Impact of SARS-CoV-2 on male fertility: A systematic review and meta-analysis
David Le Nguyen1, Kelly D. Cobey 2, Ryan Chow 1, Denise Smith 3, Georges Khalaf 4, Faris Almoli 5, Matthew T. Roberts1,6.
1Faculty of Medicine , University of Ottawa , Ottawa , ON, Canada; 2Ottawa Methods Centre , Ottawa Hospital Research Institute , Ottawa, ON, Canada; 3Faculty of Health Sciences , McMaster University , Hamilton, ON, Canada; 4Faculty of Engineering , University of Ottawa, Ottawa, ON, Canada; 5Faculty of Life Sciences , McMaster University , Hamilton, ON, Canada; 6Department of Urology , The Ottawa Hospital , Ottawa, ON, Canada
Introduction: Current evidence shows that the novel severe acute respiratory syndrome coronavirus-2 (COVID-19) can travel across the blood testes barrier and enter the seminiferous tubules.1 COVID-19 has the potential to induce a cytokine storm that can affect the testes.1 The objective of this study was to identify and analyze the available information on male fertility for changes in sperm and seminal parameters and disruption of the male sex hormone profile.
Methods: This study was registered a priori on Open Science Framework (ID: gkpn5). A comprehensive search of OVID Medline, EMBASE, Web of Science, and Clinicaltrials.gov was conducted from inception to October 15, 2021. Primary studies that examined COVID-19 or a COVID-19 vaccine on male fertility-related parameters, such as sperm count or morphology and sex hormone changes, were included. DerSimonian and Laird’s random effects meta-analysis was conducted to evaluate the effect of COVID-19 on sperm count and testosterone levels. Heterogeneity was assessed with Cochran’s Q and I2.
Results: The search yielded 2065 results, of which 1005 (51%) were duplicates; 44 studies met the final inclusion criteria, of which six studies fit the criteria for meta-analysis on the effect of COVID-19 infection on sperm count (Figure 1). The analysis indicated a significant reduction in sperm count in men (n=448) recovered from COVID-19 infection (mean difference -7.99, 95% confidence interval [CI] 1.07, 14.9, I2=31.26%, p=0.024) (Figure 2). Three studies were included in the meta-analysis on the effect of COVID-19 infection on testosterone levels, which revealed no significant difference in men (n=161) recovered from COVID-19 infection (mean difference -10.42, 95% CI -52.79, 31.95, I2=36.36%, p=0.63) (Figure 3).
Conclusions: This study suggests that seminal parameters may be affected by COVID-19 infection. A significant decrease in sperm count was detected, however, a difference in testosterone levels was not.
[1] Olaniyan OT, Dare A, Okotie GE, et al. Testis and blood-testis barrier in Covid-19 infestation: role of angiotensin-converting enzyme 2 in male infertility. J Basic Clin Physiol Pharmacol 2020;10.1515
