https://doi.org/10.4081/aiua.2021.1.115
COVID-19 and male fertility: Taking stock of one year after the outbreak began
Published: March 22, 2021
Abstract Views: 3850
PDF: 1754
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Objectives: The aim of this review is to summarize, following a timeline, the current knowledge regarding the effects of the Sars-cov2 virus on male fertility, researching the pathological and clinical results of the studies published in the last year. Methods: A systematic research was performed on the major international online databases; Thirty-five articles were selected. Results: A statistically significant reduction in testosterone levels and sperm quality in subjects with COVID-19 has been highlighted in several papers; however, in many cases the tests have been conducted in patients with active disease and long-term consequences are still not known. Some studies have confirmed the presence of the virus in the testis in a low percentage of patients; viral presence in sperm has only been found in one study. Testicular discomfort, which could indicate viral orchitis, was highlighted in several works, with an incidence of up to 19% percent of patients. The presence of inflammatory lymphocytic infiltrates, IgG and inflammatory cytokines have been documented in several works; pathological signs of inflammation were found in 60.9% of testicular biopsies performed in one study. The entry of the virus into the testis cells, both stromal and seminal cells appeared to be Angiotensin Converting Enzyme-2 (ACE2) mediated, as it also occurs in other tissues. DNA fragmentation, reactive oxygen species (ROS) formation, autoantibody production and ACE2 mediated effect have all been hypothesized as cause of cellular damage. Conclusions: The results on effects of COVID-19 infection on the male reproductive system are currently insufficient as they are based on a small number of patients and therefore are often contradictory.Certain mechanisms of testicular damage are still to be assessed, as any risk categories like age, ethnicity, or others. As for the transmission of the virus through sperm, there is insufficient evidence to ensure that this cannot happen.
Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends in Microbiology 2016;24:490-502
DOI: https://doi.org/10.1016/j.tim.2016.03.003
Ferran Garcìa J, Alvarez Gonzales JG, Corral Molina JM. Infección por SARS-CoV-2: implicaciones para la salud Sexual y reproductiva. Una declaraciòn de la posición de la Asociación Espanola de Andrología, Medicina Sexual y reproductora (ASESA). Rev Int Androl. 2020; 18:117-123.
John Hopkins University of Medicine, Coronavirus resource center, http://coronavirus.jhu.edu/map.html
Peng L, Liu J, Xu W, et al. 2019 Novel Coronavirus can be detected in urine, blood, anal swabs and oropharyngeal swabs samples. J Med Virol. 2020; 92:1676-1680.
DOI: https://doi.org/10.1002/jmv.25936
Lu R, Zhao X., Li J, et. al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus Origins and Receptor binding. Lancet 2020; 395:565-574.
DOI: https://doi.org/10.1016/S0140-6736(20)30251-8
Hoffmann M, Kleine-Weber H, Schroeder 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.
DOI: https://doi.org/10.1016/j.cell.2020.02.052
Zou X, Chen K, Zou J, et al. Single-cell RNAseq Data analysis on the receptor ACE2 Expression reveals the potential risk of different human organs vulnerable to 2019nCoV infection. Front Med. 2020;14:185-92.
DOI: https://doi.org/10.1007/s11684-020-0754-0
Reis AB, Araújo FC, Pereira VM. Angiotensin (1-7) and its receptor Mas are expressed in the human testis: implications for male infertility. J Mol Histol. 2010; 41:75-80.
DOI: https://doi.org/10.1007/s10735-010-9264-8
Ma L, Xie W, Li D, et al. Effect of SARS-CoV-2 infection upon male gonadal function: A single centerbased study. Medxriv March 2020, doi.org/10.1101/2020.03.21.20037267.
DOI: https://doi.org/10.1101/2020.03.21.20037267
Rastrelli G, Di Stasi V, Inglese F, et al. Low testosterone levels predict clinical ad¬verse outcomes in SARS-CoV-2 pneumonia patients. Andrology 2020; 00:1-11, doi.org/10.1111/andr.12821.
DOI: https://doi.org/10.1111/andr.12821
Schroeder M, Tuku B, Jarczak D, et al. The majority of male patients with COVID-19 pres¬ent low testosterone levels on admission to intensive care in Hamburg, Germany: a retrospective cohort study. medRxiv May 2020, doi.org/10.1101/2020.05.07.20073817.
Holtmann N, Edimiris P, Andree M, et al. Assessment of SARSCoV-2 in human semen—a cohort study. Fertil Steril. 2020;114:233-238.
DOI: https://doi.org/10.1016/j.fertnstert.2020.05.028
Xu H, Wang Z, Feng C, et al. Effects of SARS-CoV-2 infection on male sex-related hormones in recovering patients. Andrology. 2020 Nov 5. doi: 10.1111/andr.12942.
DOI: https://doi.org/10.1111/andr.12942
Song C, Wang Y, Li W, et al. Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients. Biol Reprod. 2020;103:4-6.
DOI: https://doi.org/10.1093/biolre/ioaa050
Shen Q, Xiao X, Aierken A, et al. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. J Cell Mol Med. 2020; 24:9472-9477.
DOI: https://doi.org/10.1111/jcmm.15541
Yang M, Chen S, Huang B, et al. Pathological findings in the testes of COVID-19 patients: clinical implications. Eur Urol Focus. 2020; 6:1124-1129.
