Article being reviewed is “Should women undergoing in vitro fertilization treatment or who are in the first trimester of pregnancy be vaccinated immediately against COVID-19” published in Fertility & Sterility May 13, 2021.
DISCLAIMER: A non-biased review of a recent debate article published in the medical journal ‘Fertility & Sterility’ of the pros and cons of COVID-19 vaccination when trying to get pregnant, before IVF, or during pregnancy. This podcast is only intended to help deliver the up-to-date conversation in the reproductive medical world so that women and couples can make informed decisions.
Summary Points pro Women undergoing in vitro fertilization treatment or who are in the first trimester of pregnancy SHOUD be vaccinated against COVID-19:
- Pregnant women are estimated to account for approximately 1% of the general population, whereas almost 8% of women of reproductive age are believed to be pregnant, seeking pregnancy, or up to 6 weeks postpartum at any given time.
- Although the overall risk of severe COVID-19 among pregnant women is relatively low for an individual patient, those who get infected and develop symptoms are at increased risk of more severe illness compared with their non-pregnant counterparts.
- Pregnant women with symptomatic COVID-19 demonstrate an increased risk of admission to an intensive care unit, need for mechanical ventilation, and death compared with that in symptomatic non-pregnant individuals
- A recent systematic review and meta-analysis of 42 studies involving 438,548 pregnancies concluded that SARS-CoV-2 infection may be associated with increased risk of preeclampsia, preterm birth, and stillbirth.
- Preventing disease in pregnancy, in major part through active vaccination against SARS-CoV-2, and specifically early vaccination either in the periconceptional period or first trimester, is of paramount importance to potentially reduce both maternal and fetal COVID-19–related morbidity and mortality.
- Non-live-attenuated vaccines are widely utilized and recommended in pregnancy. Maternal immunization through prenatal vaccination has improved maternal and neonatal health with regard to numerous infectious conditions. Although the advantage of vaccination during pregnancy sometimes focuses on the potential fetal and infant benefit through passive immunization, the impact of severe maternal infectious disease prevention in pregnancy should not be minimized.
- The current vaccines developed and demonstrated to have significant potential for prevention of severe infection related to SARS-CoV-2 among the general population undoubtedly will in addition provide substantial benefit to pregnant individuals. This is the primary reason that the leading professional societies in women’s and reproductive health recommend that the vaccine should not be withheld from this population.
- Those who received two doses of these vaccines had a 94%–95% lower risk of contracting COVID-19 compared with a non-vaccinated control group.
- American Society of Reproductive Medicine (ASRM, formerly The American Fertility Society) Coronavirus/COVID Task Force states that “since the vaccine is not a live virus, there is no reason to delay pregnancy attempts because of vaccination administration or to defer [fertility] treatment.
Development and Reproductive Toxicity (DART)
Animal studies demonstrated no increased adverse reproductive effects such as on female fertility or embryonic/fetal/postnatal development when these vaccines were delivered pre-mating or during early or late gestation. The theoretical concept that has grown from unclear sources about vaccines against COVID-19 being linked to infertility is wholly unfounded and has thus been discredited by leading societies in reproductive health.
It is acknowledged that there are relatively limited safety data regarding the use of COVID-19 vaccines in human pregnancy, because the vaccines currently available under the EUA have not yet been tested directly in pregnant women.
- Early data collected from over 1200 completed pregnancies in the v-safe pregnancy registry do not indicate any safety concerns with regard to pregnancy and neonatal outcomes following COVID-19 vaccination with mRNA vaccines
- Miscarriage was the most frequently reported pregnancy-specific adverse event, the observed rate among women receiving one of the mRNA COVID-19 vaccines was 12.6% (104/827 completed pregnancies), falling well within published and expected background rates of miscarriage.
- Available vaccines against COVID-19 appear to be relatively safe and highly effective in preventing severe illness, and there is no evidence to date that COVID-19 vaccination in the periconception or prenatal period is associated with increased reproductive, pregnancy, or neonatal adverse outcomes compared with background rates.
- Avoid vaccination within three days before or after an elective surgical or fertility-related procedure such as oocyte retrieval, embryo transfer, or intrauterine insemination.
Delaying vaccination while undergoing fertility treatment could lead to an unknown period of delay as fertility and IVF treatments are often not successful on the first attempt and may require numerous attempts to achieve an ongoing pregnancy. Treatment success relies on numerous variables, and despite the clinical team’s best attempts, cannot always be predicted. Of those patients who conceive a successful pregnancy, time to pregnancy after initiation of fertility treatment could be 8–12 months (27, 28) or longer. Some patients will not ever conceive. Therefore, given the uncertainty surrounding treatment success, it is reasonable to recommend vaccination once eligibility criteria are met and “at the soonest possible time, whether pre-conception or during pregnancy”, as supported by ASRM.
