<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/NCT04414761</url>
  </required_header>
  <id_info>
    <org_study_id>JIAI 2020-06</org_study_id>
    <nct_id>NCT04414761</nct_id>
  </id_info>
  <brief_title>Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response</brief_title>
  <official_title>A Randomized Control Trial to Compare the Live Birth Rate Between the Progestin-primed Ovarian Stimulation Protocol and the GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response Undergoing IVF</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ShangHai Ji Ai Genetics &amp; IVF Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ShangHai Ji Ai Genetics &amp; IVF Institute</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Progestin can inhibit the pituitary LH surge during ovarian stimulation and various studies&#xD;
      show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH surge in&#xD;
      IVF. More and more centers in China are using PPOS because this regimen appears simpler and&#xD;
      cheaper.A randomized trial to compare the effectiveness of PPOS and GnRH antagonist protocol&#xD;
      in IVF in terms of the live birth rate is urgently needed.&#xD;
&#xD;
      Trial objectives: To compare the live birth rate between the PPOS protocol and the antagonist&#xD;
      protocol used for ovarian stimulation during IVF&#xD;
&#xD;
      Eligible women will be randomised into one of the two groups:&#xD;
&#xD;
      Antagonist group : Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once&#xD;
      subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.&#xD;
&#xD;
      PPOS group: Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd&#xD;
      daily from Day 3 till the day of ovulation trigger.&#xD;
&#xD;
      There will be no fresh transfer. Only one blastocyst will be allowed to replaced in the first&#xD;
      FET and a maximum of two blastocysts will be replaced in the subsequent FET cycles.&#xD;
&#xD;
      The primary outcome is the live birth rate of the first frozen-thawed transfer cycle.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 4, 2020</start_date>
  <completion_date type="Actual">October 10, 2022</completion_date>
  <primary_completion_date type="Actual">October 10, 2022</primary_completion_date>
  <phase>Phase 3</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>live birth rate</measure>
    <time_frame>deliveries ≥22 weeks gestation with heartbeat and breath</time_frame>
    <description>live birth rate of the first frozen embryo transfer cycle</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>positive serum hCG</measure>
    <time_frame>2 weeks after FET</time_frame>
    <description>serum β-hCG ≥10 mIU/mL of the first FET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical pregnancy</measure>
    <time_frame>6 weeks' gestation</time_frame>
    <description>presence of intrauterine gestational sac by trans-vaginal ultrasound at 6 gestational weeks of the first FET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biochemical pregnancy</measure>
    <time_frame>6 weeks' gestation</time_frame>
    <description>positive serum hCG not followed by clinical pregnancy of the first FET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>implantation rate</measure>
    <time_frame>6 weeks' gestation</time_frame>
    <description>the number of gestational sacs per blastocyst transferred of the first FET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ongoing pregnancy</measure>
    <time_frame>12 weeks' gestation</time_frame>
    <description>a viable pregnancy beyond 12 weeks' gestation of the first FET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cumulative live birth</measure>
    <time_frame>2 years' after FET</time_frame>
    <description>cumulative live birth within 6 months of randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of oocytes retrieved</measure>
    <time_frame>1 day after oocyte retrieval</time_frame>
    <description>number of oocytes retrieved</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number and grading of blastocysts</measure>
    <time_frame>1 week after oocyte retrieval</time_frame>
    <description>number and grading of blastocysts suitable for biopsy and freezing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>multiple pregnancy</measure>
    <time_frame>multiple pregnancy beyond gestation 12 weeks</time_frame>
    <description>more than one intrauterine sacs on scanning</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ectopic pregnancy</measure>
    <time_frame>ectopic pregnancy during 12 weeks gestation</time_frame>
    <description>pregnancy outside the uterine cavity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>birthweight of newborns</measure>
    <time_frame>1 year after FET</time_frame>
    <description>the birth weight of newborns</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum baseline FSH</measure>
    <time_frame>day 2-3 of period</time_frame>
    <description>baseline FSH of period day 2-3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>estradiol level on the trigger day</measure>
    <time_frame>2 days before oocyte retrieval</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progesterone level on the trigger day</measure>
