Antioxidants for male subfertility.

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dc.contributor.author Smits, Roos M en
dc.contributor.author Mackenzie-Proctor, Rebecca en
dc.contributor.author Yazdani, Anusch en
dc.contributor.author Stankiewicz, Marcin T en
dc.contributor.author Jordan-Cole, Vanessa en
dc.contributor.author Showell, Marian en
dc.date.accessioned 2019-05-27T03:01:10Z en
dc.date.issued 2019-03-14 en
dc.identifier.citation Cochrane database of systematic reviews 3:CD007411 14 Mar 2019 en
dc.identifier.issn 1469-493X en
dc.identifier.uri http://hdl.handle.net/2292/46567 en
dc.description.abstract BACKGROUND:The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility. This review did not examine the use of antioxidants in normospermic men. OBJECTIVES:To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men. SEARCH METHODS:The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers were searched on 1 February 2018, together with reference checking and contact with study authors and experts in the field to identify additional trials. SELECTION CRITERIA:We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included fertile men attending a fertility clinic because of female partner infertility. DATA COLLECTION AND ANALYSIS:We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes. MAIN RESULTS:We included 61 studies with a total population of 6264 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing assisted reproductive techniques (ART). Investigators compared and combined 18 different oral antioxidants. The evidence was of 'low' to 'very low' quality: the main limitation was that out of the 44 included studies in the meta-analysis only 12 studies reported on live birth or clinical pregnancy. The evidence is current up to February 2018.Live birth: antioxidants may lead to increased live birth rates (OR 1.79, 95% CI 1.20 to 2.67, P = 0.005, 7 RCTs, 750 men, I2 = 40%, low-quality evidence). Results suggest that if in the studies contributing to the analysis of live birth rate, the baseline chance of live birth following placebo or no treatment is assumed to be 12%, the chance following the use of antioxidants is estimated to be between 14% and 26%. However, this result was based on only 124 live births from 750 couples in seven relatively small studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.38, 95% CI 0.89 to 2.16; participants = 540 men, 5 RCTs, P = 0.15, I2 = 0%).Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 2.97, 95% CI 1.91 to 4.63, P < 0.0001, 11 RCTs, 786 men, I2 = 0%, low-quality evidence) compared to placebo or no treatment. This suggests that if in the studies contributing to the analysis of clinical pregnancy, the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 7%, the chance following the use of antioxidants is estimated to be between 12% and 26%. This result was based on 105 clinical pregnancies from 786 couples in 11 small studies.Adverse eventsMiscarriage: only three studies reported on this outcome and the event rate was very low. There was no difference in miscarriage rate between the antioxidant and placebo or no treatment group (OR 1.74, 95% CI 0.40 to 7.60, P = 0.46, 3 RCTs, 247 men, I2 = 0%, very low-quality evidence). The findings suggest that in a population of subfertile men with an expected miscarriage rate of 2%, the chance following the use of an antioxidant would result in the risk of a miscarriage between 1% and 13%.Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal upsets when compared to placebo or no treatment (OR 2.51, 95% CI 1.25 to 5.03, P = 0.010, 11 RCTs, 948 men, I2 = 50%, very low-quality evidence). This suggests that if the chance of gastrointestinal upsets following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 9%. However, this result was based on a low event rate of 35 out of 948 men in 10 small or medium-sized studies, and the quality of the evidence was rated very low and was high in heterogeneity.We were unable to draw any conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions. AUTHORS' CONCLUSIONS:In this review, there is low-quality evidence from seven small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-quality evidence suggests that clinical pregnancy rates may also increase. Overall, there is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal upsets but the evidence is of very low quality. Subfertilte couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials reporting on pregnancy and live births are still required to clarify the exact role of antioxidants. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries The Cochrane database of systematic reviews en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri https://documentation.cochrane.org/display/EPPR/Standard+%7C+Cochrane+Review en
dc.subject Spermatozoa en
dc.subject Humans en
dc.subject Gastrointestinal Diseases en
dc.subject Infertility, Male en
dc.subject Abortion, Spontaneous en
dc.subject DNA Damage en
dc.subject Antioxidants en
dc.subject Sperm Count en
dc.subject Pregnancy Rate en
dc.subject DNA Fragmentation en
dc.subject Sperm Motility en
dc.subject Oxidative Stress en
dc.subject Pregnancy en
dc.subject Female en
dc.subject Male en
dc.subject Live Birth en
dc.subject Randomized Controlled Trials as Topic en
dc.title Antioxidants for male subfertility. en
dc.type Journal Article en
dc.identifier.doi 10.1002/14651858.cd007411.pub4 en
pubs.begin-page CD007411 en
pubs.volume 3 en
dc.rights.holder Copyright: The Cochrane Collaboration en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Meta-Analysis en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Systematic Review en
pubs.subtype systematic-review en
pubs.subtype Journal Article en
pubs.elements-id 766891 en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Obstetrics and Gynaecology en
dc.identifier.eissn 1469-493X en
pubs.record-created-at-source-date 2019-03-14 en
pubs.dimensions-id 30866036 en


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