<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/NCT02262117</url>
  </required_header>
  <id_info>
    <org_study_id>P130929</org_study_id>
    <nct_id>NCT02262117</nct_id>
  </id_info>
  <brief_title>Evaluate the Interest of the Pre-conceptional Endometrial Immune Profiling to Increase Birth Rates</brief_title>
  <acronym>PRECONCEPTIO</acronym>
  <official_title>A Prospective, Randomized, Controlled, Two-arm Study to Evaluate the Interest of the Pre-conceptional Endometrial Immune Profiling to Increase Birth Rates Through a Care Personalization in Reproductive Medicine Before IVF</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, randomized, controlled, open two-arm study to evaluate the interest of the&#xD;
      pre-conceptional endometrial immune profiling to increase birth rates.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Birth rates following an embryo transfer with a mean of two embryos transferred stagnate&#xD;
      around 23% per transfer (annual report of the Agency of Biomedicine). Some estimates that&#xD;
      half of infertile patients treated are partially or totally concerned by problem of&#xD;
      inadequate uterine receptivity.&#xD;
&#xD;
      The investigators' hypothesis is that a pre-conceptional immune endometrial evaluation may&#xD;
      increase significantly birth rates since successful implantation results from both the&#xD;
      matching of a competent embryo within a competent endometrium.&#xD;
&#xD;
      The identification of endometrial biomarkers documenting the immune uterine environment&#xD;
      during the implantation window would be able to improve the efficacy of ART through a&#xD;
      personalization of treatment accordingly to the ability of the patients to receive their&#xD;
      embryos. All patients with all inclusion criteria and no exclusion criteria will be included.&#xD;
      Only patients with a deregulation (immune analysis) will be randomized.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 20, 2015</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Live birth rate (without congenital abnormality or malformation)/transfer following the first (fresh) embryo transfer after uterine immune analysis</measure>
    <time_frame>up to 18 months</time_frame>
    <description>Live birth rate/transfer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate/transfer following the first embryo transfer at 12 weeks of amenorrhea</measure>
    <time_frame>12 amenorrhea weeks</time_frame>
    <description>Ongoing pregnancy rate/transfer following the first embryo transfer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of physiological pregnancies after personalization</measure>
    <time_frame>up to 18 months</time_frame>
    <description>Physiological pregnancies are defined by a normal growth of the fetus and a birth at term.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy rate/transfer following the first embryo transfer</measure>
    <time_frame>8 amenorrhea weeks</time_frame>
    <description>Pregnancy rate/transfer following the first embryo transfer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of embryo implanted/number of embryos replaced)</measure>
    <time_frame>at 8, 12 and 40 amenorrhea weeks</time_frame>
    <description>Implantation rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of early miscarriage in the first trimester</measure>
    <time_frame>12 amenorrhea weeks</time_frame>
    <description>Number of early miscarriage in the first trimester</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of late miscarriage</measure>
    <time_frame>between 13 and 24 amenorrhea weeks</time_frame>
    <description>Number of late miscarriage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Term of birth (for babies without congenital anormality or malformation)</measure>
    <time_frame>up to 18 months</time_frame>
    <description>Term of birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight at birth</measure>
    <time_frame>up to 18 months</time_frame>
    <description>A weight of birth below the 10 percentile according to the table of reference with distribution of birth weight in function of the term of birth in the overall population define the intrauterine growth retardation (for babies without congenital anormality or malformation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of prematurity (A birth below 37 weeks of amenorrhea defines the premature birth and before 28 weeks of amenorrhea the severe preterm birth) (for babies without congenital anormality or malformation)</measure>
    <time_frame>between 28 and 37 amenorrhea weeks</time_frame>
    <description>Number of prematurity (A birth below 37 weeks of amenorrhea)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of pre-eclampsia (defined as the association of hypertension over 14/9 mm of hg with proteinuria occuring during the pregnancy- this pathology is related to insufiscient invasion during the first trimester)</measure>
