<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/NCT04424784</url>
  </required_header>
  <id_info>
    <org_study_id>HKUSZH201902022</org_study_id>
    <nct_id>NCT04424784</nct_id>
  </id_info>
  <brief_title>Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome</brief_title>
  <official_title>Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong-Shenzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong-Shenzhen Hospital</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>
      Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex&#xD;
      vivo culture conditions comparable to those in vivo. Various culturing condition such as&#xD;
      temperature and pH parameters have been adjusted according to in vivo values in order to&#xD;
      improve in-vitro fertilization (IVF) outcomes. Embryos of most mammals, including that of&#xD;
      humans, are not exposed to oxygen concentration higher than 8%. Thus, embryos and gametes&#xD;
      should be kept in a low oxygen environment during manipulation in assisted reproduction&#xD;
      treatment.&#xD;
&#xD;
      Culturing embryos in low oxygen concentrations is now a general practice in IVF laboratories.&#xD;
      However, there are still laboratory procedures when the oocytes/embryos are exposed to&#xD;
      atmospheric oxygen. In most laboratories, oocytes retrieval is performed under atmospheric&#xD;
      oxygen concentration. Oocyte is very sensitive to environmental changes, for instance,&#xD;
      transient cooling to room temperature can cause irreversible disruption of the meiotic&#xD;
      spindle in human oocytes and oocyte in vitro maturation can lead to the decline of energy&#xD;
      metabolism in human oocytes. Whether oocyte exposed to atmospheric oxygen during oocyte&#xD;
      retrieval has detrimental effect on embryo development and IVF outcomes is unknown.&#xD;
&#xD;
      Previous studies showed that low oxygen tension during embryo culture improved implantation&#xD;
      rate and clinical outcomes, but embryo quality was not affected. In other studies, embryo&#xD;
      quality was improved but overall pregnancy was not affected. The reason for the discrepancies&#xD;
      could be because the oxygen tension during oocyte/embryo manipulation was not under well&#xD;
      control. For instance, oocyte retrieval, fertilization check and embryo grading were&#xD;
      performed under atmospheric oxygen. It is difficult to predict how these factors negatively&#xD;
      impact the IVF outcomes.&#xD;
&#xD;
      In this project, the investigators hypothesize that lower oxygen tension during oocyte/embryo&#xD;
      manipulation improves IVF outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the experimental group, oocyte pickup will be performed in a lower oxygen tension&#xD;
      environment (5% oxygen, 89% nitrogen, 6% carbon dioxide); oocyte pickup will be performed in&#xD;
      a special workstation with reduced oxygen tension environment while fertilization check and&#xD;
      embryo grading will be performed in conventional and time lapse embryo culture system. The&#xD;
      time lapse culture system can provide a constant lower oxygen tension culture environment to&#xD;
      the embryos. In the control group, oocyte pickup, fertilization check and embryo grading will&#xD;
      be performed in atmospheric oxygen environment. Under this arrangement, the difference&#xD;
      between the 2 groups is the oxygen tension during oocyte/embryo manipulation. The&#xD;
      investigators believe that a solid conclusion can be drawn about whether lower oxygen tension&#xD;
      environment can benefit IVF outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 22, 2021</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</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>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>live birth rate</measure>
    <time_frame>4 years</time_frame>
    <description>delivery of a live birth beyond 24 weeks of gestation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>clinical pregnancy rate</measure>
    <time_frame>3 years</time_frame>
    <description>presence of at least one gestational sac on ultrasound of 6 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ongoing pregnancy rate</measure>
    <time_frame>3 years</time_frame>
    <description>presence of at least heart pulsation on ultrasound beyond 20 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fertilization rate</measure>
    <time_frame>3 years</time_frame>
    <description>No. of fertilized oocyte divided by No. of inseminated cumulus-oocyte complexes (COCs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cleavage rate</measure>
    <time_frame>3 years</time_frame>
    <description>No. of cleaved embryo divided by No. of fertilized oocyte</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1160</enrollment>
  <condition>Embryo Hypoxia</condition>
  <arm_group>
    <arm_group_label>20% O2</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In the control group, oocyte pickup will be performed in atmospheric oxygen environment (20% oxygen, 89% nitrogen, 6% carbon dioxide).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5% O2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the experimental group, oocyte pickup will be performed in a low oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide). If time lapse embryo culture system is used, fertilization check and embryo grading will also be conducted under the low oxygen tension environment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>5% O2</intervention_name>
    <description>5% oxygen will be used during oocyte retrieval, fertilization check and embryo grading</description>
    <arm_group_label>5% O2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  all the couples undergoing conventional IVF cycle in the reproductive medicine center&#xD;
             of the University of Hong Kong-Shenzhen Hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Intracytoplasmic sperm injection (ICSI) cycle&#xD;
&#xD;
          -  Preimplantation genetic testing (PGT) cycle&#xD;
&#xD;
          -  cycle with fertilization failure ≥3&#xD;
&#xD;
          -  cycle using sperm from percutaneous epididymal sperm aspiration (PESA)/testicular&#xD;
             sperm extraction (TESE) or cryopreserved sperm&#xD;
&#xD;
          -  cycle using cryopreserved oocyte&#xD;
&#xD;
          -  cycle with no oocyte retrieved&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shubiu Yeung, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong-Shenzhen Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Qian Peng, PhD</last_name>
    <phone>8675586917836</phone>
    <email>qianpeng_77@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Reproductive medicine center</name>
      <address>
        <city>Shenzhen</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>QIAN PENG, PHD</last_name>
      <email>qianpeng_77@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.</citation>
    <PMID>8107053</PMID>
  </reference>
  <reference>
    <citation>Kovacic B, Vlaisavljevic V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod Biomed Online. 2008 Aug;17(2):229-36. doi: 10.1016/s1472-6483(10)60199-x.</citation>
    <PMID>18681997</PMID>
  </reference>
  <reference>
    <citation>Waldenstrom U, Engstrom AB, Hellberg D, Nilsson S. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil Steril. 2009 Jun;91(6):2461-5. doi: 10.1016/j.fertnstert.2008.03.051. Epub 2008 Jun 12.</citation>
    <PMID>18554591</PMID>
  </reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>May 21, 2021</last_update_submitted>
  <last_update_submitted_qc>May 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoxia</mesh_term>
  </condition_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/NCT04424784
org study id: HKUSZH201902022
nct id: NCT04424784
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex
      vivo culture conditions comparable to those in vivo. Various culturing condition such as
      temperature and pH parameters have been adjusted according to in vivo values in order to
      improve in-vitro fertilization (IVF) outcomes. Embryos of most mammals, including that of
      humans, are not exposed to oxygen concentration higher than 8%. Thus, embryos and gametes
      should be kept in a low oxygen environment during manipulation in assisted reproduction
      treatment.

