xml: <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/NCT06023472</url>
    </required_header>
    <id_info>
      <org_study_id>UW 23-297</org_study_id>
      <nct_id>NCT06023472</nct_id>
    </id_info>
    <brief_title>Microfluidic Chip vs Density Gradient Centrifugation on the Euploidy Rate of Pre-implantation Genetic Testing</brief_title>
    <official_title>A Randomized Comparison of Microfluidic Chip vs Density Gradient Centrifugation on the Euploidy Rate of Pre-implantation Genetic Testing</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Professor Ernest Hung-Yu Ng</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The University of Hong Kong</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Infertile women attending for PGT at the Centre of Assisted Reproduction and Embryology,&#xD;
        Queen Mary Hospital and Kwong Wah Hospital will be recruited during ovarian stimulation for&#xD;
        IVF. Subsequently, they will be randomly assigned on the day of oocyte retrieval by a&#xD;
        laboratory staff into one of the following two groups in a 1:1 ratio : (1) the microfluidic&#xD;
        chip group and (2) the density gradient centrifugation group for sperm preparation and&#xD;
        subsequent use in fertilization. Other IVF procedures will be the same as the standard&#xD;
        practice of the Centre. Both women and clinicians will be blinded from the group allocation&#xD;
        i.e. a double blind study.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study aims to investigate the treatment of couples undergoing in vitro fertilization&#xD;
        (IVF). Eligible couples will be recruited for the study after providing informed written&#xD;
        consent following counseling. The IVF protocol involves various steps. Women will undergo&#xD;
        preimplantation genetic testing (PGT) as clinically indicated. Ovarian stimulation will be&#xD;
        carried out using gonadotropin injections, and regular ultrasound monitoring will be&#xD;
        conducted to track the growth of follicles. To prevent a premature LH surge, progestin primed&#xD;
        ovarian stimulation or a GnRH antagonist will be administered. Once at least three follicles&#xD;
        reach a size of over 17 mm, a trigger injection of either human chorionic gonadotrophin or a&#xD;
        GnRH agonist will be given to induce final maturation. Oocyte retrieval will be performed 36&#xD;
        hours after the trigger under transvaginal ultrasound guidance.&#xD;
  &#xD;
        The recruited women will be randomly assigned to one of two groups: the microfluidic chip&#xD;
        group or the density gradient centrifugation group. Randomization and blinding will be&#xD;
        ensured to maintain the integrity of the study. Only the laboratory staff involved in sperm&#xD;
        preparation will be aware of the group assignment, while the women and clinicians will be&#xD;
        blinded to the treatment groups.&#xD;
  &#xD;
        Semen specimens will be collected by masturbation on the day of oocyte retrieval, following a&#xD;
        period of 2-7 days of sexual abstinence. The semen samples will undergo evaluation according&#xD;
        to WHO guidelines, including semen volume, sperm concentration, and percent motile&#xD;
        spermatozoa. Sperm DNA damage will be assessed using an alkaline single-cell gel&#xD;
        electrophoresis (Comet) assay. The extent of DNA damage in spermatozoa will be examined using&#xD;
        specific parameters.&#xD;
  &#xD;
        Sperm preparation will be performed based on the randomization list. In the microfluidic chip&#xD;
        group, the Sperm Separation Device will be used, and the prepared sample will be collected in&#xD;
        a test tube. In the density gradient centrifugation group, sperm preparation will be&#xD;
        completed using a discontinuous density gradient centrifugation method, and the resulting&#xD;
        sperm pellet will be washed and resuspended.&#xD;
  &#xD;
        Oocytes will be fertilized through intracytoplasmic sperm injection, and normal fertilization&#xD;
        will be confirmed by the presence of two pronuclei. A few cells will be taken from the&#xD;
        blastocysts for comprehensive chromosome analysis. Cryopreservation of all blastocysts will&#xD;
        be done, and only euploid blastocysts without aneuploidies will be replaced in subsequent&#xD;
        frozen embryo transfer cycles.&#xD;
  &#xD;
        Frozen embryo transfer (FET) will be performed in subsequent natural or hormonal replacement&#xD;
        cycles, depending on the women's menstrual cycle regularity.&#xD;
  &#xD;
        Pregnancy outcomes will be monitored through urine pregnancy tests and transvaginal&#xD;
        ultrasounds. If the pregnancy test is positive, further ultrasounds will be done to confirm&#xD;
        fetal viability and the number of fetuses. Pregnancy and delivery data will be retrieved&#xD;
        after delivery, and information on pregnancy outcomes, number of babies born, birth weights,&#xD;
        and obstetric complications will be recorded.&#xD;
  &#xD;
        The study aims to assess the effectiveness of the two different sperm preparation methods and&#xD;
        their impact on IVF outcomes, including pregnancy rates and obstetric complications.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2027</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>
      <intervention_model_description>On the day of oocyte retrieval, recruited women will be randomly assigned into one of the following two groups according to a computer-generated randomization list with a 1:1 ratio and a block size of 10. The randomization list will be prepared by a designated research nurse who is not involved in care of the women and opened by a laboratory staff.&#xD;
  The microfluidic chip group and&#xD;
  The density gradient centrifugation group</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>On the day of oocyte retrieval, recruited women will be randomly assigned into one of the following two groups according to a computer-generated randomization list with a 1:1 ratio and a block size of 10. The randomization list will be prepared by a designated research nurse who is not involved in care of the women and opened by a laboratory staff.&#xD;
  The microfluidic chip group and&#xD;
  The density gradient centrifugation group&#xD;
  The women and clinicians will be blinded to the treatment groups they are assigned. Only the laboratory staff in the IVF laboratory performing sperm preparation will be aware of the group assignment.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Euploid rate of blastocysts</measure>
      <time_frame>3 months</time_frame>
      <description>Euploid rate of blastocysts biopsied</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Live birth rate of the first embryo transfer</measure>
      <time_frame>3 years</time_frame>
      <description>No. of live birth beyond 22 weeks of gestation per the first embryo transfer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Positive urine pregnancy test rate per the first embryo transfer</measure>
      <time_frame>3 years</time_frame>
      <description>No. of positive urine pregnancy test per the first embryo transfer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical pregnancy rate of the first embryo transfer</measure>
      <time_frame>3 years</time_frame>
