Severe infertility may dispose males to lower cognitive function

A new study is suggesting that severe male factor infertility may predispose a man to lower cognitive function.

Researchers presented data at the AUA annual meeting in Chicago that support further investigating this relationship to determine whether affected men demonstrate specific genetic defects.

Investigators at Baylor College of Medicine looked at men who either had no sperm in the ejaculate or very few (<10 million sperm/mL) and compared them to men who fathered children without difficulty. They found that men with severe infertility had an IQ score that was about 7.1 points lower than fertile controls.

“Although this was statistically significant, this is not considered to be a significant difference by most cognitive experts and would be unlikely to manifest in a day-to-day fashion,” said study investigator Jonathan Beilan, MD, clinical fellow in male reproductive medicine and surgery at Baylor College of Medicine, Houston, working with Larry Lipshultz, MD, and co-authors.

He said there is growing evidence that suggests genetics are involved in male infertility and this may be important to neural development and cognitive function. Currently, it is unknown if male infertility and lower cognitive function are due to shared genetic abnormalities.

“Further understanding this potential link could aid in counseling couples and direct future treatment plans for affected men,” wrote the authors.

This current study is an update to the research team’s previous series exploring the association between male infertility and cognitive function, anxiety, and depressive symptoms. Dr. Beilan et al prospectively identified and enrolled 70 men (mean age, 38.5 years) presenting to a single academic andrology practice. More than half of the men (N=42) presented with non-obstructive azoospermia or severe oligospermia (<5 million sperm/mL) and 28 had proven fertility (control group).

For this investigation, all the men completed the validated Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Test of Nonverbal Intelligence, 4th edition (TONI-4) IQ evaluation under the supervision of a trained technician. The authors analyzed patient occupations and they used U.S. Census Bureau statistics to estimate incomes by occupation. A psychologist in blinded fashion analyzed the TONI-4 results to determine final IQ scores.

When the authors compared the test and questionnaire results between the two groups, they found the mean estimated income in the infertile group was $76,474 compared to $97,340 for the control group (p=.14). Slightly more of the men in the infertile group (22 of 41, 53.7%) had at least a bachelor's degree compared to the control group (14 of 28, 50.0%) (p=.77). The mean IQ for the infertile cohort was 99.2 points compared to the mean IQ of 106.3 for the control group (mean difference: 7.1 points; p=.001). The mean PHQ-9 scores and the mean GAD-7 scores were similar between both groups and these test results ensured that other psychologic factors did not impact the IQ findings.

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“It’s important to remember that our study focused on men with only the most severe forms of infertility and that our findings cannot be extrapolated to all men with infertility,” said Dr. Beilan. “We found an average difference of 7.1 IQ points between the infertile and control groups. While statistically significant, the clinical or real world implications of this are less profound.”

He said this difference represents roughly 0.5 standard deviations from the mean, so clinically it is unlikely to change practice patterns. However, it does point to the potential and interesting connection between fertility and cognitive function.

Dr. Beilan said in recent years fertility in men has emerged as a measure of health. Individuals with very low sperm counts are not as healthy as those with normal semen counts, as evidenced by increased cancer risk, lower testosterone levels, and increased morbidity/mortality rates, according to Dr. Beilan. He noted that many of these men may have genetic defects that explain their low sperm counts, but these same defects can affect more than just the reproductive system.

“Although our study was not designed to elucidate the mechanism behind this connection, it reaffirms that there is an intrinsic relationship that deserves further investigation,” said Dr. Beilan.