Effect of BNT162b2 mRNA COVID-19 vaccine on sperm morphokinetics and DNA integrity: A prospective observational study in Japan

Objective: To assess whether the coronavirus disease 2019 (COVID-19) mRNA vaccine affects sperm morphokinetics using a computer-assisted semen analyzer and other semen parameters using a sperm chromatin structure assay. Method(s): Healthy male volunteers in two Japanese clinics between May 2021 and December 2021 were prospectively analyzed. Participants donated sperm twice, two days apart, in the following phases: before vaccination, 2 weeks after the first vaccine dose, and 2, 4, and 12 weeks after the second dose. Basic sperm parameters, sperm motility characteristics, and the percentage of DNA-damaged sperm were compared among the different phases. Result(s): Ninety-six semen samples from ten volunteers, who were vaccinated with the BNT162b2 mRNA vaccine, were evaluated. There were no significant differences between any phases in basic semen findings and parameters of the sperm chromatin structure assays. Regarding sperm motion characteristics, the average linear velocity, beat-cross frequency, and sperm motility index significantly decreased after the second vaccine dose (P=0.018, P=0.003, and P=0.027, respectively), with no significant differences between any two phases by post-hoc pairwise comparisons. Conclusion(s): After COVID-19 mRNA vaccination, while sperm motion characteristics might fluctuate, no apparent deterioration of basic sperm parameters or sperm DNA integrity was observed. Given the adverse effects of COVID-19 on sperm, our findings suggest that there might be no reason to refrain from vaccination for healthy individuals.Copyright © 2023 Asian Pacific Journal of Reproduction Produced by Wolters Kluwer- Medknow.

Male fertility: summary overview of the publications January - March 2022.

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January - March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Male fertility: summary overview of the publications January - March 2022.

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January - March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Male fertility: summary overview of the publications January - March 2022.

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January - March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Male fertility: a summary overview of the publications April - September 2022.

The article provides an overview of the most significant publications on male infertility. The main selection criteria were the practical relevance of the article, as well as the impact factor of the journal it was published, according to the ScImago Journal Rank (SJR). As a result, a list of 10 papers published in Q2 - Q3 (April - September) 2022 was formed. The summary overview includes articles on the following topics: role of coronavirus infection in disorders of spermatogenesis, efficacy of hormonal stimulation before surgical sperm extraction, therapy consequences of diabetes mellitus on progeny reproductive health, new methods for selecting spermatozoa in IcSI, the efficacy of antioxidants, the safety of vaccines against SARS-coV-2, the importance of genetic tests and predictive factors for micro-TESE success.Copyright © 2022 Authors. All rights reserved.

Semen quality changes during infection and recovery phases of mild-to-moderate COVID-19 in reproductive-aged patients: a prospective case series.

BACKGROUND: Despite the documented effects of the coronavirus disease 2019 (COVID-19) on spermatogenesis, the reversibility of these effects is uncertain. We aimed to assess the changes of sperm quality between the infection and recovery phases of COVID-19 in reproductive-aged men. The semen quality of men with mild-to-moderated COVID-19 (defined by the degrees of symptoms and chest involvement on computed tomography) was studied during October, 2020-May, 2021 at our hospital. Two semen samples were analyzed at timings estimated to represent spermatogenic cycles during the infection and recovery phases of COVID-19. RESULTS: A total of 100 patients were included with mean ± SD (range) age of 24.6 ± 3.3 (21-35) years. During infection, 33% of patients had abnormal semen quality. However, a significant reduction was found in this abnormality from 33 to 11% (P < 0.001) after recovery from infection. In a comparison of the two semen analyses, there were significant improvements in the mean values of sperm progressive motility (P =0.043) and normal morphology (P < 0.001). However, the mean sperm concentration showed a statistically insignificant increase (P = 0.844). CONCLUSIONS: In reproductive-aged patients with mild-to-moderate COVID-19, the effects on seminal quality were recoverable, represented by significant improvements in the means of progressive sperm motility and normal morphology between the infection and recovery phases of COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04595240 .

