<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/NCT04477356</url>
  </required_header>
  <id_info>
    <org_study_id>CS/BVMDPN/20/02</org_study_id>
    <nct_id>NCT04477356</nct_id>
  </id_info>
  <brief_title>SU Versus GD for Sperm Preparation in IUI</brief_title>
  <official_title>The Effectiveness of Swim-up Versus Gradient Density for Sperm Preparation in Patients Undergoing Intrauterine Insemination: A Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mỹ Đức Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mỹ Đức Phú Nhuận Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mỹ Đức Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intrauterine insemination (IUI) is the first-line treatment for couples with unexplained and&#xD;
      mild male factor infertility. The result of IUI depends on many factors including the sperm&#xD;
      preparation techniques. Swim-up (SU) and Density Gradient (DG) are the two most commonly used&#xD;
      techniques in sperm preparation for IUI. There is discussion about the effectiveness of these&#xD;
      two techniques for IUI outcomes. The effectiveness of SU and DG methods on IUI success rate&#xD;
      is not clearly understood and is controversial. This multicenter, randomized controlled trial&#xD;
      will be conducted to determine which method (DG or SU) is better for IUI treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Potentially eligible patients will be given information about the study on day 2 or day 3 of&#xD;
      the menstrual cycle, when the ovarian stimulation starts. Screening for eligibility will be&#xD;
      performed by treating physicians on the day of IUI, after having obtained the semen qualified&#xD;
      for inclusion criteria from the husband. Eligible participants will be invited to a full&#xD;
      discussion with investigators about the study and will be given the informed consent form.&#xD;
      Couples will have enough time to decide if they agree to participate in the study or not.&#xD;
      Written informed consent will be obtained by the investigators from all couples prior to&#xD;
      enrolment. When a participant signs an informed consent, she is considered to be enrolled in&#xD;
      the study.&#xD;
&#xD;
      Eligible patients who have provided informed consent will be randomized in a 1:1 ratio to&#xD;
      either SU or GD. Assignment to treatment allocation will be done via a web portal hosted by&#xD;
      HOPE Research Center, Vietnam. The randomization schedule will be computer-generated at HOPE&#xD;
      Research Center, with a permuted random block size of 2, 4, and 6. Blinding will not be&#xD;
      possible due to the nature of interventions.&#xD;
&#xD;
      Ovarian stimulation will be performed by using human menopausal gonadotrophins (hMG) (IVF-M,&#xD;
      LG Life science, Korea) and follicular development will be monitored by transvaginal&#xD;
      ultrasound every 3 - 5 days begin on day 2 or day 3 of the menstrual cycle. An injection of&#xD;
      human chorionic gonadotropin (hCG) (IVF-C 5000 IU, LG Life Science, Korea) will be given to&#xD;
      trigger ovulation when the mean diameter of the dominant follicle reached ≥ 18 mm. Those who&#xD;
      have more than 7 follicles ≥ 14 mm will be subjected to cancel or convert to IVM. IUI will be&#xD;
      scheduled 36 - 38 hours after hCG injection.&#xD;
&#xD;
      A sperm sample will be obtained in the clinic by masturbation after 2-5 day of abstinence.&#xD;
      Spoken and written instructions about the collection of the semen sample will be given in&#xD;
      advance. The time between semen production and processing will be up to 1 hour. Sperm&#xD;
      preparation will be performed after the patient agrees to participate in the study.&#xD;
&#xD;
      In couples allocated to the sperm swim-up technique (SU): the normal and highly motile sperm&#xD;
      will move against the gravity and separate from the dead or abnormal sperms to swim up to the&#xD;
      upper media culture layer In couples allocated to the sperm density gradient centrifugation&#xD;
      technique (GD): the density in which mature and normal sperms are capable of passing through&#xD;
      filtration layer to be isolated from dead or abnormal sperms in semen Prepared sperms will be&#xD;
      transferred into uterus by soft catheter (Gynétics, Belgium). Luteal-phase support will be&#xD;
      done with vaginal progesterone 400 mg per day (Cyclogest 200 mg, Actavis, UK) until 7th week&#xD;
      of gestation. In both groups, clinicians who perform insemination will be blinded to the&#xD;
      intervention.&#xD;
&#xD;
      The prepared sperms will be proceeded to medical doctor who will carry the IUI and have no&#xD;
      information about the semen preparation step. After insemination, the patient will be asked&#xD;
      to immobilize for 15 minutes. The patient will receive luteal phase support using vaginal&#xD;
      micronized progesterone for 14 days. In both groups, blood hCG will be measured at day 14&#xD;
      after insemination, and positive results indicate biochemical pregnancy. If the gestational&#xD;
      sac is observed with ultrasonography at week 7 after transferring, clinical pregnancy will be&#xD;
      confirmed. At the 11th and 12nd weeks of gestation, participants will be referred to the&#xD;
      Outpatient clinic, OB/GYN Department at My Duc hospital or at My Duc Phu Nhuan hospital for&#xD;
      prenatal care until delivery. When the participant attends for delivery, data on labor and&#xD;
      delivery, any complications experienced by participant, and the neonates will be collected.&#xD;
      For those who cannot participate the prenatal care program at either the two hospitals, for&#xD;