DOI: https://doi.org/10.1016/j.euf.2020.05.009
Li H, Xiao X, Zhang J, et al. Impaired spermatogenesis in COVID-19 patients, EClinicalMedicine. 2020; 28:100604.
DOI: https://doi.org/10.1016/j.eclinm.2020.100604
Achua JK, Chu KY, Ibrahim E, et al. Histopathology and ultrastructural findings of fatal COVID-19 infections on testis. World J Mens Health 2021; 39:65-74.
DOI: https://doi.org/10.5534/wjmh.200170
Paoli D, Pallotti F, Colangelo S, et al. Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. J Endocrinol Invest. 2020; 43:1819-1822.
DOI: https://doi.org/10.1007/s40618-020-01261-1
Ning J, Li W, Ruan Y, et al. Effects of 2019 novel coronavirus on male reproductive system: a retrospec¬tive study. Preprints 2020,2020040280, doi: 10.20944/preprints202004.0280.v1
DOI: https://doi.org/10.20944/preprints202004.0280.v1
Li D, Jin M, Bao P, et al. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open. 2020; 3:e208292.
DOI: https://doi.org/10.1001/jamanetworkopen.2020.8292
Pan F, Xiao X, Jingtao G, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020; 113:1135-1139.
DOI: https://doi.org/10.1016/j.fertnstert.2020.04.024
Khalili MA, Leisegang K, Majzoub A, et al. Male Fertility and the COVID-19 Pandemic: Systematic Review of the Literature. World J Mens Health. 2020; 38: 506-520
DOI: https://doi.org/10.5534/wjmh.200134
Anifandis G, Messini CI, Daponte A, et al. COVID-19 and fertility: a virtual reality. Reprod Biomed Online. 2020;41:157-159.
DOI: https://doi.org/10.1016/j.rbmo.2020.05.001
Barbagallo F, Calogero A, Cannarella R, et al. The testis in patients with COVID-19: virus reservoir or immunization resource? Transl Androl Urol. 2020; 9:1897-1900.
DOI: https://doi.org/10.21037/tau-20-900
Xu J, Lihua Q, Chi X, et al. Orchitis: A5. complication of severe acute respiratory syndrome (SARS). Biol Reprod. 2006; 74:410-416.
DOI: https://doi.org/10.1095/biolreprod.105.044776
Santi D, Spaggiari G, Simoni M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management - Meta-analyses. Reprod Biomed Online. 2018; 37:315-326
DOI: https://doi.org/10.1016/j.rbmo.2018.06.023
Haghpanah A, Masjedi F, Alborzi S, et al. Potential mechanisms of SARS-CoV-2 action on male gonadal function and fertility: Current status and future prospects. Andrologia. 2020; e13883.
DOI: https://doi.org/10.1111/and.13883
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.
DOI: https://doi.org/10.3390/cells9040920
Mahmudpour M, Roozbeh J, Keshavarz M, et al. COVID-19 cytokine storm: The anger of inflammation. Cytokine, 2020;133:155151.
DOI: https://doi.org/10.1016/j.cyto.2020.155151
Fan C, Li K, Ding Y, et al. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019- nCoV infection. Preprint from medRxiv. Febr 2020 22418, doi.org/10.1101/2020.02.12.20022418
DOI: https://doi.org/10.1101/2020.02.12.20022418
Li R, Yin T, Fang F, et al. Potential risks of SARS-CoV-2 infection on reproductive health. Reprod Biomed Online. 2020; 41:89-95.
DOI: https://doi.org/10.1016/j.rbmo.2020.04.018
Yokoyama Y, Aikawa T, Takagi H, et al. Association Of reninangiotensin-aldosterone system inhibitors with mortality and testing positive of COVID-19: Meta-analysis. J Med Virol 2020;10.1002/jmv.26588.
DOI: https://doi.org/10.1002/jmv.26588
Papathanasiou A. COVID-19 screening during fertility treatment: how do guidelines compare against each other? J Assist Reprod Genet 2020; 37:1831-1835.
DOI: https://doi.org/10.1007/s10815-020-01885-5
Adiga SK, Tholeti P, Uppangala S, et al. Fertility preservation during the COVID-19 pandemic: mitigating the viral contamination risk to reproductive cells in cryostorage, Reprod Biomed Online 2020; 41:991-997.
DOI: https://doi.org/10.1016/j.rbmo.2020.09.013
Dell’Atti L, Galosi AB. The role of the serum testosterone levels as a predictor of prostate cancer in patients with atypical small acinar proliferation at the first prostate biopsy. Asian J Androl. 2018; 20:15-18.
DOI: https://doi.org/10.4103/aja.aja_17_17
Maretti C, Privitera S, Arcaniolo D, et al. COVID-19 pandemic and its implications on sexual life: Recommendations from the Italian Society of Andrology. Arch Ital Urol Androl. 2020; 92:73-77.
DOI: https://doi.org/10.4081/aiua.2020.2.73
How to Cite
delle Fave, R. F., Polisini, G., Giglioni, G., Parlavecchio, A., Dell’Atti, L., & Galosi, A. B. (2021). COVID-19 and male fertility: Taking stock of one year after the outbreak began. Archivio Italiano Di Urologia E Andrologia, 93(1), 115–119. https://doi.org/10.4081/aiua.2021.1.115
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.