Researchers in a 2022 study performed a systematic review and meta-analysis on infertile men who used antioxidant supplements, and found a benefit in pregnancy and semen parameter outcomes.
Male infertility can be caused by a number of factors, including sperm damage caused by reactive oxygen stress (ROS). ROS may be increased due to varicocele or lifestyle choices and the use of antioxidant supplements might help in neutralizing this. Itโs not clear if the use of antioxidants can improve outcomes in infertile males.
Agarwal et al. (2022), in their systematic review and meta-analysis, compared pregnancy outcomes and semen parameters between infertile men who used antioxidants and those who didnโt. They combined the results of 45 randomized controlled trials (RCTs) that totaled 4,332 infertile men.
This study didnโt include any IVF patients, as far as I can tell, but it represents a massive analysis of infertile men using antioxidants and to date is the most complete meta-analysis. They donโt specify which antioxidants are used in each study, and is meant to be a very broad look at the impact of antioxidants in general on male infertility.
Hereโs a list of most of the supplements included:
- Docosahexaenoic acid (DHA)
- L-arginine
- Glutathione
- Zinc
- Vitamin B9
- Vitamin B12
- Selenium
- Folic acid
- Vitamin E
- L-acetyl-carnitine
- L-carnitine
- Lycopene
- Vitamin D
- Melatonin
- Vitamin C
- Fumarate
- N-acetyl cysteine (NAC)
- Tamoxifen citrate
- CoQ10
๐ Original studies are referenced in this post or within the linked Remembryo posts.
๐ก Reminder: Terms underlined with a dotted black line are linked to glossary entries. Clicking these does not count toward your paywall limit.
Note that this study looked at the spontaneous pregnancies and not IVF outcomes. But this is still indicative of improved sperm quality if spontaneous rates are improving.
Table of Contents
Spontaneous pregnancy rates
Based on 16 RCTs and 1,355 participants, there was a statistically significant increase in spontaneous pregnancy rates in men who used antioxidant supplements compared to those who didnโt (17.2% vs 9.9%, odds ratio [95%] CI: 1.97 [1.28-3.04]). This means that infertile men who took antioxidants had a 97% increase in the odds of spontaneous pregnancy compared to men who didnโt take supplements or placebo. The quality of evidence was moderate.
Live birth rates (from spontaneous pregnancies)
Based on 4 RCTs and 388 participants, there was no statistically significant difference in live birth rates in men who used antioxidant supplements compared to those who didnโt (odds ratio [95%] CI: 1.21 [0.53-2.76]). The quality of evidence was very low.
Miscarriage rates (from spontaneous pregnancies)
Based on 4 RCTs and 459 participants, there was no statistically significant difference in miscarriage rates in men who used antioxidant supplements compared to those who didnโt (odds ratio [95%] CI: 1.01 [0.34-3.00]). The quality of evidence was very low.
Sperm DNA fragmentation
Based on 3 RCTs and 135 participants, there was no statistically significant differences in sperm DNA fragmentation in men who used antioxidant supplements for 3 months or less compared to those who didnโt. The quality of evidence was very low.
There are several types of sperm DNA fragmentation assays, and all the studies here used the TUNEL assay.
Total antioxidant capacity
Total antioxidant capacity (TAC) is a measure of the total antioxidants in seminal plasma.
Based on 6 RCTs and 316 participants, there was a statistically significant increase in total antioxidant capacity in men who used antioxidant supplements compared to those who didnโt (increase was on average 1.87). The quality of evidence was low.
Sperm concentration
Based on 36 RCTs and 4,310 participants, there was a statistically significant increase in sperm concentration in men who used antioxidant supplements compared to those who didnโt (increase was on average 5.93 million/ml). The quality of evidence was moderate.
These increases were significant in men who took supplements for 3 months or less, or for up to 6 months, but not in those who used them for more than 9 months. Itโs not clear if the men using supplements for longer than 9 months have a greater degree of infertility and are resistant to any positive effect, or if the effect of the supplement itself deteriorates over time.
Sperm morphology
Based on 18 RCTs and 1,828 participants, there was a statistically significant increase in sperm morphology in men who used antioxidant supplements compared to those who didnโt (increase was on average 3.28%). The quality of evidence was low.
These increases were significant in men who took the supplements for 3 months or less, 6 months, or for 9 months or more.
Subgroup analyses that removed patients with varicocele repair show a persistent benefit of antioxidant supplements
Varicoceles are a common condition that can lead to reduced sperm quality. As varicocele repair can improve many of the outcomes examined in this study, the authors did a subgroup analysis to remove studies that included varicocele repair.
In most cases this didnโt change the results. This means that antioxidants had a positive effect that wasnโt related to the benefit from varicocele repair.
Conclusions
This study found statistically significant benefits in using antioxidants for:
- Spontaneous pregnancy rates
- Sperm concentration
- Sperm morphology
- Total antioxidant capacity in semen
These benefits persisted even when removing studies that included men who had varicocele repair.
There was no statistically significant benefit in live birth rates, miscarriage rates, or sperm DNA fragmentation.
Limitations of this study include the low number of RCTs that examined live birth rates and sperm DNA fragmentation, as well as a high amount of variability (heterogeneity) due to the large numbers of supplements used. However the authors confirm that they adjusted for this statistically.
The findings of this study mostly agree with a 2019 Cochrane review (Smits et al. 2019), and increase the number of studies reviewed and overall quality of evidence, while also examining additional outcomes.
The authors conclude that antioxidants can be used to treat male infertility to improve spontaneous pregnancy rates, semen parameters and in those with elevated oxidative stress.
Even though this study looked at spontaneous pregnancy outcomes, and not IVF outcomes, this still relates to sperm quality (along with the improved semen parameters). So the use of antioxidants for infertile men will likely improve IVF outcomes.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Masterโs in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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