|Year : 2021 | Volume
| Issue : 2 | Page : 52-57
COVID-19 and male fertility
Department of Reproductive Medicine, Mother and Child Hospital, New Delhi, India
|Date of Submission||16-Aug-2022|
|Date of Acceptance||14-Oct-2022|
|Date of Web Publication||30-Dec-2022|
Dr. Nalini Kaul
Department of Reproductive Medicine, Mother and Child Hospital, D-64, Defence Colony, New Delhi 110024
Source of Support: None, Conflict of Interest: None
COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global health crisis. The virus entry into the host cell is facilitated by the coexpression of angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 receptors. The male genital system is vulnerable to infection because of the presence of ACE2 and TRMPSS2 on the spermatogonial and somatic cells. Testicular damage leading to the impairment of spermatogenesis and semen parameters has been documented, though the exact mechanism of testicular injury is not confirmed. Immune response to infection, dysfunction of the steroidogenic pathway, impairment of the blood–testes barrier, and fever per se are implicated. The alteration in semen parameters has been demonstrated with COVID-19 infection leading to reproductive compromise. The recovery of semen parameters occurs within 3 months of the infection. It is recommended to wait for 3 months after infection to start infertility treatment. The possibility of sexual transmission and vertical transmission remains a concern, even though the virus has not been detected in semen in most studies. Fertility preservation procedures (semen and testicular tissue cryopreservation) must not be deferred because of their time-sensitive nature. Safety protocols to prevent crosscontamination in cryostorage and to maintain the safety of laboratory personnel should be strictly adhered to. ESHRE and ASRM recommend screening patients before initiating fertility preservation procedures. Testing semen samples for SARS-CoV-2 by RT-PCR has also been advocated to improve safety. Long-term follow-up should be considered in men and young boys exposed to infection and in children conceived during the infection. Vaccination for COVID-19 should be promoted as it does not compromise male fertility.
Keywords: COVID-19, cryopreservation, male fertility, SARS-CoV-2, semen
|How to cite this article:|
Kaul N. COVID-19 and male fertility. Onco Fertil J 2021;4:52-7
| Introduction|| |
COVID-19 or the “coronavirus disease” is caused by a highly transmissible and lethal respiratory virus named the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). Reports of the infection first emerged from Wuhan (China) in November 2019, and the virus was isolated on January 7, 2020. Within a few months, the SARS-CoV-2 virus had the world in its lethal grip, and by March 2020, WHO had declared COVID-19 a pandemic. In an attempt to contain the virus, strict travel restrictions and lockdowns were imposed worldwide. The world came to a near standstill witnessing an unprecedented health and economic crisis.
In this atmosphere of fear and uncertainty, routine health services including fertility treatments were severely impacted. Globally, fertility societies proposed the cessation of routine assisted reproductive technology (ART) procedures and even advised against planning natural conception. Fertility preservation was permitted because of its time-sensitive nature. Guidelines/recommendations were put in place to reduce the risk of infection for both patients and health workers. The fertility needs of women of advanced maternal age or those with a poor ovarian reserve were largely ignored, despite the knowledge that delay could compromise their reproductive outcome. Precious time would be lost till fertility services opened up again. These decisions were made based on the highly infectious nature of the disease, high mortality rates, insufficient knowledge of viral effects on the reproductive organs and gametes, fear of vertical transmission, and crosscontamination in cryostorage. This review will focus on the effect of COVID-19 on the male reproductive system, the possible implications for fertility, concerns of sexual transmission, and the need for long-term follow-up. It will also touch upon any research conducted on the effects of COVID vaccination on male reproduction/fertility.
| Viral structure and host entry|| |
The coronavirus is an enveloped positive-sense, single-stranded RNA virus with special glycoprotein spikes around the viral envelope giving it a crown-like appearance. The angiotensin-converting enzyme 2 (ACE2) receptor and the enzyme transmembrane protease serine 2 (TMPRSS2) facilitate entry of the SARS-CoV-2 virus into the host cell, coexpression of the two being essential for tissue damage. TMPRSS2 primes and cleaves the SARS-CoV-2 spike protein (S) into two; subsequently S1 protein binds to the ACE2 receptor to enter the host cell by endocytosis, and S2 facilitates membrane fusion., Tissue susceptibility is, therefore, proportional to the number of ACE receptors present. Pulmonary tissue is the primary target because of the large number of ACE receptors present in the alveoli. Viral transmission occurs primarily through respiratory droplets, but SARS-CoV-2 has been isolated from blood samples, urine, and feces from infected patients leading to concerns about the presence of the virus in other body fluids, especially semen.
