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Asian Journal of Andrology logoLink to Asian Journal of Andrology
. 2022 Dec 9;25(4):468–473. doi: 10.4103/aja2022100

The effect of COVID-19 vaccines on sperm parameters: a systematic review and meta-analysis

Yu-Cheng Ma 1,*, Chao Cheng 1,*, Chi Yuan 1, Li-Yuan Xiang 1, Jun Wen 1, Xi Jin 1,
PMCID: PMC10411248  PMID: 36510860

Abstract

Published data were gathered for a meta-analysis to determine the difference in sperm parameters before and after administration of different types of coronavirus disease 2019 (COVID-19) vaccines, because the reproductive toxicity of COVID-19 vaccines has not yet been evaluated in clinical trials and COVID-19 has been associated with decreases in sperm quality. The preferred procedures for systematic reviews and meta-analyses were followed in the conduct and reporting of this study. The average sperm parameters of all sperm donors’ multiple sperm donations were compared before and after receiving various COVID-19 vaccinations. Semen volume, total sperm motility, total sperm count, morphological change, and sperm concentration were the primary outcome measures. We compiled and analyzed the results of six studies on total sperm motility, six studies on semen volume, six studies on sperm concentration, two studies on morphological change, and two studies on total sperm count. Parameter comparisons with patients who had and had not been vaccinated were only reported in one of the included studies. When different types of COVID-19 vaccine injections were compared, no discernible differences in parameters were observed. According to the available data, the parameters of semen are unaffected by inactivated or messenger RNA (mRNA) COVID-19 vaccinations. To support these findings, additional prospectively designed research is required.

Keywords: COVID-19, mRNA vaccine, sperm parameters, sperm quality, vaccine safety

INTRODUCTION

The coronavirus disease 2019 (COVID-19) outbreak was deemed a pandemic by the general director of the World Health Organization (WHO) in 2020, adversely affecting the lives of millions of people worldwide.1 The spread of this virus has resulted in severe diseases, countless fatalities, and serious medical, economic, and societal problems.2 In randomized controlled trials and real-world effectiveness study, vaccines have been shown to lower COVID-19 infections, transmission, hospitalizations, and fatalities.3 However, individuals are concerned about the potential harm of the two main types of COVID-19 vaccines used globally: the inactivated virus vaccine, and the viral mRNA vaccine. Scientists are still gathering safety data related to these types of vaccines.4 Aside from expected side effects, such as the usual low-grade fever or injection site soreness, serious adverse events have also been observed during the postmarketing surveillance phase.5,6 Despite clinical trials showing high efficacy and few adverse events, there is still much resistance to COVID-19 vaccinations.7

Among the nonrespiratory effects of COVID-19 infections, effects on male fertility are of concern,8 with poor spermatogenesis possibly reflecting the progression of COVID-19.9 Angiotensin-converting enzyme 2 (ACE2) receptors are expressed abundantly in spermatogonia, Leydig cells, and Sertoli cells, which may be direct viral targets, and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to react with them. Steroidogenesis and local vascular control are also regulated by ACE2.10,11 COVID-19 may affect testosterone levels in patients,12 which may lead to changes in spermatozoa.

In the USA, only 56% of people are willing to be vaccinated.13 Those unwilling to receive a COVID-19 vaccine have probably been influenced by social media, which have questioned the safety of the recently authorized vaccines and declared their impacts on fertility, despite the lack of scientific data.12,14

Although COVID-19 has been associated with deteriorating sperm quality, its toxicity to the reproductive system has not been clinically assessed.15 Previous studies have related sperm quality and fertility to the mortality and health of the population,16,17 thus vaccination may have significant effects on sperm parameters. To investigate this, we gathered relevant data for pooled analysis of sperm parameters before and after COVID-19 vaccination.