RéSUMé: CONTEXTE: Malgré les effets documentés de la maladie à coronavirus 2019 (COVID-19) sur la spermatogenèse, la réversibilité de ces effets reste incertaine. Notre objectif était d'évaluer les changements de la qualité du sperme entre les phases d'infection et de récupération de la COVID-19 chez des hommes en âge de procréer. La qualité du sperme d'hommes atteints d'une forme de COVID-19 de légère à modérée (définie par les degrés de symptômes et l'atteinte thoracique lors de la tomodensitométrie) a été étudiée entre octobre 2020 et mai 2021 dans notre hôpital. Deux échantillons de sperme ont été analysés à des moments estimés représenter les cycles de spermatogénèse pendant les phases d'infection et de rétablissement de la COVID-19. RéSULTATS: Au total, 100 patients ont été inclus avec un âge moyen ± ET (intervalle) de 24,6 ± 3,3 ans (21-35). Au cours de l'infection, 33% des patients avaient une qualité anormale de sperme. Une réduction significative de cette anomalie de 33 à 11% (p < 0,001) a toutefois été observée après la guérison de l'infection. La comparaison des deux analyses de sperme montre des améliorations significatives des valeurs moyennes de la motilité progressive (p = 0,043) et de la morphologie normale (p< 0,001) des spermatozoïdes. Cependant, la concentration moyenne de spermatozoïdes a montré une augmentation statistiquement non significative (p = 0,844). CONCLUSIONS: Chez les patients en âge de procréer atteints d'une forme de COVID-19 légère à modérée, les effets sur la qualité spermatique étaient récupérables, avec des améliorations significatives des valeurs moyennes de la motilité progressive et de la morphologie normale des spermatozoïdes entre les phases d'infection et de récupération de la COVID-19.

Comparison of spermatozoal DNA quality and fragmentation in COVID-19 survivor with non-COVID-19 survivor

Background: SARS-CoV-2 is known to infect the testes and reduce the quality of spermatozoa so that it is at risk of causing male infertility. Data related to the effect of SARS-CoV-2 infection on sperm parameters from Southeast Asia, especially Indonesia, are still very limited, so it is necessary to investigate further which parameters are most affected by COVID-19. Destination: This study aims to compare the concentration, motility, morphology, and DNA fragmentation of spermatozoa in the COVID-19 survivor group and the non-COVID-19 survivor group in Indonesia. Method: This research was conducted at two fertility centers in Indonesia, namely BOCAH Indonesia, Primaya Hospital Tangerang, and the Laboratory of Biomedical Sciences, Faculty of Medicine, Airlangga University, Surabaya. The research subjects were taken from two groups of volunteers, COVID-19 survivors, and non-COVID-19 survivors. The semen analysis was carried out including for all samples, including concentration, motility, and morphology-based on guidelines from the World Health Organization (WHO) 2010. Meanwhile, spermatozoa DNA fragmentation was assessed using the sperm chromatin dispersion (SCD) method.

Validation of a SARS-CoV-2 RT-PCR assay: a requirement to evaluate viral contamination in human semen.

RESEARCH QUESTION: Is it possible to validate an accurate and reliable method for direct detection of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) in human semen fractions? DESIGN: This qualitative improvement study aimed to provide a prospective validation of SARS-CoV-2 detection in male semen. The SARS-CoV-2 genome was detected by multiplex real-time RT-PCR on patient samples that underwent routine semen analyses for infertility at the Center for Reproductive Medicine at the University Hospital of Clermont-Ferrand. Samples comprised surplus semen collected for treatment with assisted reproductive technology. Seminal fluid and spermatozoa fractions were isolated with density gradient centrifugation and cryopreserved. Positive samples were prepared with a standard of inactivated SARS-CoV-2 particles. RESULTS: The analytical method was validated in both seminal fluid and spermatozoa fractions. In both semen fractions, the assay was repeatable, reproducible and showed high sensitivity with a limit of detection of 0.33 SARS-CoV-2 genome copies/µl. The limit of quantification was 1 copy of the SARS-CoV-2 genome/µl. The method was effective regardless of semen quality (normal and altered sperm parameters), number of spermatozoa or the cryoprotectant media used to freeze spermatozoa. CONCLUSION: This validated RT-PCR assay provided accurate and reliable screening of SARS-CoV-2 in seminal fluid and spermatozoa fractions. This method is essential to ensure protection against viral contamination in the cryobanking process.

