We retrospectively investigated 118 sexually active male patients aged between 18 and 50 years whose partners had no problem and who attended Recep Tayyip Erdogan University Training and Research Hospital Andrology Laborotary between January 2021 and April 2022 and had received either Sinovac/CoronaVac vaccine (Group 1) or Pfizer/BioNTech vaccine (Group 2). Sixty-five patients were included in the study, and 53 patients who did not meet the inclusion criteria were excluded from the study (Figure 1). Ethical approval was obtained from the Recep Tayyip Erdogan University Non-Interventional Clinical Research Ethics Committee before the study (decision no: 2023/17 date: January 1, 2023). Anthropometric data of patients [age, body mass index (BMI)], the time of the second semen analysis after the second dose of vaccine, and semen analysis parameters (volume, pH, count, motility, and morphology) before and after two doses of vaccination were evaluated from the patient’s files. Patients younger than 18 years old, older than 50 years old, using medication affecting spermatogenesis, diagnosed with endocrinological disease affecting spermatogenesis, presence of genetic disease, gender disorders, history of varicocele or cryptorchidism operations, having only one sample, and diagnosed with azoospermia according to the spermiogram analyzes were excluded from the study. After exclusion criteria, a total of 65 patients’ data were recorded and analyzed Semen samples obtained by masturbation after 2-5 days of sexual abstinence were evaluated in the andrology laboratory by an experienced embryologist according to the guidelines of the WHO laboratory manual (6th edition) (Table 1) (15).Patients who were azospermic (n=6), had not completed two doses of vaccine (n=6), or had a history of COVID-19 (n=41) were excluded from the study. The remaining 65 patients were divided into two groups: Group 1 (n=17) and Group 2 (n=48). The pre-and post-vaccination BMI, semen volume, semen pH, sperm count per milliliter, total sperm count, sperm motility, and morphology values of patients in both groups were recorded and compared.
Statistical Analyses
Statistical analysis was performed using IBM SPSS Statistics (SPSS Inc., Chicago, IL, USA) software. After normality analysis of continuous numerical variables, the data showing the normal distribution were calculated as mean ± standard deviation and median (minimum-maximum). Differences between groups were evaluated using the independent samples t-test or Mann-Whitney U test, depending on the distribution of the data. Within-group and between-group pre- and post-vaccination comparisons in Sinovac/CoronaVac and Pfizer/BioNTech groups were performed using the Wilcoxon Signed-Rank test. For sperm morphology, 4 normal morphology was considered normal, and 4 was considered pathological. The McNemar test was used for comparisons made by dichotomizing the data. A p<0.05 was considered statistically significant.
Results
The mean ages of the patients in Groups 1 and 2 were calculated as 37±5 and 34±7 years, respectively. There was no significant difference between the groups in terms of BMI and duration. The mean time between vaccination and second semen analysis in Group 1 and Group 2 was 4±2.4 and 3.5±1.9 month (Table 2). No significant difference was found between Groups 1 and 2 in terms of volume, pH, total motility, the percentage of motile sperm changes, and morphology. We observed that the total sperm count (p=0.021) and sperm count per mL (p=0.014) significantly decreased in Group 1 and increased in Group 2 (Table 3).
In Group 1, no significant difference was observed in volume, sperm count per ml, motile sperm count, or total motility before and after Sinovac/CoronaVac vaccination. However, a statistically significant decrease was observed in pH (p=0.004) and total sperm count (p=0.019) due to the Sinovac/CoronaVac vaccine (Table 4). There was no significant difference in sperm morphology before or after the Sinovac/CoronaVac vaccine.
In Group 2, no significant differences were observed in volume, total sperm count, sperm count per mL, motile sperm count, or total motility before and after the vaccination. However, a statistically significant decrease was observed in pH because of the Pfizer/BioNTech vaccine (p<0.001) (Table 5). There was no significant difference in sperm morphology before and after administration of the Pfizer/BioNTech vaccine.
Discussion
This study was designed to identify the potential effects of Sinovac/CoronaVac and Pfizer/BioNTech vaccines on male fertility. Compared with previous studies that reported a decline in semen parameters in active COVID-19 and recovered patients (16,17), our study showed a significant decrease in total sperm count and sperm count per milliliter in infertile patients after Sinovac/CoronaVac vaccination but an increase in these parameters after Pfizer/BioNTech vaccination.
Gonzales and colleagues examined the sperm parameters of 45 patients before and after two doses of COVID-19 mRNA vaccines and reported a significant increase in all sperm parameters at an average of 75 days after the second dose (Pfizer/BioNTech n=21 and Moderna n=24) (18). In contrast, Barda’s study showed no negative effect on sperm parameters in patients who received two doses of Pfizer/BioNTech and were evaluated 72 days after the second dose, and that total sperm and total motile sperm counts increased significantly after the second dose (19). A study by Myriam Safrai evaluated sperm parameters in 72 patients an average of 71 days after the second dose of the Pfizer/BioNTech vaccine and reported that it did not affect sperm parameters in normospermic or infertile patients (20). Similarly, Reschini et al. (21) reported that there was no negative effect on sperm parameters or fertilisation rates after PfizerBioNTech (n=73) and Moderna (n=20) vaccinations. Gat and colleagues examined semen samples after two doses of Pfizer/BioNTech vaccine on days 15-45, 75-125, and 145 and reported that the decreased sperm concentration and total motile sperm count in the first two-time intervals improved in the third time interval (22). Abd and colleagues compared semen samples before and after the second dose of the Pfizer/BioNTech vaccine 90 days after vaccination and found impaired total sperm motility and progressive motility, but other parameters were normal (23). In our study, we did not observe any changes in sperm parameters before or after two doses of the Pfizer/BioNTech vaccine. Although normal sperm morphology decreased before and after vaccination, it was not statistically significant. Interestingly, the pH value was significantly lower after vaccination.
In a study of 128 individuals vaccinated with Sinovac/CoronaVac and Sinopharm inactivated vaccines in China, no difference in semen parameters was observed before or after the second vaccination within 90 days (24). In another study using Sinovac/CoronaVac vaccine, a slight decrease in motility and morphology was observed after the second dose, which was attributed to the length of time between semen collection before and after vaccination (10). Zhu Hong and colleagues examined semen parameters at an average of 60 days after inactivated vaccine administration in 43 healthy volunteers and observed no changes (25). In their study, Xia et al. (26) also showed that there was no difference in semen parameters or in vitro fertilization outcomes after vaccination with Sinovac (n=105) or Sinopharm (n=155) vaccines. In contrast to these studies, our study showed a decrease sperm count and pH values after Sinovac/CoronaVac vaccination.
In the first study in which Sinovac/CoronaVac and PfizerBioNTech vaccines were compared, we showed that sperm count per milliliter and total sperm count increased in favor of PfizerBioNTech. We did not detect any difference between the groups in other sperm parameters.
Study Limitations
The major limitation of this study was the retrospective design. Single-center design, heterogeneous sample distribution among the groups, and lack of serum testosterone values were the other limitations of our study. Pre-vaccination evaluation in idiopathic infertile men, evaluation of the same patient cohort, and comparison of two different vaccine groups were the strengths of our study.
Conclusion
We observed that the milliliter and total sperm count decreased in idiopathic infertile patients in the Sinovac/CoronaVac group, whereas it increased in the PfizerBioNTech group following COVID-19 vaccination. The findings show that inactive and mRNA vaccines do not significantly affect semen parameters in infertile men. Therefore, both vaccines can be considered safe for men’s reproductive health.
Ethics
Ethics Committee Approval: Ethical approval was obtained from the Recep Tayyip Erdogan University Non-Interventional Clinical Research Ethics Committee before the study (decision no: 2023/17 date: January 1, 2023).
Informed Consent: Retrospective study.
Peer-review: Externally peer-reviewed.
Conflict of Interest: No conflict of interest was declared by the author.
Financial Disclosure: The author declare that they have no relevant financial.