PATIENTS AND METHODS

This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).18

Original study search

The databases of PubMed and Embase were combined to identify candidate studies, with COVID-19, vaccination, and sperm parameters used as search terms. Supplementary Table 1 includes a full description of the search technique. The reference of each candidate paper was located, and August 1, 2022, was the most recent search date. We chose papers that matched the following inclusion criteria for the meta-analysis following the PICOS (population, intervention, comparison, and outcomes principles). (1) P (population): individuals free of any conditions that could harm the quality of their spermatozoa; (2) I (intervention): COVID-19 vaccinations were the sole intervention (all vaccine types were considered in this review); (3) C (comparison): comparison between the population with and without vaccinations and the included patients themselves (before and after the vaccination); (4) O (outcomes): outcomes included relevant metrics, such as semen volume, sperm concentration, total sperm motility, and total motile sperm count. Some studies were excluded, such as reviews, conference abstracts, letters, and comments. For the retrospectively designed studies in the meta-analysis, we performed quality evaluations based on the Newcastle–Ottawa Scale (NOS).

Supplementary Table 1.

Sample searching strategy for different database

Database Searching strategy
PubMed (((((((((((((((((((((((((((((((((((((COVID 19 [Title/Abstract]) OR (SARS-CoV-2 Infection[Title/Abstract])) OR (Infection, SARS-CoV-2[Title/Abstract])) OR (SARS CoV 2 Infection[Title/Abstract])) OR (SARS-CoV-2 Infections[Title/Abstract])) OR (2019 Novel Coronavirus Disease[Title/Abstract])) OR (2019 Novel Coronavirus Infection[Title/Abstract])) OR (2019-nCoV Disease[Title/Abstract])) OR (2019 nCoV Disease[Title/Abstract])) OR (2019-nCoV Diseases[Title/Abstract])) OR (Disease, 2019-nCoV[Title/Abstract])) OR (COVID-19 Virus Infection[Title/Abstract])) OR (COVID 19 Virus Infection[Title/Abstract])) OR (COVID-19 Virus Infections[Title/Abstract])) OR (Infection, COVID-19 Virus[Title/Abstract])) OR (Virus Infection, COVID-19[Title/Abstract])) OR (Coronavirus Disease 2019[Title/Abstract])) OR (Disease 2019, Coronavirus[Title/Abstract])) OR (Coronavirus Disease-19[Title/Abstract])) OR (Coronavirus Disease 19[Title/Abstract])) OR (Severe Acute Respiratory Syndrome Coronavirus 2 Infection[Title/Abstract])) OR (SARS Coronavirus 2 Infection[Title/Abstract])) OR (COVID-19 Virus Disease[Title/Abstract])) OR (COVID 19 Virus Disease[Title/Abstract])) OR (COVID-19 Virus Diseases[Title/Abstract])) OR (Disease, COVID-19 Virus[Title/Abstract])) OR (Virus Disease, COVID-19[Title/Abstract])) OR (2019-nCoV Infection[Title/Abstract])) OR (2019 nCoV Infection[Title/Abstract])) OR (2019-nCoV Infections[Title/Abstract])) OR (Infection, 2019-nCoV[Title/Abstract])) OR (COVID 19[Title/Abstract])) OR (COVID-19 Pandemic[Title/Abstract])) OR (COVID 19 Pandemic[Title/Abstract])) OR (Pandemic, COVID-19[Title/Abstract])) OR (COVID-19 Pandemics[Title/Abstract])) AND ((Vaccines[Title/Abstract]) OR (mRNA vaccines[Title/Abstract]))) AND ((Semen[Title/Abstract]) OR (sperm[Title/Abstract]))

The search strategies used for the other databases were almost identical or slightly modified depending on the circumstances of each database

Data extraction

The effect of mRNA COVID-19 vaccinations on semen volume, sperm concentration, total sperm motility, and total sperm count before and after COVID-19 vaccinations was assessed. The data gathering procedures were double-checked by two coauthors (YCM and CC).

