<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/NCT02238431</url>
  </required_header>
  <id_info>
    <org_study_id>Lucrin depot FET cycle</org_study_id>
    <secondary_id>FET cycle cancellation</secondary_id>
    <nct_id>NCT02238431</nct_id>
  </id_info>
  <brief_title>Down-regulated Hormonally Controlled Cycles for Vitrification-warmed Blastocyst Transfers</brief_title>
  <official_title>Down-regulated Hormonally Controlled Cycles for Vitrification-warmed Blastocyst Transfers: Reduces Time to Transfer and Cycle Cancellation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Antalya IVF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Antalya IVF</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently all patients that have freeze-all ICSI treatment cycles have the start of their FET&#xD;
      cycle scheduled with the use of OCP. While an excellent pregnancy rate (75%) for the patients&#xD;
      that have a blastocyst transfer has been maintained over time, 15% of started FET cycles are&#xD;
      being cancelled because of premature luteinization, and the treatment (to transfer) takes&#xD;
      approximately 89 days. The use of a Lucrin depot may reduce the number of cycles cancelled&#xD;
      and reduce the treatment time to approximately 69 days. The use of no drugs and allowing the&#xD;
      normal menstrual cycle to determine the time to start the FET cycle may suit some patients.&#xD;
      Whether these benefits can be obtained while still maintaining the current FET pregnancy rate&#xD;
      will be the main focus of the trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The patients will undergo standard assisted conception procedures; controlled ovarian&#xD;
      stimulation (COS), oocyte pickup procedure (OPU), ICSI, embryo culture, blastocyst&#xD;
      vitrification and frozen embryo transfer. If sufficient (&gt;2) viable blastocyst develop from&#xD;
      the in vitro culture of their embryos, all viable blastocysts will be cryopreserved using a&#xD;
      routine vitrification procedure. This is the eligible patient population. On the day the last&#xD;
      blastocyst(s) are frozen the patients will be given a further opportunity to ask questions&#xD;
      and if satisfied they will be asked to complete a trial consent. At this point patients will&#xD;
      be randomized by numeric code and given a schedule and drug prescription for scheduling the&#xD;
      start of their hormone supplemented frozen embryo transfer cycle. During the scheduling&#xD;
      period the patients will follow the drug prescription provided . After the completion of&#xD;
      their treatment - the transfer of one or two vitrified-warmed blastocyst - the patients from&#xD;
      both groups will receive identical luteal support drug schedules and prescriptions. A blood&#xD;
      test will be performed on the 15th day of progesterone supplementation, to determine the βhCG&#xD;
      blood concentration. Currently at Antalya IVF, approximately 75% of patients who have&#xD;
      blastocysts transferred in a frozen embryo transfer cycle have a positive biochemical&#xD;
      pregnancy test, &gt;29 international units per litre (IU/L) of human chorionic gonadotropin&#xD;
      (βhCG). If pregnant, patients will continue using estrogen and progesterone supplementation&#xD;
      for a further 8 weeks. At 7 weeks of gestation (5 weeks after embryo transfer ) the patients&#xD;
      will receive a transvaginal ultrasound scan (TVUS) to check for pregnancy viability (fetal&#xD;
      sac with cardiac activity). Thereafter the patients will have regular TVUS to follow fetal&#xD;
      development. At 20 weeks of gestation a TVUS will be performed to confirm an ongoing&#xD;
      pregnancy (normal fetal development).&#xD;
&#xD;
      All drug packs are delivered to the clinic by the pharmacy after receiving the prescription.&#xD;
      A staff member will verify the code on the prescription with randomization code allocated to&#xD;
      the patient. The pack will then be given to the patient after verbally confirming patient&#xD;
      identity. The packs will also contain a drug use instruction sheet and a trial information&#xD;
      sheet.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    no patient uptake&#xD;
  </why_stopped>
  <start_date>December 2014</start_date>
  <completion_date type="Anticipated">June 2016</completion_date>
  <primary_completion_date type="Anticipated">May 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cycle cancellation</measure>
    <time_frame>On day 14 of estrogen supplementation</time_frame>
    <description>blood progesterone concentration (&gt;2nmol/L) as a measure of premature luteinization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate</measure>
    <time_frame>20 weeks of gestation</time_frame>
    <description>TVUS normal fetal development &gt;20 weeks of gestation, in case of a pregnancy</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pregnancy</measure>
    <time_frame>15 days after start the start of progesterone supplementation</time_frame>
    <description>&gt;29 IU/L βhCG on day 15 from the start of progesterone supplementation</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pregnancy</condition>
  <arm_group>
    <arm_group_label>Lucrin depot, artificial cycle start</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intramuscular administration of Lucrin depot (half dose of 3.75mg) on the 5th day following oocyte retrieval</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OCP active, artificial cycle start</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>to take active OCP tablets (1 per day) from the 10th day following oocyte retrieval for at least 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Natural, menstrual period</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>to wait for the second bleed to commence the artificial FET cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lucrin depot</intervention_name>
    <description>scheduling the start of the artificial cycle and hormone down regulation during the artificial cycle</description>
    <arm_group_label>Lucrin depot, artificial cycle start</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OCP</intervention_name>
    <description>to schedule the start of the artificial cycle</description>
    <arm_group_label>OCP active, artificial cycle start</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Natural</intervention_name>
    <description>to use the normal menstrual period to schedule treatment start</description>
    <arm_group_label>Natural, menstrual period</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  If patients have &gt;2 blastocysts vitrified&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All patients not willing to participate in the study&#xD;
&#xD;
          -  Patients with any known adverse reaction to one or the other of the drugs prescribed&#xD;
&#xD;
          -  All patients that have no surviving blastocysts for transfer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>42 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Antalya IVF</name>
      <address>
        <city>Antalya</city>
        <zip>07080</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <reference>
    <citation>Gelbaya TA, Nardo LG, Hunter HR, Fitzgerald CT, Horne G, Pease EE, Brison DR, Lieberman BA. Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study. Fertil Steril. 2006 Mar;85(3):603-9. doi: 10.1016/j.fertnstert.2005.09.015.</citation>
    <PMID>16500326</PMID>
  </reference>
  <reference>
    <citation>Hill MJ, Miller KA, Frattarelli JL. A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles. Fertil Steril. 2010 Feb;93(2):416-22. doi: 10.1016/j.fertnstert.2008.11.027. Epub 2009 Jan 26.</citation>
    <PMID>19171338</PMID>
  </reference>
  <results_reference>
    <citation>Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261.</citation>
    <PMID>23820515</PMID>
  </results_reference>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>May 25, 2016</last_update_submitted>
  <last_update_submitted_qc>May 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 26, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Antalya IVF</investigator_affiliation>
    <investigator_full_name>Kevin Coetzee</investigator_full_name>
    <investigator_title>Scientific Advisor</investigator_title>
  </responsible_party>
  <keyword>Lucrin depot,</keyword>
  <keyword>frozen embryo transfer,</keyword>
  <keyword>artificial cycle,</keyword>
  <keyword>pregnancy,</keyword>
  <keyword>cancellation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leuprolide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02238431
org study id: Lucrin depot FET cycle
secondary id: FET cycle cancellation
nct id: NCT02238431
lead sponsor: 
has dmc: No
Currently all patients that have freeze-all ICSI treatment cycles have the start of their FET
      cycle scheduled with the use of OCP. While an excellent pregnancy rate (75%) for the patients
      that have a blastocyst transfer has been maintained over time, 15% of started FET cycles are
      being cancelled because of premature luteinization, and the treatment (to transfer) takes
      approximately 89 days. The use of a Lucrin depot may reduce the number of cycles cancelled
      and reduce the treatment time to approximately 69 days. The use of no drugs and allowing the
      normal menstrual cycle to determine the time to start the FET cycle may suit some patients.
      Whether these benefits can be obtained while still maintaining the current FET pregnancy rate
      will be the main focus of the trial.
The patients will undergo standard assisted conception procedures; controlled ovarian
      stimulation (COS), oocyte pickup procedure (OPU), ICSI, embryo culture, blastocyst
      vitrification and frozen embryo transfer. If sufficient (>2) viable blastocyst develop from
      the in vitro culture of their embryos, all viable blastocysts will be cryopreserved using a
      routine vitrification procedure. This is the eligible patient population. On the day the last
      blastocyst(s) are frozen the patients will be given a further opportunity to ask questions
      and if satisfied they will be asked to complete a trial consent. At this point patients will
      be randomized by numeric code and given a schedule and drug prescription for scheduling the
      start of their hormone supplemented frozen embryo transfer cycle. During the scheduling
      period the patients will follow the drug prescription provided . After the completion of
      their treatment - the transfer of one or two vitrified-warmed blastocyst - the patients from
      both groups will receive identical luteal support drug schedules and prescriptions. A blood
      test will be performed on the 15th day of progesterone supplementation, to determine the βhCG
      blood concentration. Currently at Antalya IVF, approximately 75% of patients who have
      blastocysts transferred in a frozen embryo transfer cycle have a positive biochemical
      pregnancy test, >29 international units per litre (IU/L) of human chorionic gonadotropin
      (βhCG). If pregnant, patients will continue using estrogen and progesterone supplementation
      for a further 8 weeks. At 7 weeks of gestation (5 weeks after embryo transfer ) the patients
      will receive a transvaginal ultrasound scan (TVUS) to check for pregnancy viability (fetal
      sac with cardiac activity). Thereafter the patients will have regular TVUS to follow fetal
      development. At 20 weeks of gestation a TVUS will be performed to confirm an ongoing
      pregnancy (normal fetal development).

      All drug packs are delivered to the clinic by the pharmacy after receiving the prescription.
      A staff member will verify the code on the prescription with randomization code allocated to
      the patient. The pack will then be given to the patient after verbally confirming patient
      identity. The packs will also contain a drug use instruction sheet and a trial information
      sheet.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Cycle cancellation
time frame: On day 14 of estrogen supplementation
description: blood progesterone concentration (>2nmol/L) as a measure of premature luteinization
measure: Ongoing pregnancy rate
time frame: 20 weeks of gestation
description: TVUS normal fetal development >20 weeks of gestation, in case of a pregnancy
measure: Pregnancy
time frame: 15 days after start the start of progesterone supplementation
description: >29 IU/L βhCG on day 15 from the start of progesterone supplementation
arm group label: Lucrin depot, artificial cycle start
arm group type: Experimental
description: intramuscular administration of Lucrin depot (half dose of 3.75mg) on the 5th day following oocyte retrieval
arm group label: OCP active, artificial cycle start
arm group type: Active Comparator
description: to take active OCP tablets (1 per day) from the 10th day following oocyte retrieval for at least 21 days
arm group label: Natural, menstrual period
arm group type: Experimental
description: to wait for the second bleed to commence the artificial FET cycle
intervention type: Drug
intervention name: Lucrin depot
description: scheduling the start of the artificial cycle and hormone down regulation during the artificial cycle
arm group label: Lucrin depot, artificial cycle start
intervention type: Drug
intervention name: OCP
description: to schedule the start of the artificial cycle
arm group label: OCP active, artificial cycle start
intervention type: Other
intervention name: Natural
description: to use the normal menstrual period to schedule treatment start
arm group label: Natural, menstrual period
criteria: 
gender: All
minimum age: 20 Years
maximum age: 42 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Turkey
citation: Gelbaya TA, Nardo LG, Hunter HR, Fitzgerald CT, Horne G, Pease EE, Brison DR, Lieberman BA. Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study. Fertil Steril. 2006 Mar;85(3):603-9. doi: 10.1016/j.fertnstert.2005.09.015.
PMID: 16500326
citation: Hill MJ, Miller KA, Frattarelli JL. A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles. Fertil Steril. 2010 Feb;93(2):416-22. doi: 10.1016/j.fertnstert.2008.11.027. Epub 2009 Jan 26.
PMID: 19171338
citation: Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261.
PMID: 23820515
responsible party type: Principal Investigator
investigator affiliation: Antalya IVF
investigator full name: Kevin Coetzee
investigator title: Scientific Advisor
mesh term: Leuprolide