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

  1. Y Bentov
  2. O Beharier
  3. A Moav-Zafrir
  4. M Kabessa
  5. M Godin
  6. C S Greenfield
  7. M Ketzinel-Gilad
  8. E Ash Broder
  9. H E G Holzer
  10. D Wolf
  11. E Oiknine-Djian
  12. I Barghouti
  13. D Goldman-Wohl
  14. S Yagel
  15. A Walfisch
  16. A Hersko Klement

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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.

Article activity feed

  1. Version published to 10.1093/humrep/deab182
  2. ScreenIT

    SciScore for 10.1101/2021.04.09.21255195: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Eligibility criteria were age older than 18 years and willingness to participate and provide informed consent.
    Randomizationnot detected.
    BlindingThe analysis of the blood and FF samples for all outcome parameters was conducted with blinding of the COVID / Vaccine status of the participant.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    As a result, together with the negative anti-COVID serum antibody test, we could safely presume that all control patients in this study were indeed COVID-19 negative.
    anti-COVID
    suggested: None
    Software and Algorithms
    SentencesResources
    Serum and follicular fluid anti-COVID IgG measurement: The levels of specific anti-SARS–CoV-2 spike protein receptor binding domain (RBD) IgG were assessed in serum and follicular fluid specimens, using the Architect SARS-CoV-2 IgG II Quant assay (Abbott Diagnostics, Chicago, USA), according to the manufacturer’s specifications.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Assessment of ovarian follicle functions: Statistical analysis: All analyses were performed using SPSS 23.0 (SPSS Inc., Chicago, IL).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and limitations: To the best of our knowledge this is the first study to examine the presence of natural or vaccine-elicited humoral immune response in the ovarian follicle. In addition, we also investigated the possible association between its presence and several aspects of follicular function and oocyte yield. We chose not to examine the rate of fertilization and embryo formation and development, as they involve the male gametes and may introduce differences unrelated to the study question. This is however a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies. Due to its timing, our study was able to assess short term affects of vaccine and disease but cannot rule out later sequelae.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04822012RecruitingAnti COVID-19 Antibodies in Follicular Fluid and Spermatic F…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.04.09.21255195v1 on medRxiv