Nutrient Supplementation

Improving Male Fertility Fourfold

Cesar Mora-Esteves, MD; David Shin, MD


Semin Reprod Med. 2013;31(4):293-300. 

In This Article


Male infertility can often be a frustrating problem because it is a multifactorial disorder for which an identifiable cause cannot be found in a significant percentage of cases.[16]

The damaging effects of OS are reported to play a role in 30 to 80% of subfertile men.[17] Unlike genetic factors, nutritional factors can be changed by altering the patient's diet. Treatment strategies to reduce seminal OS levels may enhance natural conception and the outcome of assisted reproductive technologies. Antioxidants are the most important defense against free radical-induced infertility. Increases in ROS are thought to be due to environmental, lifestyle, and medical exposures (Table 1). Treatment with antioxidants is a widely used therapy for several medical indications including male-factor infertility, although its efficacy has yet to be well established. It is unknown whether ROS production can be used as a criterion to select men for antioxidant therapy, since intracellular sperm antioxidant status, sperm count, abstinence time, and other confounding factors must also be considered. Seminal fluid OS levels can be quantified either by direct methods such as chemiluminescence assays, cytochrome-c and nitroblue tetrazolium reduction, flow cytometry, electron spin resonance spectroscopy, and xylenol orange-based assay or by indirect methods that measure the levels of biomarkers of OS such as thiobarbituric acid-reactive substances, isoprostane, DNA damage, and total antioxidant capacity. The measurement of ROS may help to identify those patients who could benefit from antioxidant supplementation.[17] Bykova et al demonstrated that sperm samples from infertile men had higher levels of ROS and suggested that these men may benefit from antioxidant supplementation.[18] ROS negatively affect male fertility by altering sperm's membranes and its DNA. When a sperm's membranes are damaged, both motility and the ability to break down oocyte membranes are compromised.[19] Spermatozoal DNA integrity plays a major role in fertilization and subsequent embryo growth (for both natural and assisted conception).[13,20–22]

The Cochrane Collaboration

In 2011, the Cochrane Collaboration reviewed antioxidant use in infertile men. The objective of this review was to determine whether supplemented oral antioxidants compared with placebo, no treatment or another antioxidant improve outcomes for couples undergoing assisted reproduction with a subfertile male partner (Cochrane).[19]

The two main questions asked in this review were as follows: (1) do supplemented oral antioxidants improve assisted reproductive outcomes for couples with male-factor or unexplained infertility and (2) do different types of antioxidants given to infertile men have varying effects on assisted reproductive outcomes.[19]

This review pooled data from 34 randomized, controlled trials that included 2,876 couples. The primary outcome was live birth rate per couple. Secondary outcome measures included pregnancy rate, miscarriage rate, stillbirth rate, level of sperm DNA damage, sperm concentration/motility, and treatment-related side effects.

Use of antioxidants resulted in a statistically significant (p = 0.0008) increase in live birth rates when compared with men taking placebo (using three trials; pooled odds ratio [OR], 4.85; 95% confidence interval [CI], 1.92 to 12.24). Likewise, the increase in pregnancy rate was statistically significant (p < 0.0001) using 15 trials where 96 pregnancies occurred in 964 couples (pooled OR, 4.18; 95% CI, 2.65 to 6.59). Due to low-quality evidence, conclusions regarding the effect of antioxidants on sperm quality were not possible. The authors did conclude, however, that antioxidant supplementation might improve live birth and pregnancy rate outcomes for subfertile couples undergoing assisted reproduction.[19]

There continues to be a need for larger, randomized, controlled trials looking at the use of antioxidants and nutrient supplements for improving male fertility. Antioxidant supplements continue to be used because of the low cost and relatively low toxicity profile. In this review, we examine the potential role of antioxidants in the treatment of OS-induced male-factor infertility. Table 2 outlines antioxidant options.