    <time_frame>up to 18 months</time_frame>
    <description>Number of pre-eclampsia (defined as the association of hypertension over 14/9 mm of hg with proteinuria occuring during the pregnancy- this pathology is related to insufiscient invasion during the first trimester)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of pathologic pregnancy included stillbirth and congenital abnormality</measure>
    <time_frame>up to 18 months</time_frame>
    <description>Number of pathologic pregnancy included stillbirth and congenital abnormality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigate if immunologic events studying on endometrial level have an impact on blood level or are independent.</measure>
    <time_frame>up to 15 months</time_frame>
    <description>Quantification by flow cytometry of circulating NK cells (CD56 +/CD16 -), T regulatory T cells (FoxP3) with study of the repretory of circulating and uterine NK receptors (NPp46, Nkp30, NKp44).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Reproductive Medicine</condition>
  <arm_group>
    <arm_group_label>standard care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>No specific treatment (standard care)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>specific treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>As a deregulation has been diagnosed by immune analysis, a personalization of the medical care for this IVF/ICSI attempt will be dispensed Personalization of treatment should follow a step-to step decision tree.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>standard care</intervention_name>
    <description>No specific medical care</description>
    <arm_group_label>standard care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>specific treatment</intervention_name>
    <description>Regarding the immune endometrial profiling, medical care (personalization of treatment) should follow a step by step decision tree.</description>
    <arm_group_label>specific treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infertile patients will be included at the beginning of their medical care in&#xD;
             reproduction once the indication to perform either an IVF with or without ICSI has&#xD;
             been established. The indication for IVF will be: tubal infertility, endometriosis,&#xD;
             ovarian dysovulation with failure of intra-uterine insemination, idiopathic&#xD;
             infertility The indication for ICSI will be: male infertility&#xD;
             (oligo-astheno-teratospermia), previous failure of oocytes fertilization in IVF&#xD;
&#xD;
          -  Patients should be younger than 38 years old (Age &lt; 38)&#xD;
&#xD;
               -  with a normal ovarian reserve (AMH&gt;1.5ng/ml, FSH&lt;10 IU/l on day-3, antral&#xD;
                  follicles count (AFC) over 6 on day-3 of the cycle by ultrasound)&#xD;
&#xD;
               -  The range of the IVF or ICSI attempt should be lower than 3 or equal at 2 (first&#xD;
                  or second IVF/ICSI). If a live birth occurred in the past by IVF/ICSI, the range&#xD;
                  of the new attempt is 1.&#xD;
&#xD;
          -  With a signed informed and consent form&#xD;
&#xD;
          -  With medical insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Azoospermia or cryptozoospermia (Patient's partner)&#xD;
&#xD;
          -  IVF/ICSI attempt scheduled in another ART unit&#xD;
&#xD;
          -  Contraindication to any experimental treatment (Cortancyl, Intralipids, Human&#xD;
             Chorionic Gonadotropin)&#xD;
&#xD;
          -  Maternal serology positive for hepatite C or B&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>38 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nathalie LEDEE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nathalie LEDEE, MD</last_name>
    <phone>06 41 67 46 25</phone>
    <email>nathalie-ledee@orange.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Saint-Louis - Laboratoire MatriceLAb Innove</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathalie LEDEE, MD</last_name>
      <phone>06 41 67 46 25</phone>
      <email>nathalie-ledee@orange.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>June 10, 2022</last_update_submitted>
  <last_update_submitted_qc>June 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IVF, immune endometrial profile, treatment personalization</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/NCT02262117
org study id: P130929
nct id: NCT02262117
lead sponsor: 
has dmc: No
A prospective, randomized, controlled, open two-arm study to evaluate the interest of the
      pre-conceptional endometrial immune profiling to increase birth rates.
Birth rates following an embryo transfer with a mean of two embryos transferred stagnate
      around 23% per transfer (annual report of the Agency of Biomedicine). Some estimates that
      half of infertile patients treated are partially or totally concerned by problem of
      inadequate uterine receptivity.