The expression of ACE2 has been found in the reproductive organs of both men and women. The coexpression of ACE2 and TMPRSS2 receptors has also been identified in the trophectoderm of the late blastocyst, making it susceptible to infection. Trophectoderm contributes to the formation of placental tissue, and therefore infection may impact the fetal development. Recently, infection with various mutated though less-lethal strains of SARS-CoV-2 has been observed, but their individual effect on the reproductive system remains to be elucidated.
| Signs and symptoms|| |
The SARS-CoV viruses are known to cause respiratory and gastrointestinal infections. SARS-CoV-2 is primarily transmitted through respiratory droplets. The symptoms of COVID-19 range from a mild cough, fever, fatigue, myalgia, and ageusia to severe respiratory distress and multiorgan failure., Many people harboring the virus may remain asymptomatic. Men appear to be more susceptible to the infection and exhibit a higher mortality rate. The classic picture on computerized tomography is the ground-glass appearance of the lungs. The associated cytokine storm and hypercoagulability contribute to the complications of COVID-19. Coronavirus-induced orchitis and testicular dysfunctions have also been identified, and a case of priapism has also been reported.
| COVID-19 AND THE MALE REPRODUCTIVE TISSUE|| |
High levels of ACE2 receptors have been identified on the spermatogonia, adult Leydig cells (LC), and Sertoli cells (SC). Within the LC, ACE2 regulates the testosterone production and the balance of interstitial fluid volume by modulating the conversion of angiotensin II to angiotensin I. The downregulation of ACE2 expression in LC is correlated with severe impairment of spermatogenesis. TMPRSS2 is highly expressed in the prostate, epididymis, and testes. The coexpression of ACE2 and TMPRSS2 in the male reproductive organs including the corpus cavernosum increases susceptibility to the virus, leading to concerns of erectile dysfunction, altered semen parameters, sexual transmission, and disturbed androgen metabolism., These factors individually or in combination may lead to male factor infertility.
The earliest report on orchitis and extensive testicular damage due to SARS-CoV infection was made by Xu et al. (2006) after doing an autopsy on six infected individuals. They identified germ cell destruction, a thickened basement membrane, few or no spermatozoa in the seminiferous tubules, and leukocyte infiltration in the testes. An increased number of CD3+ T lymphocytes and CD68+ macrophages detected were indicative of an immune response. They could not detect the SARS viral genomic sequences in the testes by in situ hybridization (ISH) and suggested that testicular damage was caused by the immune response. The detection of the SARS coronaviruses in testicular epithelial cells and LC by electron microscopy combined with ISH was reported by Zhao et al. (2003). More specifically, a report of testicular examination of COVID-19 infection in 12 patients in autopsy revealed extensive damage to the germ cells (SC swelling, cytoplasmic rarefaction, detachment from tubular basement membrane, thinning of seminiferous epithelium, and leukocyte infiltration). CD3+ T lymphocytes and CD68+ macrophages in the testicular interstitium were also increased. The virus could be detected only in one patient with a high viral load. Massive germ cell destruction in infected males was also reported by Ma et al. (2021). A systematic review conducted by He et al. (2021) reported the presence of SARS-CoV-2 in 10 of 33 testicular samples from 14 studies on the testis/epididymis or scrotum, with a total of 333 patients. The existence of the virus in testes is yet to be confirmed; however, testicular damage due to COVID-19 has been documented with certitude. The examination of prostatic fluid has not revealed the presence of SARS-CoV-2 so far.
