In a recent article published in Andrology, researchers explored the impact of coronavirus disease 2019 (COVID-19) BNT162b2 (Pfizer) vaccinations on male fertility among semen donors (SD) in Israel.
COVID-19 vaccine development is a noteworthy medical achievement; however, the potentially deleterious effects of COVID-19 vaccinations on male fertility have raised some concerns. Studies have reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) receptors for entry into host cells and that several testicular cells (Sertoli, Leydig, spermatozoa, and spermatogonia) express ACE2 receptors.
Furthermore, the regulation of autophagy, orchitis, dysfunction, and injury to the blood-testis barrier has been reported to be caused by the cytokine storm or excessive cytokine production observed in SARS-CoV-2 infections. Thus, deleterious effects of COVID-19 on the production of testosterone and spermatogenesis seem to be obvious outcomes; however, the results of studies emphasizing SARS-CoV-2 detection in testis and semen are contradictory.
About the study
In the present retrospective longitudinal multicenter study, researchers explored the impact of BNT162b2 vaccinations on several semen parameters among SD in Israel.
The study comprised 220 semen samples of 37 donors from the sperm banks (SB) of Shamir, Sheba, and Herzlyia Medical Centers, Israel. The study participants had received double BNT162b2 vaccinations, were (SARS-CoV-2)-negative based on polymerase chain reaction (PCR) analysis and/or serological tests, and did not have any symptoms of SARS-CoV-2 infections.
SD was considered vaccinated after one week of the second BNT162b2 vaccination between 1 February 2021 and 16 April 2021. The study was divided into four study phases as follows: baseline or pre-vaccination phase (T0) encompassing one to two semen samples per donor, short-term evaluation phase (T1), intermediate-term evaluation phase (T2), and long-term evaluation phase (T3).
The T1, T2, and T3 phases included one to three samples per SD and were obtained 15 to 45 days, 75 to 120 days, and after >150 days of completion of vaccination, respectively. The changes in sperm concentration, semen volume, sperm motility, and total motility count (TMC) after completion of the BNT162b2 vaccination were evaluated.
Statistical analyses were performed using generalized estimated equation (GEE) modeling and either the paired T-test or the Wilcoxon test. The mean differences between the T1 phase, T2 phase, and T3 phase compared to T0 were evaluated by analyzing 1) only the initial sample of each SD and; 2) average values of the samples of each SD per phase.
Serum samples were collected from nine, 12, and 16 SD at the sperm banks of Shamir, Sheba, and Herzylia Medical Centers, which yielded 63 samples, 78 samples, and 79 samples for the analysis. The average age of the donors was 26 ± 4.2 years. The baseline (T0) serum samples were obtained prior to vaccination (≤2 serum samples from each SD), and the mean time intervals for sample collection after BNT162b2 vaccination was 27 ± 10 days, 93 ± 13 days, and 175 ± 27 days after BNT162b2 vaccination for the T1 phase, T2 phase, and T3 phase, respectively.
Compared to the T0 phase, the sperm concentration was reduced by 15.4%, with a 22% reduction in the total motile count during the T2 phase. Likewise, analysis of only the first sample showed reductions in sperm concentrations by 12 x 106/ml and in TMC by 31 x 106 spermatozoa during the T2 phase in comparison to the T0 phase.
On considering the average sperm parameter values, the corresponding reductions were 9.5 x106/ml and 27 x 106 spermatozoa, respectively; however, the counts recovered during the T3 phase, indicating the detrimental effects of BNT162b2 vaccination on male fertility were transient. Of note, no significant changes in semen volume and sperm motility were observed.
Overall, the study findings showed that while sperm concentration reduced after three months of BNT162b2 vaccination with subsequent recovery, sperm motility and semen volume remained largely unaffected. The findings indicated that BNT162b2 vaccinations were safe for males of reproductive age in the long-term and support vaccine administration. However, further research with prospective analysis of different vaccines and emphasizing subfertility patients among the general population rather than SD must be undertaken.
The authors believe that the present study is the first of its kind to longitudinally assess semen parameters post-vaccination beyond the period of spermatogenesis in males and the study and believed that the transient decline in male fertility was due to the development of febrile systemic immune responses rather than direct effects of BNT162b2 vaccinations on the testicular cells.