<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/NCT03237117</url>
  </required_header>
  <id_info>
    <org_study_id>MarGen</org_study_id>
    <nct_id>NCT03237117</nct_id>
  </id_info>
  <brief_title>Effect of Growth Hormone on Uterine Receptivity in Women With RIF in an Oocyte Donation Program</brief_title>
  <official_title>Effect of Growth Hormone on Uterine Receptivity in Women With RIF in an Oocyte Donation Program: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Competence Centre on Health Technologies</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universidad de Granada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Competence Centre on Health Technologies</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>
      105 infertile women are enrolled in the randomized controlled trial: 70 women with a history&#xD;
      of RIF with donated oocytes and 35 infertile women undergoing the first oocyte donation&#xD;
      attempt. Women receiving donated oocytes are treated with progressively increasing doses of&#xD;
      oral estradiol followed by intravaginal progesterone after previous pituitary desensitization&#xD;
      with GnRH agonist. 35 RIF patients are treated with GH (GH patients) while the rest 35 RIF&#xD;
      patients (non-GH patients) and 35 first-attempt patients (positive control group) are not.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study includes in total 105 infertile couples treated by assisted reproduction with&#xD;
      oocyte donation. Seventy couples that have experienced at least two previous failures with&#xD;
      this approach at our clinic are referred to as recurrent implantation failure (RIF) patients&#xD;
      throughout this study. Thirty five of these couples are included in the GH-treatment&#xD;
      protocol, while the remaining 35 couples are treated in a usual way (non-GH group). Other 35&#xD;
      couples, treated in the same period and undergoing their first oocyte donation attempt, are&#xD;
      included as a positive control group.&#xD;
&#xD;
      RIF patients are randomly allocated into two groups (labeled I and II). Then the assignments&#xD;
      are concealed in sealed opaque envelopes until the time of enrollment: group I (GH patients)&#xD;
      and group II (non-GH patients). All injections are performed by an independent nurse who is&#xD;
      informed by the trial coordinator of each woman´s number and the treatment allocation.&#xD;
      Consequently, both the clinician and the patients are blinded as to the treatment received.&#xD;
      The positive control (non-RIF) group is created by allocating all consecutive couples&#xD;
      undergoing their first oocyte donation attempt. This allocation started immediately after the&#xD;
      allocation of the first RIF couple and will be terminated as soon as 35 cases are enrolled.&#xD;
&#xD;
      Ovarian stimulation of the oocyte donors is as follows: oocyte donors are stimulated with the&#xD;
      use of a long GnRH agonist protocol and human recombinant FSH (Puregon or Gonal F). Human&#xD;
      menopausal gonadotropin (Menopur) is added when blood LH concentration, which is repeatedly&#xD;
      determined during ovarian stimulation, falls below 1 IU/l. Final oocyte maturation is&#xD;
      triggered by subcutaneous injection of 250 micrograms recombinant hCG (Ovitrelle), when at&#xD;
      least 5 follicles measure 18 mm or more. Ovarian puncture for oocyte recovery is performed&#xD;
      36.5 h after recombinant hCG injection.&#xD;
&#xD;
      Oocyte recipients are treated with progressively increasing doses of orally administered pure&#xD;
      estradiol (Provames) or estradiol valerate (Progynova) after previous pituitary&#xD;
      desensitization with a single injection of the long-acting preparation of GnRH agonist&#xD;
      triptorelin (Decapeptyl 3,75 mg). The interval between triptorelin injection and the&#xD;
      beginning of oral estradiol treatment is ranging between 8 and 20 days. This interval is&#xD;
      determined individually, in each case, in view of the optimal synchronization of the&#xD;
      recipient's endometrial development and the follicular growth of the corresponding donor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2010</start_date>
  <completion_date type="Anticipated">December 31, 2017</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2017</primary_completion_date>
  <phase>Early Phase 1</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>
    <intervention_model_description>105 infertile women are enrolled in the randomized controlled trial: 70 women are with a history of RIF with donated oocytes and 35 infertile women undergoe the first oocyte donation attempt. 35 RIF patients are treated with GH (GH patients, study group) while the rest 35 RIF patients (non-GH patients, negative control group) and 35 first-attempt patients (positive control group) are not.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>The assignments are concealed in sealed opaque envelopes until the time of enrollment: group I (GH patients) and group II (non-GH patients). All injections are performed by an independent nurse who is informed by the trial coordinator of each woman´s number and the treatment allocation. Consequently, both the clinician and the patients are blinded as to the treatment received.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pregnancy rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>Pregnancy rate is calculated as the number of patients with positive beta-hCG test divided by the number of patients in whom embryos were transferred</description>
  </primary_outcome>
  <primary_outcome>
    <measure>live birth rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>Live birth rate is calculated as the number of babies born by the number of embryos transferred</description>
  </primary_outcome>
  <primary_outcome>
