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The impact of vitamin E supplementation on sperm analysis in varicocelectomy patients: a triple-blind randomized controlled trial.

Journal: Trials 2025;26(1):36

PMID: 39891146

Plain Language Summary

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Varicocele is an abnormal condition of the veins of the scrotum and associated with male infertility. Varicocelectomy is a surgery used to correct abnormal scrotal veins, however it does not always improve sperm quality. As a result the use of adjunct treatments to improve sperm quality following varicocelectomy is being investigated. This randomised controlled trial investigated the effects of vitamin E supplementation (400 units per day) on sperm quality in men aged 15–25 years who had undergone varicocelectomy compared to placebo.

The results showed that both groups experienced significant improvements in sperm motility, count, and morphology over the three-month period following surgery. However, when the two groups were compared directly, only sperm motility improved significantly more in the vitamin E group than in the placebo group. There were no significant differences between the two groups in sperm count or morphology, meaning vitamin E did not offer additional benefit over placebo for these parameters.

In conclusion, vitamin E supplementation following varicocelectomy may specifically improve sperm motility beyond the benefit of surgery alone, though it does not appear to offer additional benefit for sperm count or morphology. As varicocelectomy itself produced significant improvements in all three sperm parameters in both groups, the surgery remains the primary effective intervention. Healthcare professionals managing men with varicocele-related infertility may consider vitamin E supplementation as an adjunct to surgery to further support sperm motility.

Expert Review

Reviewer: Michelle Barrow
1st Jun 2026
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Conflict of interest

None

Take home message

  • Vitamin E added after varicocelectomy modestly improved sperm parameters, especially motility, compared with placebo.

  • Varicocelectomy alone also improved semen results.

  • Vitamin E may be a helpful adjunct, not a replacement for surgery.

  • The benefit of Vitamin E supplementation in this study appears supportive rather than substantial.

  • This study did not define the units of vitamin E utilised or the form of vitamin E used.

Evidence category

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

Summary review

Introduction:

This study evaluated the effect of vitamin E supplementation on sperm analysis results in patients undergoing varicocelectomy. It compared vitamin E with placebo to determine whether adjunctive antioxidant therapy improved treatment efficacy in male infertility.

Methods:

A single-centre, triple-blind, randomized controlled trial conducted in Iran. 90 participants, mean age 30.68 ± 6.31 years, with infertility related to varicocele, were blindly assigned to intervention or placebo.

The intervention group received 400 units of vitamin E daily for 3 months. The placebo was identical in appearance.

This study did not define the units of vitamin E utilised or the form of vitamin E.

Prior to varicocelectomy sperm analysis was conducted and there was no significant difference in sperm movement, count or morphology between groups. After 3 months, a repeat sperm analysis was conducted.

Results:

The varicocelectomy alone led to significant improvements in sperm count and morphology in both groups, but those taking vitamin E had enhanced outcomes, including

  • Improvement in sperm motility was significantly higher in the intervention group 10% (IQR: 5–15) vs. 6% (IQR: 3–11.5) in the placebo group (P = 0.03).

  • Sperm count improvement was 6.95 million/mL (SD: 9.45) in the intervention group vs. 4.64 million/mL (SD: 8.56) in the placebo group (P = 0.22).

  • Sperm morphology improvement was 0.71% (SD: 1.01) in the intervention group vs. 0.46% (SD: 0.89) in the placebo group (P = 0.22).

Conclusion:

Although varicocelectomy alone was effective, adding Vitamin E supplementationsignificantly improved sperm motility, indicating it may offer additional benefit in managing varicocele-related male infertility.

Clinical practice applications

  • Oxidative stress is a key pathophysiological mechanism for varicocele related infertility

  • Antioxidants, such as vitamin E may help to mitigate sperm damage from oxidative stress.

  • Vitamin E may be a helpful adjunct, not a replacement for surgery.

  • Consider supplementing a range of antioxidants rather than focusing on single nutrients

Considerations for future research

  • Further studies should clarify the units of vitamin E utilised or the form of vitamin E

  • Broad spectrum antioxidant supplementation could be considered in future research

  • Studies focusing on single nutrient interventions, such as this study, should determine the long-term risks and effects.

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Abstract

OBJECTIVE

To evaluate the impact of vitamin E supplementation on sperm analysis results in patients post-varicocelectomy.

MARTIALS AND METHOD

This single-center, triple-blind, randomized controlled trial was conducted at Imam Reza Hospital, Mashhad, Iran. Ninety male patients, aged 15-25 years, with infertility and varicocele grade 2 or 3, were randomized into two groups. The intervention group received 400 units of vitamin E daily for 3 months, while the control group received a placebo. Sperm analysis was conducted before and 3 months after the intervention. Statistical analyses were performed using SPSS version 23, with significance set at P < 0.05.

RESULTS

A total of 90 patients were enrolled and equally randomized into two groups (n = 45 per group). The mean age was 30.68 ± 6.31 years. Post-intervention, the improvement in sperm motility was significantly higher in the vitamin E group compared to the placebo group (P = 0.03). Both groups showed significant improvements in sperm motility, count, and morphology from pre- to post-intervention (P < 0.001).

CONCLUSION

Vitamin E supplementation post-varicocelectomy is associated with improved sperm parameters, suggesting potential benefits in the management of male infertility related to varicocele. However, varicocelectomy alone also results in significant improvements.

TRIAL REGISTRATION

This study is registered at the Iranian Registry of Clinical Trials (IRCT20200911048689N1). Registered on October 10, 2020.

© 2025. The Author(s).

Address: Department of Radiology, Babol University of Medical Sciences, Babol, Iran.; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.; Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.; Department of Urology, Ghaem Hospital, Mashhad University of Medical Science, Mashhad, Iran. [email protected].

Patient Centred Factor

Jadad Score

Allocation Concealment

Psychological/Emotional Environment

Bioactive Substances

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