Statistical analyses

The data were processed with the program RevMan 5.4.1 (Cochrane Collaboration, London, UK). Means and standard deviations were calculated using an online calculator provided by Professor Tie-Jun Tong (https://www.math.hkbu.edu.hk/tongt/papers/median2mean.html).19,20 The inverse-variance (IV) combined mean difference (MD) method was used as the primary estimate for continuous variables. A random effects model was used to synthesize the data. All confidence intervals (CIs), unless otherwise stated, were set at 95%. We present the synthesized results in forest plots. Heterogeneity was evaluated using I2 and the P-value of the Q-test. Funnel plots were generated to evaluate possible publication bias. For the meta-analysis results, the trim-and-fill method was used to adjust any detected publication bias. Since data from different types of vaccines were pooled, subgroup analysis was necessary to provide more information. Statistical significance in this study was defined as two-tailed P < 0.05.

RESULTS

Study selection

Seven screened studies in the database were assessed for quality and included in the quantitative analysis. The details on screening the articles are in the flowchart (Figure 1). Data from different studies were used for comparing semen variables before and after COVID-19 vaccination: six studies (comprising 1674 patients)1,7,2124 for total sperm motility, six studies (920 patients)1,2125 for semen volume and sperm concentration, two studies (1110 patients)7,21 for total sperm count, and two studies (332 patients)21,24 for morphological change. Out of seven included studies, five followed the WHO 5th edition, one study followed the WHO 6th edition, and one study did not report its methodology. We carefully read the manuals from the WHO and found that there were no obvious changes in parameters we were concerned with in this study (Table 1).

Figure 1.

Figure 1

The flowchart of literature screening.

Table 1.

Basic information of included studies

Study Year Country Study design Mean age (year) Sample size (n) Vaccine applied Treatment involved Intervention Control Semen analysis time point after second vaccine Sperm parameter testing standard Efficiency outcome assessment NOS
Reschini et al.21 2022 Italy RCS 39 212 BNT162b2 and mRNA-1273 Semen evaluation COVID-19 vaccination Before vaccination 75 days WHO 5th edition Volume, total motility, sperm concentration, total spermatozoa 7
Gonzalez et al.1 2021 Miami RCS 28 90 BNT162b2 and mRNA-1273 Semen analyses mRNA COVID-19 vaccination Before vaccination 70 days NR Volume, total motility, sperm concentration 7
Barda et al.7 2022 Israel PCS 27 898 BNT162b2 Semen analyses mRNA COVID-19 vaccination Before vaccination 72 days WHO 5th edition Total motility, total spermatozoa 6
Safrai et al.25 2022 Israel RCS 35.7 144 BNT162b2 Semen analysis mRNA COVID-19 vaccination Before vaccination About 70 days WHO 5th edition Volume, sperm concentration 7
Xia et al.23 2022 China PCS 31.8 260 Inactivated vaccine Semen analyses mRNA COVID-19 vaccination Patients didn’t receive vaccination NR WHO 5th edition Volume, sperm concentration, total motility 7
Olana et al.22 2022 Italy PCS 29.3 94 BNT162b2 Semen analyses mRNA COVID-19 vaccination Before vaccination 3 months WHO 5th edition Volume, sperm concentration, total motility 7
Abd et al.24 2022 UK PCS 37.2 120 BNT162b2 Semen analyses mRNA COVID-19 vaccination Before vaccination 90 days WHO 6th edition Total motility, volume, sperm concentration 7

RCS: retrospective cohort study; PCS: prospective cohort study; NOS: Newcastle–Ottawa Scale; WHO: World Health Organization; COVID-19: coronavirus disease 2019; NR: not report; mRNA: messenger RNA

Total motility comparison

There were no significant differences in total sperm motility before and after the COVID-19 vaccine (IV, MD: 1.36, 95% CI: −0.73–3.44, P = 0.20), and heterogeneity was observed (I2 = 52%, P = 0.07), as shown in Figure 2a. The funnel plot revealed that there was no significant publication bias in this comparison (Figure 3a). Main heterogeneity was introduced by Gonzalez et al.,1 and this may be caused by potential abstinence.

Figure 2.

