<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/NCT01718210</url>
  </required_header>
  <id_info>
    <org_study_id>HC0005</org_study_id>
    <nct_id>NCT01718210</nct_id>
  </id_info>
  <brief_title>Use of GM-CSF Supplemented IVF Medium in Patients With Recurrent Implantation Failure</brief_title>
  <official_title>GM-CSF Supplemented Medium for IVF Embryo Growth in Patients With Recurrent Implantation Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Endocrinology and Reproductive Medicine, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre for Endocrinology and Reproductive Medicine, Italy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether in Assisted Reproductive Technologies the&#xD;
      use of culture medium supplemented with GM-CSF, a growth factor working on stem cells, may&#xD;
      improve the embryo implantation in patients experiencing recurrent implantation failure in&#xD;
      IVF cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Assisted Reproductive Technologies the rate of pregnancy for cycle and the implantation&#xD;
      rate remain low nevertheless the improvement in the last years. In particular there are a&#xD;
      group of patients, in young reproductive age, experiencing recurrent implantation failure,&#xD;
      nevertheless the good embryos produced and transferred. Recently, it has been showed that&#xD;
      culture medium supplemented with GM-CSF, may improve the embryo outcomes in IVF. In this&#xD;
      trial the investigators will test the potential benefits of this culture medium on embryos of&#xD;
      patients experiencing recurrent implantation failure. 100 women with recurrent implantation&#xD;
      failure, at least three failed previous IVF attempts with at least 8 good embryos transferred&#xD;
      no more than 40 years old will be selected. These patients will be assigned to two arms, one&#xD;
      experimental and one other of control by a computer generated sequence. After the oocyte&#xD;
      retrieval and fertilization by ICSI procedure, the fertilised oocyte (2PN)will cultured with&#xD;
      the GM-CSF supplemented culture medium (EmbryoGen, Origio, Denmark), or in normal culture in&#xD;
      micro drop of 30microliters under oil until the day of transfer (day three or 8 cells sage&#xD;
      embryos). A maximum of three embryos will be transferred. The pregnancy rate the implantation&#xD;
      rate will be the outcomes considered&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pregnancy rate</measure>
    <time_frame>9 months</time_frame>
    <description>The number of patients become pregnant after IVF where GM-CSF medium is used, compared with the number of patients become pregnant in the control group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>9 months</time_frame>
    <description>number of embryos implanted</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>GM-CSF medium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patient's embryos are incubated after fertilization with mediun supplemented with GM-CSF</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CONTROL</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>50 women with recurrent implantation failure (at leat three previous IVF attempts failed with at least 8 good embryos transferred in uterus)that the obtained with IVF are incubated with a standard medium for IVF, and utilized as control group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GM-CSF medium</intervention_name>
    <description>incubation of IVF embryos with a specific medium containing GM-CSF</description>
    <arm_group_label>GM-CSF medium</arm_group_label>
    <other_name>Embryogen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CONTROL</intervention_name>
    <description>group of controls treated with a standard IVF medium</description>
    <arm_group_label>CONTROL</arm_group_label>
    <other_name>NORMAL MEDIUM</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  woman age 40 years old or less,&#xD;
&#xD;
          -  3 or more consecutive previous failed IVF cycles with a total of at least 8 good&#xD;
             embryos replaced in uterus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  chromosomal defects in the couple,&#xD;
&#xD;
          -  metabolic diseases (diabetes, etc),&#xD;
&#xD;
          -  other genetic diseases (thalassemia, cystic fibrosis, etc.)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marco Sbracia, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Centre for Endocrinology and Reproductive Medicine, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Villa Salaria Fisiopatologia Riproduzione</name>
      <address>
        <city>Rome</city>
        <zip>00198</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>March 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>April 25, 2016</last_update_submitted>
  <last_update_submitted_qc>April 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 27, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GM-CSF</keyword>
  <keyword>recurrent implantation failure</keyword>
  <keyword>pregnancy rate</keyword>
  <keyword>IVF</keyword>
  <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/NCT01718210
org study id: HC0005
nct id: NCT01718210
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether in Assisted Reproductive Technologies the
      use of culture medium supplemented with GM-CSF, a growth factor working on stem cells, may
      improve the embryo implantation in patients experiencing recurrent implantation failure in
      IVF cycles.
In Assisted Reproductive Technologies the rate of pregnancy for cycle and the implantation
      rate remain low nevertheless the improvement in the last years. In particular there are a
      group of patients, in young reproductive age, experiencing recurrent implantation failure,
      nevertheless the good embryos produced and transferred. Recently, it has been showed that
      culture medium supplemented with GM-CSF, may improve the embryo outcomes in IVF. In this
      trial the investigators will test the potential benefits of this culture medium on embryos of
      patients experiencing recurrent implantation failure. 100 women with recurrent implantation
      failure, at least three failed previous IVF attempts with at least 8 good embryos transferred
      no more than 40 years old will be selected. These patients will be assigned to two arms, one
      experimental and one other of control by a computer generated sequence. After the oocyte
      retrieval and fertilization by ICSI procedure, the fertilised oocyte (2PN)will cultured with
      the GM-CSF supplemented culture medium (EmbryoGen, Origio, Denmark), or in normal culture in
      micro drop of 30microliters under oil until the day of transfer (day three or 8 cells sage
      embryos). A maximum of three embryos will be transferred. The pregnancy rate the implantation
      rate will be the outcomes considered
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Pregnancy rate
time frame: 9 months
description: The number of patients become pregnant after IVF where GM-CSF medium is used, compared with the number of patients become pregnant in the control group
measure: Implantation rate
time frame: 9 months
description: number of embryos implanted
arm group label: GM-CSF medium
arm group type: Experimental
description: patient's embryos are incubated after fertilization with mediun supplemented with GM-CSF
arm group label: CONTROL
arm group type: Placebo Comparator
description: 50 women with recurrent implantation failure (at leat three previous IVF attempts failed with at least 8 good embryos transferred in uterus)that the obtained with IVF are incubated with a standard medium for IVF, and utilized as control group.
intervention type: Drug
intervention name: GM-CSF medium
description: incubation of IVF embryos with a specific medium containing GM-CSF
arm group label: GM-CSF medium
other name: Embryogen
intervention type: Drug
intervention name: CONTROL
description: group of controls treated with a standard IVF medium
arm group label: CONTROL
other name: NORMAL MEDIUM
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: No
last name: Marco Sbracia, MD
role: Study Chair
affiliation: Centre for Endocrinology and Reproductive Medicine, Italy
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Infertility