COVID-19 reduces fertility in men, study suggests
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COVID-19 may negatively affect sperm quality and reduce fertility in men, and the magnitude of that effect may depend on the severity of disease, researchers reported.
“Little is known about the virus-host interaction of COVID-19 in sperm cells,” Behzad Hajizadeh Maleki, a doctoral student and research assistant in the department of psychology and sports science at Justus Liebig University in Germany, and Bakhtyar Tartibian, PhD, of the physical education and sports science department at Urmia University in Iran, wrote in in the journal Reproduction.
“We are the first to address the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19,” they said.
Hajizadeh Malekiand Tartibian conducted a prospective, longitudinal cohort study of 84 men with laboratory-confirmed COVID-19 and 105 men without the disease in Iran. The researchers analyzed changes in angiotensin-converting enzyme 2 (ACE2) activity, markers of inflammation and oxidative stress, apoptotic variables and semen quality, all of which were evaluated at 10-day intervals for up to 60 days.
Most of the men in the study were in their 30s and “differed substantially” in body weight, body fat percent and BMI, according to the researchers. Among those with COVID-19, all but one had either a moderate, severe or critical form of the disease. A urology expert confirmed that all the men were fertile in the study. Men with COVID-19 were treated with corticosteroids and/or antiviral therapies.
The researchers reported that at baseline and during subsequent follow-ups, the COVID-19 group showed significantly higher levels of seminal plasma ACE2 enzyme, as well as higher levels of both pro- and anti-inflammatory cytokines in sperm — including interleukin (IL) 1-beta, IL-6, IL8, IL-10, transforming growth factor (TGF)-beta, tumor necrosis factor-alpha, and interferons alpha and gamma. They also had higher levels of reactive oxygen species and lower superoxide dismutase activity compared with healthy controls.
The markers of inflammation and oxidative stress in sperm cells of men with COVID-19 were increased by more than 100% compared with controls, according to the researchers. Sperm concentration was reduced by 516%, mobility by 209% and sperm cell shape was altered by 400%.
Although these effects tended to improve over time — representing “a transient state of male subfertility like those with oligoasthenoteratozoospermia” — the researchers wrote they remained “significantly and abnormally higher in the COVID-19 patients, and the magnitude of these changes were also related to disease severity.”
In an interview with Healio Primary Care, Hajizadeh Maleki recommended that couples who want to have children should proceed with caution.
“Female partners of men recovering from the disease should decide not to conceive until a specialist carefully examines and certifies their fertility status,” he said.
The reason why COVID-19 affects seminal inflammatory mediators is not yet clear, according to the researchers, but they suggested “the perturbated immune factors may be just a reflection of general immune response, like in serum.”
They acknowledged that antiviral therapies for COVID-19 may have “additional harmful consequences” on male fertility, and that further research is needed.
Perspective
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The complete spectrum of sequelae following SARS-CoV-2 infection is not fully known at this time. While COVID-19 has been reported in testicular tissue, Maleki and colleagues take the first steps to evaluate its deleterious effects on male reproductive health. This included significantly reduced sperm parameters (concentration, motility and morphology) and elevated seminal oxidative stress after COVID-19 infection.
Even with the introduction of the vaccine, health care providers should use these findings to counsel reproductive aged couples on the importance of properly following the CDC guidelines regarding social distancing, masking and hand washing. Many questions remain unanswered, and larger scale studies with longer follow-up evaluating hormonal profiles and semen analyses are needed to know the long-term consequences after recovering from COVID-19 on male fertility.
Furthermore, most patients in this study received treatment with corticosteroids and/or antiviral therapies, which have been associated with testicular dysfunction. Health care providers should reassure patients that there are no randomized trials with adequate controls that can draw definite conclusions regarding the short- and long-term impacts of the drugs used to treat COVID-19 on male reproduction. Finally, as andrology laboratories take measure to safely and effectively deliver reproductive care, men who have had COVID-19 and fertility concerns should be evaluated by a male reproductive urologist.
Perspective
Back to TopFirst and foremost, kudos to the research team for publishing this comprehensive analysis on changes within the male reproductive system following acute COVID-19 infection over a 60-day time period. The study highlights changes to known indicators of fertility potential within the male testicle, and the researchers are honest about the limitations of their study protocols. It was promising to see that the initial significant decline in semen parameters did show progressive improvement over the length of the study.
Beyond providing a starting point for conversation on fertility risk factors, we cannot make any general population-based conclusions on how COVID-19 infection affects future fertility potential or pregnancy rates. My fear is that the general public may draw alarming conclusions about their fertility through headlines or summaries of the data. As a specialist in male infertility, I feel the information stated in this study will not lead to any major changes to the way we manage patients.
It is a well-known fact that any acute state of stress like viral infections can lead to a decline in fertility parameters like sperm counts/quality as well as a decline in the environment that nurtures the sperm. In the case of COVID-19 or any other infection, the treatments (steroids, antivirals, etc.) can also compromise fertility parameters. Plus, the sheer mental stress that comes from a diagnosis can also contribute to a decline in fertility parameters.
Fertility is a complex and intimate process. As physicians, we need to stress that there are much stronger, well-known, research-proven risk factors to a declining fertility status, which include poor lifestyle decisions, excess weight, and general stress. Fortunately, these risk factors have proven treatment strategies like quitting smoking, limiting alcohol intake, weight loss through exercise and diet modification and focusing on mental wellness.
President, Florida Urological Society
Perspective
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While at face value, the data in this article are somewhat concerning, the issues that make these data less meaningful include the lack of a control group of young men with inflammatory or respiratory diseases such as rheumatoid arthritis, diabetes, COPD or a control group of young men who were taking medications such as steroids and/or antiviral therapy.
Further, we are not told if the patients who tested positive for COVID-19 remained on their steroids and antiviral therapy throughout the 60-day course of the study, which confounds the data.
Thus, while these data are intriguing, there are several flaws in the study that impact the data’s value. Therefore, these data should be interpreted with extreme caution until such time as an appropriate control group is studied.
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