    <time_frame>2 days before oocyte retrieval</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>estradiol and progesterone levels in the follicular fluid</measure>
    <time_frame>1 year after FET</time_frame>
    <description>estradiol and progesterone levels in the follicular fluid</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>miscarriage</measure>
    <time_frame>22 weeks of pregnancy</time_frame>
    <description>clinically recognised pregnancy loss before 22 weeks of pregnancy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">784</enrollment>
  <condition>IVF</condition>
  <condition>GnRH Antagonist</condition>
  <condition>PPOS</condition>
  <arm_group>
    <arm_group_label>Antagonist group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PPOS group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Progesterone</intervention_name>
    <description>oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger</description>
    <arm_group_label>PPOS group</arm_group_label>
    <other_name>medroxyprogesterone</other_name>
    <other_name>duphaston</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GnRH Antagonist</intervention_name>
    <description>GnRH antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger</description>
    <arm_group_label>Antagonist group</arm_group_label>
    <other_name>Cetrorelix</other_name>
    <other_name>Ganirelix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age of women &lt;43 years at the time of ovarian stimulation for IVF&#xD;
&#xD;
          -  The first IVF cycle&#xD;
&#xD;
          -  Antral follicle count (AFC) &gt;15 on day 2-5 of the period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of a functional ovarian cyst with E2&gt;100 pg/mL&#xD;
&#xD;
          -  Recipient of oocyte donation&#xD;
&#xD;
          -  Undergoing preimplantation genetic testing&#xD;
&#xD;
          -  Presence of hydrosalpinx or endometrial polyp which is not surgically treated&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>43 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>XIAOXI SUN, PHD</last_name>
    <role>Study Director</role>
    <affiliation>Shanghai JiAi Genetics &amp; IVF Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ShangHai JIAI Genetics&amp;IVF Institute</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Begueria R, Garcia D, Vassena R, Rodriguez A. Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019 May 1;34(5):872-880. doi: 10.1093/humrep/dez034.</citation>
    <PMID>30927417</PMID>
  </reference>
  <reference>
    <citation>Yu S, Long H, Chang HY, Liu Y, Gao H, Zhu J, Quan X, Lyu Q, Kuang Y, Ai A. New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles. Hum Reprod. 2018 Feb 1;33(2):229-237. doi: 10.1093/humrep/dex367.</citation>
    <PMID>29300975</PMID>
  </reference>
  <reference>
    <citation>Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017 Mar 1;23(2):211-220. doi: 10.1093/humupd/dmw047.</citation>
    <PMID>28062551</PMID>
  </reference>
  <reference>
    <citation>Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.</citation>
    <PMID>25956370</PMID>
  </reference>
  <reference>
    <citation>Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, Long H, Wang L, Tian H, Lyu QF, Lu XF, Chen QJ, Kuang YP. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG. 2017 Jun;124(7):1048-1055. doi: 10.1111/1471-0528.14622.</citation>
    <PMID>28276192</PMID>
  </reference>
  <reference>
    <citation>Alexandru P, Cekic SG, Yildiz S, Turkgeldi E, Ata B. Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis. Reprod Biomed Online. 2020 Jun;40(6):894-903. doi: 10.1016/j.rbmo.2020.01.027. Epub 2020 Feb 5.</citation>
    <PMID>32327297</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>August 28, 2023</last_update_submitted>
  <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Medroxyprogesterone Acetate</mesh_term>
    <mesh_term>Medroxyprogesterone</mesh_term>
    <mesh_term>Cetrorelix</mesh_term>
    <mesh_term>Progesterone</mesh_term>
    <mesh_term>Dydrogesterone</mesh_term>
    <mesh_term>Ganirelix</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results after deidentification (text, tables, figures, and appendices) and study protocol will be shared.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data will be available when beginning 3 months and ending 5 years following article publication.</ipd_time_frame>
    <ipd_access_criteria>To achieve aims in the approved proposal, researchers who provide a methodologically sound proposal will be shared with. Proposals should be sent to lihe198900@163.com.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04414761
org study id: JIAI 2020-06
nct id: NCT04414761
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Progestin can inhibit the pituitary LH surge during ovarian stimulation and various studies
      show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH surge in
      IVF. More and more centers in China are using PPOS because this regimen appears simpler and
      cheaper.A randomized trial to compare the effectiveness of PPOS and GnRH antagonist protocol
      in IVF in terms of the live birth rate is urgently needed.

