<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/NCT02215135</url>
  </required_header>
  <id_info>
    <org_study_id>SKH-8302-101-DR-15</org_study_id>
    <nct_id>NCT02215135</nct_id>
  </id_info>
  <brief_title>Corifollitropin Alfa Application in PCOS Patients</brief_title>
  <official_title>Corifollitropin Alfa in Combination With Elective Cryopreservation of All Embryos After GnRH Agonist Triggering of Final Oocyte Maturation in PCOS Patients- a Prospective, Observational Proof-of -Concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shin Kong Wu Ho-Su Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shin Kong Wu Ho-Su Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Corifollitropin alfa, single dose administered sustains multiple follicular development for 7&#xD;
      days. However, It may induce ovarian hyperstimulation syndrome (OHSS), especially in high&#xD;
      responder women such as patients of polycystic ovary syndrome (PCOS). In GnRH antagonist&#xD;
      protocol with agonist triggering of final oocyte maturation, following embryo&#xD;
      cryopreservation can almost eliminate the risk of OHSS. To decrease the injection burden and&#xD;
      prevent OHSS in PCOS patients undergoing IVF treatment, ovarian hyperstimulation with&#xD;
      Corifollitropin alfa in GnRH antagonist protocol and GnRH agonist triggering of final oocyte&#xD;
      maturation, following elective embryo cryopreservation was designed in this study. The&#xD;
      purpose of this trial was conducted to confirmed whether this novel protocol could prevent&#xD;
      OHSS, decreased the injection burden of PCOS patients and single dose corifollitropin alfa&#xD;
      could support multiple follicular growth for 7 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUNG: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of&#xD;
      ovulation induction. Therefore, Corifollitropin alfa, long acting recombinant follicular&#xD;
      stimulation hormone (rFSH) application in PCOS women is warning. However, corifollitropin&#xD;
      alfa could decrease the injection burden of patients undergoing IVF/ICSI treatment. In&#xD;
      previous studies, embryo cryopreservation following GnRH agonist triggering final oocyte&#xD;
      maturation in GnRH antagonist protocol can almost eliminate the risk of OHSS. This study was&#xD;
      designed to analyze whether ovarian hyperstimulation in PCOS women with Corifollitropin alfa&#xD;
      in GnRH antagonist protocol and GnRH agonist triggering, following freezing all embryos can&#xD;
      decrease the injection burden without OHSS complication.&#xD;
&#xD;
      PURPOSE: To assess whether single dose Corifollitropin alfa sustains multiple follicular&#xD;
      growth for seven days in GnRH antagonist protocol application in PCOS women, following embryo&#xD;
      cryopreservation after GnRH agonist triggering can decrease injection benefit without OHSS&#xD;
      complication.&#xD;
&#xD;
      METHODS: This prospective ,single center, observational study, thirty to fifty PCOS women&#xD;
      aged 20-38 years old, In GnRH antagonist protocol, a single dose corifollitropin alfa was&#xD;
      administered for ovarian stimulation (S1, stimulation D1). Seven days later, rFSH was daily&#xD;
      injected to stimulate follicle development according to the ovarian response. GnRH antagonist&#xD;
      was administered daily from S5 until the day of final oocyte maturation. GnRH agonist was&#xD;
      given to replace hCG to trigger final oocyte maturation when three follicles reached 17 mm in&#xD;
      size. The IVF or ICSI was planned then all embryos were elective cryopreservation. Transfer&#xD;
      of embryos was performed in a subsequent frozen-thawed ET cycles. Primary outcome measure was&#xD;
      the incidence of OHSS. The secondary outcome measures were numbers of oocytes retrieval,&#xD;
      numbers of embryos frozen and pregnancy rate of subsequent FET cycles.&#xD;
&#xD;
      ANTICIPATED RESULTS: Decreasing the injection burden and maximal oocytes were retrieved&#xD;
      without severe OHSS complication.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2014</start_date>
  <primary_completion_date type="Anticipated">June 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with severe OHSS</measure>
    <time_frame>one month</time_frame>
    <description>The patients were assessed for signs and symptoms of OHSS on 3, 6, and 9 days after oocyte retrieval including history taking, physical examination, ultrasound scan, and blood tests for hematocrit, complete blood counts.The severity of OHSS was according to the classification of Golan et al. [Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E.Ovarian hyperstimulation syndrome: an update review. ObstetGynecol Surv. 1989;44:430-40].</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>numbers of oocytes retrieved</measure>
    <time_frame>one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>embryo quality</measure>
    <time_frame>one month</time_frame>
    <description>Grade 1 embryos consisted of symmetrical blastomeres of approximately equal size and without anucleate fragments.&#xD;
Grade 2 embryos had blastomeres of even or uneven size and had 10% of the volume of embryos filled with anucleate fragments.&#xD;
Grade 3 embryos had anucleate fragments occupying between 10 and 50% of the volume of the embryos.&#xD;
Grade 4 embryos had anucleate fragments .50% of the volume of the embryos.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>No. of embryo frozen</measure>
    <time_frame>one month</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Clinical pregnancy rate in the frozen-thawed embryo transfer cycle</measure>
    <time_frame>6 months</time_frame>
    <description>Serum β-HCG level was measured 14 days after embryo transfer. Clinical pregnancy was defined as the presence of fetal cardiac activity on transvaginal ultrasonography at 7 weeks of gestation.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>In Vitro Fertilization</condition>
  <arm_group>
    <arm_group_label>Corifollitropin in PCOS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In GnRH antagonist protocol, a single dose corifollitropin alfa was administered for ovarian stimulation following rFSH daily injection to stimulate follicle development. GnRH agonist was given to trigger final oocyte maturation when three follicles reached 17 mm in size. The IVF or ICSI was planned then all embryos were elective cryopreserved.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Corifollitropin alfa</intervention_name>
    <description>In GnRH antagonist protocol, ovarian stimulation with single dose of 100μg (BW≦60 kg) or 150μg (BW&gt; 60 kg) corifollitropin alfa (Elonva, SC), followed 1 week later (stimulation day 8) by a daily dose of rFSH to the day of GnRH agonist triggering final oocyte maturation.</description>
    <arm_group_label>Corifollitropin in PCOS</arm_group_label>
    <other_name>elonva</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        The diagnosis of PCOS was according Rotterdam criteria ( twoi of three) included:&#xD;
&#xD;
          -  chronic anovulation manifested by the symptoms of oligomenorrhoea&#xD;
&#xD;
          -  ultrasonographic evidence of polycystic enlarged ovary with over 10 peripherally&#xD;
             located follicles of 3-8mm diameter around a dense central stroma&#xD;
&#xD;
          -  hyperandrogenaemia (serum testosterone concentrations over 0.8 ng/ml) or clinical&#xD;
             hyperandrogenism.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A diagnosis of congenital adrenal hyperplasia, Cushing's syndrome, androgen-producing&#xD;
             tumours, hyperprolactinaemia and thyroid dysfunction were all excluded.&#xD;
&#xD;
          -  patients older than 38 years or with serum FSH level over 12 mIU/ml.&#xD;
&#xD;
          -  patients wiht previous ovarian surgery&#xD;
&#xD;
          -  husband with non-obstructive azoospermia&#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>Jiann-Loung Hwang, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jiann-Loung Hwang, MD</last_name>
    <phone>886-2-28332211</phone>
    <phone_ext>3879</phone_ext>
    <email>m001015@ms.skh.org.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Obstetrics and Gynecology, Shin-Kong Wu Ho-Su Memorial Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiann-Loung Hwang, MD</last_name>
      <phone>886-2-28332211</phone>
      <phone_ext>3879</phone_ext>
      <email>m001015@ms.skh.org.tw</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>June 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 11, 2014</last_update_submitted>
  <last_update_submitted_qc>August 11, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Corifollitropin alfa</keyword>
  <keyword>polycystic ovarian syndrome (PCOS)</keyword>
  <keyword>controlled ovarian hyperstimulation (COS)</keyword>
  <keyword>GnRH antagonist protocol</keyword>
  <keyword>Ovarian hyperstimulation syndrome (OHSS)</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/NCT02215135
org study id: SKH-8302-101-DR-15
nct id: NCT02215135
lead sponsor: 
has dmc: Yes
Corifollitropin alfa, single dose administered sustains multiple follicular development for 7
      days. However, It may induce ovarian hyperstimulation syndrome (OHSS), especially in high
      responder women such as patients of polycystic ovary syndrome (PCOS). In GnRH antagonist
      protocol with agonist triggering of final oocyte maturation, following embryo
      cryopreservation can almost eliminate the risk of OHSS. To decrease the injection burden and
      prevent OHSS in PCOS patients undergoing IVF treatment, ovarian hyperstimulation with
      Corifollitropin alfa in GnRH antagonist protocol and GnRH agonist triggering of final oocyte
      maturation, following elective embryo cryopreservation was designed in this study. The
      purpose of this trial was conducted to confirmed whether this novel protocol could prevent
      OHSS, decreased the injection burden of PCOS patients and single dose corifollitropin alfa
      could support multiple follicular growth for 7 days.