      any reasons, we will contact the participants via telephone/email monthly until delivery to&#xD;
      collect data. We also ask these participants to scan their profile in every contact.&#xD;
&#xD;
      All analyses will be conducted on an intention-to-treat basis using the R statistical program&#xD;
      The rate of live birth and the associated 95% confidence interval (CI) will be estimated and&#xD;
      compared between groups using the exact method for binomial proportion.&#xD;
&#xD;
      Differences between groups in secondary outcome variables will be analyzed using Student&#xD;
      t-test or Wilcoxon signed-rank test for normally distributed or skewed variables, and&#xD;
      Fisher's exact test for categorical variables, and reported as relative risk (RR) with 95%&#xD;
      CI. Besides that, we will conduct the subgroup analysis to compare the effectiveness of DG&#xD;
      and that of SU for each of criteria within the following categories including causes of&#xD;
      infertility, quality of pre-washing semen, and total number of post-washing motile sperms.&#xD;
      For the number of motile sperms after washing, we divide it into 5 subgroups including &lt; 1&#xD;
      million sperms, 1-5 million sperms, 5-10 million sperms, 10-20 million sperms, and &gt; 20&#xD;
      million sperms.&#xD;
&#xD;
      For missing population characteristics, first, we will analyze by removing the missing data;&#xD;
      then we perform multiple imputations of lost values and perform another analysis to estimate&#xD;
      the certainty of these obtained results. In case of losing track of patients or making&#xD;
      protocol mistakes, we will try performing sensitivity analysis to evaluate the effects of&#xD;
      these factors in the study. A statistical analysis plan will be made and signed before&#xD;
      data-lock.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 30, 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>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
    <masking_description>The prepared sperms will be proceeded to medical doctor who will carry the IUI and have no information about the semen preparation step.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Live birth rate</measure>
    <time_frame>At 24 weeks of gestation</time_frame>
    <description>Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilization, after 24 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown. In the analysis for the primary endpoint, twin delivery will be considered.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total motile sperm count after sperm preparation</measure>
    <time_frame>At 5 minutes after sperm preparation for IUI</time_frame>
    <description>Total motile sperm count after sperm preparation, measured by million sperm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical pregnancy rate</measure>
    <time_frame>At 14 days after insemination</time_frame>
    <description>Biochemical pregnancy defined as a serum beta-hCG level greater than 25 mIU/ml at day 14 after insemination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rate</measure>
    <time_frame>At 7 weeks of gestation</time_frame>
    <description>Clinical pregnancy defined as the presence of at least one gestational sac on ultrasound at week 7 of gestation with the detection of heart beat activity, after insemination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate (OPR)</measure>
    <time_frame>At the 12 weeks of gestation</time_frame>
    <description>Ongoing pregnancy is defined as a living intrauterine fetus at the 12th week of gestation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ectopic pregnancy rate</measure>
    <time_frame>At 5-7 weeks of gestation</time_frame>
    <description>Ectopic pregnancy defined as a pregnancy in which implantation takes place outside the uterine cavity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple pregnancy rate</measure>
    <time_frame>At 7 weeks of gestation</time_frame>
    <description>Multiple pregnancy defined as two or more gestational sacs or two or more positive heart beats by transvaginal sonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vanishing twin rate</measure>
    <time_frame>In the first trimester pregnancy</time_frame>
    <description>Vanishing twin defined as the spontaneous reduction of a fetus while still in uterus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Miscarriage rate</measure>
    <time_frame>Before 22 weeks of gestational age</time_frame>
    <description>Miscarriage defined as spontaneous loss of a clinical pregnancy before week 22 of gestational age, in which the embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gestational age at delivery</measure>
    <time_frame>At birth</time_frame>
    <description>Gestational age at delivery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stillbirth rate</measure>
    <time_frame>After 28 completed weeks of gestational age</time_frame>
    <description>Stillbirth defined as the death of a fetus prior to the complete expulsion or extraction from its mother.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preterm labor rate</measure>
    <time_frame>At birth</time_frame>
    <description>Preterm delivery is defined as any delivery at &lt;24, &lt;28, &lt;32, &lt;37 completed weeks' gestation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spontaneous preterm birth rate</measure>
    <time_frame>At birth</time_frame>
    <description>Spontaneous preterm birth is defined as delivery spontaneously at &lt;24, &lt;28, &lt;32, &lt;37 completed weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iatrogenic preterm birth rate</measure>
    <time_frame>At birth</time_frame>