Reproductive toxicity of ritonavir in male: Insight into mouse sperm capacitation.

Since COVID-19 began in 2019, therapeutic agents are being developed for its treatment. Among the numerous potential therapeutic agents, ritonavir (RTV), an anti-viral agent, has recently been identified as an important element of the COVID-19 treatment. Moreover, RTV has also been applied in the drug repurposing of cancer cells. However, previous studies have shown that RTV has toxic effects on various cell types. In addition, RTV regulates AKT phosphorylation within cancer cells, and AKT is known to control sperm functions (motility, capacitation, and so on). Although deleterious effects of RTV have been reported, it is not known whether RTV has male reproduction toxicity. Therefore, in this study, we aimed to investigate the effects of RTV on sperm function and male fertility. In the present study, sperm collected from the cauda epididymis of mice were incubated with various concentrations of RTV (0, 0.1, 1, 10, and 100 µM). The expression levels of AKT, phospho-AKT (Thr308 and Ser473), and phospho-tyrosine proteins, sperm motility, motion kinematics, capacitation status, and cell viability were assessed after capacitation. The results revealed that AKT phosphorylation at Thr308 and Ser473 was significantly increased, and the levels of tyrosine-phosphorylated proteins (at approximately 25 and 100 kDa) were significantly increased in a dose-dependent manner. In addition, RTV adversely affected sperm motility, motion kinematics, and cell viability. Taken together, RTV may have negative effects on sperm function through an abnormal increase in tyrosine phosphorylation and phospho-AKT levels. Therefore, individuals taking or prescribing RTV should be aware of its reproductive toxicity.

Investigating Impacts of CoronaVac Vaccination in Males on In Vitro Fertilization: A Propensity Score Matched Cohort Study.

PURPOSE: This study aimed to evaluate the influences of SARS-CoV-2 vaccination (CoronaVac) on male fertility and investigate the impact of a history of the CoronaVac vaccination in males on gamete and embryo development and in vitro fertilization (IVF) outcomes. MATERIALS AND METHODS: A prospective cohort study enrolled couples undergoing IVF cycles between June and August 2021 at Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in China. According to the history of SARS-CoV-2 vaccination in males, the participants were divided into the vaccination group and the non-vaccination group. A self-controlled study of semen analyses for males before and after CoronaVac vaccination was conducted. Baseline characteristics were matched using propensity score matching. Participants were categorized into the unexposed group (non-vaccination) and exposed group (vaccination), and the population was 271 for each. Semen parameters and IVF outcomes were the main outcomes. RESULTS: Generally, no statistically significant differences were exhibited between the matched cohorts regarding embryo developmental parameters, including fertilization rate, cleavage rate, high-quality embryo rate, blastocyst formation rate, and available blastocyst rate, as well as clinical outcomes, such as implantation rate, biochemical pregnancy rate, and clinical pregnancy rate. Moreover, males after vaccination seemed to have fluctuating semen parameters including increased semen volume, lower motility, and decreased normal forms of sperm, while the motile sperm counts were similar. In addition, all semen parameters were above the lower reference limits. CONCLUSIONS: Our findings suggested that CoronaVac vaccinations in males may not have adverse effects on patient performance or the gamete and embryonic development potential during assisted reproductive technology (ART) treatments.

COVID-19: a risk for diabetes induced male subfertility. (Special Issue: Covid-19 in India.)

