The effect of COVID-19 vaccination during IVF stimulation on cycle outcomes- a retrospective cohort study

The COVID-19 vaccinations were introduced at the end of 2020. As pregnant women were not included in the initial trials of the messenger ribonucleic acid (mRNA) vaccine BNT162b2 (Pfizer), concerns regarding short- and long-term consequences on fertility and pregnancy outcomes were initially raised (Carbone et al., 2021, Deruelle et al., 2021, Robinson et al., 2021, Egloff et al., 2022). These were mostly based on the similarity between syncytin-1, a human placental fusion protein, and the SARS-CoV-2 spike protein expressed after administration of the COVID-19 vaccine (Kloc et al., 2021, Markert et al., 2021). Concomitantly, large multicenter cohort studies found an association between SARS-CoV-2 infection during pregnancy and higher maternal morbidity and mortality, intensive care unit admissions, preterm deliveries, and cesarean delivery rate (Di Mascio et al., 2020; Huntley et al., 2020; Rasmussen et al., 2020). These maternal and fetal pregnancy outcomes led the American Society for Reproductive Medicine (ASRM, 2022) and the European Society for Human Reproduction and Embryology (ESHRE, 2022) to encourage women either pre-conception or during all stages of pregnancy to get vaccinated.

The effect of the vaccine on ovarian reserve, sperm parameters, IVF treatment outcomes and pregnancy outcomes has been addressed in several prospective and retrospective studies refuting most concerns regarding its possible short-term consequences, and presenting reassuring results, thus reducing vaccine hesitancy in the population undergoing fertility treatments (Bentov et al., 2021, Gonzalez et al., 2021, Mohr-Sasson et al., 2021, Aharon et al., 2022, Avraham et al., 2022, Horowitz et al., 2022, Jacobs et al., 2022, Chamani et al., 2023, Chen et al., 2023). To date, studies examining the effect of vaccines on IVF treatment outcomes were limited to vaccines administered pretreatment (Bentov et al., 2021, Aharon et al., 2022, Albeitawi et al., 2022, Avraham et al., 2022, Dong et al., 2022, Jacobs et al., 2022, Chamani et al., 2023, Chen et al., 2023). Immune activation and fever, possible side effects of the vaccine, may have a negative impact on cycle outcomes (Kim et al., 1996, Awwad et al., 2012). This may have caused both physicians and patients to avoid vaccination during IVF treatment, and even the ESHRE COVID-19 working group stated that in men and women who receive the vaccine, it seems prudent to postpone assisted reproduction treatments for at least a few days after the completion of vaccination (ESHRE 2022). Some patients deferred fertility treatment until completion of the vaccination program, while others became pregnant prior to vaccine administration, thus risking SARS-CoV-2 infection complications during pregnancy. To be able to provide physicians and patients with evidence-based data, assuming that annual boosters will be recommended (Rubin, 2021), we conducted a study comparing cycle outcomes of patients receiving the first or second vaccine during the stimulation, to two control groups undergoing stimulation: unvaccinated patients and patients receiving the vaccine 3–10 weeks prior to the beginning of stimulation, to avoid the immediate side effects of the vaccine.

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