Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age?

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Sep 19 2022

In a recent study published in Vaccine, researchers assessed the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on human fertility.

Background

Claims that the coronavirus disease 2019 (COVID-19)  vaccines could cause irreparable harm to the population and may increase the risk of female infertility were made in response to the emergency licensing of the vaccines. The cross-reactivity with syncytin-1 and its potential similarity to the spike protein was proposed as the potential mechanism that purportedly associated vaccinations with decreased fertility in women of reproductive age.

Syncytin-1 is crucial for implantation, and its dysfunction could lead to early pregnancy loss, failed implantation, or later issues from aberrant placentation, such as preeclampsia. In males, it was hypothesized that the vaccine could influence spermatogenesis and sperm parameters, noting that the SARS-CoV-2 virus has been linked to male reproductive impairment.

About the study

In the present study, researchers summarized and assessed the available information related to the potential effect of COVID-19 vaccines on female and male fertility.

The study included studies that explored the impact of COVID-19 vaccines on fertility in females and males. The systematic review involved only studies that reported primary data. The team obtained data such as the first author, country, year, population, study design, age, gender, vaccine type, time vaccination-recruitment, number of vaccine doses, indicator employed to assess fertility, and main results corresponding to each study. Additionally, the researchers performed a descriptive analysis based on information including population, age, gender, indicator employed to assess fertility, and vaccine type.

When appropriate, the team performed random-effect meta-analyses for the same outcome concerning fertility indicators reported in two or more studies. The effect measure utilized for most fertility indicators comprised mean concentrations or rates. The first meta-analysis was conducted for any vaccine type used, followed by the analysis of the subgroup based on the specific vaccine administered.

The included studies were assessed with respect to the methodological quality of the study design. The cohort studies were assessed with the Newcastle-Ottawa scale that evaluated quality parameters, including study group selection, comparability of the groups, and ascertainment of the results. The pre-post studies were assessed with the Before and After Quality Assessment scale to evaluate parameters such as clarity of study objective, enrollment of participants, description of eligibility criteria, sample size, and outcome.

Results

The search for relevant studies resulted in a total of 1,489 records after excluding duplicate records. The screening process produced 39 articles that were deemed pertinent for the study. Eventually, 29 articles were included in the systematic review, while 20 were part of the meta-analysis. The 29 articles included ten performed in Israel, seven in the USA, six in Russia, three in China, one in Italy, one in North America, and one in Turkey.

In 16 of the studies conducted in Israel and the USA and one in Turkey, the COVID-19 vaccines assessed were two messenger ribonucleic acid (mRNA) vaccines, namely mRNA-1273 and BNT162b2. Additionally, six studies performed in Russia explored the adenovirus-vector vaccine Gam-COVID-Vac, three from China studied the inactivated vaccines, while three studies from Italy, the USA, and North America assessed vaccines including mRNA and viral vector-based.

Furthermore, 51.7% of the total studies were performed on females, 37.9% on males, and 10.3% on both populations. Approximately 52% of the studies included in vitro fertilization (IVF)/IVG patients, including 11 studies on females and two on males. Two studies performed in Russia, one in Turkey, and one in Israel involved healthy women subjects.

Additionally, seven studies were conducted on healthy males, one on two comparative cohorts of unhealthy and healthy men, two on men undergoing IVG or assisted reproduction technology (ART), and one on men belonging to a big database. With respect to the study design, 14 articles were pre-post studies, and 15 were cohort studies.

Quality assessment of cohort studies using the Newcastle-Ottawa scale showed that 13.3% of the studies were of good quality, 33.3% were of moderate quality, and 53.3% were of poor quality. Furthermore, the meta-analysis of five pre-post studies included 298 males who did not display a remarkable difference with respect to progressive motility prior to post-vaccination with any COVID-19 vaccine type. Notably, there was no significant difference in the subgroup analysis conducted based on the vaccine type used.

Sperm concentration post-COVID-19 vaccination with any type of vaccine did not remarkably vary in the meta-analysis of eight pre-post studies that included 451 males. The meta-analysis of six studies that included 346 males did not exhibit any significant variation in the sperm volume prior to or after vaccination with any vaccine type.

Furthermore, the biochemical pregnancy rate and clinical pregnancy rate did not differ significantly among the vaccinated and the unvaccinated cohorts. Also, estradiol levels did not show any significant difference between the vaccinated and unvaccinated women.

Conclusion

Overall, the study findings showed no association between COVID-19 vaccination and fertility impairment in women and men.