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

dc.contributor.authorTso, Leopoldo O. [UNIFESP]
dc.contributor.authorCostello, Michael F.
dc.contributor.authorAlbuquerque, Luiz Eduardo T.
dc.contributor.authorAndriolo, Regis B.
dc.contributor.authorMacedo, Cristiane R. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionRoyal Hosp Women & IVF Australia
dc.contributor.institutionFertivitro Ctr Reprod Humana
dc.contributor.institutionUniv Estado Para
dc.contributor.institutionCtr Estudos Saude Baseada Evidencias & Avaliacao
dc.description.abstractBackgroundThe 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. As a consequence, it is suggested that metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy and live birth rates.ObjectivesTo 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 methodsWe searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials and reference lists of articles (up to 15 October 2014).Selection criteriaTypes 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.Types of outcome measures: live birth rate, clinical pregnancy rate, miscarriage rate, incidence of ovarian hyperstimulation syndrome, incidence of participant-reported side effects, serum oestradiol level on the day of trigger, serum androgen level, and fasting insulin and glucose levels.Data collection and analysisTwo review authors independently selected the studies, extracted the data according to the protocol and assessed study quality. the overall quality of the evidence was assessed using GRADE methods.Main resultsWe included nine randomised controlled trials involving a total of 816 women with PCOS. When metformin was compared with placebo there was no clear evidence of a difference between the groups in live birth rates (OR 1.39, 95% CI 0.81 to 2.40, five RCTs, 551 women, I-2 = 52%, low-quality evidence). Our findings suggest that for a woman with a 32 % chance of achieving a live birth using placebo or other treatment, the corresponding chance using metformin treatment would be between 28% and 53%.When metformin was compared with placebo or no treatment, clinical pregnancy rates were higher in the metformin group (OR 1.52; 95% CI 1.07 to 2.15; eight RCTs, 775 women, I-2 = 18%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving a clinical pregnancy using placebo or no treatment, the corresponding chance using metformin treatment would be between 32% and 49%.The risk of ovarian hyperstimulation syndrome was lower in the metformin group (OR 0.29; 95% CI 0.18 to 0.49, eight RCTs, 798 women, I-2 = 11%, moderate-quality evidence). This suggests that for a woman with a 27% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 15%.Side effects (mostly gastrointestinal) were more common in the metformin group (OR 4.49, 95% CI 1.88 to 10.72, for RCTs, 431 women, I-2= 57%, low quality evidence)The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. the main limitations in the evidence were imprecision and inconsistency.Authors' conclusionsThis review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.en
dc.description.affiliationUniversidade Federal de São Paulo, BR-04042034 São Paulo, Brazil
dc.description.affiliationRoyal Hosp Women & IVF Australia, Sch Womens & Childrens Hlth, Div Obstet & Gynaecol, Sydney, NSW, Australia
dc.description.affiliationFertivitro Ctr Reprod Humana, Human Reprod Ctr, São Paulo, Brazil
dc.description.affiliationUniv Estado Para, Dept Publ Hlth, Belem, Para, Brazil
dc.description.affiliationCtr Estudos Saude Baseada Evidencias & Avaliacao, Brazilian Cochrane Ctr, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, EPM, BR-04042034 São Paulo, Brazil
dc.description.affiliationUnifespBrazilian Cochrane Centre, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFederal University of São Paulo (UNIFESP/EPM), Brazil
dc.description.sponsorshipNuffield Department of Obstetrics and Gynecology, UK
dc.description.sponsorshipSchool of Women's and Children's Health, Division of Obstetrics and Gynecology, Royal Hospital for Women, Australia
dc.identifier.citationCochrane Database of Systematic Reviews. Hoboken: Wiley-Blackwell, n. 11, 60 p., 2014.
dc.relation.ispartofCochrane Database of Systematic Reviews
dc.rightsAcesso restrito
dc.subjectFertilization in Vitroen
dc.subjectHyperandrogenism [drug therapy]en
dc.subjectHyperinsulinism [drug therapy]en
dc.subjectHypoglycemic Agents [therapeutic use]en
dc.subjectLive Birthen
dc.subjectMetformin [therapeutic use]en
dc.subjectPolycystic Ovary Syndrome [complications]en
dc.subjectPregnancy Rateen
dc.subjectRandomized Controlled Trials as Topicen
dc.subjectSperm Injections, Intracytoplasmicen
dc.titleMetformin treatment before and during IVF or ICSI in women with polycystic ovary syndromeen