January 29, 2021

expert reaction to study looking at COVID-19 and male reproductive function

A prospective, longitudinal cohort study published in Reproduction looks at male fertility and COVID-19.

Dr Alison Campbell, Director of Embryology of the CARE Fertility Group, said:

“Very little is known about the possible impact of the coronavirus responsible for COVID-19, or the disease itself, on sperm and the male reproductive system. 

“The authors of this research study performed an assessment of biological and sperm quality markers in 84 previously-fertile men with confirmed COVID-19 infection and compared the results to men without the infection. They concluded that COVID-19 infection impaired male reproductive function.

“One issue with this study is that it only examined sperm quality for up to 60 days. As the length of the spermatogenic cycle (time to a man to produce mature sperm) is longer than this, most of the sperm analysed will have undergone part of their development prior to the COVID-19 infection. Further studies are required to follow up for a longer period after infection to monitor the recovery period more fully.

“Furthermore, the study group of men with COVID-19 were treated to varying degrees with corticosteroids and antiviral therapies which may have impacted their results. The control group were not exposed to these medications.

“It’s important to note that viral infections, and elevated temperature generally, can have a negative impact of sperm quality, and this negative impact is usually reversed upon full recovery. It is too soon to say whether COVID-19 is any different to this.

“Overall, men should not be unduly alarmed by this research. There is currently no definitive evidence of long-lasting damage caused by COVID-19, to sperm or male reproductive potential. More, larger studies are required in order to confirm whether COVID-19 may be damaging to male reproductive health and sperm function, and whether this is short lived.

“If men have concerns or require information, they should speak with their GP or a fertility specialist.”

Prof Allan Pacey, Professor of Andrology, University of Sheffield, said:

“Since the start of the Covid-19 pandemic, there has been an understandable (but theoretical) concern about whether this coronavirus might have a detrimental impact on the fertility of men who become infected. This is because the same receptors which the virus uses to gain access to the tissues of the lung, are also found in the testicles.

“To date, more has been written raising this as a concern, than actual primary data which seeks to confirm or refute the hypothesis. Just before Christmas, in preparation for a lecture I was giving at the Progress Educational Trust annual conference, I reviewed over 14 primary papers that had so far been published which had attempted to answer this theoretical question. My view at the time, was that the data published to date seemed broadly reassuring that any measurable effect of coronavirus on male fertility was probably only slight and temporary.

“Therefore, the paper published today in the journal Reproduction comes to a surprising conclusion, as it seems to suggest otherwise. However, I think the paper and the press release seriously over claim the value of the findings and I need to raise a strong note of caution in their interpretation of this data.

“For example, the authors state that their data demonstrates that “COVID-19 infection causes significant impairments of male reproductive function” yet it only actually shows an association. For example, there are some significant differences in the characteristics of the men who were infected with covid and those who were not (the control group), such as the body mass index and the waist circumference of the control group which were significantly different. This could explain many of the findings.

“Also, the fact that men with COVID-19 were very sick and therefore hospitalised and treated with a variety of medications, whereas the control group were not, is a critical significant difference in itself regardless of whether or not the men had COVID-19. Therefore, all I see in this dataset are possible differences in the sperm quality between men who are sick with a febrile illness and those who were well. We already know that a febrile illness can impact on sperm production, regardless of what caused it.

“In addition, the authors of this paper have used a blinding array of measurements to look at the effect of inflammatory markers, or markers of oxidative stress, in the semen of these men and have reported some interesting differences. But again these are not a surprise.

“That the study was able to repeat these measurements every 10 days over a 60 day period is no mean feat and this is a nice part of the study. However, since sperm production takes just under 3 months (roughly) to be completed from start to finish, in my opinion they ended the study 30 days too soon!

“It would have been more useful to see whether there was a difference at 90 days between the two groups. A paper published last year suggested only a small difference in sperm concentration existed by that time.

“So, to be honest, I don’t think this paper really adds much to the literature about the possible impact of COVID-19 and male fertility.

“It is of course important that we keep this under review and men who are worried about their fertility following coronavirus infection should discuss the matter with their family doctor.” 

Prof Alison Murdoch, Head of Newcastle Fertility Centre at Life, Newcastle University, said:

“This study finds evidence of impaired semen production and sperm function in men after significant Covid-19 infection. It is well documented that adverse changes are frequently seen after systemic illness with recovery typically taking at least 3 months. As the authors acknowledge, their findings may be such a nonspecific response. Thus, longer term studies are needed before the testes is considered to be a high-risk organ specific to Covid-19.

“It is important to note that there is no evidence of Covid-19 virus in the semen and that there is no evidence that virus can be transmitted via semen.”

Dr Channa Jayasena, Reader in Reproductive Endocrinology & Andrology, Imperial College London, said:

“COVID-19 enters host cells by bindings its spike glycoprotein to the ACE2 receptor which is found at high levels within the testes. This has made us concerned that COVID-19 could impair male infertility. Being ill from any virus such as flu can temporarily drop your sperm count (sometimes to zero) for a few weeks or months. This makes it difficult to work out how much of the reductions observed in this study were specific to COVID-19 rather than just from being ill. This study suggests there may be an inflammatory response in the testes following COVID-19, which makes it more plausible that COVID-19 influences male fertility. This makes it important to study the long-term effects of COVID-19 on male fertility.”

Prof Sheena Lewis, Honorary Professor, Queen’s University Belfast, said:

“This is a topical study. My concerns are that the men with COVID had substantially higher body weight and were on a number of therapeutic treatments.  We know that obesity alone reduces sperm quality. The COVID treatments may also have affected these men’s sperm quality, rather that COVID itself.”   

‘COVID-19 and male reproductive function: a prospective, longitudinal cohort study’ by Behzad Hajizadeh Maleki et al. was published in Reproduction at 00:01 UK time on Friday 29^th January.

https://doi.org/10.1530/REP-20-0382

Declared interests

Dr Alison Campbell: “Dr Alison Campbell is an employee of CARE Fertility, a private company providing fertility services.”

Prof Allan Pacey: “Chairman of the advisory committee of the UK National External Quality Assurance Schemes in Andrology, Editor in Chief of Human Fertility, Trustee of the Progress Educational Trust (Charity Number: 1139856) and Trustee of the British Fertility Society (Charity Number:1075661) (all unpaid).”

Dr Channa Jayasena: No conflicts of interest relevant to this work.

Dr. Channa Jayasena is a Reader in Reproductive Endocrinology & Andrology at Imperial College London. He holds a National Institute for Healthcare Research (NIHR) Fellowship in male infertility research. he is also a media ambassador for the Society for Endocrinology.

Prof Alison Murdoch: No conflict of interest

Prof Sheena Lewis: “SEM Lewis is CEO of Examenlab Ltd, a university molecular diagnostics company specialising in male reproductive health.”