COVID-19 infection may have a detrimental and lasting impact on male reproductive health, while showing limited consequences for female fertility or assisted reproductive technology (ART) outcomes, according to a new umbrella review published this week in the journal Vaccine. The analysis, conducted by researchers at Sichuan University in Chengdu, China, assessed 14 studies encompassing 40 distinct fertility and ART metrics.
The review indicates that among men, COVID-19 infection is associated with diminished semen quality, including reductions in semen volume and concentration, as well as total sperm count, viability, and motility. Elevated levels of the hormones estradiol and prolactin were as well observed in infected men, though testosterone levels remained largely unaffected. Critically, these negative effects on male fertility persisted for at least three months after initial infection.
“Notably, even after recovery (over 90 days), sperm concentration and motility remained lower compared to uninfected individuals,” the researchers wrote. The findings align with the biological understanding of the virus’s potential impact, given the high expression of ACE2 and TMPRSS2 receptors – key entry points for the SARS-CoV-2 virus – within male reproductive organs. “Given the high expression of ACE2 and TMPRSS2 in the testes…the male reproductive system is theoretically prone to SARS-CoV-2 infection,” the study states. “This infection, leading to orchitis [inflammation of the testicles] and disruption of spermatogenesis [the creation of mature sperm]might result in reduced sperm count, motility, and overall semen quality.”
In contrast, the review found no significant association between COVID-19 infection and negative female fertility outcomes. “COVID-19 showed minimal impact on female ovarian reserve…or ART outcomes,” the researchers reported, despite the presence of ACE2 receptors in ovarian tissues and the uterine lining.
Notably, the analysis revealed no evidence of reproductive harm linked to COVID-19 vaccination for either men or women. “The current evidence does not substantiate concerns linking COVID-19 vaccines to impaired fertility or ART failure,” the study concludes.
Researchers acknowledge the need for further investigation, particularly given the low quality of evidence in some of the included studies. They call for more high-quality, prospective studies with extended follow-up periods. Specifically, they emphasize the need for longitudinal research to assess the long-term effects of COVID-19 infection on male fertility and live birth rates.
The West China Hospital of Sichuan University has been at the forefront of COVID-19 vaccine development in China, having received emergency employ authorization for its recombinant COVID-19 vaccine, Coviccine, developed using insect cell technology in 2023, according to the university. In December 2024, a team from the hospital published research in Nature Communications detailing a trivalent recombinant protein vaccine, Tri-Vac, that induces cross-neutralization against XBB lineage and JN.1 subvariants, receiving emergency use authorization from the Chinese Government in June 2023.
