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/NCT05978947</url>
    </required_header>
    <id_info>
      <org_study_id>UW 23-233</org_study_id>
      <nct_id>NCT05978947</nct_id>
    </id_info>
    <brief_title>Microfluidic Chip Method Versus Density Gradient Centrifugation Method on Semen Parameters</brief_title>
    <official_title>Effect of Sperm Preparation by a Microfluidic Chip Method Versus a Density Gradient Centrifugation Method on Semen Parameters</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>
        Infertility affects many couples, with male infertility being a common cause. In vitro&#xD;
        fertilization (IVF) is an effective treatment, but its success rates are not high. Semen&#xD;
        quality can affect IVF outcomes, and the current method used to process semen can damage the&#xD;
        sperm and DNA. Scientists are now testing a new method called microfluidic chip technology,&#xD;
        which reduces DNA damage and increases sperm movement. This study will compare the&#xD;
        effectiveness of the chip method and the current method on semen quality in men attending a&#xD;
        fertility clinic. The study will randomly assign semen collected to one of the two methods&#xD;
        and assess the semen quality using different tests, as well as the difference in using two&#xD;
        different microfluidic chip platform . The primary outcome will be DNA fragmentation, and&#xD;
        other outcomes include sperm count and motility. Semen samples would be collected from study&#xD;
        subjects for analysis and that both the samples and results would not be used in patients'&#xD;
        treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Infertility affects one in six couples and is getting more common as many women delay&#xD;
        marriage and childbirth for various reasons. In vitro fertilization (IVF) is the most&#xD;
        effective treatment for couples with long standing infertility and has treated millions of&#xD;
        infertile couples over the world since the first birth of IVF was reported more than 40 years&#xD;
        ago. However, despite advances in technology, the pregnancy and birth rates remain around 35%&#xD;
        and 25% per transfer in Europe in 2018. Among all infertile couples, 20-30% are due to male&#xD;
        infertility. Semen parameters may affect the IVF outcomes and it was hypothesized that the&#xD;
        relative contribution of sperm to a live birth is around 10-15%.&#xD;
  &#xD;
        IVF involves hormone injections to stimulate a woman's ovaries to produce a number of oocytes&#xD;
        which are collected by a minor operation and then mixed with sperm to form embryos in the&#xD;
        laboratory. Usually, one or two embryos are transferred to the uterus 2-5 days after oocyte&#xD;
        retrieval. In IVF, semen samples produced by husbands are commonly processed by a density&#xD;
        gradient centrifugation method to isolate the better spermatozoa for fertilization. The&#xD;
        density gradient centrifugation can enrich spermatozoa with relatively good motility and&#xD;
        normal morphology. It is possible to recover spermatozoa from semen specimens with a very low&#xD;
        sperm density. It can provide a relatively good yield. However, it requires technical&#xD;
        training to set up the density gradient consisting of two media with different densities.&#xD;
        During semen processing, spermatozoa are centrifuged through the gradient. It is known that&#xD;
        centrifugation causes considerable damage to spermatozoa by the reactive oxygen species&#xD;
        produced during the process. Reactive oxygen species are known to be one of the major causes&#xD;
        leading to sperm DNA fragmentation and subsequent adverse outcomes including implantation&#xD;
        failure and miscarriage. A meta-analysis showed sperm DNA damage has a negative effect on&#xD;
        clinical pregnancy following IVF.&#xD;
  &#xD;
        A microfluidic chip, which is a miniaturized device containing channels and chambers in the&#xD;
        microscale range for nanoparticle preparation, is being used as an alternative sperm&#xD;
        preparation technique recently. By employing microfluidic technology, spermatozoa can go&#xD;
        through the chip that closely simulates the natural selection in the female genital tract&#xD;
        microenvironment. The technology enables the selection of high-quality motile spermatozoa&#xD;
        from semen samples without the need for centrifugation, leading to reduced reactive oxygen&#xD;
        species formation.&#xD;
  &#xD;
        Studies have consistently demonstrated that the use of a microfluidic chip method greatly&#xD;
        reduces DNA fragmentation and increases motility when compared with the density gradient&#xD;
        centrifugation method.&#xD;
  &#xD;
        This randomized controlled trial aims compare the effect of sperm preparation by a&#xD;
        microfluidic chip method versus a density gradient centrifugation method on semen parameters&#xD;
        prior to the start of a randomized trial comparing the effects of the two sperm preparation&#xD;
        methods on the cumulative live birth rates of in vitro fertilization.&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        The first objective of this randomized controlled trial is to compare the effect of sperm&#xD;
        preparation by a microfluidic chip method versus a density gradient centrifugation on semen&#xD;
        parameters. The hypothesis is that the use of sperm preparation by a microfluidic chip method&#xD;
        improves semen parameters.&#xD;
  &#xD;
        The second objective is to compare the effect of two different microfluidic chip platforms on&#xD;
        semen parameters.&#xD;
  &#xD;
        Trial design:&#xD;
  &#xD;
        Men attending at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital for&#xD;
        fertility treatment will be recruited.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 1, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2024</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>This randomized controlled trial aims compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation method on semen parameters prior to the start of a randomized trial comparing the effects of the two sperm preparation methods on the cumulative live birth rates of in vitro fertilization.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Only the laboratory staff in the IVF laboratory performing sperm preparation will be aware of the group assignment. Another laboratory staff who is not involved in performing sperm preparation and is not aware of the group assignment will perform the semen analysis.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>DNA fragmentation by Comet assay</measure>
      <time_frame>1 months</time_frame>
      <description>Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Sperm count</measure>
      <time_frame>1 months</time_frame>
      <description>Sperm count</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Forward motility</measure>
      <time_frame>1 months</time_frame>
      <description>Assessment of forward motility of sperm by manual observation using the World Health Organization (WHO) criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sperm velocities measured by CASA</measure>
      <time_frame>1 months</time_frame>
      <description>Quantitative analysis of sperm velocities using computer-assisted sperm analysis (CASA) system, including assessment of forward motility, curvilinear velocity, and linearity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Morphology</measure>
      <time_frame>1 months</time_frame>
      <description>Quantitative assessment of sperm morphology by manual observation using the Tygerberg strict criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sperm aneuploidy</measure>
      <time_frame>1 months</time_frame>
      <description>Quantitative measurement of sperm aneuploidy by fluorescence in situ hybridization (FISH) using probes for chromosomes X, Y, 13, 18, and 21.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Calcium ionophore A23187 -induced acrosome reaction assay</measure>
      <time_frame>1 months</time_frame>
      <description>Quantitative measurement of acrosome reaction in sperm induced by calcium ionophore A23187 using flow cytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Artificial intelligence analysis</measure>
      <time_frame>1 months</time_frame>
      <description>Quantitative analysis of sperm morphology using artificial intelligence algorithms.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intact oocyte/hemizona binding assay</measure>
      <time_frame>1 months</time_frame>
      <description>Quantitative measurement of sperm binding to intact oocytes or hemizona using the intact oocyte/hemizona binding assay.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Infertility</condition>
    <arm_group>
      <arm_group_label>Microfluidic Chip Method</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The Sperm Separation Device - ZyMōt Multi 850µL device (ZyMōt Fertility, Inc) will be used. The microfluidic chamber will be used based on the manufacturer's instructions. 850 μL of the semen sample will be added to the inlet port of the device and 750 μL 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 of the prepared sample at the outlet port will be removed and pipetted into a labelled test tube. The final volume will be adjusted to 1mL for sperm counting.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Density Gradient Centrifugation Method</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 500 μL. The final volume will be adjusted to 1mL for sperm counting.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>ZyMōt Multi 850µL device</intervention_name>
      <description>The ZyMōt Multi 850µL device is a laboratory tool designed for use in assisted reproductive technology (ART) procedures such as intrauterine insemination (IUI) and in vitro fertilization (IVF). It is a sperm preparation device that uses a proprietary patented technology to isolate and select motile sperm from semen samples for use in ART procedures.</description>
      <arm_group_label>Microfluidic Chip Method</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Density Gradient Centrifugation Method</intervention_name>
      <description>Density gradient centrifugation is a laboratory technique used to separate and isolate different types of cells or particles based on their density. It is commonly used in various applications, including cell biology, immunology, and assisted reproductive technology (ART).</description>
      <arm_group_label>Density Gradient Centrifugation Method</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Sperm concentration of the raw semen with at least 5 million motile sperm per ml with&#xD;
               a total volume of not less than 1.5ml.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Sperm concentration of the raw semen of less than 5 million motile sperm per ml&#xD;
  &#xD;
            -  Men unable to provide an ejaculated semen sample&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</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>
      <status>Recruiting</status>
      <contact>
        <last_name>Ernest HY NG, MD</last_name>
        <phone>852-22553400</phone>
        <email>nghye@hku.hk</email>
      </contact>
      <investigator>
        <last_name>Ernest HY NG, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </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>July 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 6, 2023</last_update_submitted>
    <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 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>Semen parameters</keyword>
    <keyword>Microfluidic chip</keyword>
    <keyword>Density Gradient Centrifugation</keyword>
    <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>
  
