COVID-19 Vaccine and Ovarian Reserve

June 19, 2023 updated by: Dr. Aya Mohr-Sasson, Sheba Medical Center

The Effect of COVID -19 mRNA Vaccine on Ovarian Reserve

As Israel is the first country to widely vaccinate its population using the mRNA vaccine against COVID-19, evaluating its influence on ovarian reserve is essential .

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Introduction:

Although there is as yet no scientific evidence that a SARS-CoV-2 virus infection could have negative effects on fertility, currently the possibility that the virus could affect sperm function and egg performance cannot be excluded. Previous studies have already shown an association between influenza and infertility. SARS-CoV-2 seems to be far more aggressive in terms of severe illness, morbidity and mortality in comparison to common influenzas, thus it is reasonable to hypothesize a possible substantial effect of Covid-19 on fertility.

At the cellular level, common influenza viruses promote oxidant-sensitive pathways, leading to increased oxidative stress. This mechanism has been blamed to cause male infertility through a reduction of progressive motility in spermatozoa and a simultaneous increase in sperm DNA fragmentation. Based on this pathogenic pathway, it can be hypothesized that SARS-CoV-2 could increase sperm DNA fragmentation, which might affect fertilizing potential. Along the same lines, SARS-CoV-2 may affect oocyte performance through mechanisms that increase oxidative stress.

As SARS-CoV-2 acts through the angiotensin-converting enzyme 2 (ACE2) receptor, this was proposed as an additional pathway affecting ovaria follicles and oocytes. ACE2 receptors are expressed in human ovaries, while angiotensin has been detected in measurable amounts in the follicular fluid . Therefore, a possible negative impact of the virus through an interaction between the oocyte and the somatic cells cannot be ruled out.

The COVID-19 pandemic exerted tremendous pressure on scientists to develop safe and effective vaccines. A few delivery systems for next-generation vaccines against COVID-19 were introduced. The new-generation vaccines include only a specific antigen or antigens of the pathogen, instead of the whole pathogen, thus providing a better safety profile. While SARS-CoV-2 has four main structural proteins, the spike protein (S) which is located at the outer surface of the virus particles and can bind to ACE2 on the cell surface and causes receptor-mediated endocytosis of the virus, is the main target to evoke the self-immune system.

The mRNA vaccines represent the newest generation of vaccines in which all components can be engineered via chemical synthesis. Due to the mRNA molecules' low apparent transfection efficacy, lipid nanoparticles (LNPs) are often used to incorporate the mRNA molecules for transfection purposes. An additional advantage of the mRNA vaccine is that the antigen expression generated by the mRNA is a transient process and therefore the risk of host DNA integration is negligible. Furthermore, elimination of live materials poses an advantage from a quality control standpoint and allows quick product switching in manufacturing facilities. Since the process is fully-synthetic it also eliminates the risk of disease transmissions from the manufacturing facility. The effect of the systemic generation and introduction of just the S protein of the SARS-CoV-2 could have a negative influence on ovarian follicles and oocytes has not been studied yet.

Anti Mullarian Hormone (AMH) is a glycoprotein produced by the granulosa cells of the antral follicles. Its circulating levels are associated with the fertility state of the ovary and in contrast to other hormones are not influenced by the state of the menstrual cycle. Therefore, AMH levels are considered the measurement of choice for estimating ovarian reserve.

As Israel is the first country to widely vaccinate its population using the mRNA vaccines and due to all the aforementioned, the aim of this study is to evaluate the influence of the mRNA vaccines on ovarian reserve estimated by the change in AMH before and three-month following vaccination.

Material and Methods:

This is a prospective study including females that are planning to be vaccinated in Israel. Women will be asked to sign an informed consent to participate in the study while visiting the ambulatory vaccinating clinics before being vaccinated. Medical information will be collected by the research team during this visit using computerized questionnaire. Blood samples will be collected for AMH analysis before administration of the first mRNA vaccine shot. A follow up visit will be scheduled at three months after the first vaccination. During this visit, blood samples will be collected for AMH levels and for anti Covid-19 antibody levels (Serology). Additionally, women will be asked to complete a second computerized questionnaire which focused on possible adverse effects following vaccinations and gynecological well-being at 3,6 and 12 months from recruitment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Ramat-Gan, Israel, 56506
        • Sheba Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

11 years to 42 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Females (age 11 to 42) that are planning to be vaccinated in Israel

Description

Inclusion Criteria:

  • Age 11-42
  • No previous exposure to Covid-19 vaccine (first or second dose)
  • No known past Covid-19 infection

Exclusion Criteria:

  • Premature ovarian failure
  • Pregnancy
  • Fertility treatment
  • Past Covid-19 infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Study Group: Women who are planning to be vaccinated
Women that are planning to be vaccinated, before receiving the first shot of the vaccine
Biological: SARS-CoV-2 virus vaccines
mRNA SARS-CoV-2 virus vaccines ( By Pfizer or Moderna)
Diagnostic test: AMH sampling
Blood sample for AMH on recruitment and after three months
Diagnostic test: anti Covid-19 antibody levels (Serology)
Blood sample for IgG against S1 protein after three months

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Delta in AMH levels
Time Frame: From first vaccination until the second AMH sampling - after three month
AMA levels on recruitment minos AMH levels after three months
From first vaccination until the second AMH sampling - after three month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sheba Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 6, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 8121-21-SMC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

On request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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