    <description>Iatrogenic preterm birth is defined as delivery non-spontaneously at &lt;24, &lt;28, &lt;32, &lt;37 completed weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birth weight</measure>
    <time_frame>At birth</time_frame>
    <description>Weight of newborn</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low birth weight rate</measure>
    <time_frame>At birth</time_frame>
    <description>Low birth weight is defined as &lt;2500 gm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Very low birth weight rate</measure>
    <time_frame>At birth</time_frame>
    <description>Very low birth weight is defined as &lt;1500 gm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High birth weight rate</measure>
    <time_frame>At birth</time_frame>
    <description>High birth weight is defined as &gt;4000 gm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Very high birth weight rate</measure>
    <time_frame>At birth</time_frame>
    <description>Very high birth weight is defined as &gt;4500 gm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-minute Apgar score</measure>
    <time_frame>1 minute after delivery</time_frame>
    <description>1-minute Apgar score (0-10 score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5-minutes Apgar score</measure>
    <time_frame>5 minutes after delivery</time_frame>
    <description>5-minutes Apgar score (0-10 score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Admission to NICU rate</measure>
    <time_frame>7 days after delivery</time_frame>
    <description>The admittance of the newborn to NICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Congenital abnormalities rate</measure>
    <time_frame>At birth</time_frame>
    <description>Any congenital abnormalities detected in the newborn</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">912</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Swim-up technique (SU)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The SU method's principle is that the normal and highly motile sperm will move against the gravity and separate from the dead or abnormal sperms to swim up to the upper media culture layer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Density gradient centrifugation technique (DG)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The DG method is based on the density in which mature and normal sperms are capable of passing through filtration layer to be isolated from dead or abnormal sperms in semen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>SU</intervention_name>
    <description>Aliquot 1.2 ml Ferticult Flushing media (Fertipro, Belgium) into 14 ml tube and then gently add 1 ml semen sample to the bottom of the tube (in case of larger semen volume, use multiple 14 ml tubes). The tubes then will be hold at an angle of 45 degrees for 45-60 minutes at 37C. Collect 1 ml of supernatant and then wash with 2 ml Ferticult Flushing media by centrifugation at 1200 RPM for 10 minutes. Keeping 0.3 ml washed semen for IUI, sperm density counting. Prepared sperms will be transferred into uterus by soft catheter (Gynétics, Belgium).</description>
    <arm_group_label>Swim-up technique (SU)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>DG</intervention_name>
    <description>Add 1.5 ml Sil-select 90% first and then 1.5 ml Sil-select 45% (Fertipro, Belgium) into centrifuge tube, then gently add 1 - 1.5 ml semen on the top of Sil-select layer and centrifuge at 1200 RPM for 15 minutes. Discard upper layer, collect 0.5 ml lower layer into new tube and then wash with 2 ml Ferticult Flushing media at 1200 RPM for 10 minutes. Discard upper layer then collect 0.3 ml lower layer for IUI, sperm density counting. Prepared sperms will be transferred into uterus by soft catheter (Gynétics, Belgium).</description>
    <arm_group_label>Density gradient centrifugation technique (DG)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient undergoing IUI&#xD;
&#xD;
          -  Undergone ≤ 2 previous IUI cycles&#xD;
&#xD;
          -  Progressive motility (PR) before sperm preparation: ≥ 32%&#xD;
&#xD;
          -  Sperm concentration before sperm preparation: ≥ 5 million/ml&#xD;
&#xD;
          -  Total progressive motility sperm count before sperm preparation: &gt; 5million&#xD;
&#xD;
          -  Agree to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Using frozen semen&#xD;
&#xD;
          -  High viscosity semen&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Vinh Q Dang, MD</last_name>
    <phone>+84908225481</phone>
    <email>BSVINH.DQ@MYDUCHOSPITAL.VN</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tuyen D Duong, MSc</last_name>
    <phone>+8497 9369699</phone>
    <email>tuyen.dnd@myduchospital.com.vn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dang Q Vinh</name>
      <address>
        <city>Hochiminh city</city>
        <country>Vietnam</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vinh Q Dang, MD</last_name>
      <phone>+84908225481</phone>
      <email>BSVINH.DQ@MYDUCHOSPITAL.VN</email>
    </contact>
  </location>
  <location_countries>
    <country>Vietnam</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>March 16, 2023</last_update_submitted>
  <last_update_submitted_qc>March 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Swim-up (SU)</keyword>
  <keyword>Gradient density (GD)</keyword>
  <keyword>IUI</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>


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/NCT04477356
org study id: CS/BVMDPN/20/02
nct id: NCT04477356
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Intrauterine insemination (IUI) is the first-line treatment for couples with unexplained and
      mild male factor infertility. The result of IUI depends on many factors including the sperm
      preparation techniques. