Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials

References

• Palomba S. Is fertility reduced in ovulatory women with polycystic ovary syndrome? An opinion paper. Hum Reprod. 2021;36(9):2421–2428.
   PubMed Web of Science ®Google Scholar
• Bozdag G, Mumusoglu S, Zengin D, et al. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841–2855.
   PubMed Web of Science ®Google Scholar
• March WA, Moore VM, Willson KJ, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544–551.
   PubMed Web of Science ®Google Scholar
• Alvarez-Blasco F, Botella-Carretero JI, San Millán JL, et al. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med. 2006;166(19):2081–2086.
   PubMedGoogle Scholar
• Yu H-F, Chen HS, Rao DP, et al. Association between polycystic ovary syndrome and the risk of pregnancy complications: a PRISMA-compliant systematic review and meta-analysis. Medicine. 2016;95(51):e4863.
   PubMed Web of Science ®Google Scholar
• Qin JZ, Pang LH, Li MJ, et al. Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2013;11(1):14.
   PubMedGoogle Scholar
• Kjerulff LE, Sanchez-Ramos L, Duffy D. Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis. Am J Obstet Gynecol. 2011;204(6):558.e1–558.e6.
   Web of Science ®Google Scholar
• Homburg R. Pregnancy complications in PCOS. Best Pract Res Clin Endocrinol Metab. 2006;20(2):281–292.
   PubMed Web of Science ®Google Scholar
• Palomba S, de Wilde M, Falbo A, et al. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21(5):575–592.
   PubMed Web of Science ®Google Scholar
• Glueck CJ, Wang P, Kobayashi S, et al. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril. 2002;77(3):520–525.
   PubMed Web of Science ®Google Scholar
• Palomba S, Falbo A, Zullo F, et al. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev. 2009;30(1):1–50.
   PubMed Web of Science ®Google Scholar
• Glueck CJ, Phillips H, Cameron D, et al. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril. 2001;75(1):46–52.
   PubMed Web of Science ®Google Scholar
• Palomba S, Daolio J, La Sala G. Oocyte competence in women with polycystic ovary syndrome. Trends Endocrinol Metab. 2017;28(3):186–198.
   PubMed Web of Science ®Google Scholar
• Palomba S, Piltonen T, Giudice L. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum Reprod Update. 2021;27(3):584–618.
   PubMed Web of Science ®Google Scholar
• Zhao J, Liu X, Zhang W. The effect of metformin therapy for preventing gestational diabetes mellitus in women with polycystic ovary syndrome: a meta-analysis. Exp Clin Endocrinol Diabetes. 2020;128(3):199–205.
   PubMedGoogle Scholar
• Zeng XL, Zhang YF, Tian Q, et al. Effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome: a meta-analysis. Medicine. 2016;95(36):e4526.
   PubMed Web of Science ®Google Scholar
• Feng L, Lin XF, Wan ZH, et al. Efficacy of metformin on pregnancy complications in women with polycystic ovary syndrome: a meta-analysis. Gynecol Endocrinol. 2015;31(11):833–839.
   PubMed Web of Science ®Google Scholar
• Zhuo Z, Wang A, Yu H. Effect of metformin intervention during pregnancy on the gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and meta-analysis. J Diabetes Res. 2014;2014:381231.
   PubMed Web of Science ®Google Scholar
• Zheng J, Shan PF, Gu W. The efficacy of metformin in pregnant women with polycystic ovary syndrome: a meta-analysis of clinical trials. J Endocrinol Invest. 2013;36(10):797–802.
   PubMedGoogle Scholar
• Andrae F, Abbott D, Stridsklev S, et al. Sustained maternal hyperandrogenism during PCOS pregnancy reduced by metformin in non-obese women carrying a male fetus. J Clin Endocrinol Metab. 2020;105(12):3762–3770.
   Web of Science ®Google Scholar
• Løvvik TS, Carlsen SM, Salvesen Ø, et al. Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(4):256–266.
   PubMed Web of Science ®Google Scholar
• Løvvik TS, Stridsklev S, Carlsen SM, et al. Cervical length and androgens in pregnant women with polycystic ovary syndrome: has metformin any effect? J Clin Endocrinol Metab. 2016;101(6):2325–2331.
   PubMedGoogle Scholar
• Helseth R, Vanky E, Stridsklev S, et al. Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin. Eur J Endocrinol. 2014;170(5):769–775.