      The investigators' hypothesis is that a pre-conceptional immune endometrial evaluation may
      increase significantly birth rates since successful implantation results from both the
      matching of a competent embryo within a competent endometrium.

      The identification of endometrial biomarkers documenting the immune uterine environment
      during the implantation window would be able to improve the efficacy of ART through a
      personalization of treatment accordingly to the ability of the patients to receive their
      embryos. All patients with all inclusion criteria and no exclusion criteria will be included.
      Only patients with a deregulation (immune analysis) will be randomized.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Live birth rate (without congenital abnormality or malformation)/transfer following the first (fresh) embryo transfer after uterine immune analysis
time frame: up to 18 months
description: Live birth rate/transfer
measure: Ongoing pregnancy rate/transfer following the first embryo transfer at 12 weeks of amenorrhea
time frame: 12 amenorrhea weeks
description: Ongoing pregnancy rate/transfer following the first embryo transfer
measure: Number of physiological pregnancies after personalization
time frame: up to 18 months
description: Physiological pregnancies are defined by a normal growth of the fetus and a birth at term.
measure: Pregnancy rate/transfer following the first embryo transfer
time frame: 8 amenorrhea weeks
description: Pregnancy rate/transfer following the first embryo transfer
measure: Number of embryo implanted/number of embryos replaced)
time frame: at 8, 12 and 40 amenorrhea weeks
description: Implantation rate
measure: Number of early miscarriage in the first trimester
time frame: 12 amenorrhea weeks
description: Number of early miscarriage in the first trimester
measure: Number of late miscarriage
time frame: between 13 and 24 amenorrhea weeks
description: Number of late miscarriage
measure: Term of birth (for babies without congenital anormality or malformation)
time frame: up to 18 months
description: Term of birth
measure: Weight at birth
time frame: up to 18 months
description: A weight of birth below the 10 percentile according to the table of reference with distribution of birth weight in function of the term of birth in the overall population define the intrauterine growth retardation (for babies without congenital anormality or malformation)
measure: Number of prematurity (A birth below 37 weeks of amenorrhea defines the premature birth and before 28 weeks of amenorrhea the severe preterm birth) (for babies without congenital anormality or malformation)
time frame: between 28 and 37 amenorrhea weeks
description: Number of prematurity (A birth below 37 weeks of amenorrhea)
measure: Number of pre-eclampsia (defined as the association of hypertension over 14/9 mm of hg with proteinuria occuring during the pregnancy- this pathology is related to insufiscient invasion during the first trimester)
time frame: up to 18 months
description: Number of pre-eclampsia (defined as the association of hypertension over 14/9 mm of hg with proteinuria occuring during the pregnancy- this pathology is related to insufiscient invasion during the first trimester)
measure: Number of pathologic pregnancy included stillbirth and congenital abnormality
time frame: up to 18 months
description: Number of pathologic pregnancy included stillbirth and congenital abnormality
measure: Investigate if immunologic events studying on endometrial level have an impact on blood level or are independent.
time frame: up to 15 months
description: Quantification by flow cytometry of circulating NK cells (CD56 +/CD16 -), T regulatory T cells (FoxP3) with study of the repretory of circulating and uterine NK receptors (NPp46, Nkp30, NKp44).
arm group label: standard care
arm group type: Placebo Comparator
description: No specific treatment (standard care)
arm group label: specific treatment
arm group type: Experimental
description: As a deregulation has been diagnosed by immune analysis, a personalization of the medical care for this IVF/ICSI attempt will be dispensed Personalization of treatment should follow a step-to step decision tree.
intervention type: Other
intervention name: standard care
description: No specific medical care
arm group label: standard care
intervention type: Drug
intervention name: specific treatment
description: Regarding the immune endometrial profiling, medical care (personalization of treatment) should follow a step by step decision tree.
arm group label: specific treatment
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 38 Years
healthy volunteers: No
last name: Nathalie LEDEE, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Nathalie LEDEE, MD
phone: 06 41 67 46 25
email: nathalie-ledee@orange.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor