COVID-19 impact in fertility
Since December 2019, the world’s focus has been on the appearance of a new Coronavirus causing Severe Acute Respiratory Syndrome (SARS-CoV-2).
This virus is responsible for the pandemic that is currently affecting us globally and is having a profound impact on people’s lives.
Clinically, the disease, known as COVID-19, can present itself through multiple symptoms such as persistent fever, cough, pneumonia, etc. We learned in a short period of time that, in addition to these typical respiratory symptoms, infected people also suffered other types of non-respiratory manifestations, such as neurological, cardiovascular and thrombotic alterations, among others.
Our concern, as specialists in assisted reproduction, was to find out, from that moment to present day, the COVID-19 impact on the reproductive health of the population.
To this end, we are constantly reviewing the works and studies that are being published on the subject.
Some of the questions that can help us understand this impact are the following:
- If we know the mechanism by which the virus enters the cells, is it possible to find the virus in semen?
- Could this virus be considered a sexually transmitted disease?
- Does the virus affect semen quality?
- Can it cause inflammation of the testicles (orchitis) or erectile dysfunction?
The first aspect we must consider is, being a virus with unpredictable evolution, the number of publications and papers has limitations in terms of number of cases studied and the design of these studies.
Therefore, and as noted above, the results should be interpreted with caution and more robust studies are needed to arrive at clear scientific evidence.
SARS-CoV-2 presence in the sperm
In general, it is known that SARS-CoV-2 needs to infect a cell in order to use all its “cellular machinery” to multiply and infect the patient’s new cells.
The virus surface what is known as protein S or “Spike” which acts as a “key”. This “key” fits into the “lock” which is the ACE2 receptor on the surface of the cells to be infected. In addition, the cell to be infected must have another necessary requirement: the presence of a transmembrane protease known as TMPRSS2.
Studies to date show that, in both testes and spermatozoa, the presence of both requirements (ACE2 receptor and TMPRSS2) occurs in a very low proportion (less than 0.01% of cells)1.
Thus, it is reasonable to assume that the testis would not be susceptible to direct virus infection.
The above, together with the fact that SARS-CoV-2 has not been found in the semen of infected and recovered patients, suggests that there is no possibility of infection from a male to his partner.
In summary, this virus cannot be considered a sexually transmitted disease (STD).
This is of particular importance in couples who are seeking pregnancy, either spontaneously or through assisted reproduction treatments. It is also relevant information from the sperm donation programmes point of view.
Affecting sperm quality
The proposed hypotheses in this regard are based on indirect mechanisms, since, as we have explained above, sperm do not meet the necessary requirements to be infected.
Some of the proposals, according to which infected men could present alterations in their seminal quality2, are the following:
- Fever: it is well known that the presence of fever (hyperthermia) above 38.5-39ºC for 3 or more days can reduce sperm quality in men, resulting in a lower sperm count and lower sperm motility, temporarily, recovering a few weeks after the infection.
- Hormonal alterations: adequate levels of testosterone are necessary for the correct production of spermatozoa. Decreased levels of this hormone have been observed in infected men compared to uninfected men. This could explain the decrease in sperm quality.
These hormonal alterations can be explained in several ways: the stress to which the infected patient is subjected, possible testicular damage secondary to the infection or the administration of corticosteroids to control certain inflammatory processes.
- Inflammatory processes: as is already known, the disease caused by this virus can trigger different inflammatory processes that can be more or less generalised or localised. These processes can lead to an immune defence response with production of different types of pro-inflammatory proteins (cytokines). These proteins are likely to reach the testicle, damaging the seminiferous tubules (the site responsible for sperm production and maturation), thus altering seminal quality.
We must underline the major limitation of all published studies on semen quality, as the semen quality of males prior to infection was not known.
Orchitis and erectile disorders
Inflammatory processes focused at testicular level and the possible presence of microthrombi in the testicular blood vessels can lead to the development of orchitis or inflammation in one or both testicles.
This complication is closely related to the disease severity and the patient’s age. In fertile age males and with mild to moderate symptoms, there’s a published probability of 5-10% 1.
Also, the possible presence of microthrombi in the male genital trac vascular network, together with decreased testosterone levels and the patient’s stress from the situation he’s experiencing, can lead to erectile dysfunction.
In the event of either complication, it is advisable to consult a urologist to assess the situation and reach a satisfactory solution.
Now that we have analysed the relationship between male fertility and COVID-19, we ask ourselves the following questions:
- Has the virus been found in the female genital tract?
- Does the infection affect female fertility?
- Does the quality of oocytes worsen in women who have been infected?
With regard to the impact of COVID-19 on female fertility, we must say that the number of published studies is still much lower than those of male fertility.
This may be due, in part, to the fact that female gametes (oocytes) are less available.
Presence of SARS-CoV-2 in the female genital tract
To date, there are no published studies that demonstrate with strong evidence the presence of the virus in the female genital tract3.
However, some studies show the presence of the ACE2 receptor and the TMPRSS2 protease in ovarian and endometrial tissue.
Affecting female fertility
In contrast to men, no significant hormonal changes in oestradiol, progesterone and anti-mullerian hormone levels have been detected in infected women to date4.
Despite this, the study does find differences in the composition of some proteins and hormones present in the follicular fluid containing the oocytes. These authors suggest the hypothesis that the oocytes quality from infected women may be lower than in uninfected women4.
As a conclusion, and as we noted at the beginning of the text, in the case of both men and women, studies on fertility have been carried out on a very small number of patients and with designs that are not always accurate, so we must consider these results with great caution.
In any case, the studies published to date suggest alterations that are, in any case, temporary and potentially recoverable after overcoming the acute phase of the infection, especially in those cases with mild or moderate symptomatology.
- Tur-Kaspa I., Tur-Kaspa T., Hildebrand G., Cohen D. “COVID-19 may affect male fertility but is not sexually transmitted: a systematic review”. Fertil Steril Rev Vol.2, Nº 2, April 2021. doi.org/10.1016/j.xfnr.2021.01.002
- Collins A., Zhao L., Zhu Z., Givens N., Bai Q., Wakefield M., Fang Y. “Impact of COVID-19 on Male Fertility”. Urology 00:1-7,2022. doi.org/10.1016/j.urology.2021.12.025
- Boudry L., Essahib W., Mateizel I., Van de Velde H., De Geyter D, Piérard D., Waelput W., Uvin V., Tournaye H., De Vos M., De Brucker M. “Undetectable viral RNA in folicular fluid, cumulus cells and endometrial tissue simples in SARS-CoV-2 positive women”.Fertil Steril Rev, December 2021. doi.org/10.1016/j.fertnstert.2021.12.032
- Herrero H., Pascuali N., Velázquez C., Oubiña G., Hauk V., Zúñiga I, Gómez Peña M., Martínez G., Lavolpe M., Veiga F., Neuspiller F., Abramovich D., Scotti L., Parborell F. “SARS-CoV-2 infection negatively affects ovarian function in ART patients”. BBA-Molecular Basis of Disease 1868 (2022)166295. doi.org/10.1016/j.bbadis.2021.16629
Dra. Ana Fabregat farmacéutica, del Instituto Bernabeu.