The Effect of Nutritional Supplements on Semen Quality and Pregnancy Rates in Patients With Male Factor Infertility: A Systematic Literature Review and Network Meta-Analysis
Author(s)
Lauren Rengger, MSc1, Conor McCloskey, PhD2, Srinivas Jowndla, DPharm3, Sakshi Vakharia, MPharm1, Anu Priya, MPharm3, Shanmukha Sai Bharathi Kalakonda, MPharm3, Sunita Nair, PhD3.
1Clarivate, London, United Kingdom, 2Clarivate, Belfast, United Kingdom, 3Clarivate, Bengaluru, India.
1Clarivate, London, United Kingdom, 2Clarivate, Belfast, United Kingdom, 3Clarivate, Bengaluru, India.
OBJECTIVES: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to investigate the relative effect of nutritional supplements on semen quality and pregnancy rate in male-factor infertility.
METHODS: An SLR was conducted in May 2025 following PRISMA guidelines, searching Embase, MEDLINE, Cochrane Library, and grey literature sources. Randomised controlled trials (RCTs) involving over-the-counter supplements, in adult men with any type of infertility, were included if treatment lasted ≥8 weeks and semen quality outcomes or pregnancy rate were reported. Sperm parameter changes from baseline (CFB) to 3±1 months were analysed; mean differences (MD) and 95% credible intervals (CrI) versus placebo/no treatment reported. Fixed and random effects Bayesian NMAs were fitted, and heterogeneity and inconsistency assessed.
RESULTS: The review included 64 RCTs (N=8,372 men), investigating 34 supplements or combinations of ≤3 supplements. All trials investigated at least one semen parameter. Pregnancy was inconsistently described and often reported ad hoc in the discussion. Semen parameter improvements varied, with significant heterogeneity across studies. Lycopene, Alpha-Lipoic Acid (ALA) and a combination of selenium + vitamins ranked highest for improving sperm motility over 3 months, respectively. Significant treatment effects versus placebo were observed for ALA (MD[95%CrI]= 13.28% [5.43,21.28]) and selenium + vitamins (MD[95%CrI]= 12.03% [2.67,21.36]), the difference did not reach significance for lycopene (MD[95%CrI]= 17.25% [-0.32,34.84]). ALA was the only supplement to significantly improve sperm concentration after 3 months versus placebo (MD[95%CrI]= 15.33x10⁶/ml [5.31,25.42]). Pregnancy was reported in 25 trials with variable follow-up. Three trials reported zero events in all treatment arms. No supplement showed a significant benefit on pregnancy rates relative to placebo.
CONCLUSIONS: While certain supplements show potential to improve semen quality over a 3-month period, substantial between-study heterogeneity was observed. No supplements demonstrated evidence of increasing pregnancy rates, a key clinical outcome that should be included in future evaluations of male-factor infertility treatments.
METHODS: An SLR was conducted in May 2025 following PRISMA guidelines, searching Embase, MEDLINE, Cochrane Library, and grey literature sources. Randomised controlled trials (RCTs) involving over-the-counter supplements, in adult men with any type of infertility, were included if treatment lasted ≥8 weeks and semen quality outcomes or pregnancy rate were reported. Sperm parameter changes from baseline (CFB) to 3±1 months were analysed; mean differences (MD) and 95% credible intervals (CrI) versus placebo/no treatment reported. Fixed and random effects Bayesian NMAs were fitted, and heterogeneity and inconsistency assessed.
RESULTS: The review included 64 RCTs (N=8,372 men), investigating 34 supplements or combinations of ≤3 supplements. All trials investigated at least one semen parameter. Pregnancy was inconsistently described and often reported ad hoc in the discussion. Semen parameter improvements varied, with significant heterogeneity across studies. Lycopene, Alpha-Lipoic Acid (ALA) and a combination of selenium + vitamins ranked highest for improving sperm motility over 3 months, respectively. Significant treatment effects versus placebo were observed for ALA (MD[95%CrI]= 13.28% [5.43,21.28]) and selenium + vitamins (MD[95%CrI]= 12.03% [2.67,21.36]), the difference did not reach significance for lycopene (MD[95%CrI]= 17.25% [-0.32,34.84]). ALA was the only supplement to significantly improve sperm concentration after 3 months versus placebo (MD[95%CrI]= 15.33x10⁶/ml [5.31,25.42]). Pregnancy was reported in 25 trials with variable follow-up. Three trials reported zero events in all treatment arms. No supplement showed a significant benefit on pregnancy rates relative to placebo.
CONCLUSIONS: While certain supplements show potential to improve semen quality over a 3-month period, substantial between-study heterogeneity was observed. No supplements demonstrated evidence of increasing pregnancy rates, a key clinical outcome that should be included in future evaluations of male-factor infertility treatments.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO239
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Reproductive & Sexual Health