<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/NCT02244151</url>
  </required_header>
  <id_info>
    <org_study_id>TIMING</org_study_id>
    <secondary_id>2012-005571-14</secondary_id>
    <nct_id>NCT02244151</nct_id>
  </id_info>
  <brief_title>Evaluation of Time Interval Between Ovulation Trigger With Triptorelin Acetate and Oocyte Retrieval</brief_title>
  <acronym>TIMING</acronym>
  <official_title>Evaluation of the Time Interval Between Ovulation Trigger With Triptorelin Acetate and Oocyte Retrieval in IVF Cycles: A Simple Blind, Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto de Investigacion Sanitaria La Fe</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto de Investigacion Sanitaria La Fe</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to determine what is the best time interval between GnRH agonist&#xD;
      (triptorelin acetate) ovulation induction allowing for the higher number of mature oocytes&#xD;
      (MII) collected in IVF cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Human chorionic gonadotrophin (hCG) has been the gold standard for ovulation induction for&#xD;
      several decades. When GnRH antagonist protocols were introduced, it became possible to&#xD;
      trigger final oocyte maturation and ovulation with a single bolus of a GnRH agonist (GnRHa)&#xD;
      as an alternative to hCG. The use of GnRHa to trigger final oocyte maturation has potential&#xD;
      advantages: the simultaneous induction of a FSH surge, higher numbers of mature oocytes&#xD;
      retrieved as compared to hCG and the total elimination of ovarian hyperstimulation syndrome.&#xD;
&#xD;
      From the earliest reports of GnRHa for ovulation triggering, it has been presumed that the&#xD;
      timing of the ovum pick-up (OPU) after GnRHa administration should be the same as after hCG&#xD;
      triggering (34-36 h). However, differences exist regarding the duration and profile of the&#xD;
      GnRHa induced surge of gonadotrophins when compared with that of hCG. Even more, differences&#xD;
      in the intra-follicular mechanisms involved in ovulation have been described after GnRHa and&#xD;
      hCG trigger.&#xD;
&#xD;
      No previous randomized controlled trials have been reported to evaluate the optimal interval&#xD;
      of time between ovulation induction by GnRHa and oocyte collection.&#xD;
&#xD;
      The present study compares the ovarian response and the IVF outcomes after induction by&#xD;
      triptorelin 0.2 mg at four different time intervals:&#xD;
&#xD;
      Group 1: OPU 24 hours after GnRHa administration. Group 2: OPU 30 hours after GnRHa&#xD;
      administration. Group 3: OPU 40 hours after GnRHa administration. Group 4: control group: OPU&#xD;
      36 hours after GnRHa administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">February 2, 2018</completion_date>
  <primary_completion_date type="Actual">February 1, 2018</primary_completion_date>
  <phase>Phase 2</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 (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of mature oocytes 24 hours post Decapeptyl administration</measure>
    <time_frame>24 hours post Decapeptyl administration</time_frame>
    <description>The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of mature oocytes 30 hours post Decapeptyl administration</measure>
    <time_frame>30 hours post Decapeptyl administration</time_frame>
    <description>The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of mature oocytes 36 hours post Decapeptyl administration</measure>
    <time_frame>36 hours post Decapeptyl administration</time_frame>
    <description>The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of mature oocytes 40 hours post Decapeptyl administration</measure>
    <time_frame>40 hours post Decapeptyl administration</time_frame>
    <description>The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total number of follicles &gt; 16 mm punctured.</measure>
    <time_frame>Time 0 (when Decapeptyl administration)</time_frame>
    <description>Total number of follicles &gt; 16 mm punctured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total number of oocytes retrieved</measure>
    <time_frame>24, 30, 36 and 40 hours post Decapeptyl administration</time_frame>
    <description>Total number of oocytes retrieved</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum and follicular fluid levels of Amphiregulin (AR) and Epiregulin</measure>
    <time_frame>24, 30, 36 and 40 hours post Decapeptyl administration</time_frame>
    <description>Serum and follicular fluid levels of Amphiregulin (AR) and Epiregulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum and follicular fluid hormonal levels (estradiol , LH and progesterone)</measure>
    <time_frame>Time 0 (when Decapeptyl administration) , 12 hours after Decapeptyl administration , OPU moment and day of embryo transfer</time_frame>
    <description>Serum and follicular fluid hormonal levels (estradiol , LH and progesterone)</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">130</enrollment>
  <condition>Female Urogenital Diseases</condition>
  <arm_group>
    <arm_group_label>DECAPEPTYL® diario</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1: DECAPEPTYL® diario,OPU 24 hours after GnRHa administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Decapeptyl® diaro</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 2:Decapeptyl® diario OPU 30 hours after GnRHa administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Decapeptyl® diario.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 3: Decapeptyl® diario, OPU 40 hours after GnRHa administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Decapeptyl® daily</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 4: Decapeptyl® daily OPU 36 hrs after GnRH administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decapeptyl® diario</intervention_name>
    <description>Decapeptyl® daily administration (Triptorelin acetate) and follicular puncture at 24, 30, 36 or 40 after administration.</description>
    <arm_group_label>DECAPEPTYL® diario</arm_group_label>
    <arm_group_label>Decapeptyl® diario.</arm_group_label>
    <arm_group_label>Decapeptyl® diaro</arm_group_label>
    <other_name>Decapeptyl® daily; GnRHa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decapeptyl® daily</intervention_name>
    <description>Decapeptyl® daily OPU 36 hrs after GnRH administration</description>
    <arm_group_label>Decapeptyl® daily</arm_group_label>
    <other_name>Decapeptyl® diario; GnRHa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent prior to carry out any procedure associated with the clinical&#xD;
             trial.&#xD;
&#xD;
          -  Women between 18 and 37 years of age at the time of randomization (both ages&#xD;
             included).&#xD;
&#xD;
        Basal serum levels of FSH &lt;10 mIU /ml.&#xD;
&#xD;
          -  Serum AMH &gt; 5 to &lt;45 pmol / l.&#xD;
&#xD;
          -  Antral follicle count &gt; 6 and &lt; 24.&#xD;
&#xD;
          -  Vaginal ultrasound documenting correct visualization of both ovaries and the absence&#xD;
             of significant ovarian pathology.&#xD;
&#xD;
          -  Short stimulation protocol with GnRH antagonist and conventional dose for ovarian&#xD;
             stimulation with 225-300 UI of rhFSH.&#xD;
&#xD;
          -  Number of follicles ≥ 16 mm &gt; 5 on the ovulation induction day.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of severe endometriosis (Grade III-IV).&#xD;
&#xD;
          -  Absence of one ovary due to previous surgery.&#xD;
&#xD;
          -  Presence of significant uterine pathology (submucous myomas, endometrial polyp,&#xD;
             malformations..)&#xD;
&#xD;
          -  Diagnosis of polycystic ovary syndrome (defined according to the Rotterdam criteria).&#xD;
&#xD;
          -  History of previous poor response to conventional ovarian stimulation protocols (&lt; 3&#xD;
             MII oocytes or canceled cycle)&#xD;
&#xD;
          -  Severe male factor ( TMS&lt; 1 million).&#xD;
&#xD;
          -  Participation in another RCT within the past one year.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>37 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alicia Marzal, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Grupo de Investigación en Medicina Reproductiva, IIS La Fe, Valencia ; Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>César Díaz-García, M.D</last_name>
    <role>Study Chair</role>
    <affiliation>Unidad de Reproducción Humana, Area de Salud de la Mujer, Hospital Universitaria La Fe, Valencia, Spain. Grupo de Investigación en Medicina Reproductiva, IIS La Fe, Valencia ; Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Pellicer, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Unidad de Reproducción Humana, Area de Salud de la Mujer, Hospital Universitaria La Fe, Valencia, Spain. Grupo de Investigación en Medicina Reproductiva, IIS La Fe, Valencia ; Spain.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto de Investigacion Sanitaria La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>June 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <last_update_submitted>February 14, 2018</last_update_submitted>
  <last_update_submitted_qc>February 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ovulation induction,oocyte maturation timing and collection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urogenital Diseases</mesh_term>
    <mesh_term>Female Urogenital Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triptorelin Pamoate</mesh_term>
  </intervention_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/NCT02244151
org study id: TIMING
secondary id: 2012-005571-14
nct id: NCT02244151
lead sponsor: 
has dmc: No
The aim of this study is to determine what is the best time interval between GnRH agonist
      (triptorelin acetate) ovulation induction allowing for the higher number of mature oocytes
      (MII) collected in IVF cycles.
Human chorionic gonadotrophin (hCG) has been the gold standard for ovulation induction for
      several decades. When GnRH antagonist protocols were introduced, it became possible to
      trigger final oocyte maturation and ovulation with a single bolus of a GnRH agonist (GnRHa)
      as an alternative to hCG. The use of GnRHa to trigger final oocyte maturation has potential
      advantages: the simultaneous induction of a FSH surge, higher numbers of mature oocytes
      retrieved as compared to hCG and the total elimination of ovarian hyperstimulation syndrome.

      From the earliest reports of GnRHa for ovulation triggering, it has been presumed that the
      timing of the ovum pick-up (OPU) after GnRHa administration should be the same as after hCG
      triggering (34-36 h). However, differences exist regarding the duration and profile of the
      GnRHa induced surge of gonadotrophins when compared with that of hCG. Even more, differences
      in the intra-follicular mechanisms involved in ovulation have been described after GnRHa and
      hCG trigger.

      No previous randomized controlled trials have been reported to evaluate the optimal interval
      of time between ovulation induction by GnRHa and oocyte collection.

      The present study compares the ovarian response and the IVF outcomes after induction by
      triptorelin 0.2 mg at four different time intervals:

      Group 1: OPU 24 hours after GnRHa administration. Group 2: OPU 30 hours after GnRHa
      administration. Group 3: OPU 40 hours after GnRHa administration. Group 4: control group: OPU
      36 hours after GnRHa administration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Number of mature oocytes 24 hours post Decapeptyl administration
time frame: 24 hours post Decapeptyl administration
description: The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.
measure: Number of mature oocytes 30 hours post Decapeptyl administration
time frame: 30 hours post Decapeptyl administration
description: The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.
measure: Number of mature oocytes 36 hours post Decapeptyl administration
time frame: 36 hours post Decapeptyl administration
description: The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.
measure: Number of mature oocytes 40 hours post Decapeptyl administration
time frame: 40 hours post Decapeptyl administration
description: The trial pretends to determine the interval time needed for final oocyte maturation and ovulation after triptorelin administration.
measure: Total number of follicles > 16 mm punctured.
time frame: Time 0 (when Decapeptyl administration)
description: Total number of follicles > 16 mm punctured.
measure: Total number of oocytes retrieved
time frame: 24, 30, 36 and 40 hours post Decapeptyl administration
description: Total number of oocytes retrieved
measure: Serum and follicular fluid levels of Amphiregulin (AR) and Epiregulin
time frame: 24, 30, 36 and 40 hours post Decapeptyl administration
description: Serum and follicular fluid levels of Amphiregulin (AR) and Epiregulin
measure: Serum and follicular fluid hormonal levels (estradiol , LH and progesterone)
time frame: Time 0 (when Decapeptyl administration) , 12 hours after Decapeptyl administration , OPU moment and day of embryo transfer
description: Serum and follicular fluid hormonal levels (estradiol , LH and progesterone)
arm group label: DECAPEPTYL® diario
arm group type: Experimental
description: Group 1: DECAPEPTYL® diario,OPU 24 hours after GnRHa administration.
arm group label: Decapeptyl® diaro
arm group type: Experimental
description: Group 2:Decapeptyl® diario OPU 30 hours after GnRHa administration.
arm group label: Decapeptyl® diario.
arm group type: Experimental
description: Group 3: Decapeptyl® diario, OPU 40 hours after GnRHa administration.
arm group label: Decapeptyl® daily
arm group type: Active Comparator
description: Group 4: Decapeptyl® daily OPU 36 hrs after GnRH administration
intervention type: Drug
intervention name: Decapeptyl® diario
description: Decapeptyl® daily administration (Triptorelin acetate) and follicular puncture at 24, 30, 36 or 40 after administration.
arm group label: DECAPEPTYL® diario
arm group label: Decapeptyl® diario.
arm group label: Decapeptyl® diaro
other name: Decapeptyl® daily; GnRHa
intervention type: Drug
intervention name: Decapeptyl® daily
description: Decapeptyl® daily OPU 36 hrs after GnRH administration
arm group label: Decapeptyl® daily
other name: Decapeptyl® diario; GnRHa
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 37 Years
healthy volunteers: No
last name: Alicia Marzal, M.D
role: Principal Investigator
affiliation: Grupo de Investigación en Medicina Reproductiva, IIS La Fe, Valencia ; Spain
last name: César Díaz-García, M.D
role: Study Chair
affiliation: Unidad de Reproducción Humana, Area de Salud de la Mujer, Hospital Universitaria La Fe, Valencia, Spain. Grupo de Investigación en Medicina Reproductiva, IIS La Fe, Valencia ; Spain
last name: Antonio Pellicer, Professor
role: Study Director
affiliation: Unidad de Reproducción Humana, Area de Salud de la Mujer, Hospital Universitaria La Fe, Valencia, Spain. Grupo de Investigación en Medicina Reproductiva, IIS La Fe, Valencia ; Spain.
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Urogenital Diseases
mesh term: Female Urogenital Diseases
mesh term: Triptorelin Pamoate