COVID-19 Vaccine and Ovarian Reserve
Condition: Fertility Issues; Vaccine Adverse Reaction
MeSH terms: Infertility
Study type: Observational

Summary: 
      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 .
    

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.
    

Intervention name(s): SARS-CoV-2 virus vaccines; AMH sampling; anti Covid-19 antibody levels (Serology)
Intervention type(s): Biological; Diagnostic Test; Diagnostic Test
Intervention description(s): mRNA SARS-CoV-2 virus vaccines ( By Pfizer or Moderna); Blood sample for AMH on recruitment and after three months; Blood sample for IgG against S1 protein after three months
Intervention MeSH terms: Antibodies
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Females (age 11 to 42) that are planning to be vaccinated in Israel
      
Biospecimen description: 
      Blood samples evaluated for Anti Mullarian Hormone (AMH)
    
Keywords: Ovarian reserve; Corona-19 virus; SARS-CoV-2