      <description>No. of clinical pregnancy per the first embryo transfer defined as presence of intrauterine gestational sac on scanning at gestational week 6.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ongoing pregnancy rate</measure>
      <time_frame>3 years</time_frame>
      <description>No. of ongoing pregnancy as presence of a fetal pole with pulsation at 8-10 weeks of gestation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Miscarriage rate pregnancy</measure>
      <time_frame>3 years</time_frame>
      <description>No. of miscarriage defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Multiple pregnancy rate</measure>
      <time_frame>3 years</time_frame>
      <description>Multiple pregnancy rate: presence of more than one intrauterine sac at 6 weeks of gestation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DNA fragmentation</measure>
      <time_frame>3 years</time_frame>
      <description>Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ectopic pregnancy rate</measure>
      <time_frame>3 years</time_frame>
      <description>No. of ectopic pregnancy</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">318</enrollment>
    <condition>Infertility</condition>
    <condition>Genetic Disease</condition>
    <condition>Chromosomal Rearrangement</condition>
    <condition>Aneuploidy</condition>
    <arm_group>
      <arm_group_label>The microfluidic chip group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The Sperm Separation Device - ZyMōt Multi 850µL or 3 mL device (ZyMōt Fertility, Inc) will be used according to the volume of the raw semen samples. The microfluidics chamber will be used based on the manufacturer's instructions. 850 μL (850 μL device) or 3 mL (3mL device) of the semen sample will be added to the inlet port of the device and 750 μL (850 μL device) or 2.4 mL (3 mL device) of fertilization media will be added to the outlet port. The device will then be incubated in 6% CO2 at 37°C. After 30 minutes, 500 μL (850 μL device) or 1 mL (3mL device) of the prepared sample at the outlet port will be removed and pipetted into a labelled test tube.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>The density gradient centrifugation group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>After liquefaction, sperm preparation will be completed by a discontinuous density gradient centrifugation method, using Pureception (CooperSurgical, Denmark) sperm density gradient media. The resulting sperm pellet after centrifugation will be washed once with the sperm washing medium (G-IVF Plus, Vitrolife, Sweden) The washed spermatozoa will be resuspended with the same medium, adjusting the final volume to 0.5 mL.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>microfluidic chip</intervention_name>
      <description>Microfluidic chip method has been used for sperm sorting in order to select the most motile and morphologically normal sperm for use in assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).</description>
      <arm_group_label>The microfluidic chip group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>density gradient centrifugation</intervention_name>
      <description>Density-gradient centrifugation is a commonly used method for sperm separation and purification. It is a technique that involves layering a semen sample on top of a gradient of different densities of a solution, typically a mixture of colloidal silica and sucrose, and then centrifuging the sample. The centrifugal force causes the sperm to migrate through the gradient, where they become separated based on their density.</description>
      <arm_group_label>The density gradient centrifugation group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Women aged &lt;43 years at the time of ovarian stimulation for IVF&#xD;
  &#xD;
            -  Women undergoing PGT for monogenic diseases, structural rearrangement of chromosomes&#xD;
               or aneuploidy&#xD;
  &#xD;
            -  Sperm concentration of the raw semen with at least 0.15 million motile sperm per ml or&#xD;
               100 motile sperm per 50 low power field (200x) of observation&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Use of frozen semen for insemination&#xD;
  &#xD;
            -  Use of donor oocytes and spermatozoa&#xD;
  &#xD;
            -  Submucosal fibroid or hydrosalpinx shown on pelvic scanning and not surgically&#xD;
               treated;&#xD;
  &#xD;
            -  Women who had been recruited into this study before and&#xD;
  &#xD;
            -  Women joining other randomized trials&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>43 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>YU WING TONG, MBBS</last_name>
      <phone>92707722</phone>
      <email>ptong@connect.hku.hk</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of Obstetrics and Gynaecology</name>
        <address>
          <city>Hong Kong</city>
          <state>Hong Kong</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 29, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
      <investigator_full_name>Professor Ernest Hung-Yu Ng</investigator_full_name>
      <investigator_title>Clinical Professor</investigator_title>
    </responsible_party>
    <keyword>microfluidic chip</keyword>
    <keyword>density gradient centrifugation</keyword>
    <keyword>euploidy rate</keyword>
    <keyword>pre-implantation genetic testing</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infertility</mesh_term>
      <mesh_term>Genetic Diseases, Inborn</mesh_term>
      <mesh_term>Aneuploidy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023472
  org study id: UW 23-297
  nct id: NCT06023472
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: Yes
  Infertile women attending for PGT at the Centre of Assisted Reproduction and Embryology,
        Queen Mary Hospital and Kwong Wah Hospital will be recruited during ovarian stimulation for
        IVF. Subsequently, they will be randomly assigned on the day of oocyte retrieval by a
        laboratory staff into one of the following two groups in a 1:1 ratio : (1) the microfluidic
        chip group and (2) the density gradient centrifugation group for sperm preparation and
        subsequent use in fertilization. Other IVF procedures will be the same as the standard
        practice of the Centre. Both women and clinicians will be blinded from the group allocation
        i.e. a double blind study.
  The study aims to investigate the treatment of couples undergoing in vitro fertilization
        (IVF). Eligible couples will be recruited for the study after providing informed written
        consent following counseling. The IVF protocol involves various steps. Women will undergo
        preimplantation genetic testing (PGT) as clinically indicated. Ovarian stimulation will be
        carried out using gonadotropin injections, and regular ultrasound monitoring will be
        conducted to track the growth of follicles. To prevent a premature LH surge, progestin primed
        ovarian stimulation or a GnRH antagonist will be administered. Once at least three follicles
        reach a size of over 17 mm, a trigger injection of either human chorionic gonadotrophin or a
        GnRH agonist will be given to induce final maturation. Oocyte retrieval will be performed 36
        hours after the trigger under transvaginal ultrasound guidance.
  
        The recruited women will be randomly assigned to one of two groups: the microfluidic chip
        group or the density gradient centrifugation group. Randomization and blinding will be
        ensured to maintain the integrity of the study. Only the laboratory staff involved in sperm
        preparation will be aware of the group assignment, while the women and clinicians will be
        blinded to the treatment groups.
  
        Semen specimens will be collected by masturbation on the day of oocyte retrieval, following a
        period of 2-7 days of sexual abstinence. The semen samples will undergo evaluation according
        to WHO guidelines, including semen volume, sperm concentration, and percent motile
        spermatozoa. Sperm DNA damage will be assessed using an alkaline single-cell gel
        electrophoresis (Comet) assay. The extent of DNA damage in spermatozoa will be examined using
        specific parameters.
  
        Sperm preparation will be performed based on the randomization list. In the microfluidic chip
        group, the Sperm Separation Device will be used, and the prepared sample will be collected in
        a test tube. In the density gradient centrifugation group, sperm preparation will be
        completed using a discontinuous density gradient centrifugation method, and the resulting
        sperm pellet will be washed and resuspended.
  
        Oocytes will be fertilized through intracytoplasmic sperm injection, and normal fertilization
        will be confirmed by the presence of two pronuclei. A few cells will be taken from the
        blastocysts for comprehensive chromosome analysis. Cryopreservation of all blastocysts will
        be done, and only euploid blastocysts without aneuploidies will be replaced in subsequent
        frozen embryo transfer cycles.
  
        Frozen embryo transfer (FET) will be performed in subsequent natural or hormonal replacement
        cycles, depending on the women's menstrual cycle regularity.
  
        Pregnancy outcomes will be monitored through urine pregnancy tests and transvaginal
        ultrasounds. If the pregnancy test is positive, further ultrasounds will be done to confirm
        fetal viability and the number of fetuses. Pregnancy and delivery data will be retrieved
        after delivery, and information on pregnancy outcomes, number of babies born, birth weights,
        and obstetric complications will be recorded.
  
