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/NCT06005311</url>
    </required_header>
    <id_info>
      <org_study_id>UW 23-293</org_study_id>
      <nct_id>NCT06005311</nct_id>
    </id_info>
    <brief_title>Microfluidic Chip Method Versus Density-gradient Centrifugation Method in IVF</brief_title>
    <official_title>A Randomized Double-blind Controlled Study of the Cumulative Live Birth Rate of IVF Following Sperm Preparation by Microfluidic Chip Method Versus Density-gradient Centrifugation Method</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 patients attending IVF treatment at the Centre of Assisted Reproduction and&#xD;
        Embryology, Queen Mary Hospital and Kwong Wah Hospital will be recruited during ovarian&#xD;
        stimulation for IVF. Subsequently, they will be randomly assigned on the day of oocyte&#xD;
        retrieval by a laboratory staff into one of the following two groups: (1) the microfluidic&#xD;
        chip group and (2) the density gradient group for sperm preparation and subsequent use in&#xD;
        fertilization. Other IVF procedures will be the same as our usual practice. Both patients and&#xD;
        clinicians were blinded from the group allocation i.e. a double blind study. The primary&#xD;
        outcome is the cumulative live birth rate defined as the number of pregnancies leading to&#xD;
        live birth within 6 months of randomisation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The trial will compare the use of a microfluidic chip with the use of density gradient&#xD;
        centrifugation for sperm preparation.&#xD;
  &#xD;
        The hypothesis of the study is that the use of the microfluidic chip will improve the&#xD;
        cumulative live birth rate of IVF compared to the density gradient method.&#xD;
  &#xD;
        The trial will be conducted at the Centre of Assisted Reproduction and Embryology at Queen&#xD;
        Mary Hospital and Kwong Wah Hospital. Infertile patients undergoing IVF treatment will be&#xD;
        recruited during ovarian stimulation. They will be randomly assigned to one of two groups:&#xD;
        the microfluidic chip group or the density gradient group. Both the patients and the&#xD;
        clinicians will be blinded to the group allocation.&#xD;
  &#xD;
        The inclusion criteria for the study are infertile women aged under 43 years undergoing&#xD;
        ovarian stimulation for IVF. The exclusion criteria include women undergoing certain genetic&#xD;
        testing, male factor infertility requiring surgical sperm retrieval, the use of donor oocytes&#xD;
        and spermatozoa, certain uterine conditions, previous participation in the study, and&#xD;
        participation in other randomized trials.&#xD;
  &#xD;
        The eligible women will undergo standard IVF procedures, including ovarian stimulation,&#xD;
        monitoring of follicle growth, trigger for oocyte retrieval, and oocyte retrieval itself. On&#xD;
        the day of oocyte retrieval, the women will be randomly assigned to either the microfluidic&#xD;
        chip group or the density gradient group for sperm preparation.&#xD;
  &#xD;
        Semen samples will be collected on the day of oocyte retrieval and evaluated according to&#xD;
        standard guidelines. Sperm DNA damage will also be assessed using an alkaline single-cell gel&#xD;
        electrophoresis assay. Depending on the randomization, the sperm samples will be prepared&#xD;
        either using the microfluidic chip or the density gradient centrifugation method.&#xD;
  &#xD;
        After sperm preparation, oocytes will be fertilized using either conventional insemination or&#xD;
        intracytoplasmic sperm injection. Fertilization will be confirmed by the presence of two&#xD;
        pronuclei. Fresh embryo transfer will be performed 2-5 days after egg retrieval, and luteal&#xD;
        phase support will be given. Excessive good quality embryos or blastocysts will be&#xD;
        cryopreserved for future use.&#xD;
  &#xD;
        For frozen embryo transfer, embryos or blastocysts will be replaced in subsequent natural or&#xD;
        hormonal replacement cycles. Pregnancy will be confirmed by a urine pregnancy test, and&#xD;
        transvaginal ultrasound will be performed to confirm viability and the number of fetuses.&#xD;
  &#xD;
        Follow-up will be conducted to retrieve pregnancy and delivery data. The cumulative live&#xD;
        birth rate will be calculated, and pregnancy outcomes, including birth weights and obstetric&#xD;
        complications, will be recorded and compared between the two groups.&#xD;
  &#xD;
        The study will continue until all cryopreserved embryos or blastocysts are used or until the&#xD;
        participants become pregnant within 6 months after randomization. The pregnancy complications&#xD;
        and congenital abnormalities will be monitored through hospital records or patient contact.&#xD;
  &#xD;
        Ultimately, the study aims to determine whether the use of the microfluidic chip improves the&#xD;
        cumulative live birth rate of IVF compared to the density gradient method.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">June 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>Infertile patients attending IVF treatment 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: (1) the microfluidic chip group and (2) the density gradient group for sperm preparation and subsequent use in fertilization. Other IVF procedures will be the same as our usual practice.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Both patients and clinicians were blinded from the group allocation i.e. a double blind study.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>cumulative live birth rate</measure>
