<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/NCT03817671</url>
  </required_header>
  <id_info>
    <org_study_id>GFCST11991</org_study_id>
    <nct_id>NCT03817671</nct_id>
  </id_info>
  <brief_title>The Clinical Outcome of Ultra-low Oxygen Tension on Post Thawed Human Blastocyst</brief_title>
  <official_title>The Clinical Outcome of Ultra-low Oxygen Tension on Post Thawed Human Blastocyst</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ganin Fertility Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ganin Fertility Center</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>
      The clinical outcome of Ultra-low oxygen tension on post thawed human blastocyst&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In vitro, Embryo development depends on several factors as temperature, pH, and oxygen in the&#xD;
      surrounding environment of the embryo. Impaired culture conditions are highly correlated with&#xD;
      poor embryo development. Oxygen is a powerful regulator of embryo function , as it is&#xD;
      responsible for cell respiration, energy production and rapid cell growth . Increased levels&#xD;
      of oxygen is associated with an increase in the levels of ROS , which leads to unfavorable&#xD;
      culture conditions, as it might affect the stability of cell membrane, DNA, and protein&#xD;
      function .&#xD;
&#xD;
      In the female reproductive tract, oxygen concentration fluctuates between 2-8%, which is&#xD;
      considered to be at its highest level in the fallopian tube, while the lowest level is in the&#xD;
      uterus . Pre-implantation embryo crosses the uterotubal junction after the time of compaction&#xD;
      on Day 3, where it is exposed to a shift in oxygen tension to 2%. This variation may have a&#xD;
      role in the metabolic reactions of the embryo, and in its preparation for implantation&#xD;
      process.&#xD;
&#xD;
      Some studies suggested that culturing embryos with oxygen tension below 5% may have an&#xD;
      embryological advantage mimicking nature.&#xD;
&#xD;
      Embryological laboratories routinely use low Oxygen tension (5%). Our purpose is to&#xD;
      investigate if ultra-low oxygen tension (2%) has an advantage over low oxygen tension (5%)&#xD;
      for post thawed human embryo regarding clinical outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 20, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">June 30, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Pregnancy rate</measure>
    <time_frame>Time frame: 15 days following embryo transfer</time_frame>
    <description>Defined as the pregnancy that is confirmed by both high levels of hCG and ultrasound confirmation of a gestational sac or heartbeat</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate</measure>
    <time_frame>Time frame: 20 weeks of gestation</time_frame>
    <description>Defined as the proportion of pregnancies that had completed ≥20 weeks of gestation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">168</enrollment>
  <condition>Embryo Development</condition>
  <arm_group>
    <arm_group_label>Control arm (5% O2)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>After thawing, embryos will be cultured in 25 μl drop of pre-equilibrated dishes of media covered with a layer of oil for 1.5 hours at 5.7% CO2, 5% O2, and 89.3% N2 till embryo transfer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental arm (2%O2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After thawing, embryos will be cultured in 25 μl drop of pre-equilibrated dishes of media covered with a layer of oil for 1.5 hours at 5.7% CO2, 2% O2, and 92.3% N2 till embryo transfer</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>5% O2</intervention_name>
    <description>Culturing embryos in 5% O2 just after thawing and till embryo transfer</description>
    <arm_group_label>Control arm (5% O2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>2% O2</intervention_name>
    <description>Culturing embryos in 2% O2 just after thawing and till embryo transfer</description>
    <arm_group_label>Experimental arm (2%O2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Single or Multiple Embryo transfer embryo transfer. Female age 18-40. Embryo vitrified on&#xD;
        day 5 or day 6 of insemination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Use of sperm donation. Use of Oocyte donation. Use of gestational carrier. Uterine&#xD;
        congenital anomalies. Presence of any of the endometrial factors that affect embryo&#xD;
        implantation such as hydrosalpings, adenomyosis or previously known uterine infection.&#xD;
&#xD;
        Any contradictions to undergoing in vitro fertilization or gonadotropin stimulation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Days</minimum_age>
    <maximum_age>6 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hosam Zaki, MSc, FRCOG</last_name>
    <role>Study Chair</role>
    <affiliation>Ganin Fertility Center, Cairo, Egypt.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Salma El Tanbouly, BSc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ganin Fertility Center, Cairo, Egypt.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Abd El Ghafar Hussin, BSc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ganin Fertility Center, Cairo, Egypt.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hanaa El Khedr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ganin Fertility Center, Cairo, Egypt.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hosam Zaki, MSc, FRCOG</last_name>
    <phone>00201222150018</phone>
    <email>hosamz@tedata.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Salma El Tanbouly, BSc.</last_name>
    <phone>00201279655807</phone>
    <email>salmaeltanbouly@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ganin Fertility Center</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hosam Zaki, MSc, FRCOG</last_name>
      <phone>00201222150018</phone>
      <email>hosamz@teadata.net.eg</email>
    </contact>
    <contact_backup>
      <last_name>Salma El Tanbouly, BSc</last_name>
      <phone>00201279655807</phone>
      <email>salmaeltanbouly@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Swain JE, Carrell D, Cobo A, Meseguer M, Rubio C, Smith GD. Optimizing the culture environment and embryo manipulation to help maintain embryo developmental potential. Fertil Steril. 2016 Mar;105(3):571-587. doi: 10.1016/j.fertnstert.2016.01.035. Epub 2016 Feb 3. Erratum In: Fertil Steril. 2016 May;105(5):1377.</citation>
    <PMID>26851765</PMID>
  </reference>
  <reference>
    <citation>Gardner DK. The impact of physiological oxygen during culture, and vitrification for cryopreservation, on the outcome of extended culture in human IVF. Reprod Biomed Online. 2016 Feb;32(2):137-41. doi: 10.1016/j.rbmo.2015.11.008. Epub 2015 Nov 25.</citation>
    <PMID>26687905</PMID>
  </reference>
  <reference>
    <citation>Morin SJ. Oxygen tension in embryo culture: does a shift to 2% O2 in extended culture represent the most physiologic system? J Assist Reprod Genet. 2017 Mar;34(3):309-314. doi: 10.1007/s10815-017-0880-z. Epub 2017 Feb 8.</citation>
    <PMID>28181051</PMID>
  </reference>
  <reference>
    <citation>Oliveira JB. Does embryo culture at low oxygen tension improve ART outcomes? JBRA Assist Reprod. 2017 Feb 1;21(1):1. doi: 10.5935/1518-0557.20170001. No abstract available.</citation>
    <PMID>28333022</PMID>
  </reference>
  <reference>
    <citation>Kaser DJ, Bogale B, Sarda V, Farland LV, Williams PL, Racowsky C. Randomized controlled trial of low (5%) versus ultralow (2%) oxygen for extended culture using bipronucleate and tripronucleate human preimplantation embryos. Fertil Steril. 2018 Jun;109(6):1030-1037.e2. doi: 10.1016/j.fertnstert.2018.02.119.</citation>
    <PMID>29935641</PMID>
  </reference>
  <reference>
    <citation>Ng KYB, Mingels R, Morgan H, Macklon N, Cheong Y. In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review. Hum Reprod Update. 2018 Jan 1;24(1):15-34. doi: 10.1093/humupd/dmx028.</citation>
    <PMID>29077897</PMID>
  </reference>
  <reference>
    <citation>Yang Y, Xu Y, Ding C, Khoudja RY, Lin M, Awonuga AO, Dai J, Puscheck EE, Rappolee DA, Zhou C. Comparison of 2, 5, and 20 % O2 on the development of post-thaw human embryos. J Assist Reprod Genet. 2016 Jul;33(7):919-27. doi: 10.1007/s10815-016-0693-5. Epub 2016 Mar 23.</citation>
    <PMID>27007876</PMID>
  </reference>
  <reference>
    <citation>Leese HJ. Human embryo culture: back to nature. J Assist Reprod Genet. 1998 Sep;15(8):466-8. doi: 10.1023/a:1022526219202. No abstract available.</citation>
    <PMID>9785193</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>January 24, 2019</last_update_submitted>
  <last_update_submitted_qc>January 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ganin Fertility Center</investigator_affiliation>
    <investigator_full_name>Salma El Tanbouly</investigator_full_name>
    <investigator_title>Senior Clinical Embryologist</investigator_title>
  </responsible_party>
  <keyword>Thawed blastocyst</keyword>
  <keyword>ultra low oxygen tension</keyword>
  <keyword>2%O2</keyword>
  <keyword>Degree of expansion</keyword>
  <!-- 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/NCT03817671
org study id: GFCST11991
nct id: NCT03817671
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The clinical outcome of Ultra-low oxygen tension on post thawed human blastocyst
In vitro, Embryo development depends on several factors as temperature, pH, and oxygen in the
      surrounding environment of the embryo. Impaired culture conditions are highly correlated with
      poor embryo development. Oxygen is a powerful regulator of embryo function , as it is
      responsible for cell respiration, energy production and rapid cell growth . Increased levels
      of oxygen is associated with an increase in the levels of ROS , which leads to unfavorable
      culture conditions, as it might affect the stability of cell membrane, DNA, and protein
      function .

      In the female reproductive tract, oxygen concentration fluctuates between 2-8%, which is
      considered to be at its highest level in the fallopian tube, while the lowest level is in the
      uterus . Pre-implantation embryo crosses the uterotubal junction after the time of compaction
      on Day 3, where it is exposed to a shift in oxygen tension to 2%. This variation may have a
      role in the metabolic reactions of the embryo, and in its preparation for implantation
      process.

      Some studies suggested that culturing embryos with oxygen tension below 5% may have an
      embryological advantage mimicking nature.