    <measure>live delivery rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>live delivery rate is obtained by dividing the number of births with the number of transfers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ongoing pregnancy rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>ongoing pregnancy rate is the number of patients with the presence of fetal heart activity divided by the number of transfer procedures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>implantation rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>Implantation rate is the number of embryonic sacs detected on ultrasound divided by the number of embryos transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ongoing implantation rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>ongoing implantation rate is calculated by dividing the number of living fetuses developing beyond 20 weeks divided by the number of embryos transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>miscarriage rate</measure>
    <time_frame>2010-2017</time_frame>
    <description>miscarriage rate is defined as the number of miscarriages before 20 weeks divided by the number of women with a positive pregnancy test</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">105</enrollment>
  <condition>Female Infertility</condition>
  <arm_group>
    <arm_group_label>GH group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>35 women with a history of RIF with donated oocytes. For receiving donated oocytes, the women are treated with progressively increasing doses of oral estradiol followed by intravaginal progesterone after previous pituitary desensitization with GnRH agonist. Additionally, these patients are co-treated with growth hormone (GH).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-GH group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>35 women with a history of RIF with donated oocytes. For receiving donated oocytes, the women are treated with progressively increasing doses of oral estradiol followed by intravaginal progesterone after previous pituitary desensitization with GnRH agonist. The treatment protocol is identical to the GH group, only that no GH is added.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>positive control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>35 infertile women undergoing their first oocyte donation attempt are included as a positive control group. Women receiving donated oocytes are treated with progressively increasing doses of oral estradiol followed by intravaginal progesterone after previous pituitary desensitization with GnRH agonist. The treatment protocol is identical to the non-GH group, with no GH added.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Growth Hormone (GH)</intervention_name>
    <description>to evaluate the effect of GH administration in the donated oocyte recipient program among women with RIF (repeated implantation failure)</description>
    <arm_group_label>GH group</arm_group_label>
    <arm_group_label>non-GH group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for oocyte recipients:&#xD;
&#xD;
          -  age below 51 years&#xD;
&#xD;
          -  2 or more previous implantation failures in oocyte donation program&#xD;
&#xD;
          -  voluntary participation&#xD;
&#xD;
        Inclusion Criteria for oocyte donors:&#xD;
&#xD;
          -  age up to 25 year&#xD;
&#xD;
          -  healthy&#xD;
&#xD;
          -  voluntary participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cancellation of the treatment&#xD;
&#xD;
          -  no wish to participate any longer&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>51 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Signe Altmäe, PhD</last_name>
    <phone>+34 693730222</phone>
    <email>signealtmae@ugr.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nicolas Mendoza, MD, PhD</last_name>
    <phone>+34 653673769</phone>
    <email>nicomendoza@telefonica.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Granada</name>
      <address>
        <city>Granada</city>
        <zip>18016</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Signe Altmäe, PhD</last_name>
      <phone>+34693730222</phone>
      <email>signealtmae@ugr.es</email>
    </contact>
    <contact_backup>
      <last_name>Nicolas Mendoza, MD, PhD</last_name>
      <phone>+34653673769</phone>
      <email>nicomendoza@telefonica.net</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>August 1, 2017</last_update_submitted>
  <last_update_submitted_qc>August 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Competence Centre on Health Technologies</investigator_affiliation>
    <investigator_full_name>Signe Altmäe</investigator_full_name>
    <investigator_title>Senior researcher</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No other IPD is foreseen than scientific publications.</ipd_description>
  </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/NCT03237117
org study id: MarGen
nct id: NCT03237117
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
105 infertile women are enrolled in the randomized controlled trial: 70 women with a history
      of RIF with donated oocytes and 35 infertile women undergoing the first oocyte donation
      attempt. Women receiving donated oocytes are treated with progressively increasing doses of
      oral estradiol followed by intravaginal progesterone after previous pituitary desensitization
      with GnRH agonist. 35 RIF patients are treated with GH (GH patients) while the rest 35 RIF
      patients (non-GH patients) and 35 first-attempt patients (positive control group) are not.
This study includes in total 105 infertile couples treated by assisted reproduction with
      oocyte donation. Seventy couples that have experienced at least two previous failures with
      this approach at our clinic are referred to as recurrent implantation failure (RIF) patients
      throughout this study. Thirty five of these couples are included in the GH-treatment
      protocol, while the remaining 35 couples are treated in a usual way (non-GH group). Other 35
      couples, treated in the same period and undergoing their first oocyte donation attempt, are
      included as a positive control group.

      RIF patients are randomly allocated into two groups (labeled I and II). Then the assignments
      are concealed in sealed opaque envelopes until the time of enrollment: group I (GH patients)
      and group II (non-GH patients). All injections are performed by an independent nurse who is
      informed by the trial coordinator of each woman´s number and the treatment allocation.
      Consequently, both the clinician and the patients are blinded as to the treatment received.
