Abstract
Since the beginning of the pandemic in December 2019, COVID-19 has reached significant dimensions. In this context, where all aspects of human life have been impacted, it is essential to understand the effects on male fertility, as studies suggest potential impacts on birth rates and the emotional well-being of thousands of couples. The objective of this study was to investigate the effects of the COVID-19 pandemic and its relationship with male infertility through a systematic review. Out of 99 results obtained from the search, 19 articles were selected for the review based on inclusion and exclusion criteria. Changes in seminal parameters, such as reduced concentration, motility, volume, and pH, were described and associated with various mechanisms, with inflammation and oxidative stress being the most prominent. This review concludes that there is a relationship between COVID-19 and male infertility, observable through semen analysis; however, as suggested and evidenced by all authors who assessed the post-infection period, after 2 months or more, fertility parameters are restored. Among authors who analyzed the issue of immunization, no relationship between vaccination and male infertility was reported, suggesting that the vaccine is safe. However, further studies are needed to determine whether immunization indeed interferes with male infertility.
References
Agarwal, A. et al. Male Infertility. The Lancet, v. 397, n. 10271, p. 319–333, jan. 2021.
Aitken, R. J. COVID‐19 and male infertility: An update. Andrology, v. 10, n. 1, p. 8–10, 2021.
Aksak, T. et al. Investigation of the effect of COVID‐19 on sperm count, motility, and morphology. Journal of Medical Virology, v. 94, n. 11, p. 5201–5205, 1 nov. 2022.
Aschauer J, Sima M, Imhof M. Recovery of sperm quality after COVID-19 disease in male adults under the influence of a micronutrient combination: A prospective study. Arch Ital Urol Androl. 2023 Mar 13;95(1):11157. doi: 10.4081/aiua.2023.11157. PMID: 36924370.
Barbosa, Kiriaque Barra Ferreira et al. Estresse oxidativo: conceito, implicações e fatores modulatórios. Revista de nutrição, v. 23, p. 629-643, 2010.
Barros, Bianca Maria, Taina Stefani dos Santos, and Claudemir de Carvalho. "INFERTILIDADE MASCULINA DE ORIGEM GENÉTICA: UMA REVISÃO SISTEMÁTICA." Revista Ciência e Saúde On-line 5.2 (2020).
Beelen, K. et al. [Confusion and abdominal pain after COVID-19 vaccination]. Nederlands Tijdschrift Voor Geneeskunde, v. 165, p. D6055, 20 maio 2021.
Best, J. C. et al. Evaluation of SARS-CoV-2 in Human Semen and Effect on Total Sperm Number: A Prospective Observational Study. The World Journal of Men’s Health, v. 39, 2021.
Bilotta, C. et al. COVID-19 Vaccine-Related Thrombosis: A Systematic Review and Exploratory Analysis. Frontiers in Immunology, v. 12, p. 729251, 2021.
Brotherton, J., Koch, U.J. and Hammerstein, J. (1979), The Routine Spermiogram in the Assessment of Male Fertility. International Journal of Andrology, 2: 489-500. https://doi.org/10.1111/j.1365-2605.1979.tb00080.x
Chen, Y. et al. Exploration of the common genetic landscape of COVID-19 and male infertility. Frontiers in Immunology, v. 14, 20 mar. 2023.
Chu, D. S.; Shakes, D. C. Spermatogenesis. Germ Cell Development in C. elegans, p. 171–203, 28 jun. 2012.
Collins, A. B., Zhao, L., Zhu, Z., Givens, N. T.,Bai, Q., Wakefield, M. R., & Fang, Y. (2022). Impact of Covid-19 on male fertility. Urology.
Da Silveira, A. et al. MUDANÇAS DECORRENTES DA PANDEMIA DE CORONAVÍRUS NA VOZ DE ADOLESCENTES ACOLHIDOS. Revista Enfermagem Atual In Derme, v. 95, n. 36, 4 nov. 2021.