      Embryological laboratories routinely use low Oxygen tension (5%). Our purpose is to
      investigate if ultra-low oxygen tension (2%) has an advantage over low oxygen tension (5%)
      for post thawed human embryo regarding clinical outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Clinical Pregnancy rate
time frame: Time frame: 15 days following embryo transfer
description: Defined as the pregnancy that is confirmed by both high levels of hCG and ultrasound confirmation of a gestational sac or heartbeat
measure: Ongoing pregnancy rate
time frame: Time frame: 20 weeks of gestation
description: Defined as the proportion of pregnancies that had completed ≥20 weeks of gestation
arm group label: Control arm (5% O2)
arm group type: Other
description: After thawing, embryos will be cultured in 25 μl drop of pre-equilibrated dishes of media covered with a layer of oil for 1.5 hours at 5.7% CO2, 5% O2, and 89.3% N2 till embryo transfer
arm group label: Experimental arm (2%O2)
arm group type: Experimental
description: After thawing, embryos will be cultured in 25 μl drop of pre-equilibrated dishes of media covered with a layer of oil for 1.5 hours at 5.7% CO2, 2% O2, and 92.3% N2 till embryo transfer
intervention type: Other
intervention name: 5% O2
description: Culturing embryos in 5% O2 just after thawing and till embryo transfer
arm group label: Control arm (5% O2)
intervention type: Other
intervention name: 2% O2
description: Culturing embryos in 2% O2 just after thawing and till embryo transfer
arm group label: Experimental arm (2%O2)
criteria: 
gender: All
minimum age: 5 Days
maximum age: 6 Days
healthy volunteers: No
last name: Hosam Zaki, MSc, FRCOG
role: Study Chair
affiliation: Ganin Fertility Center, Cairo, Egypt.
last name: Salma El Tanbouly, BSc.
role: Principal Investigator
affiliation: Ganin Fertility Center, Cairo, Egypt.
last name: Abd El Ghafar Hussin, BSc.
role: Principal Investigator
affiliation: Ganin Fertility Center, Cairo, Egypt.
last name: Hanaa El Khedr
role: Principal Investigator
affiliation: Ganin Fertility Center, Cairo, Egypt.
last name: Hosam Zaki, MSc, FRCOG
phone: 00201222150018
email: hosamz@tedata.net
last name: Salma El Tanbouly, BSc.
phone: 00201279655807
email: salmaeltanbouly@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Egypt
citation: Swain JE, Carrell D, Cobo A, Meseguer M, Rubio C, Smith GD. Optimizing the culture environment and embryo manipulation to help maintain embryo developmental potential. Fertil Steril. 2016 Mar;105(3):571-587. doi: 10.1016/j.fertnstert.2016.01.035. Epub 2016 Feb 3. Erratum In: Fertil Steril. 2016 May;105(5):1377.
PMID: 26851765
citation: Gardner DK. The impact of physiological oxygen during culture, and vitrification for cryopreservation, on the outcome of extended culture in human IVF. Reprod Biomed Online. 2016 Feb;32(2):137-41. doi: 10.1016/j.rbmo.2015.11.008. Epub 2015 Nov 25.
PMID: 26687905
citation: Morin SJ. Oxygen tension in embryo culture: does a shift to 2% O2 in extended culture represent the most physiologic system? J Assist Reprod Genet. 2017 Mar;34(3):309-314. doi: 10.1007/s10815-017-0880-z. Epub 2017 Feb 8.
PMID: 28181051
citation: Oliveira JB. Does embryo culture at low oxygen tension improve ART outcomes? JBRA Assist Reprod. 2017 Feb 1;21(1):1. doi: 10.5935/1518-0557.20170001. No abstract available.
PMID: 28333022
citation: Kaser DJ, Bogale B, Sarda V, Farland LV, Williams PL, Racowsky C. Randomized controlled trial of low (5%) versus ultralow (2%) oxygen for extended culture using bipronucleate and tripronucleate human preimplantation embryos. Fertil Steril. 2018 Jun;109(6):1030-1037.e2. doi: 10.1016/j.fertnstert.2018.02.119.
PMID: 29935641
citation: Ng KYB, Mingels R, Morgan H, Macklon N, Cheong Y. In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review. Hum Reprod Update. 2018 Jan 1;24(1):15-34. doi: 10.1093/humupd/dmx028.
PMID: 29077897
citation: Yang Y, Xu Y, Ding C, Khoudja RY, Lin M, Awonuga AO, Dai J, Puscheck EE, Rappolee DA, Zhou C. Comparison of 2, 5, and 20 % O2 on the development of post-thaw human embryos. J Assist Reprod Genet. 2016 Jul;33(7):919-27. doi: 10.1007/s10815-016-0693-5. Epub 2016 Mar 23.
PMID: 27007876
citation: Leese HJ. Human embryo culture: back to nature. J Assist Reprod Genet. 1998 Sep;15(8):466-8. doi: 10.1023/a:1022526219202. No abstract available.
PMID: 9785193
responsible party type: Principal Investigator
investigator affiliation: Ganin Fertility Center
investigator full name: Salma El Tanbouly
investigator title: Senior Clinical Embryologist