  
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/NCT05978947
  org study id: UW 23-233
  nct id: NCT05978947
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: Yes
  Infertility affects many couples, with male infertility being a common cause. In vitro
        fertilization (IVF) is an effective treatment, but its success rates are not high. Semen
        quality can affect IVF outcomes, and the current method used to process semen can damage the
        sperm and DNA. Scientists are now testing a new method called microfluidic chip technology,
        which reduces DNA damage and increases sperm movement. This study will compare the
        effectiveness of the chip method and the current method on semen quality in men attending a
        fertility clinic. The study will randomly assign semen collected to one of the two methods
        and assess the semen quality using different tests, as well as the difference in using two
        different microfluidic chip platform . The primary outcome will be DNA fragmentation, and
        other outcomes include sperm count and motility. Semen samples would be collected from study
        subjects for analysis and that both the samples and results would not be used in patients'
        treatment.
  Infertility affects one in six couples and is getting more common as many women delay
        marriage and childbirth for various reasons. In vitro fertilization (IVF) is the most
        effective treatment for couples with long standing infertility and has treated millions of
        infertile couples over the world since the first birth of IVF was reported more than 40 years
        ago. However, despite advances in technology, the pregnancy and birth rates remain around 35%
        and 25% per transfer in Europe in 2018. Among all infertile couples, 20-30% are due to male
        infertility. Semen parameters may affect the IVF outcomes and it was hypothesized that the
        relative contribution of sperm to a live birth is around 10-15%.
  