      The positive control (non-RIF) group is created by allocating all consecutive couples
      undergoing their first oocyte donation attempt. This allocation started immediately after the
      allocation of the first RIF couple and will be terminated as soon as 35 cases are enrolled.

      Ovarian stimulation of the oocyte donors is as follows: oocyte donors are stimulated with the
      use of a long GnRH agonist protocol and human recombinant FSH (Puregon or Gonal F). Human
      menopausal gonadotropin (Menopur) is added when blood LH concentration, which is repeatedly
      determined during ovarian stimulation, falls below 1 IU/l. Final oocyte maturation is
      triggered by subcutaneous injection of 250 micrograms recombinant hCG (Ovitrelle), when at
      least 5 follicles measure 18 mm or more. Ovarian puncture for oocyte recovery is performed
      36.5 h after recombinant hCG injection.

      Oocyte recipients are treated with progressively increasing doses of orally administered pure
      estradiol (Provames) or estradiol valerate (Progynova) after previous pituitary
      desensitization with a single injection of the long-acting preparation of GnRH agonist
      triptorelin (Decapeptyl 3,75 mg). The interval between triptorelin injection and the
      beginning of oral estradiol treatment is ranging between 8 and 20 days. This interval is
      determined individually, in each case, in view of the optimal synchronization of the
      recipient's endometrial development and the follicular growth of the corresponding donor.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 105 infertile women are enrolled in the randomized controlled trial: 70 women are with a history of RIF with donated oocytes and 35 infertile women undergoe the first oocyte donation attempt. 35 RIF patients are treated with GH (GH patients, study group) while the rest 35 RIF patients (non-GH patients, negative control group) and 35 first-attempt patients (positive control group) are not.
primary purpose: Treatment
masking: Double (Participant, Care Provider)
masking description: The assignments are concealed in sealed opaque envelopes until the time of enrollment: group I (GH patients) and group II (non-GH patients). All injections are performed by an independent nurse who is informed by the trial coordinator of each woman´s number and the treatment allocation. Consequently, both the clinician and the patients are blinded as to the treatment received.
measure: Pregnancy rate
time frame: 2010-2017
description: Pregnancy rate is calculated as the number of patients with positive beta-hCG test divided by the number of patients in whom embryos were transferred
measure: live birth rate
time frame: 2010-2017
description: Live birth rate is calculated as the number of babies born by the number of embryos transferred
measure: live delivery rate
time frame: 2010-2017
description: live delivery rate is obtained by dividing the number of births with the number of transfers
measure: ongoing pregnancy rate
time frame: 2010-2017
description: ongoing pregnancy rate is the number of patients with the presence of fetal heart activity divided by the number of transfer procedures
measure: implantation rate
time frame: 2010-2017
description: Implantation rate is the number of embryonic sacs detected on ultrasound divided by the number of embryos transferred
measure: ongoing implantation rate
time frame: 2010-2017
description: ongoing implantation rate is calculated by dividing the number of living fetuses developing beyond 20 weeks divided by the number of embryos transferred
measure: miscarriage rate
time frame: 2010-2017
description: miscarriage rate is defined as the number of miscarriages before 20 weeks divided by the number of women with a positive pregnancy test
arm group label: GH group
arm group type: Experimental
description: 35 women with a history of RIF with donated oocytes. For receiving donated oocytes, the women are treated with progressively increasing doses of oral estradiol followed by intravaginal progesterone after previous pituitary desensitization with GnRH agonist. Additionally, these patients are co-treated with growth hormone (GH).
arm group label: non-GH group
arm group type: Active Comparator
description: 35 women with a history of RIF with donated oocytes. For receiving donated oocytes, the women are treated with progressively increasing doses of oral estradiol followed by intravaginal progesterone after previous pituitary desensitization with GnRH agonist. The treatment protocol is identical to the GH group, only that no GH is added.
arm group label: positive control group
arm group type: No Intervention
description: 35 infertile women undergoing their first oocyte donation attempt are included as a positive control group. Women receiving donated oocytes are treated with progressively increasing doses of oral estradiol followed by intravaginal progesterone after previous pituitary desensitization with GnRH agonist. The treatment protocol is identical to the non-GH group, with no GH added.
intervention type: Biological
intervention name: Growth Hormone (GH)
description: to evaluate the effect of GH administration in the donated oocyte recipient program among women with RIF (repeated implantation failure)
arm group label: GH group
arm group label: non-GH group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 51 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Signe Altmäe, PhD
phone: +34 693730222
email: signealtmae@ugr.es
last name: Nicolas Mendoza, MD, PhD
phone: +34 653673769
email: nicomendoza@telefonica.net
facility: 
status: Recruiting
contact: 
contact backup: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Competence Centre on Health Technologies
investigator full name: Signe Altmäe
investigator title: Senior researcher
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Hormones
sharing ipd: No
ipd description: No other IPD is foreseen than scientific publications.