      <time_frame>within 6 months of randomisation.</time_frame>
      <description>cumulative live birth rate defined as the number of pregnancies leading to live birth within 6 months of randomisation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Live birth beyond 22 weeks of gestation per the first embryo transfer or FET</measure>
      <time_frame>3 years</time_frame>
      <description>Live birth beyond 22 weeks of gestation per the first embryo transfer or FET</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Positive urine pregnancy test per the first embryo transfer or FET</measure>
      <time_frame>3 years</time_frame>
      <description>Positive urine pregnancy test per the first embryo transfer or FET</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical pregnancy per the first embryo transfer or FET defined as presence of intrauterine gestational sac on scanning at gestational week 6.</measure>
      <time_frame>3 years</time_frame>
      <description>Clinical pregnancy per the first embryo transfer or FET defined as presence of intrauterine gestational sac on scanning at gestational week 6.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ongoing pregnancy rate as presence of a fetal pole with pulsation at 8-10 weeks of gestation</measure>
      <time_frame>3 years</time_frame>
      <description>Ongoing pregnancy rate as presence of a fetal pole with pulsation at 8-10 weeks of gestation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Miscarriage defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.</measure>
      <time_frame>3 years</time_frame>
      <description>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: presence of more than one intrauterine sac at 6 weeks of gestation</measure>
      <time_frame>3 years</time_frame>
      <description>Multiple pregnancy: presence of more than one intrauterine sac at 6 weeks of gestation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ectopic pregnancy rate</measure>
      <time_frame>3 years</time_frame>
      <description>Ectopic pregnancy rate</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1136</enrollment>
    <condition>Infertility</condition>
    <arm_group>
      <arm_group_label>microfluidic chip method</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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).&#xD;
  In the microfluidic chip method for sperm sorting, a small amount of semen sample is loaded onto the chip, which contains channels and chambers that allow for the separation of sperm based on their motility and morphology. The chip is designed to mimic the natural environment of the female reproductive tract, where sperm undergo a series of selection processes before reaching the egg.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>density-gradient centrifugation method</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <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>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Microfluidic chip</intervention_name>
      <description>The Sperm Separation Device - ZyMōt Multi 850µL (ZyMōt Fertility, Inc) will be used. The microfluidics chamber will be used according to the manufacturer's instructions. 850 μL of the semen sample will be inserted into the inlet port of the device and 750 μL of fertilization media will be inserted into the outlet port. The device with the semen sample inside will be incubated in 6% CO2 at 37°C. After 30 min, 500 μL of the sample at the outlet port will be removed from the outlet port and pipetted into a labelled test tube.</description>
      <arm_group_label>microfluidic chip method</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Density-gradient centrifugation</intervention_name>
      <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_label>density-gradient centrifugation method</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Infertile women aged &lt;43 years at the time of ovarian stimulation for IVF&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Women undergoing preimplantation genetic testing monogenic diseases, structural&#xD;
               rearrangement of chromosomes or aneuploidy;&#xD;
  &#xD;
            -  Male factor requiring surgical sperm retrieval such as microscopic epididymal sperm&#xD;
               aspiration and testicular sperm extraction;&#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 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 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>in-vitro fertilisation</keyword>
    <keyword>sperm preparation</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>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/NCT06005311
  org study id: UW 23-293
  nct id: NCT06005311
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: Yes
  Infertile patients attending IVF treatment 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: (1) the microfluidic
        chip group and (2) the density gradient group for sperm preparation and subsequent use in
        fertilization. Other IVF procedures will be the same as our usual practice. Both patients and
        clinicians were blinded from the group allocation i.e. a double blind study. The primary
        outcome is the cumulative live birth rate defined as the number of pregnancies leading to
        live birth within 6 months of randomisation.
  The trial will compare the use of a microfluidic chip with the use of density gradient
        centrifugation for sperm preparation.
  
