by Dr. Sam Ward et al. – MediQuality
“We unreservedly endorse the importance of the research report. However, we wish to put this report into perspective alongside the scientific data already known, because we have not found this critical reflection and contextualization in public information channels,” said the seven Belgian experts.
Since the mechanism by which the virus enters the host cell via two proteins (ACE2 and TMPRSS2) has been elucidated, the impact of COVID-19 on male reproduction has naturally attracted enormous interest (Hoffmann M, et al. Cell. 2020 Apr 16;181(2):271-280.e8). These proteins are expressed in many different organ systems, including the testes, where ACE2 expression has been observed in Sertoli cells—a cell population that supports spermatogenesis—spermatogonia, and Leydig cells, which are responsible for testosterone production (Wang et al. Cell. April 9, 2020;9(4):920).
Since SARS-CoV-2 can infect testicular cells, there is good reason to be concerned about transmission of the virus through other routes (sexual transmission) and the long-term consequences for male fertility. However, numerous studies have found no viral particles in the testicles of most infected or recovering patients (Achua et al. World J Mens Health. 2020;38:e56, Yang et al. Eur Urol Focus. 2020 Sep 15;6(5):1124-1129, Pan et al. 2019. Fertil Steril. 2020). Although it is not certain whether SARS-CoV-2 can be transmitted via semen, the entry of SARS-CoV-2 into the structures of the male reproductive system may also affect spermatogenesis and male reproductive function.
The cited report is merely a report containing preliminary conclusions and not a peer-reviewed research report, which calls into question its quality. Furthermore, it involves a very small group of patients (26 patients). Notably absent is a control group or data from before the COVID infection, and the study included patients between the ages of 35 and 70, which only partially corresponds to the young population we typically see for semen analysis.
Direct or indirect effect?
It was already known from similar studies that a clinically evident COVID infection affects sperm quality; these studies also showed that the severity of the clinical presentation was associated with the severity of the impairment in sperm quality (Holtmann et al. Fertilizer Sterilizer. 2020 Aug;114(2):233–238, and Li et al. EClinicalMedicine. 2020 Oct 23:100604). This could indicate a general inflammatory response, as is also seen in other forms of viral orchitis, and signs of which are indeed visible in the testicles of COVID patients who have died (Yang et al. Eur Urol Focus. September 15, 2020;6(5):1124-1129, Li et al. EClinicalMedicine. Oct 23, 2020:100604, Achua et al. World J Mens Health. 2020;38:e56.). It is therefore by no means clear whether the effects of COVID on fertility are greater than, for example, those of a severe case of the flu accompanied by fever.
Given the current data, any conclusion would be premature, and caution is warranted. It is useful to share information and contribute to the debate, but it is equally useful to acknowledge the limitations of the data: for example, the public media do not mention that a mild infection does not appear to affect sperm quality (Holtmann et al. Fertilizer Sterilizer. 2020 Aug;114(2):233–238.), or that such findings are not abnormal and are often reversible in cases of clinical viral infections caused by other known viruses.
Large-scale population-based testing for SARS-CoV-2 and semen analysis—both in symptomatic men with a wide range of COVID-19 severity and in asymptomatic men—is needed before we can better understand whether sexual transmission can occur and clearly determine the effects of SARS-CoV-2 on semen parameters. Longitudinal follow-up of patients before, during, and after clinical infection with the coronavirus would help analyze the reversibility of the findings.
About the Experts
Dr. Sam Ward, urologist, Fertility Center at the Sint-Janskliniek, Brussels
Prof. Dr. Maarten Albersen, urologist, UZ Leuven
Prof. Dr. Dr. Guy T’sjoen, endocrinologist, UZ Gent
Prof. Dr. Dirk Vanderschueren, endocrinologist, UZ Leuven
Prof. Dr. Frank Claessens, Research Director at the Laboratory for Molecular Endocrinology, KULeuven