Figure 2

Forest plots of sperm parameter comparison before and after the COVID-19 vaccine treatment. Forest plots of (a) total sperm motility, (b) semen volume, (c) sperm concentration, (d) total sperm count, and (e) sperm morphological change were compared accordingly. MD: mean difference; s.d.: standard deviation; CI: confidential interval; IV: inverse variance; df: degree of freedom.

Figure 3.

Figure 3

Funnel plots of sperm parameter comparisons. There was no linear trend in all three funnel plots of data points, and all points are relatively symmetrically distributed at both sides of the combined effect line. No significant publication bias was detected in (a) total sperm motility, (b) semen volume, and (c) sperm concentration. MD: mean difference; s.e.: standard error.

The volume of semen comparison

There were no differences in volume before and after COVID-19 vaccine (IV, MD: 0.04, 95% CI: −0.18–0.25, P = 0.72). No significant heterogeneity was detected (I2 = 28%, P = 0.22), as shown in Figure 2b. There was no significant publication bias detected in this comparison (Figure 3b). This combined result is robust, but considering that semen volume is largely affected by fluid, this parameter may mainly reflect the effect of vaccination on fluid-secreting glands.

Sperm concentration comparison

The primary results of each included study were stable, and no heterogeneity was detected (I2 = 0, P = 0.78). Overall synthetic results showed no differences in sperm concentration before and after the COVID-19 vaccine (IV, MD: 1.81, 95% CI: −1.25–4.87, P = 0.25; Figure 2c). There was no significant publication bias detected (Figure 3c). This result suggested that vaccine injection had no effect on the ability of seminiferous tubules to produce sperm cells.

Total sperm count comparison

There was no significant decrease in total sperm count after the COVID-19 vaccine (IV, MD: 7.33, 95% CI: −26.10–40.76, P = 0.67), but significant heterogeneity was found (I2 = 83%, P = 0.01), as shown in Figure 2d. This may weaken the robustness of pooling result. Since only two studies were included in this comparison, publication bias detection was omitted.

Morphological comparison

Three studies reported a sperm morphology comparison, among which one reported the abnormal rate, and two reported the normal rate. Therefore, we could only pool the comparison of the normal rate. There was no significant morphological change after the vaccination (IV, MD: 0.06, 95% CI: −0.35–0.47, P = 0.78) without significant heterogeneity (I2 = 0, P = 0.53; Figure 2e).

Subgroup analysis based on the different types of vaccines

In this meta-analysis, vaccine BNT162b, produced by Pfizer/BioNTech (Pfizer Inc., New York, NY, USA), was used in six of seven studies. Two studies used two different types of vaccines. There was only one study that applied inactivated vaccine. Considering the potential heterogeneity introduced by different vaccine types, we performed a subgroup analysis to provide more information (Table 2). The different types of vaccines did not alter the pooled results.

Table 2.

Subgroup analyses of comparison

Subgroup on vaccine type Pooled MD Heterogeneity


MD (95% CI) P I2 P
Total motility
 BNT162b2 0.11 (−0.79–1.01) 0.81 0 0.38
 BNT162b2/mRNA-1273 2.12 (−5.08–9.32) 0.56 84 0.01
 Inactivated 1.52 (−2.50–5.54) 0.46 - -
Sperm concentration
 BNT162b2 3.96 (−3.75–11.66) 0.31 0 0.89
 BNT162b2/mRNA-1273 2.24 (−3.92–8.39) 0.48 25 0.25
 Inactivated 0.18 (−4.46–4.82) 0.94 - -
Semen volume
 BNT162b2 −0.13 (−0.52–0.26) 0.51 0 0.68
 BNT162b2/mRNA-1273 0.27 (−0.15–0.69) 0.21 57 0.13
 Inactivated −0.13 (−0.42–0.16) 0.38 - -

MD: mean difference; CI: confidential interval; mRNA: messenger RNA; -: no value

DISCUSSION

With the identification of human coronaviruses 229E and OC43 in the late 1960s, coronaviruses began to be recognized as dangerous.26 Bats are very likely the original source of COVID-19 infection, and the virus can be transmitted to dogs and cats.27 Some coronaviruses cause serious and fatal infection symptoms in young children, the elderly, and the immunocompromised; however, human coronaviruses often cause mild symptoms similar to those of the common cold.2830 Research on the possibility of mother-to-child transmission of COVID-19 through aerosols is in progress.31

The COVID-19 enters cells via its spike protein, which has an affinity for the sugar receptors in human cells.32 Routes for viral entry into host cells include the endocytic33 and nonendosomal.34 The former is the most common pathway, but variables such as the type of virus and the host cell dictate the entry mechanism.35 The SARS-CoV-2 can enter semen, and as such, it could affect semen cryopreservation and the quality of spermatozoa.36

There is currently no specific medication available to counter SARS-CoV-2’s rapid spread; vaccination is a crucial tool to limit infection.

BNT162b vaccines received emergency USA Federal Drug Authority (FDA) approval on December 11, 2020. These vaccines encode the SARS-CoV-2 spike protein through modified RNA, which can be modified to alter the spike protein’s three-dimensional form. SARS-CoV-2 maintains this form until it attaches to human cellular ACE2 receptors. Both vaccines are typically administered through deltoid injection. The Moderna vaccine is approved for those over 16 years of age, and the BNT162b vaccine for those over 18 years. Conventional inactivated virus vaccines are frequently used, which offer effective COVID-19 population protection.37 However, questions over their reproductive toxicity, such as in assisted reproduction technology,38 have led to vaccination hesitancy.39

There have been many interesting studies published on whether COVID-19 vaccines affect sperm quality. First, given that the inactivated vaccine does not contain any live viruses and only contains antigenic components, it can only trigger an immune response without transcription and replication of the viral genome. This process causes a minimal amount of systemic inflammation, which has no impact on the quality of spermatozoa.40 A recent study evaluated sperm parameters before and after COVID-19 mRNA vaccination and found no significant decrease in any parameters after vaccination.1 Surprisingly, Gonzalez et al.1 also observed that sperm concentration and semen volume improved after vaccination.1 Although a molecular mechanism underlying the vaccine cannot be ruled out, this phenomenon may be due to abstinence before the second sperm test.1 Another study examined the effects of the BNT162b2 vaccine on 43 males and found no differences in sperm parameters following vaccination.25 A more persuasive prospective comparative investigation demonstrated that vaccination did not directly influence detectable indicators of sperm in 75 fertile males 1–2 months following a second dose of the BNT162b vaccine.14 By contrast, other studies have suggested that the COVID-19 vaccine may have an impact on sperm quality. After receiving a second dose of the vaccine, a study using human sperm banks reported a large rise in total sperm count and a significant drop in total motile count, but no significant change in the motility percentage.7 Therefore, we carried out this meta-analysis to perform an integrated study of the reported data to obtain more reliable results.

After pooling all available data from databases, our meta-analysis revealed no discernible change in semen quality between the pre- and post-COVID-19 vaccination periods. As a result, our findings should help to allay worries about the potential of vaccination to reduce male fertility and to encourage more people to be immunized against COVID-19.

This study has the following limitations. First, it only demonstrates that different COVID-19 vaccine types do not change sperm quality, not that using vaccines will not affect fertility, as sperm metrics do not fully reflect fertility. Second, only seven studies were included. Therefore, there is a need for more primary research, particularly prospectively designed studies with large samples.

CONCLUSIONS

According to currently available data, neither inactivated nor mRNA COVID-19 vaccines have deleterious effects on semen parameters. More prospectively designed studies are needed to validate this conclusion.

AUTHOR CONTRIBUTION

YCM, CC, and XJ concepted and designed this study. YCM, CC, LYX, JW, and CY performed the literature screening. YCM, CC, and CY performed the data synthesis and further analysis. YCM and CC drafted the manuscript. XJ revised the manuscript. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.

Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.

ACKNOWLEDGMENTS

This article is supported by grants from the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD2018011), and Sichuan Provincial Department of Science and Technology (2022YFS0304).

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