        IVF involves hormone injections to stimulate a woman's ovaries to produce a number of oocytes
        which are collected by a minor operation and then mixed with sperm to form embryos in the
        laboratory. Usually, one or two embryos are transferred to the uterus 2-5 days after oocyte
        retrieval. In IVF, semen samples produced by husbands are commonly processed by a density
        gradient centrifugation method to isolate the better spermatozoa for fertilization. The
        density gradient centrifugation can enrich spermatozoa with relatively good motility and
        normal morphology. It is possible to recover spermatozoa from semen specimens with a very low
        sperm density. It can provide a relatively good yield. However, it requires technical
        training to set up the density gradient consisting of two media with different densities.
        During semen processing, spermatozoa are centrifuged through the gradient. It is known that
        centrifugation causes considerable damage to spermatozoa by the reactive oxygen species
        produced during the process. Reactive oxygen species are known to be one of the major causes
        leading to sperm DNA fragmentation and subsequent adverse outcomes including implantation
        failure and miscarriage. A meta-analysis showed sperm DNA damage has a negative effect on
        clinical pregnancy following IVF.
  
        A microfluidic chip, which is a miniaturized device containing channels and chambers in the
        microscale range for nanoparticle preparation, is being used as an alternative sperm
        preparation technique recently. By employing microfluidic technology, spermatozoa can go
        through the chip that closely simulates the natural selection in the female genital tract
        microenvironment. The technology enables the selection of high-quality motile spermatozoa
        from semen samples without the need for centrifugation, leading to reduced reactive oxygen
        species formation.
  
        Studies have consistently demonstrated that the use of a microfluidic chip method greatly
        reduces DNA fragmentation and increases motility when compared with the density gradient
        centrifugation method.
  
