xml: <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/NCT05980091</url>
    </required_header>
    <id_info>
      <org_study_id>2306-ABU-013-CC</org_study_id>
      <nct_id>NCT05980091</nct_id>
    </id_info>
    <brief_title>Optimal Timing of Euploid Day 6 Blastocyst Transfer in Frozen HRT Cycles, Day 6 or Day 7 of Progesterone Administration.</brief_title>
    <official_title>Optimal Timing of Euploid Day 6 Blastocyst (Blastocyst Which Was Biopsied on Day 6 After Fertilization) Transfer in Frozen Hormonal Replacement Therapy Cycles: Day 6 or Day 7 of Progesterone Administration?</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>ART Fertility Clinics LLC</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>ART Fertility Clinics LLC</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>
        The goal of this study is to compare the difference in clinical pregnancy, miscarriage and&#xD;
        livebirth rate between day 6 euploid blastocyst transfer on the 6th and the 7th day of&#xD;
        progesterone exposure in Hormonal Replacement Therapy (HRT) FET cycles. This prospective &amp;&#xD;
        randomized study will only include euploid day 6 blastocysts. This will be the first&#xD;
        prospective study of euploid day 6 blastocysts thereby excluding aneuploidy as a cause of&#xD;
        miscarriage and implantation failure. The point of randomization will occur on the day of&#xD;
        progesterone commencement.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Traditionally the duration of progesterone exposure before embryo transfer has been&#xD;
        considered equal for day 5 and day 6 embryos but this may not be the case and warrants&#xD;
        further study. The optimal preparation of the endometrium in frozen embryo transfer (FET)&#xD;
        cycles is yet to be determined. Synchronization between the embryonic stage and the&#xD;
        endometrial window of implantation (WOI) is crucial and progesterone plays a critical role in&#xD;
        the WOI (1). Data on the optimal route of administration, the dose and duration of&#xD;
        progesterone supplementation before blastocyst transfer are inconsistent (2,3). In view of&#xD;
        the current lack of evidence, this study will be of importance.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 15, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2024</primary_completion_date>
    <phase>Phase 1</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>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Livebirth rate (LBR)</measure>
      <time_frame>41 weeks</time_frame>
      <description>Defined as the delivery of a live infant born after 24 completed weeks of gestation</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Biochemical pregnancy rate</measure>
      <time_frame>5 weeks</time_frame>
      <description>Positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen but without a further development into a clinical pregnancy)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical pregnancy rate</measure>
      <time_frame>5 weeks</time_frame>
      <description>Ultrasonographic sac visible at 5 gestational weeks</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ongoing pregnancy rate after 12 weeks</measure>
      <time_frame>13 weeks</time_frame>
      <description>Viable pregnancy with a gestational age of more than 12 weeks</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Miscarriage rate</measure>
      <time_frame>24 weeks</time_frame>
      <description>Spontaneous loss of a clinical pregnancy before 24 completed weeks of gestation</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">316</enrollment>
    <condition>Infertility</condition>
    <condition>Fertility Issues</condition>
    <condition>Infertility, Female</condition>
    <arm_group>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Embryo transfer is scheduled on the 6th full day of progesterone administration, following the initial commencement of progesterone (120 hours)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group B</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Embryo Transfer is scheduled on the 7th full day of progesterone administration, following the initial commencement of progesterone (144 hours)</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Transvaginal ultrasound</intervention_name>
      <description>Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Serum LH, E2, P4</intervention_name>
      <description>In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Estradiol Valerate 2 MG</intervention_name>
      <description>Participants will commence estradiol valerate 4 mg ( 2 x 2 mg) on day 2 / day 3 of menses.&#xD;
  Estradiol will be increased to 6 mg on day 2 of estrogen treatment, and continued at a daily dose of 6 mg (3 tablets daily)</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
      <other_name>Estradiol Valerate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Progesterone 100 Mg Vaginal Insert</intervention_name>
      <description>The initial progesterone dose of 100 mg will be commenced at 13hrs and repeated at 21hrs considered day 1 (vaginal suppository) when an optimal endometrial thickness for each participant has been achieved with a trilaminar appearance. The following day (day 2) progesterone administration will be increased to 100 mg vaginally three times daily</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
      <other_name>Progesterone 100 mg</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Serum P4 day of ET</intervention_name>
      <description>On the day of embryo transfer (ET), a blood test is taken to measure serum P4</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Embryo transfer</intervention_name>
      <description>Procedure in which embryo is transferred into the uterus</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
      <other_name>ET</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Women aged 18 years to 43 years.&#xD;
  &#xD;
            -  Having at least 1 euploid cryopreserved day 6 blastocyst of at least Grade BB quality.&#xD;
  &#xD;
            -  Endometrial trilaminar appearance on the day of progesterone start&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Uterine abnormality&#xD;
  &#xD;
            -  Hydrosalpinx&#xD;
  &#xD;
            -  Asherman syndrome&#xD;
  &#xD;
            -  Any known contraindications or allergy to oral estradiol or progesterone.&#xD;
  &#xD;
            -  Intention to treat : exclusion factors :&#xD;
  &#xD;
                 1. Spontaneous ovulation HRT cycle&#xD;
  &#xD;
                 2. Discontinuation of HRT medication&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>43 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Carol Coughlan, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>ART Fertility Clinics LLC</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Barbara Lawrenz, PhD</last_name>
      <phone>+971 800 337845489</phone>
      <email>barbara.lawrenz@artfertilityclinics.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jonalyn Edades, RN</last_name>
      <phone>+971 800 337845489</phone>
      <email>jonalyn.edades@artfertilityclinics.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>ART Fertility Clinics LLC</name>
        <address>
          <city>Abu Dhabi</city>
          <zip>60202</zip>
          <country>United Arab Emirates</country>
        </address>
      </facility>
      <contact>
        <last_name>Barbara Lawrenz, PhD</last_name>
        <phone>+971 800 337845489</phone>
        <email>barbara.lawrenz@artfertilityclinics.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>ART Fertility Clinics Dubai</name>
        <address>
          <city>Dubai</city>
          <country>United Arab Emirates</country>
        </address>
      </facility>
      <contact>
        <last_name>Carol Coughlan, PhD</last_name>
        <phone>+971 800 337845489</phone>
        <email>jonalyn.edades@artfertilityclinics.com</email>
      </contact>
    </location>
    <location_countries>
      <country>United Arab Emirates</country>
    </location_countries>
    <reference>
      <citation>Franasiak JM, Ruiz-Alonso M, Scott RT, Simon C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril. 2016 Apr;105(4):861-6. doi: 10.1016/j.fertnstert.2016.02.030.</citation>
      <PMID>26940791</PMID>
    </reference>
    <reference>
      <citation>Nawroth F, Ludwig M. What is the 'ideal' duration of progesterone supplementation before the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement protocols? Hum Reprod. 2005 May;20(5):1127-34. doi: 10.1093/humrep/deh762. Epub 2005 Feb 3.</citation>
      <PMID>15695314</PMID>
    </reference>
    <reference>
      <citation>van de Vijver A, Drakopoulos P, Polyzos NP, Van Landuyt L, Mackens S, Santos-Ribeiro S, Vloeberghs V, Tournaye H, Blockeel C. Vitrified-warmed blastocyst transfer on the 5th or 7th day of progesterone supplementation in an artificial cycle: a randomised controlled trial. Gynecol Endocrinol. 2017 Oct;33(10):783-786. doi: 10.1080/09513590.2017.1318376. Epub 2017 Apr 26.</citation>
      <PMID>28443690</PMID>
    </reference>
    <reference>
      <citation>Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017 Sep;108(3):393-406. doi: 10.1016/j.fertnstert.2017.06.005. Epub 2017 Jul 29.</citation>
      <PMID>28760517</PMID>
    </reference>
    <reference>
      <citation>Roelens C, Santos-Ribeiro S, Becu L, Mackens S, Van Landuyt L, Racca A, De Vos M, van de Vijver A, Tournaye H, Blockeel C. Frozen-warmed blastocyst transfer after 6 or 7 days of progesterone administration: impact on live birth rate in hormone replacement therapy cycles. Fertil Steril. 2020 Jul;114(1):125-132. doi: 10.1016/j.fertnstert.2020.03.017. Epub 2020 Jun 16.</citation>
      <PMID>32553469</PMID>
    </reference>
    <reference>
      <citation>Bourdon M, Pocate-Cheriet K, Finet de Bantel A, Grzegorczyk-Martin V, Amar Hoffet A, Arbo E, Poulain M, Santulli P. Day 5 versus Day 6 blastocyst transfers: a systematic review and meta-analysis of clinical outcomes. Hum Reprod. 2019 Oct 2;34(10):1948-1964. doi: 10.1093/humrep/dez163.</citation>
      <PMID>31644803</PMID>
    </reference>
    <reference>
      <citation>Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer. Fertil Steril. 2014 Jul;102(1):3-9. doi: 10.1016/j.fertnstert.2014.04.018. Epub 2014 May 17.</citation>
      <PMID>24842675</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 6, 2023</last_update_submitted>
    <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Implantation</keyword>
    <keyword>Infertility</keyword>
    <keyword>Blastocyst</keyword>
    <keyword>HRT</keyword>
    <keyword>Progesterone</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infertility</mesh_term>
      <mesh_term>Infertility, Female</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Estradiol 17 beta-cypionate</mesh_term>
      <mesh_term>Estradiol 3-benzoate</mesh_term>
      <mesh_term>Estradiol</mesh_term>
      <mesh_term>Polyestradiol phosphate</mesh_term>
      <mesh_term>Progesterone</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05980091
  org study id: 2306-ABU-013-CC
  nct id: NCT05980091
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this study is to compare the difference in clinical pregnancy, miscarriage and
        livebirth rate between day 6 euploid blastocyst transfer on the 6th and the 7th day of
        progesterone exposure in Hormonal Replacement Therapy (HRT) FET cycles. This prospective &
        randomized study will only include euploid day 6 blastocysts. This will be the first
        prospective study of euploid day 6 blastocysts thereby excluding aneuploidy as a cause of
        miscarriage and implantation failure. The point of randomization will occur on the day of
        progesterone commencement.
  Traditionally the duration of progesterone exposure before embryo transfer has been
        considered equal for day 5 and day 6 embryos but this may not be the case and warrants
        further study. The optimal preparation of the endometrium in frozen embryo transfer (FET)
        cycles is yet to be determined. Synchronization between the embryonic stage and the
        endometrial window of implantation (WOI) is crucial and progesterone plays a critical role in
        the WOI (1). Data on the optimal route of administration, the dose and duration of
        progesterone supplementation before blastocyst transfer are inconsistent (2,3). In view of
        the current lack of evidence, this study will be of importance.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Livebirth rate (LBR)
  time frame: 41 weeks
  description: Defined as the delivery of a live infant born after 24 completed weeks of gestation
  measure: Biochemical pregnancy rate
  time frame: 5 weeks
  description: Positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen but without a further development into a clinical pregnancy)
  measure: Clinical pregnancy rate
  time frame: 5 weeks
  description: Ultrasonographic sac visible at 5 gestational weeks
  measure: Ongoing pregnancy rate after 12 weeks
  time frame: 13 weeks
  description: Viable pregnancy with a gestational age of more than 12 weeks
  measure: Miscarriage rate
  time frame: 24 weeks
  description: Spontaneous loss of a clinical pregnancy before 24 completed weeks of gestation
  arm group label: Group A
  arm group type: Other
  description: Embryo transfer is scheduled on the 6th full day of progesterone administration, following the initial commencement of progesterone (120 hours)
  arm group label: Group B
  arm group type: Other
  description: Embryo Transfer is scheduled on the 7th full day of progesterone administration, following the initial commencement of progesterone (144 hours)
  intervention type: Diagnostic Test
  intervention name: Transvaginal ultrasound
  description: Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle
  arm group label: Group A
  arm group label: Group B
  intervention type: Diagnostic Test
  intervention name: Serum LH, E2, P4
  description: In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels
  arm group label: Group A
  arm group label: Group B
  intervention type: Drug
  intervention name: Estradiol Valerate 2 MG
  description: Participants will commence estradiol valerate 4 mg ( 2 x 2 mg) on day 2 / day 3 of menses.
  Estradiol will be increased to 6 mg on day 2 of estrogen treatment, and continued at a daily dose of 6 mg (3 tablets daily)
  arm group label: Group A
  arm group label: Group B
  other name: Estradiol Valerate
  intervention type: Drug
  intervention name: Progesterone 100 Mg Vaginal Insert
  description: The initial progesterone dose of 100 mg will be commenced at 13hrs and repeated at 21hrs considered day 1 (vaginal suppository) when an optimal endometrial thickness for each participant has been achieved with a trilaminar appearance. The following day (day 2) progesterone administration will be increased to 100 mg vaginally three times daily
  arm group label: Group A
  arm group label: Group B
  other name: Progesterone 100 mg
  intervention type: Diagnostic Test
  intervention name: Serum P4 day of ET
  description: On the day of embryo transfer (ET), a blood test is taken to measure serum P4
  arm group label: Group A
  arm group label: Group B
  intervention type: Procedure
  intervention name: Embryo transfer
  description: Procedure in which embryo is transferred into the uterus
  arm group label: Group A
  arm group label: Group B
  other name: ET
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: 43 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Carol Coughlan, PhD
  role: Principal Investigator
  affiliation: ART Fertility Clinics LLC
  last name: Barbara Lawrenz, PhD
  phone: +971 800 337845489
  email: barbara.lawrenz@artfertilityclinics.com
  last name: Jonalyn Edades, RN
  phone: +971 800 337845489
  email: jonalyn.edades@artfertilityclinics.com
  facility: 
  contact: 
  facility: 
  contact: 
  country: United Arab Emirates
  citation: Franasiak JM, Ruiz-Alonso M, Scott RT, Simon C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril. 2016 Apr;105(4):861-6. doi: 10.1016/j.fertnstert.2016.02.030.
  PMID: 26940791
  citation: Nawroth F, Ludwig M. What is the 'ideal' duration of progesterone supplementation before the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement protocols? Hum Reprod. 2005 May;20(5):1127-34. doi: 10.1093/humrep/deh762. Epub 2005 Feb 3.
  PMID: 15695314
  citation: van de Vijver A, Drakopoulos P, Polyzos NP, Van Landuyt L, Mackens S, Santos-Ribeiro S, Vloeberghs V, Tournaye H, Blockeel C. Vitrified-warmed blastocyst transfer on the 5th or 7th day of progesterone supplementation in an artificial cycle: a randomised controlled trial. Gynecol Endocrinol. 2017 Oct;33(10):783-786. doi: 10.1080/09513590.2017.1318376. Epub 2017 Apr 26.
  PMID: 28443690
  citation: Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017 Sep;108(3):393-406. doi: 10.1016/j.fertnstert.2017.06.005. Epub 2017 Jul 29.
  PMID: 28760517
  citation: Roelens C, Santos-Ribeiro S, Becu L, Mackens S, Van Landuyt L, Racca A, De Vos M, van de Vijver A, Tournaye H, Blockeel C. Frozen-warmed blastocyst transfer after 6 or 7 days of progesterone administration: impact on live birth rate in hormone replacement therapy cycles. Fertil Steril. 2020 Jul;114(1):125-132. doi: 10.1016/j.fertnstert.2020.03.017. Epub 2020 Jun 16.
  PMID: 32553469
  citation: Bourdon M, Pocate-Cheriet K, Finet de Bantel A, Grzegorczyk-Martin V, Amar Hoffet A, Arbo E, Poulain M, Santulli P. Day 5 versus Day 6 blastocyst transfers: a systematic review and meta-analysis of clinical outcomes. Hum Reprod. 2019 Oct 2;34(10):1948-1964. doi: 10.1093/humrep/dez163.
  PMID: 31644803
  citation: Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer. Fertil Steril. 2014 Jul;102(1):3-9. doi: 10.1016/j.fertnstert.2014.04.018. Epub 2014 May 17.
  PMID: 24842675
  responsible party type: Sponsor
  mesh term: Infertility
  mesh term: Infertility, Female
  mesh term: Estradiol 17 beta-cypionate
  mesh term: Estradiol 3-benzoate
  mesh term: Estradiol
  mesh term: Polyestradiol phosphate
  mesh term: Progesterone