Male Fertility and the COVID-19 Pandemic: Systematic Review of the Literature

Abstract

Purpose: Since its discovery in December 2019, the novel coronavirus SARS-CoV-2 has spread globally, causing the current COVID-19 (coronavirus disease-19) pandemic. As there is an increase of infections in the male population, concerns have emerged about the potential impact of COVID-19 on male reproductive organs and male fertility. Therefore, this study systematically investigates the current evidence of SARS-CoV-2 impact on male reproduction and pregnancy outcomes, discussing them in light of the evidence published on other coronaviruses.

Materials and methods: Literature search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 24 original articles were included for the analysis, investigating the effects of the infection on semen parameters, male reproductive hormones, and pregnancy outcomes. Further, a Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis was conducted based on the available evidence linking the virus with male reproduction and conception.

Results: Although there is limited data, viral mRNA has been identified in semen of infected men, with some evidence of altered seminal parameters. Low testosterone and dihydrotestosterone with raised luteinizing hormone has been reported as well as preterm delivery in pregnant women; however, data regarding vertical transmission remains contradictory and inconclusive.

Conclusions: The recent literature provides evidence that male gonads may be potentially vulnerable to SARS-CoV-2 infection, recommending caution to pregnant women and couples planning natural pregnancy or assisted reproduction.

Keywords: COVID-19; Infertility, male; Pregnancy; Semen; Severe acute respiratory syndrome coronavirus 2.

Fig. 1. Cellular entry mechanism. Severe acute respiratory syndrome-coronaviruse-2 (SARS-CoV-2) infection is mediated by the binding between viral spike proteins and angiotensin I converting enzyme 2 (ACE2) cellular receptor, and the further proteolytic cleavage and activation of spike proteins by the transmembrane protease serine 2 (TMPRSS2).

Fig. 2. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) workflow reporting the literature search strategy.

Fig. 3. The putative mechanisms by which severe acute respiratory syndrome-coronaviruse-2 (SARS-CoV-2) might affect spermatogenesis are here summarized. ACE2: angiotensin-converting enzyme 2.

Fig. 4. Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis has been conducted to define if there is an impact of the virus in the male reproduction. SARS-CoV-2: severe acute respiratory syndrome-coronaviruse-2, MERS: Middle Eastern Respiratory syndrome.

Fig. 5. Hypothesis and evidence regarding the possible severe acute respiratory syndrome-coronaviruse-2 (SARS-CoV-2) sexual transmission, as well as its impact on natural pregnancy, assisted reproduction and cryopreservation are summarized. ART: assisted reproductive technique.