        This randomized controlled trial aims compare the effect of sperm preparation by a
        microfluidic chip method versus a density gradient centrifugation method on semen parameters
        prior to the start of a randomized trial comparing the effects of the two sperm preparation
        methods on the cumulative live birth rates of in vitro fertilization.
  
        Objectives:
  
        The first objective of this randomized controlled trial is to compare the effect of sperm
        preparation by a microfluidic chip method versus a density gradient centrifugation on semen
        parameters. The hypothesis is that the use of sperm preparation by a microfluidic chip method
        improves semen parameters.
  
        The second objective is to compare the effect of two different microfluidic chip platforms on
        semen parameters.
  
        Trial design:
  
        Men attending at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital for
        fertility treatment will be recruited.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: This randomized controlled trial aims compare the effect of sperm preparation by a microfluidic chip method versus a density gradient centrifugation method on semen parameters prior to the start of a randomized trial comparing the effects of the two sperm preparation methods on the cumulative live birth rates of in vitro fertilization.
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Only the laboratory staff in the IVF laboratory performing sperm preparation will be aware of the group assignment. Another laboratory staff who is not involved in performing sperm preparation and is not aware of the group assignment will perform the semen analysis.
  measure: DNA fragmentation by Comet assay
  time frame: 1 months
  description: Measurement of DNA fragmentation by Comet assay using the Olive tail moment as the quantitative metric.
  measure: Sperm count
  time frame: 1 months
  description: Sperm count
  measure: Forward motility
  time frame: 1 months
  description: Assessment of forward motility of sperm by manual observation using the World Health Organization (WHO) criteria.
  measure: Sperm velocities measured by CASA
  time frame: 1 months
  description: Quantitative analysis of sperm velocities using computer-assisted sperm analysis (CASA) system, including assessment of forward motility, curvilinear velocity, and linearity.
  measure: Morphology
  time frame: 1 months
  description: Quantitative assessment of sperm morphology by manual observation using the Tygerberg strict criteria.
  measure: Sperm aneuploidy
  time frame: 1 months
  description: Quantitative measurement of sperm aneuploidy by fluorescence in situ hybridization (FISH) using probes for chromosomes X, Y, 13, 18, and 21.
  measure: Calcium ionophore A23187 -induced acrosome reaction assay
  time frame: 1 months
  description: Quantitative measurement of acrosome reaction in sperm induced by calcium ionophore A23187 using flow cytometry.
  measure: Artificial intelligence analysis
  time frame: 1 months
  description: Quantitative analysis of sperm morphology using artificial intelligence algorithms.
  measure: Intact oocyte/hemizona binding assay
  time frame: 1 months
  description: Quantitative measurement of sperm binding to intact oocytes or hemizona using the intact oocyte/hemizona binding assay.
  arm group label: Microfluidic Chip Method
  arm group type: Experimental
  description: The Sperm Separation Device - ZyMōt Multi 850µL device (ZyMōt Fertility, Inc) will be used. The microfluidic chamber will be used based on the manufacturer's instructions. 850 μL of the semen sample will be added to the inlet port of the device and 750 μL 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 of the prepared sample at the outlet port will be removed and pipetted into a labelled test tube. The final volume will be adjusted to 1mL for sperm counting.
  arm group label: Density Gradient Centrifugation Method
  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 500 μL. The final volume will be adjusted to 1mL for sperm counting.
  intervention type: Device
  intervention name: ZyMōt Multi 850µL device
  description: The ZyMōt Multi 850µL device is a laboratory tool designed for use in assisted reproductive technology (ART) procedures such as intrauterine insemination (IUI) and in vitro fertilization (IVF). It is a sperm preparation device that uses a proprietary patented technology to isolate and select motile sperm from semen samples for use in ART procedures.
  arm group label: Microfluidic Chip Method
  intervention type: Device
  intervention name: Density Gradient Centrifugation Method
  description: Density gradient centrifugation is a laboratory technique used to separate and isolate different types of cells or particles based on their density. It is commonly used in various applications, including cell biology, immunology, and assisted reproductive technology (ART).
  arm group label: Density Gradient Centrifugation Method
  criteria: 
  gender: Male
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: YU WING TONG, MBBS
  phone: 92707722
  email: ptong@connect.hku.hk
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  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
  sharing ipd: No