<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/NCT02251925</url>
  </required_header>
  <id_info>
    <org_study_id>Royan-Emb-019</org_study_id>
    <nct_id>NCT02251925</nct_id>
  </id_info>
  <brief_title>Frozen Embryo Transfer in Natural and Hormonal Replacement Cycles</brief_title>
  <official_title>Comparison of Pregnancy Outcomes in Frozen Embryo Transfer in Natural and Hormonal Replacement Cycles: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royan Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royan Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a prospective randomized controlled trial to compare the pregnancy outcomes of&#xD;
      frozen embryo transfer in natural and hormonal replacement cycles. The study population&#xD;
      consisted of all infertile women with regular menstrual cycles who will undergo IVF/ICSI and&#xD;
      frozen embryo transfer in Reproductive Biomedicine Research Center, Royan institute, Tehran&#xD;
      Iran.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study all patients who will undergo frozen embryo transfer are randomly allocated to&#xD;
      be prepared for transfer by using either natural cycle (with or without hCG for ovulation&#xD;
      induction) or Hormonal cycle (with or without administration of GnRH-a) In natural cycle&#xD;
      without hCG, daily monitoring of urinary LH is started from day eight of the cycle and&#xD;
      frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing&#xD;
      mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos.&#xD;
&#xD;
      In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial&#xD;
      thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed&#xD;
      3-5 days later in cleavage stage.&#xD;
&#xD;
      In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is&#xD;
      started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is&#xD;
      confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7&#xD;
      days if endometrial thickness is adequate, Estradiol administration will be continued with&#xD;
      the same dose and 100mg Progesterone is administered before embryo transfer, otherwise&#xD;
      patients are candidates for higher dosage of Estradiol till favourable endometrial thickness&#xD;
      is achieved.&#xD;
&#xD;
      In the hormonal group without GnRH-a, endometrial preparation will be started with daily&#xD;
      administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for&#xD;
      6 days. Then treatment will be continued similar to the 3rd group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">November 2015</completion_date>
  <primary_completion_date type="Anticipated">October 2015</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>Clinical pregnancy rate</measure>
    <time_frame>4 weeks</time_frame>
    <description>The pregnancy rate will be evaluated in patients of each groups 4-6 weeks after embryo transfer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>4 weeks</time_frame>
    <description>Evaluation the implantation rate in patients of each groups 4-6 weeks after frozen embryo transfer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>chemical pregnancy rates</measure>
    <time_frame>2 weeks</time_frame>
    <description>Evaluation the chemical pregnancy rates in patients of each group 2 weeks after embryo transfer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy</measure>
    <time_frame>12 weeks</time_frame>
    <description>Evaluation the ongoing pregnancy in patients of each group 12 weeks after embryo transfer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>miscarriage rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Evaluation the miscarriage rate in patients of each group 12 weeks after embryo transfer.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">460</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Natural cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In natural cycle without hCG, daily monitoring of urinary LH is started from day eight of the cycle and frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Natural cycle + hCG for ovulation induction</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hormonally controlled cycle with GnRH-a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this group , injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hormonally controlled cycle without GnRH-a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>frozen Embryo transfer</intervention_name>
    <description>In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).</description>
    <arm_group_label>Hormonally controlled cycle with GnRH-a</arm_group_label>
    <arm_group_label>Hormonally controlled cycle without GnRH-a</arm_group_label>
    <arm_group_label>Natural cycle</arm_group_label>
    <arm_group_label>Natural cycle + hCG for ovulation induction</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>10,000U hCG injection</intervention_name>
    <description>In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.</description>
    <arm_group_label>Natural cycle + hCG for ovulation induction</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GnRH agonist (Superfact)</intervention_name>
    <description>In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.</description>
    <arm_group_label>Hormonally controlled cycle with GnRH-a</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>administration of 6 mg Estradiol valerate</intervention_name>
    <description>In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.</description>
    <arm_group_label>Hormonally controlled cycle without GnRH-a</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with regular mensturation cycles&#xD;
&#xD;
          2. Age 20-37 years&#xD;
&#xD;
          3. Patients who underwent long protocol&#xD;
&#xD;
          4. Body mass index (BMI) ≤ 30 kg/m2&#xD;
&#xD;
          5. Patients who will undergo frozen embryo transfer for the first time&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Oocyte or embryo donation cycles&#xD;
&#xD;
          2. Uterine diseases or malformations&#xD;
&#xD;
          3. Hyper prolactinemia&#xD;
&#xD;
          4. Thyroid disorders&#xD;
&#xD;
          5. Tuberculosis&#xD;
&#xD;
          6. Recurrent abortion history&#xD;
&#xD;
          7. Severe endometriosis&#xD;
&#xD;
          8. Ovulation disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>37 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hamid Gourabi, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Head of Royan Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tahereh Madani, MD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ladan Mohammadi Yeganeh, MSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nasser Aghdami, MD,PhD</last_name>
    <phone>(+98)23562000</phone>
    <phone_ext>516</phone_ext>
    <email>nasser.aghdami@royaninstitute.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Leila Arab, MD</last_name>
    <phone>(+98)23562000</phone>
    <phone_ext>414</phone_ext>
    <email>Leara91@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royan Institute</name>
      <address>
        <city>Tehran</city>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nasser Aghdami, MD,PhD</last_name>
      <phone>(+98)212356000</phone>
      <phone_ext>516</phone_ext>
      <email>nasser.aghdami@royaninstitute.org</email>
    </contact>
    <contact_backup>
      <last_name>Leila Arab, MD</last_name>
      <phone>(+98)23562000</phone>
      <phone_ext>414</phone_ext>
      <email>Leara91@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Tahere Madani, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ladan Mohammadi Yegane, MSC</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Fariba Ramezani, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mahnaz Rashidi, BSC</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Narges Bagheri Lankarani, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Fatemeh Hassani, MSC</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <link>
    <url>http://Royaninstitute.org</url>
    <description>Related Info</description>
  </link>
  <verification_date>April 2012</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>May 5, 2015</last_update_submitted>
  <last_update_submitted_qc>May 5, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 6, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>infertility froze emberyo transfer hormone replacement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</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>
  </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/NCT02251925
org study id: Royan-Emb-019
nct id: NCT02251925
lead sponsor: 
has dmc: Yes
This study is a prospective randomized controlled trial to compare the pregnancy outcomes of
      frozen embryo transfer in natural and hormonal replacement cycles. The study population
      consisted of all infertile women with regular menstrual cycles who will undergo IVF/ICSI and
      frozen embryo transfer in Reproductive Biomedicine Research Center, Royan institute, Tehran
      Iran.
In this study all patients who will undergo frozen embryo transfer are randomly allocated to
      be prepared for transfer by using either natural cycle (with or without hCG for ovulation
      induction) or Hormonal cycle (with or without administration of GnRH-a) In natural cycle
      without hCG, daily monitoring of urinary LH is started from day eight of the cycle and
      frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing
      mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos.

      In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial
      thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed
      3-5 days later in cleavage stage.

      In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is
      started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is
      confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7
      days if endometrial thickness is adequate, Estradiol administration will be continued with
      the same dose and 100mg Progesterone is administered before embryo transfer, otherwise
      patients are candidates for higher dosage of Estradiol till favourable endometrial thickness
      is achieved.

      In the hormonal group without GnRH-a, endometrial preparation will be started with daily
      administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for
      6 days. Then treatment will be continued similar to the 3rd group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical pregnancy rate
time frame: 4 weeks
description: The pregnancy rate will be evaluated in patients of each groups 4-6 weeks after embryo transfer.
measure: Implantation rate
time frame: 4 weeks
description: Evaluation the implantation rate in patients of each groups 4-6 weeks after frozen embryo transfer
measure: chemical pregnancy rates
time frame: 2 weeks
description: Evaluation the chemical pregnancy rates in patients of each group 2 weeks after embryo transfer.
measure: Ongoing pregnancy
time frame: 12 weeks
description: Evaluation the ongoing pregnancy in patients of each group 12 weeks after embryo transfer.
measure: miscarriage rate
time frame: 12 weeks
description: Evaluation the miscarriage rate in patients of each group 12 weeks after embryo transfer.
arm group label: Natural cycle
arm group type: Experimental
description: In natural cycle without hCG, daily monitoring of urinary LH is started from day eight of the cycle and frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos.
arm group label: Natural cycle + hCG for ovulation induction
arm group type: Experimental
description: In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.
arm group label: Hormonally controlled cycle with GnRH-a
arm group type: Experimental
description: In this group , injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.
arm group label: Hormonally controlled cycle without GnRH-a
arm group type: Experimental
description: In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.
intervention type: Biological
intervention name: frozen Embryo transfer
description: In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).
arm group label: Hormonally controlled cycle with GnRH-a
arm group label: Hormonally controlled cycle without GnRH-a
arm group label: Natural cycle
arm group label: Natural cycle + hCG for ovulation induction
intervention type: Drug
intervention name: 10,000U hCG injection
description: In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.
arm group label: Natural cycle + hCG for ovulation induction
intervention type: Drug
intervention name: GnRH agonist (Superfact)
description: In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.
arm group label: Hormonally controlled cycle with GnRH-a
intervention type: Drug
intervention name: administration of 6 mg Estradiol valerate
description: In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.
arm group label: Hormonally controlled cycle without GnRH-a
criteria: 
gender: All
minimum age: 20 Years
maximum age: 37 Years
healthy volunteers: No
last name: Hamid Gourabi, PhD
role: Study Chair
affiliation: Head of Royan Institute
last name: Tahereh Madani, MD
role: Study Director
affiliation: Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
last name: Ladan Mohammadi Yeganeh, MSC
role: Principal Investigator
affiliation: Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
last name: Nasser Aghdami, MD,PhD
phone: (+98)23562000
phone ext: 516
email: nasser.aghdami@royaninstitute.org
last name: Leila Arab, MD
phone: (+98)23562000
phone ext: 414
email: Leara91@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Iran, Islamic Republic of
url: http://Royaninstitute.org
description: Related Info
responsible party type: Sponsor
mesh term: Infertility
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Estradiol
mesh term: Polyestradiol phosphate