Article - The Effect of Antioxidants on Sperm Quality Parameters and Pregnancy Rates for Idiopathic Male Infertility: A Network Meta-Analysis of Randomized Controlled Trials.

Plain Language Summary

Male infertility has gradually increased in recent years and is thought to be an equal contributor alongside female infertility in fertility issues. An imbalance in reactive oxygen species, which can damage sperm cells and the protective antioxidants is thought to be a major contributor to male infertility. This meta-analysis of randomised control trials aimed to determine which antioxidants have the most beneficial effect on sperm quality and count and pregnancy rates. The results showed that 10 antioxidants have been researched; L-carnitine (LC), L-carnitine+L-acetylcarnitine (LAC), coenzyme Q10 (Q10), omega-3 fatty acids (O-3), selenium (Se), zinc (Zn), vitamin E+vitamin C (VEC), folic acid (FAC), and N-acetylcysteine (NAC). LC was the most effective at improving sperm motility and morphology with reducing effectiveness for Q10, O-3, LAC, and Se. Four antioxidants improved sperm concentration starting with the most effective being 0-3, then Q10, Se, and LC. There were no effects of antioxidants on pregnancy rate. It was concluded that LC was the most effective at improving sperm motility and morphology and O-3 was the most effective at increasing sperm concentration, however this did not translate into improvements in pregnancy rate. This study could be used by healthcare professionals to understand that LC and O-3 may help to improve sperm quality and concentration, but this may not be sufficient to improve male fertility.

Expert Review

Reviewer: Dr Yassine Bendiabdallah

18th Dec 2023

Conflict of interest

None

Take home message

Consider antioxidant rich diets and increase awareness of the benefits of antioxidants and nutritional interventions in improving fertility rates
Lifestyle modifications such as maintaining a healthy weight, regular exercise and avoiding harmful substances can enhance the positive effects of antioxidants on fertility
Patients facing infertility should consider visiting a healthcare professional including nutritional therapists or fertility specialists
Patients should approach interventions including antioxidant use with a long term perspective.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

The aim of this study was to investigate the impact of antioxidants on sperm quality parameters and pregnancy rates in cases of idiopathic male infertility. The focus was on randomised controlled trials (RCTs) to provide a comprehensive analysis of existing evidence.

Methods

Utilized a network meta-analysis approach to synthesise data from 23 RCTs with 1917 patients and 10 different antioxidants
Included studies with a diverse range of antioxidants and placebo/control groups
Sample size varied across included studies, with a total number of participants analysed for each outcome.

Results

L-Carnitine, L-carnitine+L-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more effective than placebo in improving sperm quality parameters
L-Carnitine showed the most pronounced improvement in terms of sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%])
ω-3 fatty acid had the most significant improvement in terms of sperm concentration (WMD 9.89 × 106/ml, [95% CI: 7.01 to 12.77 × 106/ml])
None of these supplements showed a statistical significant improvement on pregnancy rates compared to placebo.

Conclusion

L-Carnitine showed significant improvement in terms of sperm motility and morphology
Omega-3 fatty acids significantly improved sperm concentration
Co-Q10 has shown to effectively improve sperm motility and concentration
No statistically significant result was observed in terms of pregnancy rate compared to placebo.

Clinical practice applications

Prescribing antioxidants should be considered for patients with idiopathic male infertility
L-Carnitine can significantly improve sperm motility and morphology
CoQ10 has shown to improve sperm motility and concentration
Omega-3 improved sperm concentration
Considering the patient’s needs, practitioners can tailor the antioxidant for most significant improvement and desired outcomes.

Considerations for future research

Investigate the synergistic effects of combining various antioxidants to improve sperm quality and pregnancy rates
More studies to be conducted to assess the effect of antioxidant combinations on pregnancy outcomes
Pharmacogenomics investigations could help tailor the interventions to provide individualised medicine
Investigate the integration of antioxidant formulations with therapeutic interventions, lifestyle modifications, hormonal interventions etc.

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Abstract

PURPOSE

Male infertility is a global public health issue recognized by the WHO. Recently, antioxidants are increasingly used to treat idiopathic male infertility. However, the lack of available evidence has led to the inability to rank the effects of antioxidants on the sperm quality parameters and pregnancy rate of infertile men. This network meta-analysis studied the effects of different antioxidants on the sperm quality and pregnancy rate of idiopathic male infertility.

METHODS

We searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables, respectively, with 95% CIs. The outcomes were sperm motility, sperm concentration, sperm morphology, and pregnancy rate.

RESULTS

A total of 23 RCTs with 1,917 patients and 10 kids of antioxidants were included. l-Carnitine, l-carnitine+l-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more efficacious than placebo in sperm quality parameters. l-Carnitine was ranked first in sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%]). ω-3 fatty acid was ranked first in sperm concentration (WMD 9.89 × 10/ml, [95% CI: 7.01 to 12.77 × 10/ml]). In terms of pregnancy rate, there was no significant effect as compared with placebo.

CONCLUSIONS

l-Carnitine was ranked first in sperm motility and sperm morphology. ω-3 fatty acid was ranked first in sperm concentration. Coenzyme-Q10 had better effective treatment on sperm motility and concentration. Furthermore, high-quality RCTs with adequate sample sizes should be conducted to compare the outcomes of different antioxidants.