New Study: Oxidative Stress and Infertility
Ashok Agarwal, Ph.D., HCLD

Oxidative stress might be the culprit in the etiology of infertility in men whose semen characteristics are normal, according to a new study from the Cleveland Clinic Urological Institute's Center for Advanced Research in Human Reproduction and Infertility. If this finding can be confirmed, it might finally clear up a long-standing mystery, one that can misdirect physicians toward a futile search for a female factor.

Researchers reviewed the records of 299 men at the Cleveland Clinic fertility clinic and found that only 34 ( 11%) had normal sperm and no leukocytospermia. Three causes of infertility were identified in the 34 couples: male varicocele with no female-factor infertility (n = 12), female-factor infertility (n = 16) and idiopathic infertility (n = 6). For each semen specimen, the researchers ascertained the seminal reactive oxygen species (ROS) level, the total antioxidant capacity (TAC) and the composite ROS-TAC score.

The ROS-TAC index is a novel composite score that was recently developed at the Cleveland Clinic. These measurements were compared with those taken from 52 men with male factors who had already been treated and from 19 normospermic control donors.

ROS levels were much higher in the idiopathic infertility subgroup (mean log [ROS + 1] 2.34) than in the controls (1.39; P= 0.01),and the mean ROS level in the normospermic infertile group as a whole was higher than that of the controls (1.73 vs. 1.39; P = 0.03).

Correspondingly, the TAC value was lower in the infertile group as a whole (946 Trolox equivalents) than in the controls (1651; P < 0.006), and it was significantly lower in all three subgroups than in the controls.

ROS- TAC scores were much higher in the controls than in the infertile men - in the group as a whole and in each subgroup (35.9 vs. 50.0 overall; P < 0.01).

Even men whose partners had female-factor infertility had high oxidative stress values. This suggests that the actual problem might extend beyond the female factor, and involve, at least in part, previously undiagnosed seminal oxidative stress.

In light of the results of this study, we recommend that all normospermic men who undergo an infertility evaluation be examined for oxidative stress. Those who have high oxidative stress might benefit from antioxidant supplementation.



This table shows the relationship between ROS-TAC scores and predicted chances of one-year fertility after one year follow-up in 34 infertile but normospermic men, based on comparisions with male-factor patients known to be fertile


Box-plots illustrate the ROS-TAC scores across six groups of men: controls, fertile male-factor patients, infertile male factor patients and three groups of normospermic patients (female-factor only, idiopathic and varicocele)

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Last Update : December 29, 2008
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