The latest corona virus epidemic COVID-19 triggered by the SARS-Cov2 virus has become exponentially high across the globe. Moderate and extreme pneumonia along with respiratory distress, fever, fatigue and malaise are clinically decripted among infected persons. Patients with severe COVID-19 can also develop a systemic inflammatory response that leads to multisystem organ dysfunction. Case studies across many countries suggest that severe acute respiratory syndrome corona viruses (SARS-CoV and SARS-CoV-2) can invade islet cells via angiotensin converting enzyme-2 (ACE-2) receptors and is responsible for reversible beta-cell damage and transient hyperglycemia and diabetic ketoacidosis. Also, hypercytokinemia might have indirect destabilizing effect on pancreatic islets in COVID-19 patients that accelerate development of insulin resistance and type 2 Diabetes Mellitus (T2DM). Testicular resistance of insulin and altered insulin signalling on the other hand is responsible for decreased steroidogenesis by Leydig cells. Cytokine and chemokines in diabetic testicular tissue also induce sperm cell apoptosis. Additionally, ACE2 expression in the testis is restricted to the Leydig and Sertoli cells in humans which suggests that SARS-Cov2 has the likelihood of infecting the male gonad. Autopsied testicular and epididymal tissues of COVID-19 patients also showed signature of inflammation and germ cell apoptosis. This review work hypothesize that the male subfertility observed in COVID 19 survivors may be due to direct invading of SARS Cov 2 virus in testis or by development of diabetes and transient glucose metabolic disorders.

ACE2 Receptor and Its Isoform Short-ACE2 Are Expressed on Human Spermatozoa.

Angiotensin-converting enzyme 2 (ACE2) is a protein widely expressed in numerous cell types, with different biological roles mainly related to the renin-angiotensin system. Recently, ACE2 has been in the spotlight due to its involvement in the SARS-CoV-2 entry into cells. There are no data available regarding the expression of ACE2 and its short-ACE2 isoform at the protein level on human spermatozoa. Here, protein expression was demonstrated by western blot and the percentage of sperm displaying surface ACE2 was assessed by flow cytometry. Immunocytochemistry assays showed that full-length ACE2 was mainly expressed in sperm midpiece, while short ACE2 was preferentially distributed on the equatorial and post-acrosomal region of the sperm head. To our knowledge, this is the first study demonstrating the expression of protein ACE2 on spermatozoa. Further studies are warranted to determine the role of ACE2 isoforms in male reproduction.

Assessment of the sexual level of patients with COVID-19 thorough evaluation and analysis of sperm and reproductive hormones

Since covid-19 has been shown to cause infertility in male patients, this study evaluated the sexual level of covid19 patients using sperm and reproductive hormones. For the covid-19 patients, the semen volume was 2.1 ml smaller than the healthy ones, while the sperm count was 67 ml lower than non-covid-19. A substantial difference in total sperm number was found (36 for covid-19 patients and 103 for non-covid-19), with total sperm numbers of 125.33 for patients and 447.21 x106 for healthy. In other words, the percentage of motile sperm was 21.42 for sick and 55.26 for healthy. We discovered that covid-19 sperm have less than 33.84% overall motility than healthy sperm, while the normal morphology revealed for covid-19 patients showed 8.87 per cent less than non-covid-19. The difference between covid-19 and non-covid-19 testosterone is 130.2NG/DL, while the covid-19 patients had 3.7mIU/mL less FSH than non-covid-19 individuals, indicating that covid-19 reduces FSH. LH in covid-19 patients was 3.48UI/L lower than the non-covid-19 patients. As a result, we compared covid-19 and non-covid-19 patients' sex hormone profiles. Therefore, covid-19 has a deleterious effect on sperm properties. Finally, the study adds to the expanding clinical evidence on covid19's influence on male reproductive health. Future research should focus on the effect of covid-19 on female fertility.

Rapid impact of COVID-19 infection on semen quality: a case report.

A unique opportunity to conduct a longitudinal analysis of semen quality in a male subject immediately before, during and after COVID-19 infection, has revealed new insights into the impact of this virus on male reproductive function. A moderate COVID infection that did not require hospitalization resulted in a state of azoospermia that persisted for 4 weeks. Given that the duration of spermatogenesis and epididymal sperm maturation in the human is 78 days, we calculate that a viral attack on the germ line was initiated at or before the patient was symptomatic and may have been signalled by a sudden reduction in sperm count and motility, several weeks earlier. Before the virus had been fully cleared, reinitiation of spermatogenesis occurred as evidenced by spermatozoa reappearing in the ejaculate exhibiting high levels of motility but significant levels of oxidative DNA damage as measured by a modified 8-OHdG assay protocol. These unique data indicate that even a moderate COVID-19 infection is capable of rapidly inducing a state of azoospermia that rapidly reverses as the infection wanes.

Evaluation and comparative analysis of sperm characteristics in men before and after vaccination with Sputnik V (Gam-COVID-Vac)

The study objective is to evaluate reproductive function in men who underwent vaccination with Sputnik V (Gam-COVID-Vac) based on quantitative and qualitative sperm characteristics. Materials and methods. Mean ejaculate characteristics were analyzed in 3 independent groups formed from patients examined at the Laboratory of Genetics of Impaired Reproduction of the Research Center for Medical Genetics in 2021: the comparison group consisted of 759 unvaccinated men;the group of 73 men who were vaccinated with Sputnik V and for whom the time between the full vaccination (2 components of the vaccine) and semen analysis was less than 75 days;and the group of 58 men who underwent vaccination more than 75 days prior to semen analysis. The results of semen analysis of 53 patients before and after full vaccination procedure were compared. In 32 patients, less than 75 days passed since vaccination;in 21 patients, more than 75 days;for 5 patients data prior to 75 days since vaccination and after are available. The study group included patients without history of COVID-19. Standard semen analysis was performed in accordance with the World Health Organization Guidelines. For statistical analysis of the differences between the groups Student's t-test was used with significance level of p <0.05. Results. Comparison of semen analysis of the same patients before and after vaccination procedure showed no statis- tically significant differences. Small decrease in progressive motility was observed (from 19.0 ± 0.4 to 13.8 ± 1.1 %), as well as decline in sperm morphology (from 4.53 ± 0.12 to 3.55 ± 0.31 %) in the group who underwent vaccination less than 75 days prior to the analysis. In the group who underwent vaccination more than 75 days before semen analy- sis, sperm characteristics do not differ from the unvaccinated group. Conclusion. There were no statistically significant differences in the ejaculate indices of the same patients before and after vaccination with Sputnik V (Gam-COVID-Vac). In the group of patients examined in a short time after vaccination, there is a decrease in the quality of sperm compared to the comparison group (unvaccinated). In the group of patients examined in a more distant period, there are no significant differences in the quality of sperm from the group of unvac- cinated, which indicates the absence of long-term consequences of vaccination for the quality of ejaculate. © 2021 ABC-press Publishing House. All Rights Reserved.

Antioxidant-Based Therapies in Male Infertility: Do We Have Sufficient Evidence Supporting Their Effectiveness?

Under physiological conditions, reactive oxygen species (ROS) play pivotal roles in various processes of human spermatozoa. Indeed, semen requires the intervention of ROS to accomplish different stages of its maturation. However, ROS overproduction is a well-documented phenomenon occurring in the semen of infertile males, potentially causing permanent oxidative damages to a vast number of biological molecules (proteins, nucleic acids, polyunsaturated fatty acids of biological membrane lipids), negatively affecting the functionality and vitality of spermatozoa. ROS overproduction may concomitantly occur to the excess generation of reactive nitrogen species (RNS), leading to oxidative/nitrosative stress and frequently encountered in various human pathologies. Under different conditions of male infertility, very frequently accompanied by morpho-functional anomalies in the sperm analysis, several studies have provided evidence for clear biochemical signs of damages to biomolecules caused by oxidative/nitrosative stress. In the last decades, various studies aimed to verify whether antioxidant-based therapies may be beneficial to treat male infertility have been carried out. This review analyzed the results of the studies published during the last ten years on the administration of low-molecular-weight antioxidants to treat male infertility in order to establish whether there is a sufficient number of data to justify antioxidant administration to infertile males. An analysis of the literature showed that only 30 clinical studies tested the effects of the administration of low-molecular-weight antioxidants (administered as a single antioxidant or as a combination of different antioxidants with the addition of vitamins and/or micronutrients) to infertile males. Of these studies, only 33.3% included pregnancy and/or live birth rates as an outcome measure to determine the effects of the therapy. Of these studies, only 4 were case-control studies, and only 2 of them found improvement of the pregnancy rate in the group of antioxidant-treated patients. Additionally, of the 30 studies considered in this review, only 43.3% were case-control studies, 66.7% enrolled a number of patients higher than 40, and 40% carried out the administration of a single antioxidant. Therefore, it appears that further studies are needed to clearly define the usefulness of antioxidant-based therapies to treat male infertility.

Influence of seasonal differences on semen quality and subsequent embryo development of Belgian Blue bulls.

