<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/NCT01668693</url>
  </required_header>
  <id_info>
    <org_study_id>0600-E-905-JH</org_study_id>
    <nct_id>NCT01668693</nct_id>
  </id_info>
  <brief_title>ERA Test in Patients With Recurrent Implantation Failure</brief_title>
  <acronym>ERA</acronym>
  <official_title>The Endometrial Receptivity Array (ERA) as Diagnosis and Personalized Embryo Transfer (pET) as Treatment in Patients With Receptive Implantation Failure (RIF).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Igenomix</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Igenomix</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate the clinical efficiency of the Endometrial&#xD;
      Receptivity Array (ERA) diagnostic tool in patients with repetitive implantation failure&#xD;
      (RIF), leading to the new concept of the personalized window of implantation (pWOI) as&#xD;
      diagnostic and treatment of patients with RIF of endometrial origin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intervention(s): Endometrial sampling, either at LH+7 in a natural cycle or after 5 days of&#xD;
      progesterone in a hormonal replacement cycle (HRT) and personalized embryo transfer (pET) on&#xD;
      the designated day guided by the ERA prediction.&#xD;
&#xD;
      Repeated implantation failure (RIF) is an unsolved not well characterized major cause of&#xD;
      infertility in otherwise healthy women. Although various definitions of RIF exist, the&#xD;
      clinical community agrees that after failure of three IVF cycles, in which one to two&#xD;
      morphologically high-grade embryos have been transferred, special protocols must be enforced,&#xD;
      although no hard data from RCTs demonstrates that any of the current approaches in RIF have a&#xD;
      significant clinical value .&#xD;
&#xD;
      Based on the large amount of information generated about the regulation and deregulation of&#xD;
      the genes implicated in the endometrial window of receptivity (WOR), our group has developed&#xD;
      a molecular diagnostic tool based on the specific transcriptomic signature that identifies&#xD;
      the receptive endometrium at LH+7 in a natural cycle or on day 5 of progesterone impregnation&#xD;
      (P+5) after proper estradiol priming in a hormonal replacement therapy (HRT) cycle. The&#xD;
      endometrial receptivity array (ERA) consists of a customized array containing 238 genes&#xD;
      differentially expressed that is coupled to a computational predictor able to diagnose the&#xD;
      personalized endometrial WOI of a given patient, regardless of its histological appearance.&#xD;
      The accuracy of the diagnostic tool ERA has been demonstrated to be superior to endometrial&#xD;
      histology and results are completely reproducible 29 to 40 months later.&#xD;
&#xD;
      Compelling evidence indicates the existence of an endometrial receptivity alteration in&#xD;
      patients with RIF.&#xD;
&#xD;
      The aim of this study is to demonstrate the diagnostic efficiency of the ERA test in RIF&#xD;
      patients by identifying putative alterations related to the displacement of their&#xD;
      personalized window of receptivity, and the therapeutic implications through personalization&#xD;
      of the day of embryo transfer (pET), following the diagnosis obtained by this molecular&#xD;
      diagnostic tool. An endometrial biopsy on day LH+7 in a natural cycle or on day P+5 in an HRT&#xD;
      cycle and ERA diagnosis of receptive or non-receptive is informed. In receptive cases, embryo&#xD;
      transfer (ET) will be performed in subsequent cycles on the indicated day. In non-receptive&#xD;
      ERA, the test is to be repeated on the dayindicated by the predictor, and personalized ET&#xD;
      guided in subsequent cycles according to ERA diagnosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2010</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">April 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of the Receptive or Non Receptive endometrial status according to the ERA test.</measure>
    <time_frame>1 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pregnancy</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implantation</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Repetitive Implantation Failure</condition>
  <arm_group>
    <arm_group_label>RIF ERA Receptive 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>With the &quot;receptive&quot; results from the first Endometrial Receptivity Array (ERA), the patients will undergo embryo transfer on Day 5 of Progesterone administration in the cycle following the ERA diagnosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RIF ERA Non Receptive</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The &quot;Non Receptive&quot; results of the ERA diagnotic tool will indicate how many more days of Progesterone are necesary in order to obtain the &quot;Receptive&quot; daignosis. A second ERA will take place to confirm receptivity and in the following cycle, the personalized embryo transfer will take place on the day predicted by this diagnostic tool.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ERA (Endometrial Receptivity Array)</intervention_name>
    <description>The diagnostic tool ERA will be performed on all of the patients in order to allocate them in the group &quot;Receptive&quot; or &quot;Non Receptive&quot; and to predict the number of days of Progesterone administration necesary to obtain the &quot;Receptive&quot; prediction.</description>
    <arm_group_label>RIF ERA Non Receptive</arm_group_label>
    <arm_group_label>RIF ERA Receptive 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Personalized Embryo Transfer</intervention_name>
    <description>When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.</description>
    <arm_group_label>RIF ERA Non Receptive</arm_group_label>
    <arm_group_label>RIF ERA Receptive 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Second ERA</intervention_name>
    <description>A second ERA will be performed to confirm receptivity after further administration of Progesterone.</description>
    <arm_group_label>RIF ERA Non Receptive</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women ≤38 years old&#xD;
&#xD;
          -  Normal ovarian reserve&#xD;
&#xD;
          -  FSH &lt;8mIU/mL&#xD;
&#xD;
          -  Cycle with ≥6 MII oocytes/oocyte retrieval&#xD;
&#xD;
          -  ≥3 implantation failures in previous IVF/ICSI cycles with transfer of atleast two good&#xD;
             quality embryos in each cycle Inclusion Criteria for ovum donation recipients&#xD;
&#xD;
          -  ≥3 implantation failures with transfer of atleast two good quality embryos in each&#xD;
             cycle&#xD;
&#xD;
          -  Endometrial thickness ≥ 6 mm&#xD;
&#xD;
          -  Trilaminar pattern after proper progesterone priming&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Existance of hydrosalpinx&#xD;
&#xD;
          -  Atrophic endometrium &lt; 6 mm&#xD;
&#xD;
          -  Previous ectopic or uterine miscarriages&#xD;
&#xD;
          -  Presence of myomas or polyps&#xD;
&#xD;
          -  Previous embryo transfer with high difficulty and/or bleeding&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>38 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlos Simón, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ºIGENOMIX / IVI Valencia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carlos Simón, MD PhD</last_name>
    <phone>+34963050900</phone>
    <email>carlos.simon@ivi.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carlos Gómez, MA</last_name>
    <phone>+34670506469</phone>
    <email>carlos.gomez@igenomix.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>IVI</name>
      <address>
        <city>Valencia</city>
        <state>VAencia</state>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carlos Simon</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>October 16, 2015</last_update_submitted>
  <last_update_submitted_qc>October 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 19, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Valenciano de Infertilidad, IVI VALENCIA</investigator_affiliation>
    <investigator_full_name>Carlos Simon</investigator_full_name>
    <investigator_title>MD PhD</investigator_title>
  </responsible_party>
  <keyword>Endometrial receptivity</keyword>
  <keyword>recurrent implantation failure</keyword>
  <keyword>predictor tool</keyword>
  <keyword>ERA</keyword>
  <keyword>customized microarray</keyword>
  <keyword>personalized embryo transfer</keyword>
  <!-- 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/NCT01668693
org study id: 0600-E-905-JH
nct id: NCT01668693
lead sponsor: 
has dmc: No
The purpose of this study is to demonstrate the clinical efficiency of the Endometrial
      Receptivity Array (ERA) diagnostic tool in patients with repetitive implantation failure
      (RIF), leading to the new concept of the personalized window of implantation (pWOI) as
      diagnostic and treatment of patients with RIF of endometrial origin.
Intervention(s): Endometrial sampling, either at LH+7 in a natural cycle or after 5 days of
      progesterone in a hormonal replacement cycle (HRT) and personalized embryo transfer (pET) on
      the designated day guided by the ERA prediction.

      Repeated implantation failure (RIF) is an unsolved not well characterized major cause of
      infertility in otherwise healthy women. Although various definitions of RIF exist, the
      clinical community agrees that after failure of three IVF cycles, in which one to two
      morphologically high-grade embryos have been transferred, special protocols must be enforced,
      although no hard data from RCTs demonstrates that any of the current approaches in RIF have a
      significant clinical value .

      Based on the large amount of information generated about the regulation and deregulation of
      the genes implicated in the endometrial window of receptivity (WOR), our group has developed
      a molecular diagnostic tool based on the specific transcriptomic signature that identifies
      the receptive endometrium at LH+7 in a natural cycle or on day 5 of progesterone impregnation
      (P+5) after proper estradiol priming in a hormonal replacement therapy (HRT) cycle. The
      endometrial receptivity array (ERA) consists of a customized array containing 238 genes
      differentially expressed that is coupled to a computational predictor able to diagnose the
      personalized endometrial WOI of a given patient, regardless of its histological appearance.
      The accuracy of the diagnostic tool ERA has been demonstrated to be superior to endometrial
      histology and results are completely reproducible 29 to 40 months later.

      Compelling evidence indicates the existence of an endometrial receptivity alteration in
      patients with RIF.

      The aim of this study is to demonstrate the diagnostic efficiency of the ERA test in RIF
      patients by identifying putative alterations related to the displacement of their
      personalized window of receptivity, and the therapeutic implications through personalization
      of the day of embryo transfer (pET), following the diagnosis obtained by this molecular
      diagnostic tool. An endometrial biopsy on day LH+7 in a natural cycle or on day P+5 in an HRT
      cycle and ERA diagnosis of receptive or non-receptive is informed. In receptive cases, embryo
      transfer (ET) will be performed in subsequent cycles on the indicated day. In non-receptive
      ERA, the test is to be repeated on the dayindicated by the predictor, and personalized ET
      guided in subsequent cycles according to ERA diagnosis.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Detection of the Receptive or Non Receptive endometrial status according to the ERA test.
time frame: 1 months
measure: Pregnancy
time frame: 6 weeks
measure: Implantation
time frame: 4 months
arm group label: RIF ERA Receptive 1
arm group type: Active Comparator
description: With the "receptive" results from the first Endometrial Receptivity Array (ERA), the patients will undergo embryo transfer on Day 5 of Progesterone administration in the cycle following the ERA diagnosis.
arm group label: RIF ERA Non Receptive
arm group type: Experimental
description: The "Non Receptive" results of the ERA diagnotic tool will indicate how many more days of Progesterone are necesary in order to obtain the "Receptive" daignosis. A second ERA will take place to confirm receptivity and in the following cycle, the personalized embryo transfer will take place on the day predicted by this diagnostic tool.
intervention type: Other
intervention name: ERA (Endometrial Receptivity Array)
description: The diagnostic tool ERA will be performed on all of the patients in order to allocate them in the group "Receptive" or "Non Receptive" and to predict the number of days of Progesterone administration necesary to obtain the "Receptive" prediction.
arm group label: RIF ERA Non Receptive
arm group label: RIF ERA Receptive 1
intervention type: Other
intervention name: Personalized Embryo Transfer
description: When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.
arm group label: RIF ERA Non Receptive
arm group label: RIF ERA Receptive 1
intervention type: Other
intervention name: Second ERA
description: A second ERA will be performed to confirm receptivity after further administration of Progesterone.
arm group label: RIF ERA Non Receptive
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 38 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carlos Simón, MD PhD
role: Principal Investigator
affiliation: ºIGENOMIX / IVI Valencia
last name: Carlos Simón, MD PhD
phone: +34963050900
email: carlos.simon@ivi.es
last name: Carlos Gómez, MA
phone: +34670506469
email: carlos.gomez@igenomix.com
facility: 
status: Recruiting
contact: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Instituto Valenciano de Infertilidad, IVI VALENCIA
investigator full name: Carlos Simon
investigator title: MD PhD