In conclusion, contraction of SARS-CoV-2 during pregnancy may have devastating maternal and fetal outcomes. Further, emerging data suggest vaccination may lead to maternal antibody transmission to the fetus providing potential protection against infant infection (35). Current safety data surrounding the vaccines against COVID-19 are reassuring and do not indicate safety concerns for individuals who are planning pregnancy or are in the first trimester, while at the same time demonstrate high efficacy in the general population. For those patients undergoing IVF treatment or in early pregnancy, it is in their best interests to strongly consider vaccination once eligible, and sooner rather than later, as they may incur the risk of severe COVID-related illness and associated morbidity and mortality the longer they wait.
Summary Points of against vaccination:
A universal recommendation for COVID-19 VACCINATION in women undergoing in vitro fertilization treatment or who are pregnant IS NOT SUPPORTED BY CLINICAL TRIAL DATA:
- We have not seen one woman who is pregnant enrolled in the initial clinical trials used to obtain EUA of COVID-19 vaccines by the US Food and Drug Administration (FDA), despite the propensity for more serious manifestations of COVID-19 in this population.
- Medical recommendations for vaccination of women who are pregnant ideally should be subject to the same rigid scrutiny and evidence as recommendations for vaccination in other adults. Thus far, this has not been the case for COVID-19 vaccines. A universal recommendation for COVID-19 vaccination in pregnancy cannot be made without acknowledging crucial gaps in scientific knowledge.
- Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses.
- Women who are pregnant and develop COVID-19 are at an increased risk for intensive care admission, invasive ventilation, extracorporeal membrane oxygenation, and death compared with women who are not pregnant. In addition, there are non-respiratory complications of COVID-19 in pregnant women that must be considered, including an increased risk of venous thromboembolism, hypertensive disorders of pregnancy, preterm delivery, and cesarean section.
Developmental and reproductive toxicity studies – DART
DART studies are routinely performed in animals such as rats and rabbits and may not be entirely generalizable to human populations. It should be noted that thalidomide did not display teratogenic effects in rats and only showed limb abnormalities in rabbits at doses well above those given to people (42). In addition, DART studies require significant time to complete. In fact, only preliminary DART data were available at the time of the EUA by the FDA of the Pfizer-Biotech and Moderna COVID-19 vaccines.
Because of the exclusion of pregnant women from the initial COVID-19 vaccine studies, guidance for COVID-19 vaccination in women who are pregnant is based largely on expert opinion rather than on science.
- As the pandemic rages on, is it even possible to take a true “con” side to delaying COVID-19 vaccination of individuals in this high-risk group? In some cases, advising a woman who is pregnant to defer COVID-19 vaccination could be seen as outside their best interests, given the “abundance of data” in other adult populations…
- As more vaccines are given under EUA to women who are pregnant, there will be less incentive to collect data in randomized, double-blind, placebo-controlled clinical trials.
- Pfizer-BioNTech has recently suspended enrollment in their COVID-19 vaccine pregnancy study within the United States where COVID-19 vaccines are readily available.
- Adverse pregnancy and neonatal outcomes were in line with those reported in other vaccine studies before the COVID-19 pandemic.
- The individuals assessed in this observational cohort were largely health care workers and likely differ with the historical comparator in terms of age, ethnic group, access to medical care, and other characteristics that are known to impact pregnancy and neonatal outcomes.
- Vaccine safety data in the peri-conception and early pregnancy periods are lacking, as there are relatively few of these individuals included in the registry and many of these pregnancies are still ongoing.
Expansion of programs or legislative initiatives that mitigate liability when vaccine development is a public health priority will speed vaccine development for women who are pregnant in future pandemics (51). One current example is the Countermeasures Injury Compensation Program, which provides compensation for women who are pregnant and other individuals not pregnant who are harmed by products designed to prevent or treat public health threats such as COVID-19.
COVID-19 vaccination in pregnancy illustrates a human rights issue in which a category of adults has been systematically deprived of the opportunity to participate in research or make medical decisions on the basis of evidence because of a natural condition.
Women who are pregnant do not need protection against participating in vaccine trials. They can make informed decisions.
References:
- MAIN ARTICLE – https://www.fertstert.org/article/S0015-0282(21)00436-2/fulltext
- Metz, Torri D. MD, et al; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19), Obstetrics & Gynecology: April 2021 – Volume 137 – Issue 4 – p 571-580
- Zambrano LD, Ellington S, Strid P, et al. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–October 3, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1641–1647.
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