Belgian Blue bulls are more susceptible to high temperature and humidity index (THI) than most other cattle breeds. Here, we investigated whether high ambient temperature during summer affected semen quality and subsequent embryo development in Belgian Blue cattle. For this purpose, semen samples were collected from six healthy mature Belgian Blue bulls in March (Low THI group; THI between 30.6 and 56.4) and August 2016 (High THI group; maximum THI of 83.7 during meiotic and spermiogenic stages of spermatogenesis; 14-28 days prior to semen collection) respectively. Motility, morphology, acrosome integrity, chromatin condensation, viability, and reactive oxygen species production were assessed for frozen-thawed semen. Moreover, the efficiency of blastocyst production from the frozen-thawed semen samples of the two groups was determined in vitro. Blastocyst quality was determined by assessing inner cell mass ratio and apoptotic cell ratio. Fresh ejaculates showed a higher sperm concentration in low THI when compared to the high THI group (P ≤ 0.05), whereas semen volume, subjective motility, and total sperm output were not affected (P > 0.05). In frozen-thawed semen, total and progressive motility, viability, and straight-line velocity were lower in high THI compared to the low THI group (P < 0.05), while H2O2 concentration, aberrant chromatin condensation, and abnormal spermatozoa were higher in the high THI group (P < 0.05). Blastocyst rates were significantly higher when low THI samples were used (P < 0.05). Moreover, the total cell number and trophectoderm cells were significantly higher (P < 0.05) in blastocysts derived from low THI samples, whereas the apoptotic cell ratio was significantly higher (P < 0.01) in blastocysts derived from high THI spermatozoa. In summary, our data show that elevated ambient temperature and humidity during summer can decrease the quality of frozen-thawed spermatozoa in Belgian Blue bulls and also affect subsequent embryo development.

COVID-19 and human spermatozoa-Potential risks for infertility and sexual transmission?

As COVID-19 infections wreak havoc across the globe, attention has rightly been focused on the vital organ systems (lung, kidney and heart) that are vulnerable to viral attack and contribute to the acute pathology associated with this disease. However, we should not lose sight of the fact that COVID-19 will attack any cell type in the body expressing ACE2 - including human spermatozoa. These cells possess the entire repertoire of receptors (AT1R, AT2R, MAS) and ligand processing enzymes (ACE1 and ACE2) needed to support the angiotensin signalling cascade. The latter not only provides COVID-19 with a foothold on the sperm surface but may also promote integration, given the additional presence of a range of proteases (TMPRSS2, TMPRSS11B, TMPRSS12, furin) capable of promoting viral fusion. This article reviews the roles played by these various cellular constituents in maintaining the vitality of human spermatozoa and their competence for fertilization. The reproductive consequences of a viral attack on these systems, in terms of fertility and the risk of sexual transmission, are currently unknown. However, we should be alive to the possibility that there may be reproductive consequences of COVID-19 infection in young males that go beyond their capacity to survive a viral attack.

It is currently unknown whether SARS-CoV-2 is viable in semen or whether COVID-19 damages spermatozoa.

Research is needed to understand the presence of the SARS-CoV-2 virus in semen, sexual transmissibility, and impact on sperm quality. Several studies have examined men recovering from COVID-19, but large-scale community-based testing is needed to ascertain the effects on the male reproductive tract, and the potential for prolonged transmission.

SARS-CoV-2 presence in seminal fluid: Myth or reality.

Great concerns have been raised on SARS-CoV-2 impact on men's andrological well-being, and one of the critically unanswered questions is whether it is present or not in the seminal fluid of infected subjects. The expression of ACE2 and TMPRSS2 in the testis and in the male genital tract allows speculations about a possible testicular involvement during the infection, possibly mediated by local and/or systemic inflammation that might allow a high viral load to overcome the hemato-testicular barrier. To date, few investigations have been carried out to ascertain the presence of SARS-CoV-2 in the seminal fluid with contrasting results. Furthermore, the cumulative number of subjects is far too low to answer the question unambiguously. Therefore, great caution is still needed when evaluating this data; otherwise, we risk unleashing unmotivated concerns in the scientific world with troublesome consequences in reproductive medicine.