Antioxidants for male subfertility

[Intervention Review]
Antioxidants for male subfertility

Marian G Showell1, Julie Brown1, Anusch Yazdani2, Marcin T Stankiewicz3, Roger J Hart4

1Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand. 2Clinical Research and Development, Queensland Fertility Group, Woolloongabba, Australia. 3Reproductive Medicine, Flinders Reproductive Medicine, Bedford Park, Australia. 4School of Women's and Infants Health, The University of Western Australia, King Edward Memorial Hospital and Fertility Specialists of Western Australia, Subiaco, Australia

Contact address: Marian G Showell, Obstetrics and Gynaecology, University of Auckland, Park Road Grafton, Auckland, New Zealand. m.showell@auckland.ac.nz.

Editorial group: Cochrane Menstrual Disorders and Subfertility Group.
Publication status and date: New, published in Issue 1, 2011.
Review content assessed as up-to-date: 21 August 2010.

Citation: Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD007411. DOI: 10.1002/14651858.CD007411.pub2.

Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Abstract

Background
Between 30% to 80% of male subfertility cases are considered to be due to the damaging effects of oxidative stress on sperm. Oral supplementation with antioxidants may improve sperm quality by reducing oxidative stress.

Objectives
This Cochrane review aimed to evaluate the effect of oral supplementation with antioxidants for male partners of couples undergoing assisted reproduction techniques (ART).

Search strategy
We searched the Cochrane Menstrual Disorders and Subfertility Group Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO and AMED databases (from their inception until Febuary 2010), trial registers, sources of unpublished literature, reference lists and we asked experts in the field.

Selection criteria
We included randomised controlled trials comparing any type or dose of antioxidant supplement (single or combined) taken by the male partner of a couple seeking fertility assistance with placebo, no treatment or another antioxidant. The outcomes were live birth, pregnancy, miscarriage, stillbirth, sperm DNA damage, sperm motility, sperm concentration and adverse effects.

Data collection and analysis
Two review authors independently assessed studies for inclusion and trial quality, and extracted data.

Main results
We included 34 trials with 2876 couples in total.

Live birth: three trials reported live birth. Men taking oral antioxidants had an associated statistically significant increase in live birth rate (pooled odds ratio (OR) 4.85, 95% CI 1.92 to 12.24; P = 0.0008, I2 = 0%) when compared with the men taking the control. This result was based on 20 live births from a total of 214 couples in only three studies.

Pregnancy rate: there were 96 pregnancies in 15 trials including 964 couples. Antioxidant use was associated with a statistically significant increased pregnancy rate compared to control (pooled OR 4.18, 95% CI 2.65 to 6.59; P < 0.00001, I2 = 0%).

Side effects: no studies reported evidence of harmful side effects of the antioxidant therapy used.

Authors' conclusions
The evidence suggests that antioxidant supplementation in subfertile males may improve the outcomes of live birth and pregnancy rate for subfertile couples undergoing ART cycles. Further head to head comparisons are necessary to identify the superiority of one antioxidant over another.

Plain language summary

Antioxidants for male subfertility
Oxidative stress may cause sperm cell damage. This damage can be reduced by the body's own natural antioxidant defences. Antioxidants can be part of our diet and taken as a supplement. It is believed that in many cases of unexplained subfertility, and also in instances where there may be a sperm-related problem, taking an oral antioxidant supplement may increase a couple's chance of conceiving when undergoing fertility treatment. This review identified 34 randomised controlled trials involving 2876 couples. Pooled findings support increases in live births and pregnancy rates with the use of antioxidants by the male partner. Further work is recommended to confirm these findings.

Vitamin D supplementation for improving bone mineral density in children

[Intervention Review]
Vitamin D supplementation for improving bone mineral density in children

Tania M Winzenberg1, Sandi Powell1, Kelly A Shaw2, Graeme Jones1

1Menzies Research Institute, University of Tasmania, Hobart, Australia. 2ASLaRC Aged Services Unit, Southern Cross University and Menzies Research Institute, University of Tasmania, Coffs Harbour, Australia

Contact address: Tania M Winzenberg, Menzies Research Institute, University of Tasmania, Private Bag 23, Hobart, TAS, 7001, Australia. tania.winzenberg@utas.edu.au.

Editorial group: Cochrane Musculoskeletal Group.
Publication status and date: New, published in Issue 10, 2010.
Review content assessed as up-to-date: 29 September 2009.

Citation: Winzenberg TM, Powell S, Shaw KA, Jones G. Vitamin D supplementation for improving bone mineral density in children. Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No.: CD006944. DOI: 10.1002/14651858.CD006944.pub2.

Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Abstract

Background
Results of randomised controlled trials (RCTs) of vitamin D supplementation to improve bone density in children are inconsistent.

Objectives
To determine the effectiveness of vitamin D supplementation for improving bone mineral density in children, whether any effect varies by sex, age or pubertal stage, the type or dose of vitamin D given or baseline vitamin D status, and if effects persist after cessation of supplementation.

Search strategy
We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2009), MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), AMED (1985 to present) and ISI Web of Science (1945 to present) on 9 August 2009, and we handsearched key journal conference abstracts.

Selection criteria
Placebo-controlled RCTs of vitamin D supplementation for at least three months in healthy children and adolescents (aged from one month to < 20 years) with bone density outcomes.

Data collection and analysis
Two authors screened references for inclusion, assessed risk of bias, and extracted data. We conducted meta-analyses and calculated standardised mean differences (SMD) of the percent change from baseline in outcomes in treatment and control groups. We performed subgroup analyses by sex, pubertal stage, dose of vitamin D and baseline serum vitamin D and considered these as well as compliance and allocation concealment as possible sources of heterogeneity.

Main results
We included six RCTs (343 participants receiving placebo and 541 receiving vitamin D) for meta-analyses. Vitamin D supplementation had no statistically significant effects on total body bone mineral content (BMC), hip bone mineral density (BMD) or forearm BMD. There was a trend to a small effect on lumbar spine BMD (SMD 0.15, 95% CI -0.01 to 0.31, P = 0.07). There were no differences in effects between high and low serum vitamin D studies at any site though there was a trend towards a larger effect with low vitamin D for total body BMC (P = 0.09 for difference). In low serum vitamin D studies, significant effects on total body BMC and lumbar spine BMD were approximately equivalent to a 2.6% and 1.7 % percentage point greater change from baseline in the supplemented group.

Authors' conclusions
These results do not support vitamin D supplementation to improve bone density in healthy children with normal vitamin D levels, but suggest that supplementation of deficient children may be clinically useful. Further RCTs in deficient children are needed to confirm this.

Plain language summary

Vitamin D for improving bone density in children
This summary of a Cochrane Review, presents what we know from research about the effect of vitamin D supplements on bone density in children.

The review shows that in healthy children generally, vitamin D supplementation does not improve bone density at the hip, lumbar spine, forearm or in the body as a whole.

Some of the evidence suggests that vitamin D supplements may improve bone density in children who have low levels of vitamin D but this is uncertain.

We do not have precise information about side effects and complications but the available information suggests that vitamin D supplements are well tolerated.

What is osteoporosis and what is vitamin D?

Osteoporosis is a condition where bones are weak, brittle and break easily. The risk of osteoporosis and fractures (breaks) in later life depends on how much bone is built when a child and how much bone is lost when an adult. One way to prevent osteoporosis and fractures in later life is to build stronger bones when young. Vitamin D plays an important role in improving the body’s absorption of calcium from food, reducing losses of calcium from the body and getting calcium deposited into to bone to improve the quantity of bone developed. Therefore it is thought that if vitamin D levels in the body are low in childhood, less bone will be developed and that improving vitamin D levels by supplements would result in more bone being developed. Bone density is a major measure of bone strength and the amount of bone mineral present at different sites and so is used to measure the effects of interventions, like vitamin D supplementation, to improve bone health.