   PubMedGoogle Scholar
• Ainuddin JA, Kazi S, Aftab S, et al. Metformin for preventing gestational diabetes in women with polycystic ovarian syndrome. J Coll Physicians Surg–Pak. 2015;25:237–241.
   PubMedGoogle Scholar
• Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. Version 4.2.5. West Sussex (UK): John Wiley & Sons; 2008.
   Google Scholar
• Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
   PubMed Web of Science ®Google Scholar
• Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.
   PubMedGoogle Scholar
• Wells GA , Shea B, O'Connell D, et al. Ottawa Hospital Research Institute. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. 2021 [cited 2021 July 30]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
   Google Scholar
• Morin-Papunen L, Rantala AS, Unkila-Kallio L, et al. Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab. 2012;97(5):1492–1500.
   PubMed Web of Science ®Google Scholar
• Vanky E, Stridsklev S, Heimstad R, et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab. 2010;95(12):E448–E455.
   PubMed Web of Science ®Google Scholar
• Fougner KJ, Vanky E, Carlsen SM. Metformin has no major effects on glucose homeostasis in pregnant women with PCOS: results of a randomized double-blind study. Scand J Clin Lab Invest. 2008;68(8):771–776.
   PubMed Web of Science ®Google Scholar
• Salvesen KA, Vanky E, Carlsen SM. Metformin treatment in pregnant women with polycystic ovary syndrome-is reduced complication rate mediated by changes in the uteroplacental circulation? Ultrasound Obstet Gynecol. 2007;29(4):433–437.
   PubMed Web of Science ®Google Scholar
• Vanky E, Salvesen KA, Heimstad R, et al. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum Reprod. 2004;19(8):1734–1740.
   PubMed Web of Science ®Google Scholar
• Al-Biate MA. Effect of metformin on early pregnancy loss in women with polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2015;54(3):266–269.
   PubMedGoogle Scholar
• Abd El Hameed AA, Shreif HE, Mowafy HE. The role of continuing metformin therapy during pregnancy in the reduction of gestational diabetes and improving pregnancy outcomes in women with polycystic ovary syndrome. Middle East Fertil Soc J. 2011;16(3):204–208.
   Google Scholar
• Khattab S, Mohsen IA, Aboul Foutouh I, et al. Can metformin reduce the incidence of gestational diabetes mellitus in pregnant women with polycystic ovary syndrome? Prospective cohort study. Gynecol Endocrinol. 2011;27(10):789–793.
   PubMed Web of Science ®Google Scholar
• Nawaz FH, Rizvi J. Continuation of metformin reduces early pregnancy loss in obese Pakistani women with polycystic ovarian syndrome. Gynecol Obstet Invest. 2010;69(3):184–189.
   PubMed Web of Science ®Google Scholar
• Begum MR, Khanam NN, Quadir E, et al. Prevention of gestational diabetes mellitus by continuing metformin therapy throughout pregnancy in women with polycystic ovary syndrome. J Obstet Gynaecol Res. 2009;35(2):282–286.
   PubMed Web of Science ®Google Scholar
• Nawaz FH, Khalid R, Naru T, et al. Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome? J Obstet Gynaecol Res. 2008;34(5):832–837.
   PubMed Web of Science ®Google Scholar
• Khattab S, Mohsen IA, Foutouh IA, et al. Metformin reduces abortion in pregnant women with polycystic ovary syndrome. Gynecol Endocrinol. 2006;22(12):680–684.
   PubMed Web of Science ®Google Scholar
• Glueck CJ, Pranikoff J, Aregawi D, et al. Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. Fertil Steril. 2008;89(3):625–634.
   PubMed Web of Science ®Google Scholar
• Jakubowicz DJ, Iuorno MJ, Jakubowicz S, et al. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(2):524–529.
   PubMedGoogle Scholar
• Glueck CJ, Bornovali S, Pranikoff J, et al. Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome. Diabet Med. 2004;21(8):829–836.
   PubMedGoogle Scholar
• Vanky E, DE Zegher F, Díaz M, et al. On the potential of metformin to prevent preterm delivery in women with polycystic ovary syndrome - an epi-analysis. Acta Obstet Gynecol Scand. 2012;91(12):1460–1464.
   PubMedGoogle Scholar
• Leo VD, Musacchio MC, Piomboni P, et al. The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications. Eur J Obstet Gynecol Reprod Biol. 2011;157(1):63–66.
   PubMedGoogle Scholar