Ovarian follicular function is not altered by SARS-CoV-2 infection or BNT162b2 mRNA COVID-19 vaccination

Y Bentov, O Beharier, A Moav-Zafrir, M Kabessa, M Godin, C S Greenfield, M Ketzinel-Gilad, E Ash Broder, H E G Holzer, D Wolf, E Oiknine-Djian, I Barghouti, D Goldman-Wohl, S Yagel, A Walfisch, A Hersko Klement, Y Bentov, O Beharier, A Moav-Zafrir, M Kabessa, M Godin, C S Greenfield, M Ketzinel-Gilad, E Ash Broder, H E G Holzer, D Wolf, E Oiknine-Djian, I Barghouti, D Goldman-Wohl, S Yagel, A Walfisch, A Hersko Klement

Abstract

Study question: Does the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function?

Summary answer: We were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function.

What is known already: No research data are available yet.

Study design, size, duration: This is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic.

Participants/materials, setting, methods: A consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers.

Main results and the role of chance: Both COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality.

Limitations, reasons for caution: This is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies.

Wider implications of the findings: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle.

Study funding/competing interest(s): The study was funded out of an internal budget. There are no conflicts of interest for any of the authors.

Trial registration number: CinicalTrials.gov registry number NCT04822012.

Keywords: COVID-19 / SARS–CoV-2 / BNT162b2 mRNA vaccine / IgG / follicle function / IVF / immune response / coronavirus disease 2019 / severe acute respiratory syndrome coronavirus 2.

© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
Association between follicular fluid (FF) and serum anti-SARS–CoV-2 IgG concentration. All the women undergoing IVF with positive serum anti-COVID IgG had detectable levels of anti-COVID IgG in their FF. The linear association between the serum and FF concentrations (arbitrary units) of anti-COVID IgG (R2 =0.99) suggests a non-regulated passage of anti-COVID IgG across the follicular membrane. SARS–CoV-2, severe acute respiratory syndrome Coronavirus 2; COVID, coronavirus disease.

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Source: PubMed

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