Dias, Sara Almeida; Fazenda, Juliana Maria; De Paula Ramos, Lucas. Interferência do COVID-19 na fertilidade masculina. Research, Society and Development, v. 11, n. 15, p. e169111537211-e169111537211, 2022.
Donders, G. G. 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 Sperm COVID test. Fertility and Sterility, v. 117, n. 2, p. 287–296, fev. 2022.
Dutta, S.; Sengupta, P. SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology. Reproductive Sciences, v. 28, p. 23–26, 2020.
Edition, Fifth. Examination and processing of human semen. Geneva: World Health, 2010.
Erbay G, Sanli A, Turel H, Yavuz U, Erdogan A, Karabakan M, Yaris M, Gultekin MH. Short-term effects of COVID-19 on semen parameters: A multicenter study of 69 cases. Andrology. 2021 Jul;9(4):1060-1065. doi: 10.1111/andr.13019. Epub 2021 Apr 29. PMID: 33851521; PMCID: PMC8251422.
Excesso de mortalidade associado à pandemia de COVID-19 foi de 14,9 milhões em 2020 e 2021. Organização Pan-Americana de Saúde, 2022. Disponível em:<https://www.paho.org/pt/noticias/5-5-2022-excesso-mortalidade-associado-pandemia-covid-19-foi-149-milhoes-em-2020-e-2021>. Acesso em: 23 mai. 2023.
Ferreira, A. L. A.; Matsubara, L. S. Radicais livres: conceitos, doenças relacionadas, sistema de defesa e estresse oxidativo. Revista da Associação Médica Brasileira, v. 43, n. 1, mar. 1997.
Franken, D. R., & Oehninger, S. (2012). Semen analysis and sperm function testing. Asian journal of andrology, 14(1), 6–13. https://doi.org/10.1038/aja.2011.58
Gallup JR, Gordon G.; Finn, Mary M.; Sammis, Becky. On the origin of descended scrotal testicles: the activation hypothesis. Evolutionary psychology, v. 7, n. 4, p. 147470490900700402, 2009.
Galuppo, A. G. Spermatogonial stem cells as a therapeutic alternative for fertility preservation of prepubertal boys. Einstein (São Paulo), v. 13, n. 4, p. 637–639, dez. 2015.
Garrouch S, Sallem A, Ben Fredj M, Kooli R, Bousabbeh M, Boughzala I, Sriha A, Hajjaji A, Mehdi M. Deleterious impact of COVID-19 pandemic: Male fertility was not out of the bag. PLoS One. 2023 May 8;18(5):e0284489. doi: 10.1371/journal.pone.0284489. PMID: 37155673; PMCID: PMC10166489.
Gat I, Kedem A, Dviri M, Umanski A, Levi M, Hourvitz A, Baum M. COVID-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors. Andrology. 2022 Sep;10(6):1016-1022. doi: 10.1111/andr.13209. Epub 2022 Jun 27. PMID: 35713410; PMCID: PMC9350322.
Gat, I. et al. COVID-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors. Andrology, p. 1-7, 2022.
He J, Zhao Y, Zhou Z, Zhang M. Machine learning and integrative analysis identify the common pathogenesis of azoospermia complicated with COVID-19. Front Immunol. 2023 May 22;14:1114870. doi: 10.3389/fimmu.2023.1114870. PMID: 37283758; PMCID: PMC10239851.
Ilacqua, A. et al. Lifestyle and fertility: the influence of stress and quality of life on male fertility. Reproductive Biology and Endocrinology, v. 16, n. 1, 26 nov. 2018.
Jarczak, D.; Nierhaus, A. Cytokine Storm—Definition, Causes, and Implications. International Journal of Molecular Sciences. 2022,23,11740. https://doi.org/ 10.3390/ijms231911740
Jungwirth, A., Giwercman, A., Tournaye, H., Diemer, T., Kopa, Z., Dohle, G., Krausz, C., & European Association of Urology Working Group on Male Infertility (2012). European Association of Urology guidelines on Male Infertility: the 2012 update. European urology, 62(2), 324–332. https://doi.org/10.1016/j.eururo.2012.04.048
Kumar T, Jha K, Zabihullah M, Neelu K, Kumar Y, Siddharth K. Effects of the COVID-19 pandemic on semen quality in male partners of infertile couples: a hospital-based observational study. Asian J Androl. 2023 Mar-Apr;25(2):240-244. doi: 10.4103/aja202278. PMID: 36348579; PMCID: PMC10069688.
