Effects of COVID-19 and mRNA Vaccines on Human Fertility

Fei Chen; Shiheng Zhu; Zhiqing Dai; Lanting Hao; Chun Luan; Qi Guo; Chaofan Meng; Yankun Zhang


Hum Reprod. 2022;37(1):5-13. 

In This Article

Abstract and Introduction


The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has precipitated a global health crisis of unprecedented proportions. Because of its severe impact, multiple COVID-19 vaccines are being rapidly developed, approved and manufactured. Among them, mRNA vaccines are considered as ideal candidates with special advantages to meet this challenge. However, some serious adverse events have been reported after their application, significantly increasing concerns about the safety and efficacy of the vaccines and doubts about the necessity of vaccination. Although several fertility societies have announced that COVID-19 mRNA vaccines are unlikely to affect fertility, there is no denying that the current evidence is very limited, which is one of the reasons for vaccine hesitancy in the population, especially in pregnant women. Herein, we provide an in-depth discussion on the involvement of the male and female reproductive systems during SARS-CoV-2 infection or after vaccination. On one hand, despite the low risk of infection in the male reproductive system or fetus, COVID-19 could pose an enormous threat to human reproductive health. On the other hand, our review indicates that both men and women, especially pregnant women, have no fertility problems or increased adverse pregnancy outcomes after vaccination, and, in particular, the benefits of maternal antibodies transferred through the placenta outweigh any known or potential risks. Thus, in the case of the rapid spread of COVID-19, although further research is still required, especially a larger population-based longitudinal study, it is obviously a wise option to be vaccinated instead of suffering from serious adverse symptoms of virus infection.


The link between viral infection and infertility has been studied for decades. Numerous viruses, including Zika virus, HIV and cytomegalovirus have been detected in human semen, among which some can affect male fertility potential (Mate et al., 2015; Counotte et al., 2018). Moreover, because of the contribution of the immune privilege of the testes and the resistance of blood–testis barrier (BTB) to antiviral drugs, several viruses can persist in semen and last longer than in other body fluids (Liu et al., 2018; Paz-Bailey et al., 2019). Undoubtedly, there is an urgent need for a thorough exploration of the effect of coronavirus disease 2019 (COVID-19) on the human reproductive system. Meanwhile, given the potential damage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the reproductive system, some individuals suspect that the vaccine which mimics the virus (mRNA vaccine) may also affect fertility via the same mechanism. Notably, although more than 4 billion vaccine doses have been currently administered, pregnant women are always excluded from the initial clinical trials of mRNA vaccination. However, as of 30 August 2021, the US Centers for Disease Control and Prevention (CDC) had reported more than 155 000 participants who were pregnant at the time they received vaccination, which draws attention to the safety of mRNA vaccines while pregnant. Previous studies have revealed that the type I viral envelope protein and human syncytin-1 protein involved in the formation of the placenta share analogous structural features, especially in the regions of N- and C-terminal heptad repeats (Gong et al., 2005). Some skeptics and anti-vaccination movements have claimed that vaccine mRNA-translated antibodies (Abs) against the spike protein (S protein) may cross-react with syncytin-1, leading to adverse pregnancy outcomes. Therefore, there is a significant and urgent need to review the limited data and theoretical considerations for informing clinical guidelines and our understanding regarding the various effects of COVID-19 and vaccines on the human reproductive system.