Virus in semen
Enormous efforts have been made to isolate SARS-CoV-2 in semen because the shedding of the virus in semen even in small quantities could lead to a risk of sexual transmission, crosscontamination in cryostorage, and vertical transmission to the fetus. It is believed that mature sperm can bind to the virus and replicate making it possible for sperm to act as a vector for COVID-19 infection. Unfortunately, viral detection in semen remains highly debated in the literature. SARS-CoV-2 was found in semen during both the acute (26.7%) and recovery phase (8%) of the disease by Li et al. (2020). In contrast, various other researchers,,, reported an inability to detect the virus in semen 80 days on average, after recovery from mild-to-moderate infection, acute stage of infection, and in asymptomatic men with a positive nasopharyngeal swab. A systematic review and meta-analysis that included six studies and 136 samples concluded that the number of studies on the subject was too few to make a firm conclusion. Of the six studies done mainly in the recovery phase, four reported absence and two reported presence of SARS-CoV-2 in semen. Testicular discomfort, damage to the germ cells, and alteration in semen analysis were reported in these articles. In another systematic review by He et al. (2021), only one of the 28 studies included reported the presence of SARS-CoV-2 in semen in six patients. Four of the six were in the acute phase of disease, whereas two were in the convalescence stage (six out of 304 patients). After stratifying patients according to the disease course, they reported that the virus was found in the semen at a relatively early stage of infection. The time interval from diagnosis to the collection of semen samples was 2–13 days. The risk of viral shedding in semen seems to be low nevertheless the possibility exists, especially in the presence of a high viral load. It appears that SARS-CoV-2 RNA disappears from the testes soon after recovery, so there is a possibility that it may be able to cross the blood–testes barrier.
| Hormonal alterations|| |
Hormonal alterations have been reported in COVID-19. An increase in luteinizing hormone (LH) level with a lowered testosterone to LH (T:LH) ratio has been found, and it is negatively associated with white blood cell counts and C-reactive protein levels. The alteration in T:LH ratio could also be as a result of LC damage and dysfunction of the steroidogenic pathway.
Though the presence of virus in semen is widely debated, there is no ambiguity regarding the alteration of semen parameters due to COVID-19 infection. Low semen volume, decreased sperm concentration and a total number of sperms per ejaculate, decreased motility, increased DNA fragmentation, and abnormal morphology have been described in infected individuals.,,,,, The degree of impairment appears to be related to the severity of COVID-19 infection. Fortunately, semen parameters return to normal two-three months or more after infection., In a prospective cross-sectional study on 43 sexually active men who had recovered from SARS-CoV-2, Gacci et al. (2021) reported that 25% of men were oligo-crypto-azoospermic, despite the absence of virus RNA in semen. A limitation of this study was that the pre-COVID semen parameters of the participants were not known, but many of these men had fathered children in the past.
Various hypotheses have been proposed for the observed testicular damage and altered semen parameters:
Increased production of inflammatory cytokines with a subsequent immune response and antisperm antibody production.,, The titers of specific anti-SARS-CoV-2 IgG antibody against the spike and the spike-1-receptor-region-domain antigens of the virus show a strong correlation with reduced sperm function. An increase in antisperm IgA and IgG is found to be associated with reduced sperm quality.
Impairment of the blood–testis barrier due to SC involvement allows for the transfer of cytokines. SARS-CoV-2 may also cross the blood–testis barrier and trigger an immune response in the testis or induce a secondary autoimmune response, leading to autoimmune orchitis.
Genes involved in spermatogenesis are impaired in ACE2-positive spermatogonia. This leads to altered spermatogenesis in the infected patients.
Increased DNA fragmentation—Changes in the ACE2 signaling pathway, oxidative stress, and inflammation caused by the virus may cause sperm DNA breakage and an increase of sperm DNA fragmentation index (DFI). An increased DFI (more than 25%) has been associated with gene deletion in sperm, and this could lead to miscarriage, fetal malformation, and fetal arrest.
High fever associated with the infection—Fever is known to affect spermatogenesis. Fever raises the temperature of the testis, leading to apoptosis of meiotic germ cells.
Medication administered, antibiotics, and steroids are known to impair spermatogenesis.
