<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/NCT04414748</url>
  </required_header>
  <id_info>
    <org_study_id>JIAI 2020-05</org_study_id>
    <nct_id>NCT04414748</nct_id>
  </id_info>
  <brief_title>Comparison of the Euploid Rate of Blastocyst Between PPOS and GnRH Antagonist Protocol in Patients Undergoing PGT-A</brief_title>
  <official_title>A Randomized Control Trial to Compare the Euploid Rate of Blastocyst Between the Progestin-primed Ovarian Stimulation Protocol and the GnRH Antagonist Protocol in Patients Undergoing PGT-A</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>
      This randomized trial aims to compare the euploid rate of blastocysts between PPOS and GnRH&#xD;
      antagonist protocols in patients undergoing PGT-A. Infertile women who have medical&#xD;
      indication for PGT-A will be recruited for study after explanation and counseling if they&#xD;
      fulfill the inclusion criteria and do not have the exclusion criteria. Eligible women will be&#xD;
      randomised into one of the two groups:&#xD;
&#xD;
      Antagonist group: Women will receive antagonist once subcutaneously daily from day 6 of&#xD;
      ovarian stimulation till the day of the ovulation trigger.&#xD;
&#xD;
      PPOS group: Women will receive oral Duphaston 10mg bd from Day 3 till the day of ovulation&#xD;
      trigger.&#xD;
&#xD;
      The primary outcome is the euploidy rate of blastocysts.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 10, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</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>euploidy rate</measure>
    <time_frame>1 month after oocyte retrieval</time_frame>
    <description>euploidy rate of blastocysts</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>number of mature oocytes</measure>
    <time_frame>1 day after oocyte retrieval</time_frame>
    <description>number of MII oocytes</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>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>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>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>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>live birth rate</measure>
    <time_frame>1 year after FET</time_frame>
    <description>deliveries ≥22 weeks gestation with heartbeat and breath of the first FET</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>progesterone level on the trigger day</measure>
    <time_frame>2 days before oocyte retrieval</time_frame>
    <description>progesterone level on the trigger day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>estradiol level on the trigger day</measure>
    <time_frame>2 days before oocyte retrieval</time_frame>
    <description>estradiol level on the trigger day</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="Anticipated">400</enrollment>
  <condition>Preimplantation Genetic Testing</condition>
  <condition>Progestin-primed Ovarian Stimulation</condition>
  <condition>Euploid Rate</condition>
  <condition>GnRH Antagonist</condition>
  <arm_group>
    <arm_group_label>Antagonist group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women will receive antagonist (Cetrotide 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 Duphaston 10mg bd from Day 3 till the day of ovulation trigger.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GnRH antagonist</intervention_name>
    <description>GnRH antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of COH till the day of the ovulation trigger</description>
    <arm_group_label>Antagonist group</arm_group_label>
    <other_name>Cetrorelix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral Duphaston</intervention_name>
    <description>oral Duphaston 10mg bd from Day 3 of COH till the day of ovulation trigger.</description>
    <arm_group_label>PPOS group</arm_group_label>
    <other_name>Duphaston</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;
          -  Antral follicle count (AFC) &gt;=5 on day 2-5 of the period&#xD;
&#xD;
          -  PGT-A indicated for advanced maternal age (&gt;=38 years), recurrent miscarriage (&gt;=2&#xD;
             consecutive miscarriage) and repeated implantation failure (&gt;=4 embryos replaced or&#xD;
             &gt;=2 blastocysts replaced without success), recurrent foetal aneuploidy&#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;
          -  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>
  <overall_contact>
    <last_name>HE LI, MD</last_name>
    <phone>+8613817223099</phone>
    <email>lihe198900@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>XIAOXI SUN, PHD</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai JiAi Genetics &amp; IVF Institute</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200011</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>HE LI, MD</last_name>
      <phone>+8602163459977</phone>
      <email>lihe198900@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.</citation>
    <PMID>25432917</PMID>
  </reference>
  <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>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>April 21, 2023</last_update_submitted>
  <last_update_submitted_qc>April 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 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>Cetrorelix</mesh_term>
    <mesh_term>Dydrogesterone</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/NCT04414748
org study id: JIAI 2020-05
nct id: NCT04414748
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This randomized trial aims to compare the euploid rate of blastocysts between PPOS and GnRH
      antagonist protocols in patients undergoing PGT-A. Infertile women who have medical
      indication for PGT-A will be recruited for study after explanation and counseling if they
      fulfill the inclusion criteria and do not have the exclusion criteria. Eligible women will be
      randomised into one of the two groups:

      Antagonist group: Women will receive antagonist once subcutaneously daily from day 6 of
      ovarian stimulation till the day of the ovulation trigger.

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

      The primary outcome is the euploidy rate of blastocysts.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: euploidy rate
time frame: 1 month after oocyte retrieval
description: euploidy rate of blastocysts
measure: number of mature oocytes
time frame: 1 day after oocyte retrieval
description: number of MII oocytes
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: 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: implantation rate
time frame: 6 weeks' gestation
description: the number of gestational sacs per blastocyst transferred 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: ongoing pregnancy
time frame: 12 weeks' gestation
description: a viable pregnancy beyond 12 weeks' gestation of the first FET
measure: live birth rate
time frame: 1 year after FET
description: deliveries ≥22 weeks gestation with heartbeat and breath of the first FET
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: progesterone level on the trigger day
time frame: 2 days before oocyte retrieval
description: progesterone level on the trigger day
measure: estradiol level on the trigger day
time frame: 2 days before oocyte retrieval
description: estradiol level on the trigger day
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 (Cetrotide 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 Duphaston 10mg bd from Day 3 till the day of ovulation trigger.
intervention type: Drug
intervention name: GnRH antagonist
description: GnRH antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of COH till the day of the ovulation trigger
arm group label: Antagonist group
other name: Cetrorelix
intervention type: Drug
intervention name: oral Duphaston
description: oral Duphaston 10mg bd from Day 3 of COH till the day of ovulation trigger.
arm group label: PPOS group
other name: Duphaston
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
last name: HE LI, MD
phone: +8613817223099
email: lihe198900@163.com
last name: XIAOXI SUN, PHD
facility: 
status: Recruiting
contact: 
country: China
citation: Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.
PMID: 25432917
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
responsible party type: Sponsor
mesh term: Cetrorelix
mesh term: Dydrogesterone
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.