Akbari AF. Evaluating the effect of the metformin treatment on ICSI in infertile PCOS women. Iranian Journal of Reproductive Medicine 2010;8:8.
Demirol 2006 {published data only}
    1. Demirol A, Sari T, Girgin B, Kent E, Gurgan T. The effect of metformin treatment on the ICSI cycle outcome in PCOS patients. Human Reproduction 2006;21(Suppl 1):i88.
Egbase 2001 {published data only}
    1. Egbase PE, Al Sharhan M, Buzaber M, Grudzinskas JG. Prospective randomised study of metformin in IVF and embryo transfer treatment cycles in obese patients with polycystic ovarian syndrome. Human Reproduction 2001;16 Suppl 1:202.
Geusa 2002 {published data only}
    1. Geusa S, Stanziano A, Causio F, Pansini N, Sarcina E. The efficacy of insulin-sensitizing agent (metformin) in PCOS and insulin resistance patients undergoing IVF treatment. Human Reproduction 2002;17 Suppl:115.
Ghasemi 2012 {published data only}
    1. Ghasemi N, Jahaninejad T, Sheida E, Aflatoonian A. Effectiveness of Metformin in treatment of infertility and recurrent pregnancy loss in polycystic ovarian syndrome. Iranian journal of reproductive medicine 2012;10:8. - PMC - PubMed
He 2019 {published data only}
    1. He Y, Lu Y, Zhu Q, Wang Y, Lindheim SR, Qi J, et al. Influence of metabolic syndrome on female fertility and in vitro fertilization outcomes in PCOS women. American journal of obstetrics and gynecology 2019;221(2):138. - PubMed
Immediata 2014 {published data only}
    1. Immediata V, Romualdi D, De Cicco S, Tagliaferri V, Di Florio C, Cirella E, et al. Metformin versus myoinositol: which one is better in obese PCOS patients - a crossover study on clinical, endocrine and metabolic effects. Human Reproduction (Oxford, England) 2014;29:i334.
Kahraman 2001 {published data only}
    1. Kahraman S, Vanlioglu F, Yakin K, Cengiz S, Karlikaya G. A comparative trial of metformin and oral contraceptive pretreatment in patients with polycystic ovary syndrome undergoing ICSI for severe male factor infertility. Fertility and Sterility 2001;76 Suppl 1(3):67.
Palomba 2011a {published data only}
    1. 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. Fertility and sterility 2011;96(5):1128-33. [PMID: ] - PubMed
Pourmatroud 2015 {published data only}
    1. Pourmatroud E, MohamadJafari R. Comparison of metformin and simvastatin administration in women with polycystic ovary syndrome before intracytoplasmic sperm injection cycle; a prospective, randomized, clinical trial. Human Reproduction (Oxford, England) 2014;29:i334-5. [DOI: 10.1093/humrep/29.Supplement_1.1] [CN-01473786] - DOI - PMC - PubMed
    1. Pourmatroud E, Mohammadjafari R, Roozitalab M. Comparison of Metformin and Simvastatin Administration in Women With Polycystic Ovary Syndrome Before Intra-Cytoplasmic Sperm Injection Cycle: a Prospective, Randomized, Clinical Trial Study. Iranian Red Crescent medical journal 2015;17(12):e20082. [PMID: ] - PMC - PubMed
    1. Pourmatroud E, Mohammad Jafari R. Two protocols for pretreatment in women with polycystic ovary syndrome before intracytoplasmic sperm injection cycle; a prospective, randomized, clinical trial. Iranian journal of reproductive medicine 2014;12(6 Suppl 1):4-5. [CN-01107870]
Schachter 2007 {published data only}
    1. Schachter M, Raziel A, Strassburger D, Rotem C, Ron-El R, Friedler S. Prospective, randomized trial of metformin and vitamins for the reduction of plasma homocysteine in insulin-resistant polycystic ovary syndrome. Fertility and Sterility 2007;88(1):227-30. - PubMed
Stadtmauer 1999 {published data only}
    1. Stadtmauer L, Riehl R, Toma S, Talbert L. Use of metformin in patients with PCOS undergoing IVF-ET improves outcomes. International Journal of Gynecology and Obstetrics 2000;70:B41.
    1. Stadtmauer LA, Riehl RM, Toma SK, Huang S, Barker S, Talbert LM. Metformin treatment of patients with polycystic ovarian syndrome undergoing IVF increases the number of mature oocytes, the fertilization rate and the number of embryos with changes in the levels of insulin-like growth factor. Fertility and Sterility 1999;72 Suppl 1(3):12.
Stadtmauer 2001 {published data only}
    1. 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. Fertility and Sterility 2001;75(3):505-9. - PubMed
Stadtmauer 2002 {published data only}
    1. Stadtmauer LA, Wong BC, Oehninger S. Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization. Reproductive Biomedicine Online 2002;5(2):112-6. - PubMed
Swanton 2011 {published data only}
    1. Swanton A, Lighten A, Granne I, McVeigh E, Lavery S, Trew G, et al. Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial. Human Reproduction (Oxford, England) 2011;26(8):2178-84. [DOI: 10.1093/humrep/der120] [CN-01261056] - DOI - PubMed
Tasdemir 2004 {published data only}
    1. Tasdemir S, Ficicioglu C, Yalti S, Gurbuz B, Basaran T, Yildirim G. The effect of metformin treatment to ovarian response in cases with PCOS. Archives of Gynecology and Obstetrics 2004;269(2):121-4. [PMID: ] - PubMed

References to studies awaiting assessment

Sun 2016 {published data only}
    1. Sun D, Yao G, Wu L, Wang J, Zhao Z, Zhai J. The effect of metformin on pregnancy outcome, endometrial receptivity & MIRNAs in endometrium of patients with PCOS undergoing IVF/ICSI. Fertility and sterility 2016;106(3):e260. [CN-01200009]

Additional references

Aboulghar 2003
    1. Aboulghar MA, Mansour RT. Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Human Reproduction Update 2003;9:275-89. - PubMed
Adashi 1985
    1. Adashi EY, Resnick CE, D'Ercole AJ, Svoboda ME, Van Wyk JJ. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocrine Review 1985;6:400-20. - PubMed
Al‐Inany 2011
    1. Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, et al. GnRH antagonists are safer than agonists: an update of a Cochrane review. Human Reproduction Update 2011;17:435. - PubMed
Attia 2001
    1. Attia GR, Rainey WE, Carr BR. Metformin directly inhibits androgen production in human thecal cells. Fertility and Sterility 2001;76:517-24. - PubMed
Balen 2004
    1. Balen A. The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best Practice & Research. Clinical Obstetrics & Gynaecology 2004;18:685-6. - PubMed
Barbieri 1986
    1. Barbieri RL, Makris A, Randall RW, Daniels G, Kistner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. Journal of Clinical Endocrinology and Metabolism 1986;62:904-10. - PubMed
Barbieri 2000
    1. Barbieri RL. Induction of ovulation in infertile women with hyperandrogenism and insulin resistance. American Journal of Obstetrics and Gynecology 2000;183:1412-8. - PubMed
Costello 2007
    1. Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No: CD005552. [DOI: 10.1002/14651858.CD005552.pub2] - DOI - PubMed
Dunaif 1989
    1. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165-74. - PubMed
Dunn 1995
    1. Dunn CJ, Peters DH. Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995;49:721-49. - PubMed
ESHRE/ASRM 2003
    1. Rotterdam ESHRE/ASRM - Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and Sterility 2004;81:19-25. - PubMed
Frank 1995
    1. Frank S. Polycystic ovary syndrome. New England Journal of Medicine 1995;333:853-61. - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Version accessed 7 February 2019. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at gradepro.org.
Griesinger 2006
    1. Griesinger G, Diedrich K, Tarlatzis BC, Kolibianakis EM. GnRH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polycystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis. Reproductive Biomedicine Online 2006;13:628-38. - PubMed
Higgins 2019
    1. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook. - PMC - PubMed
Jungheim 2010
    1. Jungheim ES, Odibo AO. Fertility treatment in women with polycystic ovary syndrome: a decision analysis of different oral ovulation induction agents. Fertility and Sterility 2010;94(7):2659-64. - PMC - PubMed
Knochenhauer 1998
    1. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. Journal of Clinical Endocrinology and Metabolism 1998;83:3078-82. - PubMed
Kocak 2002
    1. Kocak M, Caliskan E, Simsir C, Haberal A. Metformin therapy improves ovulatory rates, cervical scores and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertility and Sterility 2002;77:101-6. - PubMed
McKenzie 2020
    1. McKenzie JE, Brennan SE, Ryan RE, Thomson HJ, Johnston RV. Summarizing study characteristics and preparing for synthesis. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors(s). version 6.1 edition. Cochrane, 2020.
Nardo 2001
    1. Nardo LG, Rai R. Metformin therapy in the management of polycystic ovary syndrome: endocrine, metabolic and reproductive effects. Gynecology and Endocrinology 2001;15:373-80. - PubMed
Nestler 1991
    1. Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, et al. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism 1991;72:83-9. - PubMed
Nestler 2002
    1. 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. Fertility and Sterility 2002;77:209-15. - PubMed
Palomba 2010
    1. 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. Human Reproduction 2010;25(4):1005-13. - PubMed
Review Manager 2014 [Computer program]
    1. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Speroff 1995
    1. Speroff L, Glass RH, Kase NG. Anovulation and polycystic ovary [Anovulação e o ovário policístico]. In: Clinical Gynecology, Endocrinology and Infertility. 5th edition. São Paulo: Manole, 1995:477-502.
Teede 2018
    1. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ and International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human reproduction 2018;33(9):1602-18. [PMID: ] - PMC - PubMed
Thessaloniki ESHRE/ASRM‐Sponsored PCOS 2008
    1. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertility and Sterility 2008;89(3):505-22. - PubMed
Tsilchorozidou 2004
    1. Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clinical Endocrinology 2004;60(1):1-17. - PubMed
Yarali 2004
    1. Yarali H, Zeyneloglu HB. Gonadotrophin treatment in patients with polycystic ovary syndrome. Reproductive Biomedicine Online 2004;8:528-37. - PubMed

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