Antiviral drugs like ritavarin can reduce the testosterone level, leading to spermatogenesis disorders, sperm deformities, and oxidative stress.
Hormonal alteration—An increase in serum LH and a decrease in testosterone (T) have been observed. This could lead to impaired spermatogenesis.
Vasculitis associated with COVID-19 could account for an orchitis-like syndrome. Abnormalities in coagulation and segmental vascularization have been observed in testes.
Psychological stress induces systemic oxidative stress and synthesis and release of high levels of nitric oxide. This alters androgen secretion, which in turn leads to impaired spermatogenesis and inhibition of sperm motility. This may cause subfertility and adverse consequences to the fetus.
In view of these findings, it would be prudent to do a postrecovery follow-up of men for 3–6 months to check markers of reproductive function, namely, semen parameters and functional competence of the hypothalamic-pituitary-testicular axis. Male children who have suffered from COVID-19 infection should be subjected to a gonadal examination, and a long-term follow-up should be planned to look for effects on semen parameters, which would compromise future fertility. Follow-up of children conceived during the father’s infection period would also be prudent.
| Cryostorage|| |
Viruses have been known to survive in cryostorage and retain their contamination ability even after 40 years in storage. Hence the risk of crosscontamination and vertical transmission with the subsequent use of cryopreserved sperm has to be acknowledged. It is also imperative that we meet the fertility preservation needs of patients going in for gonadotoxic therapy. Even though SARS-CoV-2 has not been identified in semen unequivocally, risk mitigation strategies and good laboratory practices (GLP) have to be instituted. Risk mitigation strategies include sperm washing, the use of closed cryopreservation systems, liquid nitrogen vapor, and the use of a quarantine cryostorage tank. Sperm washing and preparation techniques remove seminal fluid, dead sperms, and infectious cells, thereby reducing the volume of sperm preserved and thereby the viral load. Closed systems and nitrogen vapor prevent the migration of viruses during cryostorage. Semen or ideally seminal plasma-free sperm samples from infected patients can be put in a quarantine cryostorage tank till a complete assessment of the sample. GLP recommend that gametes and embryos from the infected patients be stored in separate containers, and this must be strictly adhered to. Semen samples for cryopreservation should be collected 3 months after recovery and subjected to an RT-PCR test for SARS-CoV-2. In the event of an emergency semen collection for oncofertility patients, an RT-PCR test for SARS-CoV-2 is mandatory. The sample should be prepared by a double-density gradient technique to dilute viral load, and high-security cryovials should be used. The safety of personnel working in the facility must be kept in mind at all times. No reports are available for testicular tissue freezing; it can be considered only in men who do not have the infection or have recovered after appropriate screening.
| Recommendations for art and infertility treatment|| |
It is recommended that ART treatment be postponed by 3 months in male patients to allow for sperm recovery. If semen cryopreservation has to be carried out urgently prior to oncology treatment, an RT-PCR of semen should be preferably carried out to ensure that semen is not carrying the virus. All such samples should be treated as per the protocols available for viral infections. Precautions must be taken during cryopreservation to avoid crosscontamination and decrease viral load in semen. Though there is no universal recommendation for screening semen donors for SARS-CoV-2, ASRM recommends screening questions for asymptomatic donors to avoid potential infections. ESHRE and ASRM recommend the screening of patients before initiating procedure. A questionnaire-based triage and an RT-PCR test should be carried out.,
| Effect of covid vaccination on male fertility|| |
Vaccine hesitance in men has arisen from the findings that SARS-CoV-2 has an impact on male fertility and that vaccine research did not address male fertility. The first two vaccines authorized for use by the US Food and Drug Administration were the RNA-based vaccines from Pfizer-BioNTech and Moderna. A prospective study was conducted by Gonzalez et al. (2021) on 45 men between ages 18 and 50 (median age = 28 years) with abstinence of 2–7 days. Semen parameters were assessed prior to the first dose of vaccine and approximately 70 days after complete vaccination (two doses). The study of sperm parameters before and after two doses of a COVID-19 mRNA vaccine revealed no significant decreases in any sperm parameter among this small cohort of healthy men. These findings have been confirmed by other authors.,,, The study by Reschini et al. also evaluated vaccines from Astra-Zeneca, Jannsen, and mixed vaccines. Interestingly, in most studies, an increase in sperm counts was seen after vaccination. Parameters such as DNA fragmentation and mitochondrial membrane potential were not assessed. Wesselink et al. (2022) examined the associations of COVID-19 vaccination and SARS-CoV-2 infection with fertility among couples trying to conceive spontaneously. They reported that male infection was associated with a transient reduction in fecundability (FR = 0.82, 95% CI: 0.47, 1.45 for infection within 60 days; FR = 1.16, 95% CI: 0.92, 1.47 for infection >60 days). COVID-19 vaccination was not appreciably associated with fecundability in either partner. These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility; however, COVID-19 vaccination does not impair fertility.
