<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/NCT01667406</url>
  </required_header>
  <id_info>
    <org_study_id>13HH0199</org_study_id>
    <secondary_id>2012-000154-61</secondary_id>
    <nct_id>NCT01667406</nct_id>
  </id_info>
  <brief_title>The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment</brief_title>
  <official_title>The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>Yes</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>
      We want to find out if kisspeptin is successful in stimulating oocyte maturation when it is&#xD;
      used as a 'trigger' injection during IVF therapy for infertility.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants in the study will have a standard Gonadotrophin Releasing Hormone (GnRH)&#xD;
      antagonist IVF cycle, but instead of having a trigger injection of hCG (human chorionic&#xD;
      gonadotrophin) they will be randomised to receive one of 4 doses of kisspeptin injection.&#xD;
&#xD;
      Oocytes will be retrieved and graded by an embryologist to see whether or not they have&#xD;
      matured.&#xD;
&#xD;
      The reproductive hormones Luteinising hormone, follicle stimulating hormone, oestradiol and&#xD;
      progesterone will also be measured&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2012</start_date>
  <completion_date type="Actual">October 11, 2016</completion_date>
  <primary_completion_date type="Actual">October 11, 2016</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>
    <intervention_model_description>Different dose for each volunteer</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>participants and IVF physicians were blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Oocyte Maturation</measure>
    <time_frame>36 hours post Kisspeptin-54 trigger injection</time_frame>
    <description>This was assessed by oocyte yield (percentage of mature [metaphase 2; M2] oocytes collected from the number of follicles ≥ 14 mm on final ultrasound scan prior to kisspeptin-54 trigger administration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biochemical Pregnancy</measure>
    <time_frame>11 days after embryo transfer</time_frame>
    <description>Number of participants achieving biochemical pregnancy by serum βhCG &gt; 10 mIU/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of OHSS</measure>
    <time_frame>11 days following embryo transfer</time_frame>
    <description>Women were routinely screened for the development of early OHSS and late OHSS. Women were screened by symptoms, blood analysis, and ultrasound parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fertilization Rate</measure>
    <time_frame>3 days after oocyte retrieval</time_frame>
    <description>Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Embryo Formation</measure>
    <time_frame>3 days after oocyte retrieval</time_frame>
    <description>All embryos were graded at day 3 by an independent embryologist, blinded to doses of kisspeptin administered, using the British Fertility Society and Association of Clinical Embryologist embryo grading scheme for cleavage stage embryos, which describes embryos based on cell number, blastomere size, and fragmentation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinical Pregnancy</measure>
    <time_frame>6 weeks after embryo transfer</time_frame>
    <description>Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation</description>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Actual">175</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Kisspeptin-54, 1.6 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54, 3.2 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54, 6.4 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54, 12.8 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54 OHSS, 3.2 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54 OHSS, 6.4 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54 OHSS, 9.6 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54 OHSS, 12.8 single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54 OHSS, 9.6 + 9.6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kisspeptin-54 OHSS, 9.6 + saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 1.6nmol/kg</intervention_name>
    <description>single kisspeptin dose 1.6 nmol/kg subcutaneously</description>
    <arm_group_label>Kisspeptin-54, 1.6 single</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 3.2nmol/kg</intervention_name>
    <description>single kisspeptin dose 3.2 nmol/kg subcutaneously</description>
    <arm_group_label>Kisspeptin-54 OHSS, 3.2 single</arm_group_label>
    <arm_group_label>Kisspeptin-54, 3.2 single</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 6.4nmol/kg</intervention_name>
    <description>single kisspeptin dose 6.4 nmol/kg subcutaneously</description>
    <arm_group_label>Kisspeptin-54 OHSS, 6.4 single</arm_group_label>
    <arm_group_label>Kisspeptin-54, 6.4 single</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 9.6nmol/kg</intervention_name>
    <description>single kisspeptin dose 9.6 nmol/kg subcutaneously</description>
    <arm_group_label>Kisspeptin-54 OHSS, 9.6 single</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 12.8nmol/kg</intervention_name>
    <description>single kisspeptin dose 12.8 nmol/kg subcutaneously</description>
    <arm_group_label>Kisspeptin-54 OHSS, 12.8 single</arm_group_label>
    <arm_group_label>Kisspeptin-54, 12.8 single</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 9.6 nmol/kg double</intervention_name>
    <description>kisspeptin dose 9.6 nmol/kg given twice 10hrs apart subcutaneously</description>
    <arm_group_label>Kisspeptin-54 OHSS, 9.6 + 9.6</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Kisspeptin 9.6 nmol/kg + saline</intervention_name>
    <description>kisspeptin dose 9.6 nmol/kg subcutaneously and saline subcutaneously, 10hrs apart</description>
    <arm_group_label>Kisspeptin-54 OHSS, 9.6 + saline</arm_group_label>
    <other_name>kisspeptin-54</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18 - 34 years&#xD;
&#xD;
          -  Body mass index between 18 and 29 kg/m2&#xD;
&#xD;
          -  Stable body weight for at least 3 months&#xD;
&#xD;
          -  Normal early menstrual cycle follicular phase serum FSH concentration&#xD;
&#xD;
          -  Serum anti-Mullerian hormone (AMH) &gt; 40pmol/L&#xD;
&#xD;
          -  No more than one previous IVF treatment cycle&#xD;
&#xD;
          -  Both ovaries intact&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        History of any medical, psychological or other condition, or use of any medications,&#xD;
