<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/NCT02230449</url>
  </required_header>
  <id_info>
    <org_study_id>OocyteCompetenceSK001</org_study_id>
    <secondary_id>GFI-2014-#21</secondary_id>
    <nct_id>NCT02230449</nct_id>
  </id_info>
  <brief_title>Identifying Expression Markers of Cumulus Cells to Identify Oocyte Developmental Potential Through a Maturation Analysis</brief_title>
  <official_title>Identifying Markers of Oocyte Competence Through a Maturation Analysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sisli Hospital, Istanbul</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sisli Hospital, Istanbul</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to analyze the expression of genes and microRNAs potentially involved&#xD;
      in oocyte competence in follicles of different sizes (&lt;17mm and ≥17mm) at the time of oocyte&#xD;
      pick-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In ART, one of the major obstacles encountered in some patients is the wide variation in the&#xD;
      follicular size at the oocyte pick-up day and consequently, the number of available mature&#xD;
      oocytes and the number of competent embryos for implantation. The follicular size at the day&#xD;
      of oocyte pick-up reflects the synchronicity of the individual follicular responsiveness to&#xD;
      FSH.&#xD;
&#xD;
      For successful preimplantation development of an embryo, the oocyte must contain all&#xD;
      necessary maternal factors. Two of these factors are specific mRNA transcripts (GDF9, PTX3,&#xD;
      HAS2, PTGS2, TNFAIP6) and microRNA (miR-224).&#xD;
&#xD;
      For each Cumulus Oocyte Complex, the evaluation of embryo development and morphokinetics will&#xD;
      be correlated with the expression and implantation data to identify a quantitative biomarker&#xD;
      to predict the embryo with the highest chance of implantation in patients.&#xD;
&#xD;
      Experimental Design:&#xD;
&#xD;
        1. - Collection of Cumulus Oocyte Complex (COC) from patients&#xD;
&#xD;
        2. - Separation of oocytes according to the size of the follicule they have been retrieved&#xD;
           from (&lt;17mm; ≥17mm)&#xD;
&#xD;
        3. - Isolation of mRNA from both groups of cumulus cells&#xD;
&#xD;
        4. - Expression studies, qRT-PCR (GDF9, PTX3, HAS2, PTGS2, TNFAIP6)&#xD;
&#xD;
        5. - Analysis of miR-224, a negative regulator of cumulus expansion via PTX3&#xD;
&#xD;
        6. - Time-lapse culture &amp; evaluation of morphokinetics&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulus cell RNA expression correlation with blastocyst formation potential and quality</measure>
    <time_frame>6 days</time_frame>
    <description>At the day of oocyte pick-up, cumulus cells will be collected from each cumulus oocyte complex. RNA extraction will be performed from those cumulus cells and expression levels of 5 genes and 1 miRNA will be measured (compared with that of a housekeeping gene). Oocytes of those samples will be injected and cultured with routine Assisted Reproduction Techniques. At the day 5 &amp; 6, after the oocyte pick-up procedure, each blastocyst formed will be noted and the quality of each blastocyst will be recorded. The blastocyst grading will be done according to Gardner's blastocyst morphological criteria (degree of expansion of the blastocoele cavity: 1 to 5, inner cell mass morphology: A to C, trophectoderm morphology: A to C).&#xD;
The composite primary outcome measure will allow the correlation of the expression levels of 5 genes and 1 miRNA of each cumulus oocyte complex with the corresponding embryo morphology on day 5 (presence or absence of a blastocyst) and blastocyst quality.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Implantation Rate</measure>
    <time_frame>2 months</time_frame>
    <description>Implantation of the embryo(s) transferred will be checked by ultrasound 6 weeks after the pick-up. Patients for whom the number of embryo(s) transferred match the number of sac will allow the correlation of the expression data with implantation.</description>
  </secondary_outcome>
  <enrollment type="Actual">200</enrollment>
  <condition>Infertility</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Cumulus cells from each oocyte of every enrolled patient will be collected and mRNA &amp; miRNA&#xD;
      extraction will be performed.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Infertile couples applying to the clinic for assisted reproductive technologies&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  No more than 2 previous treatment cycles&#xD;
&#xD;
          -  No history of recurrent spontaneous abortions&#xD;
&#xD;
          -  Age ≤ 39 years&#xD;
&#xD;
          -  BMI &lt; 30 kg / m2&#xD;
&#xD;
          -  ≥ 8 cumulus-oocyte-complexes (COC) retrieved&#xD;
&#xD;
          -  human Chorionic Gonadotrophin (hCG) triggering&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preimplantaion Genetic Diagnosis (PGD) or Preimplantation Genetics Screening (PGS)&#xD;
             indication&#xD;
&#xD;
          -  Maximum number of 24 COC during pickup&#xD;
&#xD;
          -  Failure to culture until Day 5&#xD;
&#xD;
          -  Polycystic ovary syndrome&#xD;
&#xD;
          -  Severe endometrial factor that can influence implantation&#xD;
&#xD;
          -  Uterine malformation or congenital anomaly&#xD;
&#xD;
          -  Severe male factor (Azoospermia)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Semra Kahraman, Prof. Dr</last_name>
    <role>Study Chair</role>
    <affiliation>Manager of ART and Genetics Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Semra Kahraman, Prof. Dr.</last_name>
    <role>Study Director</role>
    <affiliation>Manager of ART and Genetics Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mehmet Ali Tufekci, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ART Center Research and Development Department</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sisli Hospital ART Center</name>
      <address>
        <city>Istanbul</city>
        <zip>34385</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>September 1, 2017</last_update_submitted>
  <last_update_submitted_qc>September 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Memorial Sisli Hospital, Istanbul</investigator_affiliation>
    <investigator_full_name>Prof. Dr. Semra Kahraman</investigator_full_name>
    <investigator_title>Director of ART and Genetics Center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <!-- 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/NCT02230449
org study id: OocyteCompetenceSK001
secondary id: GFI-2014-#21
nct id: NCT02230449
lead sponsor: 
has dmc: No
The aim of the study is to analyze the expression of genes and microRNAs potentially involved
      in oocyte competence in follicles of different sizes (<17mm and ≥17mm) at the time of oocyte
      pick-up.
In ART, one of the major obstacles encountered in some patients is the wide variation in the
      follicular size at the oocyte pick-up day and consequently, the number of available mature
      oocytes and the number of competent embryos for implantation. The follicular size at the day
      of oocyte pick-up reflects the synchronicity of the individual follicular responsiveness to
      FSH.