| Conclusions|| |
Male reproductive system is potentially susceptible to SARS-CoV-2 infection because of the presence of ACE2 receptors and TMPRSS2. Testicular damage due to direct viral effects, inflammation, an exaggerated immune response, autoimmune orchitis, fever, or drugs leading to the alteration of semen parameters has been authenticated. Though the presence of SARS-CoV-2 has not been demonstrated conclusively in semen, the possibility of viral shedding into semen in the presence of a high viral load exists. Semen parameters are altered transiently reducing fecundability. The recovery of sperm counts and motility occurs within 3 months of the infection, but long-term studies are required to understand the full effects of COVID-19 on the offspring of these men. Sperm DNA damage subsequent to COVID-19 may lead to higher miscarriage rates. Infertility treatment must be delayed until full recovery to avoid the risk of miscarriage or vertical transmission. It is unclear whether unprotected sex should be allowed till full recovery; it is better to err on the side of caution. Fertility preservation is an emergency situation; semen cryopreservation should not be deferred. Semen should be carried out with strict adherence to GLP. A nasopharyngeal and preferably a seminal fluid RT-PCR for SARS-CoV-2 should be performed prior to semen collection.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization. Coronavirus Disease 2019 (COVID-19): Situation Report—38, Geneva, Switzerland: World Health Organization; 2020.
COVID—Coronavirus 19. ESHRE statement on pregnancy and conception. Available from: https://www.eshre.eu/Press-Room/ESHRE-News#COVID19WG
. [Last accessed on 21 May 2020].
Geber S, Prates N, Sampaio M, Valle M, Meseguer M COVID-19 should be a novel indication for fertility preservation. JBRA Assist Reprod 2020;24:233-4.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al
. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al
. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367:1260-3.
Wang W, Xu Y, Gao R, Lu R, Han K, Wu G Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020;323:1843-4.
Cheng GP, Guo SM, Zhou LQ Suggestions on cleavage embryo and blastocyst vitrification/transfer based on expression profile of ACE2 and TMPRSS2 in current COVID-19 pandemic. Mol Reprod Dev 2021;88:211-6.
Guruprasad L Human SARS-CoV-2 spike protein mutations. Proteins 2021;89:569-76.
Borges do Nascimento IJ, Cacic N, Abdulazeem HM, von Groote TC, Jayarajah U, Weerasekara I, et al
. Novel coronavirus infection (COVID-19) in humans: A scoping review and meta-analysis. J Clin Med 2020;9:941.
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al
. Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017-32.
He W, Liu X, Feng L, Xiong S, Li Y, Chen L, et al
. Impact of SARS-CoV-2 on male reproductive health: A review of the literature on male reproductive involvement in COVID-19. Front Med (Lausanne) 2020;7:594364.
Lamamri M, Chebbi A, Mamane J, Abbad S, Munuzzolini M, Sarfati F, et al
. Priapism in a patient with coronavirus disease 2019 (COVID-19): A case report. Am J Emerg Med 2020;S0735-675730514-3.
Pan PP, Zhan QT, Le F, Zheng YM, Jin F Angiotensin-converting enzymes play a dominant role in fertility. Int J Mol Sci 2013;14: 21071-86.
Wang Z, Xu X scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia, Leydig and Sertoli cells. Cells 2020;9:920.
