PREGNANCY DATA IN THE CLINICAL TRIALS OF THE mRNA VACCINES
Authors: Raphaelle Beau-Lejdstrom, Ph.D.
Contributors: Task Force on Vaccine
Published date: 12 Jan 2021
Questions have been recently raised related to the fertility of women receiving the Covid-19 Vaccine. While some studies have attempted to address the issue of the reproductive impact of patients with Covid-19 (biological and psychobehavioral), we present below what is known to date on the fertility/pregnancy outcomes of women receiving the Covid19 vaccines in the two Phase 2/3 trials today approved by several regulatory agencies (e.g EMA, FDA) to protect patients from Covid19:
1- Data in clinical trials
In both trials (Pfizer BioNtech and Moderna), women were screened for pregnancy and excluded at the start, if the test was positive. However, the trial collected outcomes on reported pregnancies occurring during the trial.
Both briefings mention that pregnancy outcomes are otherwise unknown at this time
2- Animal studies on Fertility
The Moderna Briefing adds that a combined study on postnatal outcomes in rats were submitted to FDA on December 4th 2020 using doses of 100µg of their mRNA vaccine which did not conclude to any significant adverse effects on female reproduction, embryonal development or postnatal development.
Pfizer/BioNtech also submitted a toxicological dossier showing the results of studies on fertility in rats showing no effects on the estrous cycle or fertility index (see EMA assessment report) and no vaccine-related effects on female fertility, gestation, or embryo-foetal or offspring development up to weaning.
3- Pharmacovigilance activities
Use in Pregnancy and lactation are classified as missing information by the FDA, imposing both passive and active surveillance activities.
Pfizer/BioNtech: Plans for a clinical study to assess safety and immunogenicity in pregnant women will be submitted and active surveillance to monitor vaccination during pregnancy in the population will be carried out. This means that pregnancy outcomes will be part of the outcomes measures in future post approval studies (3 known to this date: Protocols C4591008, C4591011, C4591011) and that voluntary reports on pregnancy outcomes will also be regularly monitored.
Moderna pharmacovigilance plan includes a passive pregnancy registry to monitor vaccination for women expected to receive the vaccine and active safety follow-up of patients using medical and pharmacy claims until December 2022 and a prospective cohort (Real World Effectiveness) until December 2023.
Pregnant and lactating women were excluded from the Phase 2/3 trials leading the authorities to classify the use in Pregnancy and lactation are classified as missing information.
However, a total of 36 pregnancies were reported during the follow-up of the two trials (18 for the vaccine arm/ 18 for placebo) showing no imbalance between both arms and no significant pregnancy outcomes that could be related to the vaccination are known to this date (although the Follow-up is still short).
Data is therefore very limited at this stage. Several toxicological assessments on rats provided by both Sponsors do not suggest any potential harms related to fertility and pregnancy outcomes.
Pharmacovigilance plans impose on Sponsors to collect data in pregnant women vaccinated after the emergency authorization until 2023 .
Data are extracted from Moderna Covid-19 Vaccine VRBPAC FDA Briefing Document and Pfizer-BioNTech COVID-19 Vaccine VRBPAC Briefing Document issued by the Food and Drug administration receptively on December 17th and 10th 2020.
See https://www.fda.gov/media/144245/download and https://www.fda.gov/media/144434/download
Madjunkov, M., M. Dviri, and C. Librach, A comprehensive review of the impact of COVID-19 on human reproductive biology, assisted reproduction care and pregnancy: a Canadian perspective. J Ovarian Res, 2020. 13(1): p. 140.