Published 18 January 2021
A recent statement from ESHRE’s COVID-19 working group, also evident in the vaccines’ product information, notes limited data on vaccination in pregnancy and none before conception with assisted reproduction. Eligibility for COVID-19 vaccination in and before pregnancy so far rests on an individual assessment of risks and benefits.
New year, new vaccines . . . and with them questions about eligibility for vaccination in and before pregnancy and ahead of fertility treatment. But first the facts (what few of them there are).
Three vaccines have so far been approved variously in the EU, US and UK – from Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca (with additional types reportedly available from India, Russia and China). The EU and UK product information for the Pfizer vaccine (‘Comirnaty’) notes that there is ‘limited experience’ in pregnant women (indeed, pregnancy was an exclusion from the phase 3 clinical trial), that animal studies indicate no harmful effects in pregnancy or post-natal development, and that administration in pregnancy ‘should only be considered when the potential benefits outweigh any potential risks for the mother and foetus’.(1) The EMA product information for the COVID-19 Moderna vaccine in pregnancy is identical, while the UK data for the AstraZeneca vaccine reiterate the ‘limited experience’ and risks vs benefits caveats in pregnancy.(2,3)
The Pfizer-BioNTech vaccine was reviewed by WHO for emergency listing in late 2020 and its report of 31 December noted that 23 participants in the trial did become pregnant, nine of whom withdrew, but follow-up details were not available. WHO thus repeats the mantra that vaccination should only be considered when its benefits outweigh the risks. However, one week later, in a ‘Newsroom’ feature on who can take the vaccine, WHO said it could not recommend vaccination in pregnant women ‘at this time’ because of insufficient data.(4) In terms of risks and benefits WHO noted that ‘pregnant women are at higher risk of severe COVID-19 than non-pregnant women, and COVID-19 has been associated with an increased risk of pre-term birth’. Vaccination, therefore, might be considered if a pregnant woman has an unavoidable risk of high exposure (for example in a health worker), but otherwise WHO leant towards caution and advised avoiding pregnancy ‘for 2 to 3 months post-vaccination’.
This cautious approach has been adopted in ESHRE’s recent statement on COVID-19 vaccination before and during pregnancy, particularly with reference to assisted conception.(5) The ESHRE statement, published on 12 January from the COVID-19 Working Group, is framed around three questions, which each refer to conception and pregnancy, if not specifically to the ‘assisted reproduction’ of the title. And as in the product information for the three vaccines, ESHRE prefixes its answers with reference to a paucity of information, which precludes any recommendation on vaccination before ART. However, on the question of whether ‘couples’ who received COVID-19 vaccination should postpone treatment, ESHRE edges towards the cautious approach of WHO, finding it ‘prudent to postpone the start of assisted reproduction treatments (sperm collection, ovarian stimulation, embryo transfer) for at least a few days after the completion of vaccination’ (ie, after the second dose). ESHRE adds that ‘a more cautious approach could be considered (i.e. postpone the start of ART treatment for up to 2 months)’.
ESHRE’s comment on vaccination during pregnancy acknowledges the greater COVID-19 morbidity found in pregnancy than otherwise and the need to assess this and other risks and benefits in each candidate. Significantly, in its modelling of vaccine roll-out strategies the ECDC does not list pregnancy as a ‘precondition’ for prioritisation, but in the USA the American College of O&G makes pregnancy the first of many preconditions listed as ‘high-risk medical conditions’.(6,7) Thus, the ASRM in its latest COVID-19 update (issued on 16 December) states that ‘patients undergoing fertility treatment and pregnant patients should be encouraged to receive vaccination based on eligibility criteria’.(8) This clearly does not represent pregnancy as a wall-to-wall indication for vaccination; ‘eligibility criteria’ still require an assessment of vaccination risks and benefits, as in all other guidance. However, notes ASRM considering the risks, ‘since the vaccine is not a live virus, there is no reason to delay pregnancy attempts because of vaccination administration or to defer treatment until the second dose has been administered’. This seems somewhat less cautious than the approach we see in Europe.
However, there’s still much in common: a limited evidence base, assessment of vaccination risks and benefits in each case, and, despite the growing vaccination programmes, a need to maintain risk mitigation measures in all clinics - as outlined in ESHRE’s October guidance on continuing fertility treatments as infection rates escalate.(9)
A recent pre-proof review of COVID-19’s effects in pregnancy has analysed levels of symptom severity and reports October findings from the CDC comparing symptoms in 23,434 pregnant women with 386,028 non-pregnant.(10,11) Despite acknowledged limitations but after adjustments for age, preconditions and ethnicity, the CDC results showed that pregnant women were significantly more likely to be admitted to an ICU and need ventilation (and with a higher mortality rate) than the non-pregnant subjects. This review also laments the exclusion of pregnancy in the vaccine trials and a continuing lack of evidence to guide vaccination programmes, but nevertheless concludes that ‘pregnancy appears to be an independent risk factor for severe COVID-19-associated complications’.
If there is a common theme to these various statements, it seems likely found in the ASRM’s ‘eligibility criteria’ for vaccination and the formal vaccine product information that administration in pregnancy should only be considered when the potential benefits outweigh the potential risks. Just what those overall benefits and risks actually are, however, remains inconclusive and, as ESHRE’s statement recommends, a matter for ‘close consultation with a healthcare professional’. The statement also advises that access to fertility treatment should not depend on an individual’s decision about vaccination or not.
10. Joseph NT, Rasmussen SA, Jamieson DJ. The effects of COVID-19 on pregnancy and implications for reproductive medicine. Fertil Steril 2020; doi.org/10.1016/j.fertnstert.2020.12.032
11. Zambrano LD, Ellington SR, Strid P, et al. Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020. Morb Mortal Wkly Rep 2020; 69(25): 769–775.
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