      For successful preimplantation development of an embryo, the oocyte must contain all
      necessary maternal factors. Two of these factors are specific mRNA transcripts (GDF9, PTX3,
      HAS2, PTGS2, TNFAIP6) and microRNA (miR-224).

      For each Cumulus Oocyte Complex, the evaluation of embryo development and morphokinetics will
      be correlated with the expression and implantation data to identify a quantitative biomarker
      to predict the embryo with the highest chance of implantation in patients.

      Experimental Design:

        1. - Collection of Cumulus Oocyte Complex (COC) from patients

        2. - Separation of oocytes according to the size of the follicule they have been retrieved
           from (<17mm; ≥17mm)

        3. - Isolation of mRNA from both groups of cumulus cells

        4. - Expression studies, qRT-PCR (GDF9, PTX3, HAS2, PTGS2, TNFAIP6)

        5. - Analysis of miR-224, a negative regulator of cumulus expansion via PTX3

        6. - Time-lapse culture & evaluation of morphokinetics
observational model: Cohort
time perspective: Prospective
measure: Cumulus cell RNA expression correlation with blastocyst formation potential and quality
time frame: 6 days
description: At the day of oocyte pick-up, cumulus cells will be collected from each cumulus oocyte complex. RNA extraction will be performed from those cumulus cells and expression levels of 5 genes and 1 miRNA will be measured (compared with that of a housekeeping gene). Oocytes of those samples will be injected and cultured with routine Assisted Reproduction Techniques. At the day 5 & 6, after the oocyte pick-up procedure, each blastocyst formed will be noted and the quality of each blastocyst will be recorded. The blastocyst grading will be done according to Gardner's blastocyst morphological criteria (degree of expansion of the blastocoele cavity: 1 to 5, inner cell mass morphology: A to C, trophectoderm morphology: A to C).
The composite primary outcome measure will allow the correlation of the expression levels of 5 genes and 1 miRNA of each cumulus oocyte complex with the corresponding embryo morphology on day 5 (presence or absence of a blastocyst) and blastocyst quality.
measure: Implantation Rate
time frame: 2 months
description: Implantation of the embryo(s) transferred will be checked by ultrasound 6 weeks after the pick-up. Patients for whom the number of embryo(s) transferred match the number of sac will allow the correlation of the expression data with implantation.
Cumulus cells from each oocyte of every enrolled patient will be collected and mRNA & miRNA
      extraction will be performed.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 39 Years
healthy volunteers: No
last name: Semra Kahraman, Prof. Dr
role: Study Chair
affiliation: Manager of ART and Genetics Center
last name: Semra Kahraman, Prof. Dr.
role: Study Director
affiliation: Manager of ART and Genetics Center
last name: Mehmet Ali Tufekci, PhD
role: Principal Investigator
affiliation: ART Center Research and Development Department
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Memorial Sisli Hospital, Istanbul
investigator full name: Prof. Dr. Semra Kahraman
investigator title: Director of ART and Genetics Center
mesh term: Infertility