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)

G Corona, E Baldi, A M Isidori, D Paoli, F Pallotti, L De Santis, F Francavilla, S La Vignera, R Selice, L Caponecchia, R Pivonello, A Ferlin, C Foresta, E A Jannini, A Lenzi, M Maggi, F Lombardo, G Corona, E Baldi, A M Isidori, D Paoli, F Pallotti, L De Santis, F Francavilla, S La Vignera, R Selice, L Caponecchia, R Pivonello, A Ferlin, C Foresta, E A Jannini, A Lenzi, M Maggi, F Lombardo

Abstract

Purpose: The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) METHODS: A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria.

Results: Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects.

Conclusion: Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.

Keywords: COVID-19; Male fertility; SARS-CoV-2; Semen cryopreservation.

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

    1. Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA. Insights into the recent 2019 novel coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks. Pathog (Basel, Switzerland). 2020;9(3):186. doi: 10.3390/pathogens9030186.
    1. Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020;12:9. doi: 10.1038/s41368-020-0075-9.
    1. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R (2020) Features, evaluation and treatment coronavirus (COVID-19).
    1. CSSE at Johns Hopkins University (2020) Coronavirus resource center. Last Accessed 15/04/2020
    1. Italian Ministry of Health (2020) Covid-19, situation report update at 13 April 2020. . Last Accessed 15/04/2020
    1. Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health. 2020;25:278–280. doi: 10.1111/tmi.13383.
    1. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045. doi: 10.2807/1560-7917.ES.2020.25.3.2000045.
    1. Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang Province, China, January–March 2020: retrospective cohort study. BMJ. 2020;369:m1443. doi: 10.1136/bmj.m1443.
    1. Ling Y, Xu S-B, Lin Y-X, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl) 2020 doi: 10.1097/CM9.0000000000000774.
    1. Xie C, Jiang L, Huang G, et al. Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis. 2020;93:264–267. doi: 10.1016/j.ijid.2020.02.050.
    1. Aversa A, Jannini EA. COVID-19, or the triumph of monogamy? Minerva Endocrinol. 2020 doi: 10.23736/S0391-1977.20.03207-1.
    1. Hezavehei M, Sharafi M, Kouchesfahani HM, Henkel R, Agarwal A, Esmaeili V, Shahverdi A. Sperm cryopreservation: a review on current molecular cryobiology and advanced approaches. Reprod Biomed Online. 2018;37:327–339. doi: 10.1016/j.rbmo.2018.05.012.
    1. Corona G, Minhas S, Giwercman A, Bettocchi C, Dinkelman-Smit M, Dohle G, Fusco F, Kadioglou A, Kliesch S, Kopa Z, Krausz C, Pelliccione F, Pizzocaro A, Rassweiler J, Verze P, Vignozzi L, Weidner W, Maggi M, Sofikitis N. Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:733–757. doi: 10.1093/humupd/dmz028.
    1. ESHRE guidance on recommencing ART treatments (2020) ESHRE website, 23/04/2020.
    1. De Santis L, Anastasi A, Cimadomo D, Klinger FG, Licata E, Pisaturo V, Sosa Fernandez L, Scarica C. COVID-19: the perspective of Italian embryologists managing the IVF laboratory in pandemic emergency. Hum Reprod (Oxford, England) 2020;35(4):1004–1005. doi: 10.1093/humrep/deaa074.
    1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W, China Novel Coronavirus Iinvestigating and Research Team. (2019) A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med. 2020;382:727–733
    1. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020 doi: 10.1038/s41586-020-2179-y.
    1. 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(4):E920. doi: 10.3390/cells9040920.
    1. Thimon V, Belghazi M, Dacheux JL, Gatti JL. Analysis of furin ectodomain shedding in epididymal fluid of mammals: demonstration that shedding of furin occurs in vivo. Reproduction. 2006;132(6):899–908. doi: 10.1530/REP-06-0077.
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, NitscheA MMA, Drosten C, Pöhlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280.e8.
    1. Chen YW, Lee MS, Lucht A, Chou FP, Huang W, Havighurst TC, Kim K, Wang JK, Antalis TM, Johnson MD, Lin CY. TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells. Am J Pathol. 2010;176(6):2986–2996. doi: 10.2353/ajpath.2010.090665.
    1. Douglas GC, O’Bryan MK, Hedger MP, Lee DKL, Yarski MA, Smith AI, Lew RA. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 2004;145:4703–4711. doi: 10.1210/en.2004-0443.
    1. La Vignera S, Cannarella R, Condorelli RA, Torre F, Aversa A, Calogero AE. Sex-Specific SARS-CoV-2 mortality: among hormone-modulated ACE2 expression, risk of venous thromboembolism and hypovitaminosis D. Int J Mol Sci. 2020;21(8):E2948. doi: 10.3390/ijms21082948.
    1. Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, Peh S, Gu J. Orchitis: a complication of severe acute respiratory syndrome (SARS) Biol Reprod. 2006;74:410–416. doi: 10.1095/biolreprod.105.044776.
    1. Pozzilli P, Lenzi A. Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism (in press) 2020 doi: 10.1016/j.metabol.2020.154252.
    1. Corona G, Isidori AM, Aversa A, Bonomi M, Ferlin A, Foresta C, La Vignera S, Maggi M, Pivonello R, Vignozzi L, Lombardo F. Male and female sexual dysfunction in diabetic subjects: focus on new antihyperglycemic drugs. Rev Endocr Metab Disord. 2020;21:57–65. doi: 10.1007/s11154-019-09535-7.
    1. Manganaro L, Saldari M, Pozza C, Vinci V, Gianfrilli D, Greco E, Franco G, Sergi ME, Scialpi M, Catalano C, Isidori AM. Dynamic contrast-enhanced and diffusion-weighted MR imaging in the characterisation of small, non-palpable solid testicular tumours. Eur Radiol. 2018;28:554–564. doi: 10.1007/s00330-017-5013-7.
    1. Paoli D, Pallotti F, Colangelo S, Basilico F, Mazzuti L, Turriziani O, Antonelli G, Lenzi A, Lombardo F. Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive rino-pharyngeal swab. J Endocrinol Invest. 2020 doi: 10.1007/s40618-020-01261-1.
    1. Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, Spivak AM, Alukal JP, Zhang X, Xiong C, Li PS, Hotaling J. No evidence of SARS-CoV-2 in semen of males recovering from COVID-19. Fertil Steril. 2020 doi: 10.1016/j.fertnstert.2020.04.024.
    1. 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(5):e208292. doi: 10.1001/jamanetworkopen.2020.8292.
    1. Paoli D, Pallotti F, Turriziani O, Mazzuti L, Antonelli G, Lenzi A, Lombardo F. SARS-CoV-2 presence in seminal fluid: myth or reality. Andrology. 2020 doi: 10.1111/ANDR.12825.
    1. De Paoli P (2005) Bio-banking in microbiology: from sample collection to epidemiology, diagnosis and research. FEMS Microbiol Rev 29(5):897-910

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe