<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/NCT03787901</url>
  </required_header>
  <id_info>
    <org_study_id>EFRE Vitrification Trial</org_study_id>
    <nct_id>NCT03787901</nct_id>
  </id_info>
  <brief_title>Comparing the Ongoing Pregnancy Rate for Vitrification of Day-4 Morula With Day-5 Blast</brief_title>
  <official_title>The Ongoing Pregnancy Rate for Vitrification of Day-4 Morula and Day-5 Blastocyst</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Egyptian Foundation of Reproductive Endocrinology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Al Hayat ICSI Centre of Alexandria, Egypt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Agial IVF/ICSI Unit of Alexandria, Egypt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Al Madina Fertility centre of Alexandria, Egypt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rahem Fertility Center of Zagazig, Egypt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Egyptian Foundation of Reproductive Endocrinology</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>
      Comparing the vitrification at Day-4 (morula stage) with the blastocyst stage vitrification&#xD;
      outcomes with the transfer of all day 5 after warming seems need evaluation. To the best of&#xD;
      our knowledge, there has been no random-controlled trial conducted such comparison.&#xD;
      Altogether, this trial is to evaluate the morula stage vitrification to blastocyst&#xD;
      vitrification on the ongoing pregnancy rate after ICSI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitrification of human embryos has been a paradigm-shifting procedure for higher survival&#xD;
      rate compared with the slow freezing protocol. The evidence is scarce to support superior&#xD;
      results for vitrifying certain stages of preimplantation embryos. Anecdotal evidence suggests&#xD;
      that blastocyst vitrification is more forgiving than cleavage stages. However, data obtained&#xD;
      from the procedure of assisted shrinkage of blastocysts before vitrification show a higher&#xD;
      survival rate, suggesting that fluid accumulation insides the blastocyst can be a barrier for&#xD;
      cryoprotectant to reach the cells. Although reassuring, whether facilitating the&#xD;
      cryoprotectants transfer to cells by the laser-assisted shrinkage or other modalities is&#xD;
      completely safe remains elusive. Moreover, other claims compare between day-3 embryos&#xD;
      vitrification and blastocyst stage, suggesting no difference exists.&#xD;
&#xD;
      One of the most critical stages in embryo development is the maternal to zygotic genome&#xD;
      activation (MZA), which occurs at the 4 to 8 cell stages. Therefore, it seems the morula&#xD;
      stage is still cleavage but passed the MZA. Morula in the most grading system has compaction&#xD;
      for all or the majority of cells so if vitrified, the morula stage can bypass the earlier&#xD;
      stage of vitrification as well as the need for the artificial shrinkage for blastocyst stage.&#xD;
      Therefore, comparing the vitrification at Day-4 (morula stage) with the blastocyst stage&#xD;
      vitrification outcomes with the transfer of all day 5 after warming seems need evaluation. To&#xD;
      the best of our knowledge, there has been no random-controlled trial conducted such&#xD;
      comparison. Altogether, this trial is to evaluate the morula stage vitrification to&#xD;
      blastocyst vitrification on the ongoing pregnancy rate after ICSI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Failed to achieve sample size due to COVID19 pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">May 31, 2020</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>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The ongoing pregnancy rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Continued pregnancy at &gt; gestational week 12 or more per initiated cycle</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biochemical pregnancy rate</measure>
    <time_frame>14 days</time_frame>
    <description>positive b-hCG at ≥ 14 days following embryo transfer per initiated cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Sacs with a heartbeat on ultrasound per embryo transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative implantation rate</measure>
    <time_frame>One year</time_frame>
    <description>Sacs with a heartbeat on ultrasound per embryo transferred within one year from randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rate</measure>
    <time_frame>7 weeks</time_frame>
    <description>Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative clinical pregnancy rate</measure>
    <time_frame>One year</time_frame>
    <description>Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle within one year from randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative ongoing pregnancy rate</measure>
    <time_frame>One year</time_frame>
    <description>continued pregnancy after gestational week 12 per initiated cycle within one year from randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Twin pregnancy rate</measure>
    <time_frame>One year</time_frame>
    <description>≥ two foetuses with a heartbeat per initiated cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Embryo survival rate after thawing</measure>
    <time_frame>Five days of culture</time_frame>
    <description>Blastocyst re-expansion for day 5 vitrified embryo after two hours and blastocyst formation on day 5 for embryo vitrified on day 4</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Morula Vitrification Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Blastocyst Vitrification Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Morula Vitrification</intervention_name>
    <description>Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.</description>
    <arm_group_label>Blastocyst Vitrification Arm</arm_group_label>
    <arm_group_label>Morula Vitrification Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women age of ≥ 18 to ≤ 40&#xD;
&#xD;
          2. BMI of ≤ 31&#xD;
&#xD;
          3. Normal responder (≥ 12 antral follicle count (AFC) during basal ultrasound&#xD;
             examination) or hyper responder&#xD;
&#xD;
          4. The freeze-all groups including PCOS, OHSS, or high Progesterone at trigger day&#xD;
&#xD;
          5. Women who have ≥ 1 year of primary or secondary infertility&#xD;
&#xD;
          6. Tubal factor (unilateral, bilateral obstruction or salpingectomy)&#xD;
&#xD;
          7. Fresh semen ejaculates but not frozen or surgically retrieved sperm&#xD;
&#xD;
          8. Male factor: oligoasthenozoospermia but not globozoospermia or pinhead sperm&#xD;
&#xD;
          9. Women who are undergoing their first or second ICSI attempts with a previously&#xD;
             successful attempt&#xD;
&#xD;
         10. Women who undergo only freeze-all embryo&#xD;
&#xD;
         11. Freeze-all for poor endometrium at the fresh cycle&#xD;
&#xD;
         12. Freeze-all due to abnormal endometrial findings such as polyp or myoma with a decision&#xD;
             for freeze all for surgical correction.&#xD;
&#xD;
         13. Women who have normal endometrial thickness (≥ 8) and echo-pattern at the time of&#xD;
             progesterone start in the proposed vitrified warmed cycle&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who have uncorrectable uterine pathology or abnormality including submucous&#xD;
             myoma&#xD;
&#xD;
          2. Women or their husbands who have abnormal karyotyping&#xD;
&#xD;
          3. Women with a history of recurrent abortions or repeated implantation failures&#xD;
&#xD;
          4. Women who have uncontrolled diabetes&#xD;
&#xD;
          5. Women with diagnosed or undiagnosed liver or renal disease&#xD;
&#xD;
          6. Women who had a history of malignancy or borderline pathology&#xD;
&#xD;
          7. Women who will not meet the inclusion criteria&#xD;
&#xD;
          8. Women who will refuse to participate in the study&#xD;
&#xD;
          9. Women with endometriosis&#xD;
&#xD;
         10. Patient undergoing PGS or PGD&#xD;
&#xD;
         11. Surgically retrieved, frozen-thawed and pinpoint sperm or globozoospermia&#xD;
&#xD;
         12. Adenomyosis&#xD;
&#xD;
         13. Severe medical condition&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Agial</name>
      <address>
        <city>Alexandria</city>
        <zip>12345</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Al Hayat ICSI Centre of Alexandria</name>
      <address>
        <city>Alexandria</city>
        <zip>12345</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AlMadina IVF and ICSI Centre</name>
      <address>
        <city>Alexandria</city>
        <zip>12345</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rahem Fertility Centre of Zagazig</name>
      <address>
        <city>Zagazig</city>
        <zip>12345</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>June 10, 2022</last_update_submitted>
  <last_update_submitted_qc>June 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Egyptian Foundation of Reproductive Endocrinology</investigator_affiliation>
    <investigator_full_name>Hassan Maghraby</investigator_full_name>
    <investigator_title>MD, Director, Al Hayat ICSI Centre of Alexandria, Egypt</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03787901
org study id: EFRE Vitrification Trial
nct id: NCT03787901
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Comparing the vitrification at Day-4 (morula stage) with the blastocyst stage vitrification
      outcomes with the transfer of all day 5 after warming seems need evaluation. To the best of
      our knowledge, there has been no random-controlled trial conducted such comparison.
      Altogether, this trial is to evaluate the morula stage vitrification to blastocyst
      vitrification on the ongoing pregnancy rate after ICSI.
Vitrification of human embryos has been a paradigm-shifting procedure for higher survival
      rate compared with the slow freezing protocol. The evidence is scarce to support superior
      results for vitrifying certain stages of preimplantation embryos. Anecdotal evidence suggests
      that blastocyst vitrification is more forgiving than cleavage stages. However, data obtained
      from the procedure of assisted shrinkage of blastocysts before vitrification show a higher
      survival rate, suggesting that fluid accumulation insides the blastocyst can be a barrier for
      cryoprotectant to reach the cells. Although reassuring, whether facilitating the
      cryoprotectants transfer to cells by the laser-assisted shrinkage or other modalities is
      completely safe remains elusive. Moreover, other claims compare between day-3 embryos
      vitrification and blastocyst stage, suggesting no difference exists.

      One of the most critical stages in embryo development is the maternal to zygotic genome
      activation (MZA), which occurs at the 4 to 8 cell stages. Therefore, it seems the morula
      stage is still cleavage but passed the MZA. Morula in the most grading system has compaction
      for all or the majority of cells so if vitrified, the morula stage can bypass the earlier
      stage of vitrification as well as the need for the artificial shrinkage for blastocyst stage.
      Therefore, comparing the vitrification at Day-4 (morula stage) with the blastocyst stage
      vitrification outcomes with the transfer of all day 5 after warming seems need evaluation. To
      the best of our knowledge, there has been no random-controlled trial conducted such
      comparison. Altogether, this trial is to evaluate the morula stage vitrification to
      blastocyst vitrification on the ongoing pregnancy rate after ICSI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: The ongoing pregnancy rate
time frame: 12 weeks
description: Continued pregnancy at > gestational week 12 or more per initiated cycle
measure: Biochemical pregnancy rate
time frame: 14 days
description: positive b-hCG at ≥ 14 days following embryo transfer per initiated cycle
measure: Implantation rate
time frame: 12 weeks
description: Sacs with a heartbeat on ultrasound per embryo transferred
measure: Cumulative implantation rate
time frame: One year
description: Sacs with a heartbeat on ultrasound per embryo transferred within one year from randomization
measure: Clinical pregnancy rate
time frame: 7 weeks
description: Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle
measure: Cumulative clinical pregnancy rate
time frame: One year
description: Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle within one year from randomization
measure: Cumulative ongoing pregnancy rate
time frame: One year
description: continued pregnancy after gestational week 12 per initiated cycle within one year from randomization
measure: Twin pregnancy rate
time frame: One year
description: ≥ two foetuses with a heartbeat per initiated cycle
measure: Embryo survival rate after thawing
time frame: Five days of culture
description: Blastocyst re-expansion for day 5 vitrified embryo after two hours and blastocyst formation on day 5 for embryo vitrified on day 4
arm group label: Morula Vitrification Arm
arm group type: Experimental
arm group label: Blastocyst Vitrification Arm
arm group type: Active Comparator
intervention type: Other
intervention name: Morula Vitrification
description: Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.
arm group label: Blastocyst Vitrification Arm
arm group label: Morula Vitrification Arm
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Egyptian Foundation of Reproductive Endocrinology
investigator full name: Hassan Maghraby
investigator title: MD, Director, Al Hayat ICSI Centre of Alexandria, Egypt
mesh term: Infertility
sharing ipd: No