        The study aims to assess the effectiveness of the two different sperm preparation methods and
        their impact on IVF outcomes, including pregnancy rates and obstetric complications.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: On the day of oocyte retrieval, recruited women will be randomly assigned into one of the following two groups according to a computer-generated randomization list with a 1:1 ratio and a block size of 10. The randomization list will be prepared by a designated research nurse who is not involved in care of the women and opened by a laboratory staff.
  The microfluidic chip group and
  The density gradient centrifugation group
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: On the day of oocyte retrieval, recruited women will be randomly assigned into one of the following two groups according to a computer-generated randomization list with a 1:1 ratio and a block size of 10. The randomization list will be prepared by a designated research nurse who is not involved in care of the women and opened by a laboratory staff.
  The microfluidic chip group and
  The density gradient centrifugation group
  The women and clinicians will be blinded to the treatment groups they are assigned. Only the laboratory staff in the IVF laboratory performing sperm preparation will be aware of the group assignment.
  measure: Euploid rate of blastocysts
  time frame: 3 months
  description: Euploid rate of blastocysts biopsied
  measure: Live birth rate of the first embryo transfer
  time frame: 3 years
  description: No. of live birth beyond 22 weeks of gestation per the first embryo transfer
  measure: Positive urine pregnancy test rate per the first embryo transfer
  time frame: 3 years
  description: No. of positive urine pregnancy test per the first embryo transfer
  measure: Clinical pregnancy rate of the first embryo transfer
  time frame: 3 years
  description: No. of clinical pregnancy per the first embryo transfer defined as presence of intrauterine gestational sac on scanning at gestational week 6.
  measure: Ongoing pregnancy rate
  time frame: 3 years
  description: No. of ongoing pregnancy as presence of a fetal pole with pulsation at 8-10 weeks of gestation
  measure: Miscarriage rate pregnancy
  time frame: 3 years
  description: No. of miscarriage defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.
  measure: Multiple pregnancy rate
  time frame: 3 years
  description: Multiple pregnancy rate: presence of more than one intrauterine sac at 6 weeks of gestation
  measure: DNA fragmentation
  time frame: 3 years
  description: Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.
  measure: Ectopic pregnancy rate
  time frame: 3 years
  description: No. of ectopic pregnancy
  arm group label: The microfluidic chip group
  arm group type: Experimental
  description: The Sperm Separation Device - ZyMōt Multi 850µL or 3 mL device (ZyMōt Fertility, Inc) will be used according to the volume of the raw semen samples. The microfluidics chamber will be used based on the manufacturer's instructions. 850 μL (850 μL device) or 3 mL (3mL device) of the semen sample will be added to the inlet port of the device and 750 μL (850 μL device) or 2.4 mL (3 mL device) of fertilization media will be added to the outlet port. The device will then be incubated in 6% CO2 at 37°C. After 30 minutes, 500 μL (850 μL device) or 1 mL (3mL device) of the prepared sample at the outlet port will be removed and pipetted into a labelled test tube.
  arm group label: The density gradient centrifugation group
  arm group type: Active Comparator
  description: After liquefaction, sperm preparation will be completed by a discontinuous density gradient centrifugation method, using Pureception (CooperSurgical, Denmark) sperm density gradient media. The resulting sperm pellet after centrifugation will be washed once with the sperm washing medium (G-IVF Plus, Vitrolife, Sweden) The washed spermatozoa will be resuspended with the same medium, adjusting the final volume to 0.5 mL.
  intervention type: Device
  intervention name: microfluidic chip
  description: Microfluidic chip method has been used for sperm sorting in order to select the most motile and morphologically normal sperm for use in assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
  arm group label: The microfluidic chip group
  intervention type: Device
  intervention name: density gradient centrifugation
  description: Density-gradient centrifugation is a commonly used method for sperm separation and purification. It is a technique that involves layering a semen sample on top of a gradient of different densities of a solution, typically a mixture of colloidal silica and sucrose, and then centrifuging the sample. The centrifugal force causes the sperm to migrate through the gradient, where they become separated based on their density.
  arm group label: The density gradient centrifugation group
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: 43 Years
  healthy volunteers: No
  last name: YU WING TONG, MBBS
  phone: 92707722
  email: ptong@connect.hku.hk
  facility: 
  country: China
  responsible party type: Sponsor-Investigator
  investigator affiliation: The University of Hong Kong
  investigator full name: Professor Ernest Hung-Yu Ng
  investigator title: Clinical Professor
  mesh term: Infertility
  mesh term: Genetic Diseases, Inborn
  mesh term: Aneuploidy
  sharing ipd: Undecided