      Trial objectives: To compare the live birth rate between the PPOS protocol and the antagonist
      protocol used for ovarian stimulation during IVF

      Eligible women will be randomised into one of the two groups:

      Antagonist group : Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once
      subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.

      PPOS group: Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd
      daily from Day 3 till the day of ovulation trigger.

      There will be no fresh transfer. Only one blastocyst will be allowed to replaced in the first
      FET and a maximum of two blastocysts will be replaced in the subsequent FET cycles.

      The primary outcome is the live birth rate of the first frozen-thawed transfer cycle.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: live birth rate
time frame: deliveries ≥22 weeks gestation with heartbeat and breath
description: live birth rate of the first frozen embryo transfer cycle
measure: positive serum hCG
time frame: 2 weeks after FET
description: serum β-hCG ≥10 mIU/mL of the first FET
measure: clinical pregnancy
time frame: 6 weeks' gestation
description: presence of intrauterine gestational sac by trans-vaginal ultrasound at 6 gestational weeks of the first FET
measure: biochemical pregnancy
time frame: 6 weeks' gestation
description: positive serum hCG not followed by clinical pregnancy of the first FET
measure: implantation rate
time frame: 6 weeks' gestation
description: the number of gestational sacs per blastocyst transferred of the first FET
measure: ongoing pregnancy
time frame: 12 weeks' gestation
description: a viable pregnancy beyond 12 weeks' gestation of the first FET
measure: cumulative live birth
time frame: 2 years' after FET
description: cumulative live birth within 6 months of randomization
measure: number of oocytes retrieved
time frame: 1 day after oocyte retrieval
description: number of oocytes retrieved
measure: number and grading of blastocysts
time frame: 1 week after oocyte retrieval
description: number and grading of blastocysts suitable for biopsy and freezing
measure: multiple pregnancy
time frame: multiple pregnancy beyond gestation 12 weeks
description: more than one intrauterine sacs on scanning
measure: ectopic pregnancy
time frame: ectopic pregnancy during 12 weeks gestation
description: pregnancy outside the uterine cavity
measure: birthweight of newborns
time frame: 1 year after FET
description: the birth weight of newborns
measure: serum baseline FSH
time frame: day 2-3 of period
description: baseline FSH of period day 2-3
measure: estradiol level on the trigger day
time frame: 2 days before oocyte retrieval
measure: progesterone level on the trigger day
time frame: 2 days before oocyte retrieval
measure: estradiol and progesterone levels in the follicular fluid
time frame: 1 year after FET
description: estradiol and progesterone levels in the follicular fluid
measure: miscarriage
time frame: 22 weeks of pregnancy
description: clinically recognised pregnancy loss before 22 weeks of pregnancy.
arm group label: Antagonist group
arm group type: Active Comparator
description: Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.
arm group label: PPOS group
arm group type: Experimental
description: Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger.
intervention type: Drug
intervention name: Progesterone
description: oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger
arm group label: PPOS group
other name: medroxyprogesterone
other name: duphaston
intervention type: Drug
intervention name: GnRH Antagonist
description: GnRH antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger
arm group label: Antagonist group
other name: Cetrorelix
other name: Ganirelix
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 43 Years
healthy volunteers: No
last name: XIAOXI SUN, PHD
role: Study Director
affiliation: Shanghai JiAi Genetics & IVF Institute
facility: 
country: China
citation: Begueria R, Garcia D, Vassena R, Rodriguez A. Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019 May 1;34(5):872-880. doi: 10.1093/humrep/dez034.
PMID: 30927417
citation: Yu S, Long H, Chang HY, Liu Y, Gao H, Zhu J, Quan X, Lyu Q, Kuang Y, Ai A. New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles. Hum Reprod. 2018 Feb 1;33(2):229-237. doi: 10.1093/humrep/dex367.
PMID: 29300975
citation: Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017 Mar 1;23(2):211-220. doi: 10.1093/humupd/dmw047.
PMID: 28062551
citation: Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
PMID: 25956370
citation: Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, Long H, Wang L, Tian H, Lyu QF, Lu XF, Chen QJ, Kuang YP. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG. 2017 Jun;124(7):1048-1055. doi: 10.1111/1471-0528.14622.
PMID: 28276192
citation: Alexandru P, Cekic SG, Yildiz S, Turkgeldi E, Ata B. Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis. Reprod Biomed Online. 2020 Jun;40(6):894-903. doi: 10.1016/j.rbmo.2020.01.027. Epub 2020 Feb 5.
PMID: 32327297
responsible party type: Sponsor
mesh term: Medroxyprogesterone Acetate
mesh term: Medroxyprogesterone
mesh term: Cetrorelix
mesh term: Progesterone
mesh term: Dydrogesterone
mesh term: Ganirelix
sharing ipd: Yes
ipd description: Individual participant data that underlie the results after deidentification (text, tables, figures, and appendices) and study protocol will be shared.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data will be available when beginning 3 months and ending 5 years following article publication.
ipd access criteria: To achieve aims in the approved proposal, researchers who provide a methodologically sound proposal will be shared with. Proposals should be sent to lihe198900@163.com.