COVID-19 Vaccines and Reproductive Disorders: An Analysis of the European Database EudraVigilance: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: Rare or serious Adverse Events (AEs) in the reproductive sphere have been reported following the administration of the COVID-19 vaccine, especially mRNA vaccines. Although several fertility Societies have announced that COVID-19 mRNA vaccines are unlikely to affect fertility, pregnancy, or breastfeeding, there is no denying that the current evidence is very limited [1]. Objective: Aim of this study was a post-marketing assessment of the safety profile of COVID-19 vaccines, through the analysis of the Individual Case Safety Reports (ICSRs) collected in EudraVigilance in 2021 year, by focusing on reproductive disorders. Methods: We analyzed all ICSRs that contained at least one COVID-19 vaccine as suspected and at least one AE belonging to the Standardized MedDRA Query (SMQ) level 1 "Fertility disorders" or "Pregnancy and neonatal conditions". We performed a descriptive analysis and all AEs have been coded as Preferred Term (PT) according to MedDRA. Finally, we used the Reporting Odds Ratio (ROR) with a 95% of Confidence Interval (95% CI) to investigate disproportional reporting of AEs belonging to the SMQs of interest among the vaccines included in the analysis. Results: During the study period, 27,089 ICSR were collected and the total number of AEs was found to be 31,337;of these, 62.8% were referred to Comirnaty®, 20.8% to Spikevax®, 12.7% to Vaxzevria®, and 3.7% to Janssen®. For each of the four COVID-19 vaccines, 96.4% were related to female patients, aged between 18-64 years (88.1%), 71.5% were not serious, 46.0% were not resolved yet and 82.3% were reported by non-healthcare professionals. Regardless of the type of vaccine, the most reported PTs were amenorrhea, irregular menstruation, and delayed menstruation. The ROR showed that the probability to report an AE belonging to the SMQ "Fertility disorders" is greater for Comirnaty® (ROR 4.20, 95% CI 4.08-4.32) while no statistically significant difference was observed to the SMQ "Pregnancy and neonatal conditions". Conclusion: In this study, no potential signs of reproductive system safety were found regarding fertility, pregnancy or breastfeeding. Most of the reported events were related to changes in the menstrual cycle, although these disorders are temporary and normally common in the female population. At the time, the EMA's PRAC concluded that the evidence did not support a causal link between these vaccines and menstrual disorders, however, it decided to further studies collecting data from real life contexts are strongly needed to assess their safety profile in relation to reproductive function.