        including over-the-counter products, which, in the opinion of the investigators, would&#xD;
        either interfere with the study or potentially cause harm to the volunteer&#xD;
&#xD;
          -  Without access at home to a telephone, or other factor likely to interfere with&#xD;
             ability to participate reliably in the study&#xD;
&#xD;
          -  Treatment with an investigational drug within the preceding 2 months&#xD;
&#xD;
          -  Donated blood during the preceding 3 months or intention to do so before the end of&#xD;
             the study&#xD;
&#xD;
          -  Previous poor response to IVF treatment&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>woman undergoing IVF treatment</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>34 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Waljit S Dhillo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hammersmith Hospital</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Jayasena CN, Abbara A, Comninos AN, Nijher GM, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Sridharan M, Mason AJ, Warwick J, Ashby D, Ghatei MA, Bloom SR, Carby A, Trew GH, Dhillo WS. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. 2014 Aug;124(8):3667-77. doi: 10.1172/JCI75730. Epub 2014 Jul 18.</citation>
    <PMID>25036713</PMID>
  </results_reference>
  <results_reference>
    <citation>Abbara A, Clarke S, Islam R, Prague JK, Comninos AN, Narayanaswamy S, Papadopoulou D, Roberts R, Izzi-Engbeaya C, Ratnasabapathy R, Nesbitt A, Vimalesvaran S, Salim R, Lavery SA, Bloom SR, Huson L, Trew GH, Dhillo WS. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial. Hum Reprod. 2017 Sep 1;32(9):1915-1924. doi: 10.1093/humrep/dex253.</citation>
    <PMID>28854728</PMID>
  </results_reference>
  <results_reference>
    <citation>Abbara A, Jayasena CN, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Nijher GM, Comninos AN, Peters D, Buckley A, Ratnasabapathy R, Prague JK, Salim R, Lavery SA, Bloom SR, Szigeti M, Ashby DA, Trew GH, Dhillo WS. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy. J Clin Endocrinol Metab. 2015 Sep;100(9):3322-31. doi: 10.1210/jc.2015-2332. Epub 2015 Jul 20.</citation>
    <PMID>26192876</PMID>
  </results_reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>March 1, 2019</results_first_submitted>
  <results_first_submitted_qc>May 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 8, 2021</results_first_posted>
  <last_update_submitted>May 13, 2021</last_update_submitted>
  <last_update_submitted_qc>May 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>kisspeptin</keyword>
  <keyword>infertility</keyword>
  <keyword>in vitro fertilisation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data will be presented in anonymised groups</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 1, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT01667406/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 24, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT01667406/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Parallel study, volunteers received only one type of dose</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Kisspeptin-54 1.6 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg</description>
        </group>
        <group group_id="P2">
          <title>Kispeptin-54 3.2 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
        </group>
        <group group_id="P3">
          <title>Kisspeptin-54 6.4 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
        </group>
        <group group_id="P4">
          <title>Kisspeptin-54 12.8 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
        </group>
        <group group_id="P5">
          <title>OHSS - Kisspeptin-54 3.2 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
        </group>
        <group group_id="P6">
          <title>OHSS - Kisspeptin-54 6.4 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
        </group>
        <group group_id="P7">
          <title>OHSS - Kisspeptin-54 9.6 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg</description>
        </group>
        <group group_id="P8">
          <title>OHSS - Kisspeptin-54 12.8 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
        </group>
        <group group_id="P9">
          <title>Kisspeptin-54 9.6 + 9.6</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
        </group>
        <group group_id="P10">
          <title>Kisspeptin-54 9.6 + Saline</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="24"/>
                <participants group_id="P4" count="24"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="20"/>
                <participants group_id="P7" count="15"/>
                <participants group_id="P8" count="20"/>
                <participants group_id="P9" count="31"/>
                <participants group_id="P10" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="24"/>
                <participants group_id="P4" count="24"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="20"/>
                <participants group_id="P7" count="15"/>
                <participants group_id="P8" count="20"/>
                <participants group_id="P9" count="31"/>
                <participants group_id="P10" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Kisspeptin-54 1.6 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg</description>
        </group>
        <group group_id="B2">
          <title>Kispeptin-54 3.2 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
        </group>
        <group group_id="B3">
          <title>Kisspeptin-54 6.4 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
        </group>
        <group group_id="B4">
          <title>Kisspeptin-54 12.8 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
        </group>
        <group group_id="B5">
          <title>OHSS - Kisspeptin-54 3.2 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
        </group>
        <group group_id="B6">
          <title>OHSS - Kisspeptin-54 6.4 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
        </group>
        <group group_id="B7">
          <title>OHSS - Kisspeptin-54 9.6 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg</description>
        </group>
        <group group_id="B8">
          <title>OHSS - Kisspeptin-54 12.8 Single</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
        </group>
        <group group_id="B9">