      Culturing embryos in low oxygen concentrations is now a general practice in IVF laboratories.
      However, there are still laboratory procedures when the oocytes/embryos are exposed to
      atmospheric oxygen. In most laboratories, oocytes retrieval is performed under atmospheric
      oxygen concentration. Oocyte is very sensitive to environmental changes, for instance,
      transient cooling to room temperature can cause irreversible disruption of the meiotic
      spindle in human oocytes and oocyte in vitro maturation can lead to the decline of energy
      metabolism in human oocytes. Whether oocyte exposed to atmospheric oxygen during oocyte
      retrieval has detrimental effect on embryo development and IVF outcomes is unknown.

      Previous studies showed that low oxygen tension during embryo culture improved implantation
      rate and clinical outcomes, but embryo quality was not affected. In other studies, embryo
      quality was improved but overall pregnancy was not affected. The reason for the discrepancies
      could be because the oxygen tension during oocyte/embryo manipulation was not under well
      control. For instance, oocyte retrieval, fertilization check and embryo grading were
      performed under atmospheric oxygen. It is difficult to predict how these factors negatively
      impact the IVF outcomes.

      In this project, the investigators hypothesize that lower oxygen tension during oocyte/embryo
      manipulation improves IVF outcomes.
In the experimental group, oocyte pickup will be performed in a lower oxygen tension
      environment (5% oxygen, 89% nitrogen, 6% carbon dioxide); oocyte pickup will be performed in
      a special workstation with reduced oxygen tension environment while fertilization check and
      embryo grading will be performed in conventional and time lapse embryo culture system. The
      time lapse culture system can provide a constant lower oxygen tension culture environment to
      the embryos. In the control group, oocyte pickup, fertilization check and embryo grading will
      be performed in atmospheric oxygen environment. Under this arrangement, the difference
      between the 2 groups is the oxygen tension during oocyte/embryo manipulation. The
      investigators believe that a solid conclusion can be drawn about whether lower oxygen tension
      environment can benefit IVF outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Care Provider)
measure: live birth rate
time frame: 4 years
description: delivery of a live birth beyond 24 weeks of gestation
measure: clinical pregnancy rate
time frame: 3 years
description: presence of at least one gestational sac on ultrasound of 6 weeks
measure: ongoing pregnancy rate
time frame: 3 years
description: presence of at least heart pulsation on ultrasound beyond 20 weeks
measure: fertilization rate
time frame: 3 years
description: No. of fertilized oocyte divided by No. of inseminated cumulus-oocyte complexes (COCs)
measure: cleavage rate
time frame: 3 years
description: No. of cleaved embryo divided by No. of fertilized oocyte
arm group label: 20% O2
arm group type: No Intervention
description: In the control group, oocyte pickup will be performed in atmospheric oxygen environment (20% oxygen, 89% nitrogen, 6% carbon dioxide).
arm group label: 5% O2
arm group type: Experimental
description: In the experimental group, oocyte pickup will be performed in a low oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide). If time lapse embryo culture system is used, fertilization check and embryo grading will also be conducted under the low oxygen tension environment.
intervention type: Biological
intervention name: 5% O2
description: 5% oxygen will be used during oocyte retrieval, fertilization check and embryo grading
arm group label: 5% O2
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Shubiu Yeung, PhD
role: Principal Investigator
affiliation: The University of Hong Kong-Shenzhen Hospital
last name: Qian Peng, PhD
phone: 8675586917836
email: qianpeng_77@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
citation: Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.
PMID: 8107053
citation: Kovacic B, Vlaisavljevic V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod Biomed Online. 2008 Aug;17(2):229-36. doi: 10.1016/s1472-6483(10)60199-x.
PMID: 18681997
citation: Waldenstrom U, Engstrom AB, Hellberg D, Nilsson S. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil Steril. 2009 Jun;91(6):2461-5. doi: 10.1016/j.fertnstert.2008.03.051. Epub 2008 Jun 12.
PMID: 18554591
responsible party type: Sponsor
mesh term: Hypoxia