        The hypothesis of the study is that the use of the microfluidic chip will improve the
        cumulative live birth rate of IVF compared to the density gradient method.
  
        The trial will be conducted at the Centre of Assisted Reproduction and Embryology at Queen
        Mary Hospital and Kwong Wah Hospital. Infertile patients undergoing IVF treatment will be
        recruited during ovarian stimulation. They will be randomly assigned to one of two groups:
        the microfluidic chip group or the density gradient group. Both the patients and the
        clinicians will be blinded to the group allocation.
  
        The inclusion criteria for the study are infertile women aged under 43 years undergoing
        ovarian stimulation for IVF. The exclusion criteria include women undergoing certain genetic
        testing, male factor infertility requiring surgical sperm retrieval, the use of donor oocytes
        and spermatozoa, certain uterine conditions, previous participation in the study, and
        participation in other randomized trials.
  
        The eligible women will undergo standard IVF procedures, including ovarian stimulation,
        monitoring of follicle growth, trigger for oocyte retrieval, and oocyte retrieval itself. On
        the day of oocyte retrieval, the women will be randomly assigned to either the microfluidic
        chip group or the density gradient group for sperm preparation.
  
        Semen samples will be collected on the day of oocyte retrieval and evaluated according to
        standard guidelines. Sperm DNA damage will also be assessed using an alkaline single-cell gel
        electrophoresis assay. Depending on the randomization, the sperm samples will be prepared
        either using the microfluidic chip or the density gradient centrifugation method.
  
        After sperm preparation, oocytes will be fertilized using either conventional insemination or
        intracytoplasmic sperm injection. Fertilization will be confirmed by the presence of two
        pronuclei. Fresh embryo transfer will be performed 2-5 days after egg retrieval, and luteal
        phase support will be given. Excessive good quality embryos or blastocysts will be
        cryopreserved for future use.
  
        For frozen embryo transfer, embryos or blastocysts will be replaced in subsequent natural or
        hormonal replacement cycles. Pregnancy will be confirmed by a urine pregnancy test, and
        transvaginal ultrasound will be performed to confirm viability and the number of fetuses.
  
        Follow-up will be conducted to retrieve pregnancy and delivery data. The cumulative live
        birth rate will be calculated, and pregnancy outcomes, including birth weights and obstetric
        complications, will be recorded and compared between the two groups.
  
        The study will continue until all cryopreserved embryos or blastocysts are used or until the
        participants become pregnant within 6 months after randomization. The pregnancy complications
        and congenital abnormalities will be monitored through hospital records or patient contact.
  
        Ultimately, the study aims to determine whether the use of the microfluidic chip improves the
        cumulative live birth rate of IVF compared to the density gradient method.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Infertile patients attending IVF treatment 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: (1) the microfluidic chip group and (2) the density gradient group for sperm preparation and subsequent use in fertilization. Other IVF procedures will be the same as our usual practice.
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Both patients and clinicians were blinded from the group allocation i.e. a double blind study.
  measure: cumulative live birth rate
  time frame: within 6 months of randomisation.
  description: cumulative live birth rate defined as the number of pregnancies leading to live birth within 6 months of randomisation.
  measure: Live birth beyond 22 weeks of gestation per the first embryo transfer or FET
  time frame: 3 years
  description: Live birth beyond 22 weeks of gestation per the first embryo transfer or FET
  measure: Positive urine pregnancy test per the first embryo transfer or FET
  time frame: 3 years
  description: Positive urine pregnancy test per the first embryo transfer or FET
  measure: Clinical pregnancy per the first embryo transfer or FET defined as presence of intrauterine gestational sac on scanning at gestational week 6.
  time frame: 3 years
  description: Clinical pregnancy per the first embryo transfer or FET defined as presence of intrauterine gestational sac on scanning at gestational week 6.
  measure: Ongoing pregnancy rate as presence of a fetal pole with pulsation at 8-10 weeks of gestation
  time frame: 3 years
  description: Ongoing pregnancy rate as presence of a fetal pole with pulsation at 8-10 weeks of gestation
  measure: Miscarriage defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.
  time frame: 3 years
  description: Miscarriage defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.
  measure: Multiple pregnancy: presence of more than one intrauterine sac at 6 weeks of gestation
  time frame: 3 years
  description: Multiple pregnancy: presence of more than one intrauterine sac at 6 weeks of gestation
  measure: Ectopic pregnancy rate
  time frame: 3 years
  description: Ectopic pregnancy rate
  arm group label: microfluidic chip method
  arm group type: Experimental
  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).
  In the microfluidic chip method for sperm sorting, a small amount of semen sample is loaded onto the chip, which contains channels and chambers that allow for the separation of sperm based on their motility and morphology. The chip is designed to mimic the natural environment of the female reproductive tract, where sperm undergo a series of selection processes before reaching the egg.
  arm group label: density-gradient centrifugation method
  arm group type: Active Comparator
  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.
  intervention type: Device
  intervention name: Microfluidic chip
  description: The Sperm Separation Device - ZyMōt Multi 850µL (ZyMōt Fertility, Inc) will be used. The microfluidics chamber will be used according to the manufacturer's instructions. 850 μL of the semen sample will be inserted into the inlet port of the device and 750 μL of fertilization media will be inserted into the outlet port. The device with the semen sample inside will be incubated in 6% CO2 at 37°C. After 30 min, 500 μL of the sample at the outlet port will be removed from the outlet port and pipetted into a labelled test tube.
  arm group label: microfluidic chip method
  intervention type: Device
  intervention name: Density-gradient centrifugation
  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.
  arm group label: density-gradient centrifugation method
  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
  sharing ipd: Undecided