<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04425317</url>
  </required_header>
  <id_info>
    <org_study_id>COVIDOFF001</org_study_id>
    <nct_id>NCT04425317</nct_id>
  </id_info>
  <brief_title>Detection of SARS-CoV-2 in Follicular Fluid and Cumulus-oocyte-complexes in COVID-19 Patients</brief_title>
  <acronym>COVID_OFF</acronym>
  <official_title>Detection of SARS-CoV-2 in Follicular Fluid and Cumu-lus-oocyte-complexes From COVID-19 Patients During Controlled Ovarian Stimulation for ICSI Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CRG UZ Brussel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CRG UZ Brussel</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recently, the world was shaken awake by a pandemic caused by a novel coronavirus SARS-CoV-2&#xD;
      (Severe Acute Respiratory Syndrome Coronavirus 2). In most nations drastic isolation measures&#xD;
      were taken to minimize the further spread of the Coronavirus Disease 2019 (COVID-19). Being&#xD;
      the first pandemic sparked by a Coronavirus, little was known on COVID-19 and its&#xD;
      implications on general health. Our understanding on the virus and its potential effects on&#xD;
      health is growing. In Belgium, the situation is stabilizing, and doctors and healthcare&#xD;
      workers are slowly recommencing routine work and consultations. As also fertility treatments&#xD;
      were abruptly interrupted, many patients are in need to resume their treatment. The limited&#xD;
      evidence of SARS-CoV-2 on pregnancy seems to be rather satisfying1, but practically nothing&#xD;
      is known about the possible impact of an active SARS-CoV-2 infection on female gametes. Viral&#xD;
      transmission occurs predominantly through respiratory droplets, but transmission to gametes&#xD;
      cannot be ruled out.&#xD;
&#xD;
      Since the onset of the pandemic, knowledge about the molecular details of SARS-CoV-2&#xD;
      infection rapidly grew. Coronaviruses are enveloped RNA viruses. For a virus to deliver their&#xD;
      genome into the host cell, attachment and entrance into that cell is a crucial step. The&#xD;
      coronavirus surface protein spike (S) mediates entry into target cells by binding to a&#xD;
      cellular receptor and subsequent fusing of the viral envelope with a host cell membrane. The&#xD;
      SARS-CoV-2-S protein (SARS-S) utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor&#xD;
      for host cell entry. Host proteases such as transmembrane serine protease 2 (TMPRSS2) are&#xD;
      then needed to cleave the viral S protein, allow-ing permanent fusion of the viral and host&#xD;
      cell membranes2. Expression of ACE2 and TMPRSS2 has been shown in testicular, uterine and&#xD;
      placental cells. Based on available transcriptomic data, co-expression of ACE2 and TMPRSS2 is&#xD;
      also seen on oocyte level, but the possible impact on reproduction is unknown. The BSG&#xD;
      (basigin or CD147), a receptor on host cells, was also identified as a possible route for&#xD;
      viral invasion.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 10, 2020</start_date>
  <completion_date type="Actual">January 1, 2022</completion_date>
  <primary_completion_date type="Actual">June 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Presence or absence of SARS-CoV-2 in follicular fluid, cumulus cells, immature oocytes and endometrium</measure>
    <time_frame>1 day</time_frame>
    <description>Identification of viral RNA in cumulus-oocyte-complexes, exclusively looking at the material that is considered waste material in a normal oocyte retrieval</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Presence of ACE2, TMPRSS and BSG receptors in cumulus cells, immature oocytes and endometrium</measure>
    <time_frame>1 day</time_frame>
    <description>Presence of receptors, identified as possible steps in the entry pathway for SARS-CoV-2</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Infertility</condition>
  <condition>COVID</condition>
  <condition>IVF</condition>
  <arm_group>
    <arm_group_label>Diagnostic arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Blood sample and endometrial biopsy Collection of follicular fluid, immature oocytes and cumulus cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>Blood sample and endometrial biopsy on the moment of oocyte retrieval</description>
    <arm_group_label>Diagnostic arm</arm_group_label>
    <other_name>Endometrial biopsy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Undergoing IVF/ICSI treatment&#xD;
&#xD;
          -  Planned for an oocyte retrieval&#xD;
&#xD;
          -  PCR positive of SARS-CoV-2 or high suspicion for COVID 19 based on CT scan&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  None&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Uz Brussels</name>
      <address>
        <city>Brussels</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>February 16, 2022</last_update_submitted>
  <last_update_submitted_qc>February 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>CRG UZ Brussel</investigator_affiliation>
    <investigator_full_name>Liese Boudry</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04425317
org study id: COVIDOFF001
nct id: NCT04425317
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Recently, the world was shaken awake by a pandemic caused by a novel coronavirus SARS-CoV-2
      (Severe Acute Respiratory Syndrome Coronavirus 2). In most nations drastic isolation measures
      were taken to minimize the further spread of the Coronavirus Disease 2019 (COVID-19). Being
      the first pandemic sparked by a Coronavirus, little was known on COVID-19 and its
      implications on general health. Our understanding on the virus and its potential effects on
      health is growing. In Belgium, the situation is stabilizing, and doctors and healthcare
      workers are slowly recommencing routine work and consultations. As also fertility treatments
      were abruptly interrupted, many patients are in need to resume their treatment. The limited
      evidence of SARS-CoV-2 on pregnancy seems to be rather satisfying1, but practically nothing
      is known about the possible impact of an active SARS-CoV-2 infection on female gametes. Viral
      transmission occurs predominantly through respiratory droplets, but transmission to gametes
      cannot be ruled out.

      Since the onset of the pandemic, knowledge about the molecular details of SARS-CoV-2
      infection rapidly grew. Coronaviruses are enveloped RNA viruses. For a virus to deliver their
      genome into the host cell, attachment and entrance into that cell is a crucial step. The
      coronavirus surface protein spike (S) mediates entry into target cells by binding to a
      cellular receptor and subsequent fusing of the viral envelope with a host cell membrane. The
      SARS-CoV-2-S protein (SARS-S) utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor
      for host cell entry. Host proteases such as transmembrane serine protease 2 (TMPRSS2) are
      then needed to cleave the viral S protein, allow-ing permanent fusion of the viral and host
      cell membranes2. Expression of ACE2 and TMPRSS2 has been shown in testicular, uterine and
      placental cells. Based on available transcriptomic data, co-expression of ACE2 and TMPRSS2 is
      also seen on oocyte level, but the possible impact on reproduction is unknown. The BSG
      (basigin or CD147), a receptor on host cells, was also identified as a possible route for
      viral invasion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Presence or absence of SARS-CoV-2 in follicular fluid, cumulus cells, immature oocytes and endometrium
time frame: 1 day
description: Identification of viral RNA in cumulus-oocyte-complexes, exclusively looking at the material that is considered waste material in a normal oocyte retrieval
measure: Presence of ACE2, TMPRSS and BSG receptors in cumulus cells, immature oocytes and endometrium
time frame: 1 day
description: Presence of receptors, identified as possible steps in the entry pathway for SARS-CoV-2
arm group label: Diagnostic arm
arm group type: Other
description: Blood sample and endometrial biopsy Collection of follicular fluid, immature oocytes and cumulus cells
intervention type: Diagnostic Test
intervention name: Blood sample
description: Blood sample and endometrial biopsy on the moment of oocyte retrieval
arm group label: Diagnostic arm
other name: Endometrial biopsy
criteria: 
gender: Female
minimum age: N/A
maximum age: 45 Years
healthy volunteers: No
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: CRG UZ Brussel
investigator full name: Liese Boudry
investigator title: MD
mesh term: Infertility
sharing ipd: No