Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome

Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome

Author Bordewijk, Esmee M. Google Scholar
Nahuis, Marleen Google Scholar
Costello, Michael F. Google Scholar
Van der Veen, Fulco Google Scholar
Tso, Leopoldo de Oliveira Autor UNIFESP Google Scholar
Mol, Ben Willem J. Google Scholar
van Wely, Madelon Google Scholar
Abstract Background Clomiphene citrate (CC) is generally considered first-line treatment in women with anovulation due to polycystic ovary syndrome (PCOS). Ovulation induction with follicle-stimulating hormone (FSH

gonadotrophins) is second-line treatment for women who do not ovulate or conceive while taking CC. Metformin may increase the effectiveness of ovulation induction with gonadotrophins and may promote safety by preventing multiple pregnancy. Objectives To determine the effectiveness and safety of metformin co-treatment during ovulation induction with gonadotrophins with respect to rates of live birth and multiple pregnancy in women with PCOS. Search methods We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and the Cumulative Index to Nursing and Allied Health Literature (CINAH) on 8 June 2016, and the reference lists of included and other relevant studies. We searched ongoing trials registries in the World Health Organization (WHO) portal and on clinicaltrials.gov on 4 September 2016. Selection criteria We included randomised controlled trials (RCTs) reporting data on comparison of clinical outcomes in women with PCOS undergoing ovulation induction with gonadotrophins plus metformin versus gonadotrophins alone or gonadotrophins plus placebo. Data collection and analysis We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth rate and multiple pregnancy rate. Secondary outcomes were ovulation rate, clinical pregnancy rate, ovarian hyperstimulation syndrome (OHSS) rate, miscarriage rate, cycle cancellation rate and adverse effects. Main results We included five RCTs (with 264 women) comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in four studies and highly purified FSH in one study. Evidence was of low quality: The main limitations were serious risk of bias due to poor reporting of study methods and blinding of participants and outcome assessors. Live birth Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% confidence interval (CI) 1.23 to 4.34

two RCTs, n = 180

I-2 = 0%

lowquality evidence). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Other pregnancy outcomes Metformin use was associated with a higher ongoing pregnancy rate (OR 2.46, 95% CI 1.36 to 4.46

four RCTs, n = 232

I-2 = 0%

lowquality evidence) and a higher clinical pregnancy rate (OR 2.51, 95% CI 1.46 to 4.31

five RCTs, n = 264

I-2 = 0%

lowquality evidence). Multiple pregnancy Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95

four RCTs, n = 232

I-2 = 0%

lowquality evidence) and no evidence of a difference in rates of miscarriage or OHSS. Other adverse effects Evidence was inadequate as the result of limited available data on adverse events after metformin compared with after no metformin (OR 1.78, 95% CI 0.39 to 8.09

two RCTs, n = 91

I-2 = 0%

very lowquality evidence). Authors' conclusions Preliminary evidence suggests that metformin may increase the live birth rate among women undergoing ovulation induction with gonadotrophins. At this moment, evidence is insufficient to show an effect of metformin on multiple pregnancy rates and adverse events. Additional trials are necessary before we can provide further conclusions that may affect clinical practice.
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Date 2017
Published in Cochrane Database Of Systematic Reviews. Hoboken, v. , n. 1, p. -, 2017.
ISSN 1469-493X (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent -
Origin http://dx.doi.org/10.1002/14651858.CD009090.pub2
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000396095800034
URI https://repositorio.unifesp.br/handle/11600/56383

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