          <title>Kisspeptin-54 9.6 + 9.6</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
        </group>
        <group group_id="B10">
          <title>Kisspeptin-54 9.6 + Saline</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
        </group>
        <group group_id="B11">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="24"/>
            <count group_id="B4" value="24"/>
            <count group_id="B5" value="5"/>
            <count group_id="B6" value="20"/>
            <count group_id="B7" value="15"/>
            <count group_id="B8" value="20"/>
            <count group_id="B9" value="31"/>
            <count group_id="B10" value="31"/>
            <count group_id="B11" value="175"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="2"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="5"/>
                    <count group_id="B6" value="20"/>
                    <count group_id="B7" value="15"/>
                    <count group_id="B8" value="20"/>
                    <count group_id="B9" value="31"/>
                    <count group_id="B10" value="31"/>
                    <count group_id="B11" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30" lower_limit="28" upper_limit="32"/>
                    <measurement group_id="B2" value="31" lower_limit="31" upper_limit="32"/>
                    <measurement group_id="B3" value="32" lower_limit="29" upper_limit="34"/>
                    <measurement group_id="B4" value="30" lower_limit="29" upper_limit="33"/>
                    <measurement group_id="B5" value="30" lower_limit="28" upper_limit="31"/>
                    <measurement group_id="B6" value="30" lower_limit="28" upper_limit="31"/>
                    <measurement group_id="B7" value="32" lower_limit="30" upper_limit="33"/>
                    <measurement group_id="B8" value="31" lower_limit="28" upper_limit="34"/>
                    <measurement group_id="B9" value="30.9" lower_limit="29.1" upper_limit="32.6"/>
                    <measurement group_id="B10" value="31.2" lower_limit="27.9" upper_limit="33.4"/>
                    <measurement group_id="B11" value="31.1" lower_limit="29" upper_limit="32.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="2"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="5"/>
                    <count group_id="B6" value="20"/>
                    <count group_id="B7" value="15"/>
                    <count group_id="B8" value="20"/>
                    <count group_id="B9" value="31"/>
                    <count group_id="B10" value="31"/>
                    <count group_id="B11" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="20"/>
                    <measurement group_id="B7" value="15"/>
                    <measurement group_id="B8" value="20"/>
                    <measurement group_id="B9" value="31"/>
                    <measurement group_id="B10" value="31"/>
                    <measurement group_id="B11" value="175"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="0"/>
                    <count group_id="B6" value="0"/>
                    <count group_id="B7" value="0"/>
                    <count group_id="B8" value="0"/>
                    <count group_id="B9" value="0"/>
                    <count group_id="B10" value="0"/>
                    <count group_id="B11" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B11" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="2"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="5"/>
                    <count group_id="B6" value="20"/>
                    <count group_id="B7" value="15"/>
                    <count group_id="B8" value="20"/>
                    <count group_id="B9" value="31"/>
                    <count group_id="B10" value="31"/>
                    <count group_id="B11" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="20"/>
                    <measurement group_id="B7" value="15"/>
                    <measurement group_id="B8" value="20"/>
                    <measurement group_id="B9" value="31"/>
                    <measurement group_id="B10" value="31"/>
                    <measurement group_id="B11" value="175"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI 18-29</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="2"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="5"/>
                    <count group_id="B6" value="20"/>
                    <count group_id="B7" value="15"/>
                    <count group_id="B8" value="20"/>
                    <count group_id="B9" value="31"/>
                    <count group_id="B10" value="31"/>
                    <count group_id="B11" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23" spread="0.74"/>
                    <measurement group_id="B2" value="22" spread="0.74"/>
                    <measurement group_id="B3" value="22" spread="2.22"/>
                    <measurement group_id="B4" value="23" spread="1.48"/>
                    <measurement group_id="B5" value="22" spread="2.96"/>
                    <measurement group_id="B6" value="22" spread="5.19"/>
                    <measurement group_id="B7" value="25" spread="2.96"/>
                    <measurement group_id="B8" value="24" spread="5.19"/>
                    <measurement group_id="B9" value="26.6" spread="4.52"/>
                    <measurement group_id="B10" value="23.9" spread="4.074"/>
                    <measurement group_id="B11" value="23.35" spread="1.547"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anti-mullerian hormone (AMH)</title>
          <units>pmol/L</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="2"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="5"/>
                    <count group_id="B6" value="20"/>
                    <count group_id="B7" value="15"/>
                    <count group_id="B8" value="20"/>
                    <count group_id="B9" value="31"/>
                    <count group_id="B10" value="31"/>
                    <count group_id="B11" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21" spread="3.70"/>
                    <measurement group_id="B2" value="13" spread="5.19"/>
                    <measurement group_id="B3" value="18" spread="8.89"/>
                    <measurement group_id="B4" value="21" spread="9.63"/>
                    <measurement group_id="B5" value="35" spread="15.56"/>
                    <measurement group_id="B6" value="48" spread="22.22"/>
                    <measurement group_id="B7" value="66" spread="20.0"/>
                    <measurement group_id="B8" value="53" spread="18.52"/>
                    <measurement group_id="B9" value="44" spread="16.15"/>
                    <measurement group_id="B10" value="52.4" spread="33.33"/>
                    <measurement group_id="B11" value="37.12" spread="18.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Antral Follicle Count (AFC)</title>
          <units>Follicles</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="2"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="24"/>
                    <count group_id="B4" value="24"/>
                    <count group_id="B5" value="5"/>
                    <count group_id="B6" value="20"/>
                    <count group_id="B7" value="15"/>
                    <count group_id="B8" value="20"/>
                    <count group_id="B9" value="31"/>
                    <count group_id="B10" value="31"/>
                    <count group_id="B11" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30" spread="2.22"/>
                    <measurement group_id="B2" value="24" spread="5.93"/>
                    <measurement group_id="B3" value="20" spread="7.41"/>
                    <measurement group_id="B4" value="20" spread="6.67"/>
                    <measurement group_id="B5" value="35" spread="15.56"/>
                    <measurement group_id="B6" value="48" spread="2.22"/>
                    <measurement group_id="B7" value="66" spread="20"/>
                    <measurement group_id="B8" value="53" spread="18.52"/>
                    <measurement group_id="B9" value="33" spread="8.89"/>
                    <measurement group_id="B10" value="39" spread="16.30"/>
                    <measurement group_id="B11" value="36.8" spread="15.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Oocyte Maturation</title>
        <description>This was assessed by oocyte yield (percentage of mature [metaphase 2; M2] oocytes collected from the number of follicles ≥ 14 mm on final ultrasound scan prior to kisspeptin-54 trigger administration</description>
        <time_frame>36 hours post Kisspeptin-54 trigger injection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kisspeptin-54 1.6 Nmol/kg Single</title>
            <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 1.6nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O2">
            <title>Kisspeptin-54 3.2nmol/kg Single</title>
            <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 3.2nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O3">
            <title>Kisspeptin-54 6.4 Nmol/kg Single</title>
            <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 6.4nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O4">
            <title>Kisspeptin-54 12.8nmol/kg Single</title>
            <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 12.8nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O5">
            <title>Kisspeptin-54, OHSS 3.2nmol/Kg Single</title>
            <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 3.2nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O6">
            <title>Kisspeptin-54, OHSS 6.4nmol/Kg Single</title>
            <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 6.4nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O7">
            <title>Kisspeptin-54, OHSS 9.6nmol/Kg Single</title>
            <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 9.6nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O8">
            <title>Kisspeptin-54, OHSS 12.8nmol/Kg Single</title>
            <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 12.8nmol/kg as a trigger injection.</description>
          </group>
          <group group_id="O9">
            <title>Kisspeptin-54 OHSS, 9.6 + 9.6</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
          </group>
          <group group_id="O10">
            <title>Kisspeptin-54 OHSS, 9.6 + Saline</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Oocyte Maturation</title>
          <description>This was assessed by oocyte yield (percentage of mature [metaphase 2; M2] oocytes collected from the number of follicles ≥ 14 mm on final ultrasound scan prior to kisspeptin-54 trigger administration</description>
          <units>percentage of expected oocyte yield</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="20"/>
                <count group_id="O7" value="15"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="31"/>
                <count group_id="O10" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49" spread="29"/>
                    <measurement group_id="O2" value="36" spread="18"/>
                    <measurement group_id="O3" value="76" spread="49"/>
                    <measurement group_id="O4" value="103" spread="53"/>
                    <measurement group_id="O5" value="53" spread="41"/>
                    <measurement group_id="O6" value="86" spread="49"/>
                    <measurement group_id="O7" value="86" spread="74"/>
                    <measurement group_id="O8" value="121" spread="119"/>
                    <measurement group_id="O9" value="55" spread="18"/>
                    <measurement group_id="O10" value="46" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Data presented using descriptive statistics. Confidence intervals were derived for the difference between the means of different doses.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Fishers exact conditional test was used to confirm significance</non_inferiority_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
              <group_id>O7</group_id>
            </group_id_list>
            <groups_desc>Phase 2</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O9</group_id>
              <group_id>O10</group_id>
            </group_id_list>
            <groups_desc>Phase 3</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <estimate_desc>Estimate of difference in success rates and estimate of odds ratio for success were derived, with P value comparing 2 treatment groups, 95% conﬁdence intervals.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biochemical Pregnancy</title>
        <description>Number of participants achieving biochemical pregnancy by serum βhCG &gt; 10 mIU/mL</description>
        <time_frame>11 days after embryo transfer</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>KP-54 1.6nmol/kg Single</title>
            <description>Participants undergoing IV treatment with trigger dose 1.6nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O2">
            <title>KP-54 3.2nmol/kg Single</title>
            <description>Participants undergoing IV treatment with trigger dose 3.2nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O3">
            <title>KP-54 6.4nmol/kg Single</title>
            <description>Participants undergoing IV treatment with trigger dose 6.4nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O4">
            <title>KP-54 12.8nmol/kg Single</title>
            <description>Participants undergoing IV treatment with trigger dose 12.8nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O5">
            <title>KP-54 OHSS 3.2nmol/kg Single</title>
            <description>Participants, at high risk of ovarian hyper-stimulation syndrome, undergoing IV treatment with trigger dose 3.2nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O6">
            <title>KP-54 OHSS 6.4nmol/kg Single</title>
            <description>Participants, at high risk of ovarian hyper-stimulation syndrome, undergoing IV treatment with trigger dose 6.4nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O7">
            <title>KP-54 OHSS 9.6nmol/kg</title>
            <description>Participants, at high risk of ovarian hyper-stimulation syndrome, undergoing IV treatment with trigger dose 9.6nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O8">
            <title>KP-54 OHSS 12.8nmol/kg Single</title>
            <description>Participants, at high risk of ovarian hyper-stimulation syndrome, undergoing IV treatment with trigger dose 12.8nmol/kg had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O9">
            <title>KP-54 OHSS 9.6 +9.6 Nmol/kg</title>
            <description>Participants, at high risk of ovarian hyper-stimulation syndrome, undergoing IV treatment with trigger dose 9.6nmol/kg followed by another injection of KP-54 9.6nmol/kg 10 hours later, had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
          <group group_id="O10">
            <title>KP-54 OHSS 9.6 + Saline</title>
            <description>Participants, at high risk of ovarian hyper-stimulation syndrome, undergoing IV treatment with trigger dose 9.6nmol/kg followed by another injection of saline10 hours later, had blood level of luteinising hormone (LH) measured at T=0</description>
          </group>
        </group_list>
        <measure>
          <title>Biochemical Pregnancy</title>
          <description>Number of participants achieving biochemical pregnancy by serum βhCG &gt; 10 mIU/mL</description>
          <population>All participants</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="20"/>
                <count group_id="O7" value="15"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="31"/>
                <count group_id="O10" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="8"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="10"/>
                    <measurement group_id="O7" value="10"/>
                    <measurement group_id="O8" value="6"/>
                    <measurement group_id="O9" value="16"/>
                    <measurement group_id="O10" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
              <group_id>O7</group_id>
              <group_id>O8</group_id>
              <group_id>O9</group_id>
              <group_id>O10</group_id>
            </group_id_list>
            <groups_desc>Study data were summarised using standard descriptive methods. Continuous variables following a normal distribution have been summarised using mean and SD.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>secondary outcomes were analysed using descriptive statistics.</non_inferiority_desc>
            <other_analysis_desc>secondary outcomes were analysed using descriptive statistics.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of OHSS</title>
        <description>Women were routinely screened for the development of early OHSS and late OHSS. Women were screened by symptoms, blood analysis, and ultrasound parameters</description>
        <time_frame>11 days following embryo transfer</time_frame>
        <population>Occurence of OHSS was not analysed in the groups where number of participants analysed is zero as this first phase was to test only the hypothesis that kisspeptin-54 could be used to trigger egg maturation in women undergoing in vitro fertilization therapy.</population>
        <group_list>
          <group group_id="O1">
            <title>Kisspeptin-54, 1.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg&#xD;
Kisspeptin 1.6nmol/kg: single kisspeptin dose 1.6 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O2">
            <title>Kisspeptin-54, 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg&#xD;
Kisspeptin 3.2nmol/kg: single kisspeptin dose 3.2 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O3">
            <title>Kisspeptin-54, 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg&#xD;
Kisspeptin 6.4nmol/kg: single kisspeptin dose 6.4 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O4">
            <title>Kisspeptin-54, 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg&#xD;
Kisspeptin 12.8nmol/kg: single kisspeptin dose 12.8 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O5">
            <title>Kisspeptin-54 OHSS, 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg&#xD;
Kisspeptin 3.2nmol/kg: single kisspeptin dose 3.2 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O6">
            <title>Kisspeptin-54 OHSS, 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg&#xD;
Kisspeptin 6.4nmol/kg: single kisspeptin dose 6.4 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O7">
            <title>Kisspeptin-54 OHSS, 9.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg&#xD;
Kisspeptin 9.6nmol/kg: single kisspeptin dose 9.6 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O8">
            <title>Kisspeptin-54 OHSS, 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg&#xD;
Kisspeptin 12.8nmol/kg: single kisspeptin dose 12.8 nmol/kg subcutaneously</description>
          </group>
          <group group_id="O9">
            <title>Kisspeptin-54 OHSS, 9.6 + 9.6</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later&#xD;
Kisspeptin 9.6 nmol/kg double: kisspeptin dose 9.6 nmol/kg given twice 10hrs apart subcutaneously</description>
          </group>
          <group group_id="O10">
            <title>Kisspeptin-54 OHSS, 9.6 + Saline</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later&#xD;
Kisspeptin 9.6 nmol/kg + saline: kisspeptin dose 9.6 nmol/kg subcutaneously and saline subcutaneously, 10hrs apart</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of OHSS</title>
          <description>Women were routinely screened for the development of early OHSS and late OHSS. Women were screened by symptoms, blood analysis, and ultrasound parameters</description>
          <population>Occurence of OHSS was not analysed in the groups where number of participants analysed is zero as this first phase was to test only the hypothesis that kisspeptin-54 could be used to trigger egg maturation in women undergoing in vitro fertilization therapy.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="20"/>
                <count group_id="O7" value="15"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="31"/>
                <count group_id="O10" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="4"/>
                    <measurement group_id="O9" value="1"/>
                    <measurement group_id="O10" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fertilization Rate</title>
        <description>Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI]</description>
        <time_frame>3 days after oocyte retrieval</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Kisspeptin-54 1.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg</description>
          </group>
          <group group_id="O2">
            <title>Kispeptin-54 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
          </group>
          <group group_id="O3">
            <title>Kisspeptin-54 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
          </group>
          <group group_id="O4">
            <title>Kisspeptin-54 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
          </group>
          <group group_id="O5">
            <title>OHSS - Kisspeptin-54 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
          </group>
          <group group_id="O6">
            <title>OHSS - Kisspeptin-54 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
          </group>
          <group group_id="O7">
            <title>OHSS - Kisspeptin-54 9.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg</description>
          </group>
          <group group_id="O8">
            <title>OHSS - Kisspeptin-54 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
          </group>
          <group group_id="O9">
            <title>Kisspeptin-54 9.6 + 9.6</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
          </group>
          <group group_id="O10">
            <title>Kisspeptin-54 9.6 + Saline</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
          </group>
        </group_list>
        <measure>
          <title>Fertilization Rate</title>
          <description>Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI]</description>
          <population>All participants</population>
          <units>percentage of 2PN zygotes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="20"/>
                <count group_id="O7" value="15"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="31"/>
                <count group_id="O10" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.28" spread="20.20"/>
                    <measurement group_id="O2" value="58.33" spread="30.04"/>
                    <measurement group_id="O3" value="66.94" spread="26.98"/>
                    <measurement group_id="O4" value="76.01" spread="26.28"/>
                    <measurement group_id="O5" value="68" spread="39"/>
                    <measurement group_id="O6" value="76" spread="29"/>
                    <measurement group_id="O7" value="74" spread="33"/>
                    <measurement group_id="O8" value="73" spread="21"/>
                    <measurement group_id="O9" value="78.6" spread="26.2"/>
                    <measurement group_id="O10" value="78.9" spread="37.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Embryo Formation</title>
        <description>All embryos were graded at day 3 by an independent embryologist, blinded to doses of kisspeptin administered, using the British Fertility Society and Association of Clinical Embryologist embryo grading scheme for cleavage stage embryos, which describes embryos based on cell number, blastomere size, and fragmentation</description>
        <time_frame>3 days after oocyte retrieval</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Kisspeptin-54 1.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg</description>
          </group>
          <group group_id="O2">
            <title>Kispeptin-54 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
          </group>
          <group group_id="O3">
            <title>Kisspeptin-54 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
          </group>
          <group group_id="O4">
            <title>Kisspeptin-54 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
          </group>
          <group group_id="O5">
            <title>OHSS - Kisspeptin-54 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
          </group>
          <group group_id="O6">
            <title>OHSS - Kisspeptin-54 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
          </group>
          <group group_id="O7">
            <title>OHSS - Kisspeptin-54 9.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg</description>
          </group>
          <group group_id="O8">
            <title>OHSS - Kisspeptin-54 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
          </group>
          <group group_id="O9">
            <title>Kisspeptin-54 9.6 + 9.6</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
          </group>
          <group group_id="O10">
            <title>Kisspeptin-54 9.6 + Saline</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
          </group>
        </group_list>
        <measure>
          <title>Embryo Formation</title>
          <description>All embryos were graded at day 3 by an independent embryologist, blinded to doses of kisspeptin administered, using the British Fertility Society and Association of Clinical Embryologist embryo grading scheme for cleavage stage embryos, which describes embryos based on cell number, blastomere size, and fragmentation</description>
          <population>All participants</population>
          <units>formed embryos</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="20"/>
                <count group_id="O7" value="15"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="31"/>
                <count group_id="O10" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="2.33" spread="2.31"/>
                    <measurement group_id="O3" value="3.8" spread="2.7"/>
                    <measurement group_id="O4" value="4.5" spread="2.7"/>
                    <measurement group_id="O5" value="5.8" spread="4.8"/>
                    <measurement group_id="O6" value="9.4" spread="7"/>
                    <measurement group_id="O7" value="6.5" spread="5.6"/>
                    <measurement group_id="O8" value="11.1" spread="8.4"/>
                    <measurement group_id="O9" value="6" spread="4.44"/>
                    <measurement group_id="O10" value="5" spread="3.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinical Pregnancy</title>
        <description>Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation</description>
        <time_frame>6 weeks after embryo transfer</time_frame>
        <population>All participants</population>
        <group_list>
          <group group_id="O1">
            <title>Kisspeptin-54 1.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg</description>
          </group>
          <group group_id="O2">
            <title>Kispeptin-54 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
          </group>
          <group group_id="O3">
            <title>Kisspeptin-54 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
          </group>
          <group group_id="O4">
            <title>Kisspeptin-54 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
          </group>
          <group group_id="O5">
            <title>OHSS - Kisspeptin-54 3.2 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg</description>
          </group>
          <group group_id="O6">
            <title>OHSS - Kisspeptin-54 6.4 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg</description>
          </group>
          <group group_id="O7">
            <title>OHSS - Kisspeptin-54 9.6 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg</description>
          </group>
          <group group_id="O8">
            <title>OHSS - Kisspeptin-54 12.8 Single</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg</description>
          </group>
          <group group_id="O9">
            <title>Kisspeptin-54 9.6 + 9.6</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
          </group>
          <group group_id="O10">
            <title>Kisspeptin-54 9.6 + Saline</title>
            <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinical Pregnancy</title>
          <description>Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation</description>
          <population>All participants</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="20"/>
                <count group_id="O7" value="15"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="31"/>
                <count group_id="O10" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="10"/>
                    <measurement group_id="O7" value="10"/>
                    <measurement group_id="O8" value="6"/>
                    <measurement group_id="O9" value="7"/>
                    <measurement group_id="O10" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>KP-54 1.6nmol/kg Single</title>
          <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 1.6nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E2">
          <title>KP-54 3.2nmol/kg Single</title>
          <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 3.2nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E3">
          <title>KP-54 6.4nmol/kg Single</title>
          <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 6.4nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E4">
          <title>KP-54 12.8nmol/kg Single</title>
          <description>Participants undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 12.8nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E5">
          <title>KP-54 OHSS 3.2nmol/kg Single</title>
          <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 3.2nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E6">
          <title>KP-54 OHSS 6.4nmol/kg Single</title>
          <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 6.4nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E7">
          <title>KP-54 OHSS 9.6nmol/kg Single</title>
          <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 9.6nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E8">
          <title>KP-54 OHSS 12.8nmol/kg Single</title>
          <description>Participants with a high risk of ovarian hyper-stimulation syndrome (OHSS), undergoing IVF treatment received a single injection of Kisspeptin-54, at a dose of 12.8nmol/kg as a trigger injection.</description>
        </group>
        <group group_id="E9">
          <title>KP-54 OHSS 9.6 + 9.6 Nmol/kg</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later</description>
        </group>
        <group group_id="E10">
          <title>KP-54 OHSS 9.6nmol/kg + Saline</title>
          <description>Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Ectopic pregnancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Miscarriage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Heterotopic pregnancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Still birth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Professor Waljit Dhillo</name_or_title>
      <organization>Imperial College London</organization>
      <phone>442083833242</phone>
      <email>w.dhillo@imperial.ac.uk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01667406
org study id: 13HH0199
secondary id: 2012-000154-61
nct id: NCT01667406
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
We want to find out if kisspeptin is successful in stimulating oocyte maturation when it is
      used as a 'trigger' injection during IVF therapy for infertility.
Participants in the study will have a standard Gonadotrophin Releasing Hormone (GnRH)
      antagonist IVF cycle, but instead of having a trigger injection of hCG (human chorionic
      gonadotrophin) they will be randomised to receive one of 4 doses of kisspeptin injection.

      Oocytes will be retrieved and graded by an embryologist to see whether or not they have
      matured.

      The reproductive hormones Luteinising hormone, follicle stimulating hormone, oestradiol and
      progesterone will also be measured
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Different dose for each volunteer
primary purpose: Treatment
masking: Double (Participant, Care Provider)
masking description: participants and IVF physicians were blinded.
measure: Percentage of Oocyte Maturation
time frame: 36 hours post Kisspeptin-54 trigger injection
description: This was assessed by oocyte yield (percentage of mature [metaphase 2; M2] oocytes collected from the number of follicles ≥ 14 mm on final ultrasound scan prior to kisspeptin-54 trigger administration
measure: Biochemical Pregnancy
time frame: 11 days after embryo transfer
description: Number of participants achieving biochemical pregnancy by serum βhCG > 10 mIU/mL
measure: Occurrence of OHSS
time frame: 11 days following embryo transfer
description: Women were routinely screened for the development of early OHSS and late OHSS. Women were screened by symptoms, blood analysis, and ultrasound parameters
measure: Fertilization Rate
time frame: 3 days after oocyte retrieval
description: Percentage of M2 oocytes that fertilize to form two pronuclear [2PN] zygotes following intracytoplasmic injection with sperm [ICSI]
measure: Embryo Formation
time frame: 3 days after oocyte retrieval
description: All embryos were graded at day 3 by an independent embryologist, blinded to doses of kisspeptin administered, using the British Fertility Society and Association of Clinical Embryologist embryo grading scheme for cleavage stage embryos, which describes embryos based on cell number, blastomere size, and fragmentation
measure: Number of Participants With Clinical Pregnancy
time frame: 6 weeks after embryo transfer
description: Intrauterine gestational sac with heartbeat on ultrasound at 6 weeks' gestation
arm group label: Kisspeptin-54, 1.6 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 1.6 nmol/kg
arm group label: Kisspeptin-54, 3.2 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg
arm group label: Kisspeptin-54, 6.4 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg
arm group label: Kisspeptin-54, 12.8 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg
arm group label: Kisspeptin-54 OHSS, 3.2 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 3.2 nmol/kg
arm group label: Kisspeptin-54 OHSS, 6.4 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 6.4 nmol/kg
arm group label: Kisspeptin-54 OHSS, 9.6 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 9.6 nmol/kg
arm group label: Kisspeptin-54 OHSS, 12.8 single
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a single trigger injection of Kisspeptin, dose of 12.8 nmol/kg
arm group label: Kisspeptin-54 OHSS, 9.6 + 9.6
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of Kisspeptin, dose of 9.6 nmol/kg 10 hours later
arm group label: Kisspeptin-54 OHSS, 9.6 + saline
arm group type: Experimental
description: Participant undergoing in vitro fertilisation (IVF) treatment and who is at high risk of ovarian hyper stimulation syndrome (OHSS) will receive a trigger injection of Kisspeptin, dose of 9.6 nmol/kg and a further injection of saline10 hours later
intervention type: Drug
intervention name: Kisspeptin 1.6nmol/kg
description: single kisspeptin dose 1.6 nmol/kg subcutaneously
arm group label: Kisspeptin-54, 1.6 single
other name: kisspeptin-54
intervention type: Drug
intervention name: Kisspeptin 3.2nmol/kg
description: single kisspeptin dose 3.2 nmol/kg subcutaneously
arm group label: Kisspeptin-54 OHSS, 3.2 single
arm group label: Kisspeptin-54, 3.2 single
other name: kisspeptin-54
intervention type: Drug
intervention name: Kisspeptin 6.4nmol/kg
description: single kisspeptin dose 6.4 nmol/kg subcutaneously
arm group label: Kisspeptin-54 OHSS, 6.4 single
arm group label: Kisspeptin-54, 6.4 single
other name: kisspeptin-54
intervention type: Drug
intervention name: Kisspeptin 9.6nmol/kg
description: single kisspeptin dose 9.6 nmol/kg subcutaneously
arm group label: Kisspeptin-54 OHSS, 9.6 single
other name: kisspeptin-54
intervention type: Drug
intervention name: Kisspeptin 12.8nmol/kg
description: single kisspeptin dose 12.8 nmol/kg subcutaneously
arm group label: Kisspeptin-54 OHSS, 12.8 single
arm group label: Kisspeptin-54, 12.8 single
other name: kisspeptin-54
intervention type: Drug
intervention name: Kisspeptin 9.6 nmol/kg double
description: kisspeptin dose 9.6 nmol/kg given twice 10hrs apart subcutaneously
arm group label: Kisspeptin-54 OHSS, 9.6 + 9.6
other name: kisspeptin-54
intervention type: Drug
intervention name: Kisspeptin 9.6 nmol/kg + saline
description: kisspeptin dose 9.6 nmol/kg subcutaneously and saline subcutaneously, 10hrs apart
arm group label: Kisspeptin-54 OHSS, 9.6 + saline
other name: kisspeptin-54
criteria: 
gender: Female
gender based: Yes
gender description: woman undergoing IVF treatment
minimum age: 18 Years
maximum age: 34 Years
healthy volunteers: No
last name: Waljit S Dhillo, PhD
role: Principal Investigator
affiliation: Imperial College London
facility: 
country: United Kingdom
citation: Jayasena CN, Abbara A, Comninos AN, Nijher GM, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Sridharan M, Mason AJ, Warwick J, Ashby D, Ghatei MA, Bloom SR, Carby A, Trew GH, Dhillo WS. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. 2014 Aug;124(8):3667-77. doi: 10.1172/JCI75730. Epub 2014 Jul 18.
PMID: 25036713
citation: Abbara A, Clarke S, Islam R, Prague JK, Comninos AN, Narayanaswamy S, Papadopoulou D, Roberts R, Izzi-Engbeaya C, Ratnasabapathy R, Nesbitt A, Vimalesvaran S, Salim R, Lavery SA, Bloom SR, Huson L, Trew GH, Dhillo WS. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial. Hum Reprod. 2017 Sep 1;32(9):1915-1924. doi: 10.1093/humrep/dex253.
PMID: 28854728
citation: Abbara A, Jayasena CN, Christopoulos G, Narayanaswamy S, Izzi-Engbeaya C, Nijher GM, Comninos AN, Peters D, Buckley A, Ratnasabapathy R, Prague JK, Salim R, Lavery SA, Bloom SR, Szigeti M, Ashby DA, Trew GH, Dhillo WS. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy. J Clin Endocrinol Metab. 2015 Sep;100(9):3322-31. doi: 10.1210/jc.2015-2332. Epub 2015 Jul 20.
PMID: 26192876
responsible party type: Sponsor
mesh term: Infertility
sharing ipd: No
ipd description: Data will be presented in anonymised groups
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 