Ren X, Wang S, Chen X, Wei X, Li G, Ren S, et al
. Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19. Infect Drug Resist 2020;13:3977-90.
Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al
. Orchitis: A complication of severe acute respiratory syndrome (SARS). Biol Reprod 2006;74:410-6.
Zhao JM, Zhou GD, Sun YL, Wang SS, Yang JF, Meng EH, et al
. Clinical pathology and pathogenesis of severe acute respiratory syndrome. Zhonghua Shi Yan he Lin Chang Bing Du Xue Za Zhi 2003;17:217-21.
Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, et al
. Pathological findings in the testes of COVID-19 patients: Clinical implications. Eur Urol Focus 2020;6:1124-9.
Ma X, Guan C, Chen R, Wang Y, Feng S, Wang R, et al
. Pathological and molecular examinations of postmortem testis biopsies reveal SARS-CoV-2 infection in the testis and spermatogenesis damage in COVID-19 patients. Cell Mol Immunol 2021;18:487-9.
He Y, Wang J, Ren J, Zhao Y, Chen J, Chen X Effect of COVID-19 on male reproductive system—A systematic review. Front Endocrinol (Lausanne) 2021;12:677701.
Mao Q, Wu W, Liao Z, Li J, Jia D, Zhang X, et al
. Viral pathogens hitchhike with insect sperm for paternal transmission. Nat Commun 2019;10:955.
Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open 2020;3:e208292.
Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril 2020;113:1135-9.
Song C, Wang Y, Li W, Hu B, Chen G, Xia P, et al
. Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients. Biol Reprod 2020;103:4-6.
Holtmann N, Edimiris P, Andree M, Doehmen C, Baston-Buest D, Adams O, et al
. Assessment of SARS-CoV-2 in human semen—A cohort study. Fertil Steril 2020;114:233-8.
Ruan Y, Hu B, Liu Z, Liu K, Jiang H, Li H, et al
. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation. Andrology 2021;9:99-106.
Vahedian-Azimi A, Karimi L, Makvandi S, Jamialahmadi T, Sahebkar A A systematic review of the assessment of the presence of SARS-CoV-2 in human semen. Adv Exp Med Biol 2021;1321:335-42.
Eisenberg ML Coronavirus disease 2019 and men’s reproductive health. Fertil Steril 2020;113:1154.
Ma L, Xie W, Li D, Shi L, Ye G, Mao Y, et al
. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J Med Virol 2021;93:456-62.
Salonia A, Pontillo M, Capogrosso P, Gregori S, Tassara M, Boeri L, et al
. Severely low testosterone in males with COVID-19: A case-control study. Andrology 2021;9:1043-52.
Navarra A, Albani E, Castellano S, Arruzzolo L, Levi-Setti PE Coronavirus disease-19 infection: Implications on male fertility and reproduction. Front Physiol 2020;11:574761.
Haghpanah A, Masjedi F, Alborzi S, Hosseinpour A, Dehghani A, Malekmakan L, et al
. Potential mechanisms of SARS-CoV-2 action on male gonadal function and fertility: Current status and future prospects. Andrologia 2021;53:e13883.
Anifandis G, Messini CI, Simopoulou M, Sveronis G, Garas A, Daponte A, et al
. SARS-CoV-2 vs. human gametes, embryos and cryopreservation. Syst Biol Reprod Med 2021;67:260-9.
Guo TH, Sang MY, Bai S, Ma H, Wan YY, Jiang XH, et al
. Semen parameters in men recovered from COVID-19. Asian J Androl 2021;23:479-83.
] [Full text]
Donders GGG, Bosmans E, Reumers J, Donders F, Jonckheere J, Salembier G, et al
. Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: A prospective, observational study and validation of the SpermCOVID test. Fertil Steril 2022;117:287-96.
Gacci M, Coppi M, Baldi E, Sebastianelli A, Zaccaro C, Morselli S, et al
. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Hum Reprod 2021;36:1520-9.
Fan C, Lu, W, Ding Y, Li K, Wang J ACE2 expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front Med (Lausanne) 2021;7:563893.
Kamkar N, Ramezanali F, Sabbaghian M The relationship between sperm DNA fragmentation, free radicals and antioxidant capacity with idiopathic repeated pregnancy loss. Reprod Biol 2018; 18:330-5.
Sergerie M, Mieusset R, Croute F, Daudin M, Bujan L. High risk of temporary alteration of semen parameters after recent acute febrile illness. Fertil Steril 2007;88:970.e1-7.
Narayana K, D’Souza UJ, Rao KS Ribavirin-induced sperm shape abnormalities in Wistar rat. Mutat Res 2002;513:193-6.
Corona G, Baldi E, Isidori AM, Paoli D, Pallotti F, De Santis L, et al
. SARS-CoV-2 infection, male fertility and sperm cryopreservation: A position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità). J Endocrinol Invest 2020;43:1153-7.
Li R, Yin T, Fang F, Li Q, Chen J, Wang Y, et al
. Potential risks of SARS-CoV-2 infection on reproductive health. Reprod Biomed Online 2020;41:89-95.
Amiri I, Sheikh N, Najafi R Nitric oxide level in seminal plasma and its relation with sperm DNA damages. Iran Biomed J 2007;11:259-64.
Anifandis G, Taylor TH, Messini CI, Chatzimeletiou K, Daponte A, Ioannou D, et al
. The impact of SARS-CoV-2 on sperm cryostorage, theoretical or real risk? Medicina (Kaunas) 2021;57:946.
Hamdi S, Bendayan M, Huyghe E, Soufir JC, Amar E, El Osta R, et al
. COVID-19 and andrology: Recommendations of the French-speaking society of andrology (Société d’Andrologie de langue Française SALF). Basic Clin Androl 2020;30:10.
Adiga SK, Tholeti P, Uppangala S, Kalthur G, Gualtieri R, Talevi R Fertility preservation during the COVID-19 pandemic: Mitigating the viral contamination risk to reproductive cells in cryostorage. Reprod Biomed Online 2020;41:991-7.
American Society of Reproductive Medicine. Patient management and clinical recommendations during coronavirus (COVID-19) pandemic. Fourth update published 11th May 2020. Available from: https://www.asrm.org/blobalassets/asrm/asrm-content/news-andpublications/COVIDtaskforce4.pdf
. [Last accessed on 21 May].
European Society of Human Reproduction and Embryology. News and Statements. Assisted reproduction and COVID 19. An updated statement from ESHRE, 17th April 2020. Available from: https://www.eshre.eu/Press-Room/ESHRENews#COVID19_April2
. [Last accessed on 21 May].
American Society of Reproductive Medicine. Patient management and clinical recommendations during coronavirus (COVID-19) pandemic. Second update published 13th April 2020. Available from: https://www.asrm.org/blobalassets/asrm/asrm-content/news-andpublications/COVIDtaskforce.pdf
. [Last accessed on 21 May].
Gonzalez DC, Nassau DE, Khodamoradi K, Ibrahim E, Blachman-Braun R, Ory J, et al
. Sperm parameters before and after COVID-19 mRNA vaccination. JAMA 2021;326:273-4.
Cardona Maya WD, Omolaoye TS, du Plessis SS Re: The impact of COVID-19 vaccine on sperm quality. Eur Urol 2022;82:327-8.
Barda S, Laskov I, Grisaru D, Lehavi O, Kleiman S, Wenkert A, et al
. The impact of COVID-19 vaccine on sperm quality. Int J Gynaecol Obstet 2022;158:116-20.
Reschini M, Pagliardini L, Boeri L, Piazzini F, Bandini V, Fornelli G, et al
. COVID-19 vaccination does not affect reproductive health parameters in men. Front Public Health 2022;10:839967.
Lifshitz D, Haas J, Lebovitz O, Raviv G, Orvieto R, Aizer A Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis? Reprod Biomed Online 2022;44:145-9.
Wesselink AK, Hatch EE, Rothman KJ, Wang TR, Willis MD, Yland J, et al
. A prospective cohort study of COVID-19 vaccination, SARS-CoV-2 infection, and fertility. Am J Epidemiol 2022;191:1383-95.