La, J.; Katz, D. J. Linking COVID‐19 Vaccine and Male Infertility – Not on Fertile Ground. BJU International, p. 20-21, 2022.
Li, H. et al. Impaired spermatogenesis in COVID-19 patients. E Clinical Medicine, v. 28, 1 nov. 2020.
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 Jan;44(1):145-149. doi: 10.1016/j.rbmo.2021.09.021. Epub 2021 Oct 4. PMID: 34815157; PMCID: PMC8489287.
Lv, C. et al. Role of Selective Autophagy in Spermatogenesis and Male Fertility. Cells, v. 9, n. 11, p. 2523, 23 nov. 2020.
Machado, C. L. Entenda o que é a taxa de transmissão da COVID-19!. Secretaria de Estado de Saúde de Minas Gerais, 2023. Disponível em: <https://coronavirus.saude.mg.gov.br/blog/164-taxa-de-transmissao-covid-19>. Acesso em: 23 mai. 2023.
Malta, D. C. et al. A pandemia da COVID-19 e as mudanças no estilo de vida dos brasileiros adultos: um estudo transversal. Epidemiologia e Serviços de Saúde, v. 29, n. 4, 2020.
Martinez, M. S. et al. COVID-19 associates with semen inflammation and sperm quality impairment that reverses in the short term after disease recovery. Frontiers in Physiology, v. 14, 11 jul. 2023.
Massarotti, C. et al. mRNA and Viral Vector COVID-19 Vaccines Do Not Affect Male Fertility: A Prospective Study. The World Journal of Men’s Health, v. 40, n. 4, p. 561, 2022.
Martins, P. e Matias, O. Biologia 12, Vol.1, Areal Editores, 1ª edição, Porto, 2011.
Meo SA, Bukhari IA, Akram J, Meo AS, Klonoff DC. COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1663-1669. doi: 10.26355/eurrev_202102_24877. PMID: 33629336.
Moreira, C. (2015). Espermatogênese. Revista de Ciência Elementar, 3(2)
Nassau, D. E. et al. Impact of the SARS-CoV-2 virus on male reproductive health. BJU International, v. 129, n. 2, p. 143–150, 2022.
Organização Pan-Americana da Saúde. Histórico da pandemia de COVID-19 - OPAS/OMS | Organização Pan-Americana da Saúde. Disponível em: <https://www.paho.org/pt/covid19/historico-da-pandemia-covid-19>.
Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, Spivak AM, Alukal JP, Zhang X, Xiong C, Li PS, Hotaling JM. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020 Jun;113(6):1135-1139. doi: 10.1016/j.fertnstert.2020.04.024. Epub 2020 Apr 17. PMID: 32482249; PMCID: PMC7164916.
Paoli D, Pallotti F, Anzuini A, Bianchini S, Caponecchia L, Carraro A, Ciardi MR, Faja F, Fiori C, Gianfrilli D, Lenzi A, Lichtner M, Marcucci I, Mastroianni CM, Nigro G, Pasculli P, Pozza C, Rizzo F, Salacone P, Sebastianelli A, Lombardo F. Male reproductive health after 3 months from SARS-CoV-2 infection: a multicentric study. J Endocrinol Invest. 2023 Jan;46(1):89-101. doi: 10.1007/s40618-022-01887-3. Epub 2022 Aug 9. PMID: 35943723; PMCID: PMC9362397.
Patel, D. P. et al. The impact of SARS-CoV-2 and COVID-19 on male reproduction and men’s health. Fertility and Sterility, v. 115, n. 4, p. 813–823, 2021.
Rafiee B, Bagher Tabei SM. The effect of N-acetyl cysteine consumption on men with abnormal sperm parameters due to positive history of COVID-19 in the last three months. Arch Ital Urol Androl. 2021 Dec 21;93(4):465-467. doi: 10.4081/aiua.2021.4.465. PMID: 34933532.
Rato, L., Alves, M. G., Socorro, S., Duarte, A. I., Cavaco, J. E. Oliveira, P. F. (2012). Metabolic regulation is important for spermatogenesis. Nature Reviews Urology, 9(6), 330-338
Recomendações da Sociedade Brasileira de Patologia Clínica/ Medicina Laboratorial (SBPC/ML): BOAS PRÁTICAS EM LABORATÓRIO CLÍNICO [s.l: s.n.]. Disponível em: <https://177.69.167.178/pdf/RecomendacoesSBPCML_BoasPraticasEmLaboratorioClinico.pdf>. Acesso em: 29 out. 2023.
Reschini M, Pagliardini L, Boeri L, Piazzini F, Bandini V, Fornelli G, Dolci C, Cermisoni GC, Viganò P, Somigliana E, Coccia ME, Papaleo E. COVID-19 Vaccination Does Not Affect Reproductive Health Parameters in Men. Front Public Health. 2022 Feb 2;10:839967. doi: 10.3389/fpubh.2022.839967. PMID: 35186854; PMCID: PMC8847439.
Roser, M.; Ritchie, H. Coronavirus Disease (COVID-19). Our World in Data, v. 1, n. 1, 4 mar. 2020.
Russel, L. D.; Griswold, M. D. The Sertoli cell. 1 ed. 1993.
Seckin S, Ramadan H, Mouanness M, Gidon A, Thornton M, Merhi Z. A Case of Asthenozoospermia Following COVID-19 Infection. Reprod Sci. 2022 Sep;29(9):2703-2705. doi: 10.1007/s43032-022-00975-2. Epub 2022 May 23. PMID: 35606631; PMCID: PMC9126095.
Shen Q, Xiao X, Aierken A, Yue W, Wu X, Liao M, Hua J. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. J Cell Mol Med. 2020 Aug;24(16):9472-9477. doi: 10.1111/jcmm.15541. Epub 2020 Jun 28. PMID: 32594644; PMCID: PMC7361928.
Silva, C. T. DA; Jasiulionis, M. G. Relação entre estresse oxidativo, alterações epigenéticas e câncer. Ciência e Cultura, v. 66, n. 1, p. 38–42, 2014.
Soares, M. Infertilidade Masculina: Stress Oxidativo e o Uso de Antioxidantes, 2022. Disponível em: <https://repositorio-aberto.up.pt/bitstream/10216/141808/2/ 568803. pdf >.
Soheila, Pourmasumi et al. The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review. Vaccines, v. 10, n. 12, p. 1982–1982, 2022.
Stigliani S, Massarotti C, Bovis F, Maccarini E, Anserini P, Scaruffi P. Semen parameters and male reproductive potential are not adversely affected after three or more months of recovery from COVID-19 disease. Front Reprod Health. 2023 Jan 20;4:1114308. doi: 10.3389/frph.2022.1114308. PMID: 36743823; PMCID: PMC9895115.
Stylianou, N. Número real de mortes por COVID no mundo pode ter chegado a 15 milhões, diz OMS. BBC News Brasil, 2022. Disponível em: <https://www.bbc.com/portuguese/internacional-61332581>. Acesso em: 23 mai. 2023.
Sunder M, Leslie SW. Semen Analysis. [Updated 2022 Oct 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564369/
WHO Coronavirus (COVID-19) Dashboard. World Health Organization, 2023. Disponível em: <https://covid19.who.int/>. Acesso em: 18 mai. 2023.
World Health Organization. WHO laboratory manual for the examination and processing of human semen. 6. ed. Geneva: World Health Organization, Cop, 2021.
Yan, Qiu et al. Autophagy: A Double-Edged Sword in Male Reproduction. International Journal of Molecular Sciences, v. 23, n. 23, p. 15273, 2022.

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