<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/NCT04503915</url>
  </required_header>
  <id_info>
    <org_study_id>HRT-E2</org_study_id>
    <nct_id>NCT04503915</nct_id>
  </id_info>
  <brief_title>Estrogen Supplementation Mode in HRT-FET Cycle: a RCT</brief_title>
  <official_title>A Multicenter Randomized Controlled Trial Comparing a Step-wise Increase Versus a Constant Dose of Estrogen Supplementation in Frozen-thawed Embryo Transfer Cycles Using Hormone Replacement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</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>
      A systematic review and meta-analysis concluded that there is insufficient evidence to&#xD;
      recommend one particular protocol for HRT with regard to pregnancy rates after frozen embryo&#xD;
      transfer, and no comparison of estrogen dose or route of administration was included in the&#xD;
      review[7]. It is worth highlighting that the authors did not find any literature discussing&#xD;
      the effect of estrogen dose and route of administration for HRT on reproductive outcomes. In&#xD;
      2016, a retrospective cohort study concluded that there is no difference in live birth rates&#xD;
      between a constant dose versus an increasing dose of estrogen in oocyte donation cycles with&#xD;
      oral or transdermal supplementation[6]. In order to provide good evidence about pattern of&#xD;
      estrogen supplementation in HRT-FET, a randomized controlled study is urgently needed.&#xD;
&#xD;
      The present randomized controlled study aims to compare between a constant estrogen dose&#xD;
      protocol and a step-wise increasing estrogen dose protocol on the live birth rate of HRT-FET&#xD;
      cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective is to compare between a constant estrogen dose protocol and a step-wise&#xD;
      increasing estrogen dose protocol on live birth rate of HRT-FET cycles.&#xD;
&#xD;
      This is a multicenter randomized controlled trial. Women undergoing HRT-FET will be recruited&#xD;
      and randomized to use a constant estrogen dose protocol and a step-wise increasing estrogen&#xD;
      dose protocol.&#xD;
&#xD;
      Participation in the study is totally voluntary. The subjects can withdraw from the study at&#xD;
      any time and they will still receive standard medical care.&#xD;
&#xD;
      Women being scheduled for HRT-FET will be assessed for eligibility. Eligible women will be&#xD;
      recruited in the study and each woman will only be included in the study once.&#xD;
&#xD;
      Informed written consent will be obtained prior to recruitment. The baseline characteristics&#xD;
      will be collected. Transvaginal ultrasound will be done to measure the endometrial thickness&#xD;
      on the day of progesterone supplementation. Embryo transfer will be performed 3 days or 5&#xD;
      days after progesterone use, depending on replacement of cleaving stage embryos or&#xD;
      blastocysts respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">November 1, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2022</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>live-birth rate per ET</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Live birth was defined as the delivery of at least one live born baby beyond 28 weeks of gestation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>clinical pregnancy rate</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>- clinical pregnancy: presence of intrauterine gestational sac on pelvic ultrasound at 6 weeks of gestation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">784</enrollment>
  <condition>Hormone Replacement Therapy</condition>
  <condition>Estrogen</condition>
  <condition>Live Birth Rate</condition>
  <arm_group>
    <arm_group_label>Constant group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women will receive oral estradiol valerate (Progynova®; Bayer Schering Pharma AG, Berlin, Germany) 3 mg bid for 14 days for endometrial priming from the second or third day of the menstrual cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Step -up group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women will receive estradiol valerate 2mg once daily for 4 days from the second to fifth day,followed by 2mg bid for 4 days from the sixth to ninth day and then 3mg bid for 6 days from tenth to fifteenth day of menstrual cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>different estrogen supplementation modes</intervention_name>
    <description>The different estrogen supplementation modes are randomized into two groups.</description>
    <arm_group_label>Constant group</arm_group_label>
    <arm_group_label>Step -up group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women aged &lt;42 years at the time of HRT-FET&#xD;
&#xD;
          -  Replacing 1-2 early cleavage embryos or blastocysts after thawing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preimplantation genetic testing(PGT)&#xD;
&#xD;
          -  Use of donor oocytes&#xD;
&#xD;
          -  Hydrosalpinx shown on pelvic scanning and not surgically treated such as tubal&#xD;
             ligation or resection&#xD;
&#xD;
          -  Severe uterine adhesion&#xD;
&#xD;
          -  The endometrial thickness cannot reach 8mm in previous fresh cycles or HRT -FET cycles&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>42 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yi Zhang</last_name>
    <role>Study Chair</role>
    <affiliation>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Haiyan Lin</last_name>
    <phone>15913154456</phone>
    <email>709235159@qq.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Qingxue Zhang</last_name>
    <phone>81332233</phone>
    <phone_ext>13602797433</phone_ext>
    <email>zhangqingxue666@aliyun.com</email>
  </overall_contact_backup>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Haiyan Lin</investigator_full_name>
    <investigator_title>Attending physician</investigator_title>
  </responsible_party>
  <keyword>estrogen supplementation</keyword>
  <keyword>HRT</keyword>
  <keyword>Live birth rate</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estrogens</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Until the completion of the study.</ipd_description>
  </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/NCT04503915
org study id: HRT-E2
nct id: NCT04503915
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A systematic review and meta-analysis concluded that there is insufficient evidence to
      recommend one particular protocol for HRT with regard to pregnancy rates after frozen embryo
      transfer, and no comparison of estrogen dose or route of administration was included in the
      review[7]. It is worth highlighting that the authors did not find any literature discussing
      the effect of estrogen dose and route of administration for HRT on reproductive outcomes. In
      2016, a retrospective cohort study concluded that there is no difference in live birth rates
      between a constant dose versus an increasing dose of estrogen in oocyte donation cycles with
      oral or transdermal supplementation[6]. In order to provide good evidence about pattern of
      estrogen supplementation in HRT-FET, a randomized controlled study is urgently needed.

      The present randomized controlled study aims to compare between a constant estrogen dose
      protocol and a step-wise increasing estrogen dose protocol on the live birth rate of HRT-FET
      cycles.
The objective is to compare between a constant estrogen dose protocol and a step-wise
      increasing estrogen dose protocol on live birth rate of HRT-FET cycles.

      This is a multicenter randomized controlled trial. Women undergoing HRT-FET will be recruited
      and randomized to use a constant estrogen dose protocol and a step-wise increasing estrogen
      dose protocol.

      Participation in the study is totally voluntary. The subjects can withdraw from the study at
      any time and they will still receive standard medical care.

      Women being scheduled for HRT-FET will be assessed for eligibility. Eligible women will be
      recruited in the study and each woman will only be included in the study once.

      Informed written consent will be obtained prior to recruitment. The baseline characteristics
      will be collected. Transvaginal ultrasound will be done to measure the endometrial thickness
      on the day of progesterone supplementation. Embryo transfer will be performed 3 days or 5
      days after progesterone use, depending on replacement of cleaving stage embryos or
      blastocysts respectively.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: live-birth rate per ET
time frame: Up to 12 months
description: Live birth was defined as the delivery of at least one live born baby beyond 28 weeks of gestation.
measure: clinical pregnancy rate
time frame: Up to 6 months
description: - clinical pregnancy: presence of intrauterine gestational sac on pelvic ultrasound at 6 weeks of gestation
arm group label: Constant group
arm group type: Experimental
description: Women will receive oral estradiol valerate (Progynova®; Bayer Schering Pharma AG, Berlin, Germany) 3 mg bid for 14 days for endometrial priming from the second or third day of the menstrual cycle.
arm group label: Step -up group
arm group type: Active Comparator
description: Women will receive estradiol valerate 2mg once daily for 4 days from the second to fifth day,followed by 2mg bid for 4 days from the sixth to ninth day and then 3mg bid for 6 days from tenth to fifteenth day of menstrual cycle.
intervention type: Procedure
intervention name: different estrogen supplementation modes
description: The different estrogen supplementation modes are randomized into two groups.
arm group label: Constant group
arm group label: Step -up group
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 42 Years
healthy volunteers: No
last name: Yi Zhang
role: Study Chair
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
last name: Haiyan Lin
phone: 15913154456
email: 709235159@qq.com
last name: Qingxue Zhang
phone: 81332233
phone ext: 13602797433
email: zhangqingxue666@aliyun.com
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
investigator full name: Haiyan Lin
investigator title: Attending physician
mesh term: Estrogens
sharing ipd: No
ipd description: Until the completion of the study.