BACKGROUNG: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of
      ovulation induction. Therefore, Corifollitropin alfa, long acting recombinant follicular
      stimulation hormone (rFSH) application in PCOS women is warning. However, corifollitropin
      alfa could decrease the injection burden of patients undergoing IVF/ICSI treatment. In
      previous studies, embryo cryopreservation following GnRH agonist triggering final oocyte
      maturation in GnRH antagonist protocol can almost eliminate the risk of OHSS. This study was
      designed to analyze whether ovarian hyperstimulation in PCOS women with Corifollitropin alfa
      in GnRH antagonist protocol and GnRH agonist triggering, following freezing all embryos can
      decrease the injection burden without OHSS complication.

      PURPOSE: To assess whether single dose Corifollitropin alfa sustains multiple follicular
      growth for seven days in GnRH antagonist protocol application in PCOS women, following embryo
      cryopreservation after GnRH agonist triggering can decrease injection benefit without OHSS
      complication.

      METHODS: This prospective ,single center, observational study, thirty to fifty PCOS women
      aged 20-38 years old, In GnRH antagonist protocol, a single dose corifollitropin alfa was
      administered for ovarian stimulation (S1, stimulation D1). Seven days later, rFSH was daily
      injected to stimulate follicle development according to the ovarian response. GnRH antagonist
      was administered daily from S5 until the day of final oocyte maturation. GnRH agonist was
      given to replace hCG to trigger final oocyte maturation when three follicles reached 17 mm in
      size. The IVF or ICSI was planned then all embryos were elective cryopreservation. Transfer
      of embryos was performed in a subsequent frozen-thawed ET cycles. Primary outcome measure was
      the incidence of OHSS. The secondary outcome measures were numbers of oocytes retrieval,
      numbers of embryos frozen and pregnancy rate of subsequent FET cycles.

      ANTICIPATED RESULTS: Decreasing the injection burden and maximal oocytes were retrieved
      without severe OHSS complication.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with severe OHSS
time frame: one month
description: The patients were assessed for signs and symptoms of OHSS on 3, 6, and 9 days after oocyte retrieval including history taking, physical examination, ultrasound scan, and blood tests for hematocrit, complete blood counts.The severity of OHSS was according to the classification of Golan et al. [Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E.Ovarian hyperstimulation syndrome: an update review. ObstetGynecol Surv. 1989;44:430-40].
measure: numbers of oocytes retrieved
time frame: one month
measure: embryo quality
time frame: one month
description: Grade 1 embryos consisted of symmetrical blastomeres of approximately equal size and without anucleate fragments.
Grade 2 embryos had blastomeres of even or uneven size and had 10% of the volume of embryos filled with anucleate fragments.
Grade 3 embryos had anucleate fragments occupying between 10 and 50% of the volume of the embryos.
Grade 4 embryos had anucleate fragments .50% of the volume of the embryos.
measure: No. of embryo frozen
time frame: one month
measure: Clinical pregnancy rate in the frozen-thawed embryo transfer cycle
time frame: 6 months
description: Serum β-HCG level was measured 14 days after embryo transfer. Clinical pregnancy was defined as the presence of fetal cardiac activity on transvaginal ultrasonography at 7 weeks of gestation.
arm group label: Corifollitropin in PCOS
arm group type: Experimental
description: In GnRH antagonist protocol, a single dose corifollitropin alfa was administered for ovarian stimulation following rFSH daily injection to stimulate follicle development. GnRH agonist was given to trigger final oocyte maturation when three follicles reached 17 mm in size. The IVF or ICSI was planned then all embryos were elective cryopreserved.
intervention type: Drug
intervention name: Corifollitropin alfa
description: In GnRH antagonist protocol, ovarian stimulation with single dose of 100μg (BW≦60 kg) or 150μg (BW> 60 kg) corifollitropin alfa (Elonva, SC), followed 1 week later (stimulation day 8) by a daily dose of rFSH to the day of GnRH agonist triggering final oocyte maturation.
arm group label: Corifollitropin in PCOS
other name: elonva
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 38 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jiann-Loung Hwang, MD
role: Study Chair
affiliation: Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital
last name: Jiann-Loung Hwang, MD
phone: 886-2-28332211
phone ext: 3879
email: m001015@ms.skh.org.tw
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor