Male Infertility Linked to Increased Mortality

Laurie Barclay, MD

May 16, 2014

Men who were found to have abnormal semen parameters in an infertility evaluation had a higher risk for death compared with men who underwent an infertility evaluation but were found to have normal semen parameters, according to a cohort study published online May 16 in Human Reproduction. The higher mortality rate in these men may suggest a common cause of infertility and mortality.

Men with at least 2 semen abnormalities were more than twice as likely to die during approximately an 8-year period compared with men who had normal semen. That increased risk for mortality is comparable to that seen with either smoking or diabetes.

"But here we're seeing the same doubled risk with male infertility, which is relatively understudied," lead author Michael Eisenberg, MD, PhD, assistant professor of urology and director of male reproductive medicine and surgery at Stanford University in California, said in a news release.

Previous studies suggested either an inverse association or no association between semen quality and mortality.

In the current study, Dr. Eisenberg and colleagues examined the possible link between semen quality and mortality in men being evaluated for infertility, using a study cohort identified from 2 infertility care centers. These included men evaluated between 1994 and 2011 at the Stanford Reproductive Endocrinology and Infertility semen database and men seen between 1989 and 2009 at the andrology database at the Baylor College of Medicine Special Procedures Laboratory in Houston, Texas.

The authors used data from the National Death Index or Social Security Death Index to estimate mortality and estimated the participants' comorbidities using information from the Charlson Comorbidity Index or the Centers for Medicare & Medicaid Services–Hierarchical Condition Categories Model.

Poor Semen Quality Linked to Higher Death Risk

Overall, 11,935 men with a mean age of 36.6 years underwent an infertility workup. Of these men, 69 (0.58%) died during 92,104 person years of follow-up (mean duration of follow-up, 7.7 years). Compared with the general population, the study cohort overall had a significantly lower mortality rate (69 deaths observed vs 176.7 expected; standardized mortality rate, 0.39 [95% confidence interval (CI), 0.30 - 0.49]).

"If you're trying to have a child, you're probably reasonably healthy at the moment and in mental shape to be planning for your future," Dr. Eisenberg said in the release. The study authors also reason that men who get evaluated for infertility tend to have a higher-than-average socioeconomic status as well as better diet, education, and access to healthcare.

However, when the researchers looked at mortality rates within their study population, they found that men with impaired semen parameters, including low semen volume, sperm concentration, sperm motility, total sperm count, and total motile sperm count, had higher mortality rates than did men with normal semen parameters. Men with at least 2 abnormal semen parameters had a 2.3-fold (95% CI 1.12 - 4.65) higher risk for death compared with men with normal semen after adjusting for current health status.

Underlying Mechanism Still Unknown

"It's plausible that, even though we didn't detect it, infertility may be caused by pre-existing general health problems," Dr. Eisenberg said in the release.

"But we controlled for this factor as best we could, and while that did attenuate the measured risk somewhat, there seems to be something else going on. Could it be genetic, developmental or hormonal factors? Or could it be that something about the experience of having and raising kids — even though you may sometimes feel like they're killing you — actually lowers mortality?"

Limitations of this study include possibly low generalizability because the cohort included only infertile men, reliance on administrative data for determination of comorbidity, and lack of data on infertility diagnosis and lifestyle factors.

On the basis of their findings, the study authors conclude that men with impaired semen parameters have an increased mortality rate in the following years, suggesting that an infertility evaluation showing poor semen quality may be a marker of overall health.

In an accompanying editorial, Germaine Buck Louis, PhD, director of the Division of Intramural Population Health Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, noted that male fertility may have implications regarding health later in life.

"What is particularly concerning about the findings is the observation of greater mortality for affected compared to unaffected men in a short period of time following the infertility evaluation," Dr. Louis writes. "This finding begs the question as to whether or not a higher likelihood of mortality remains across the lifespan for men with suboptimal semen quality."

This study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and the National Institutes of Health. The authors have disclosed no relevant financial relationships.

Human Reprod. Published online May 16, 2014. Article abstract, Editorial extract

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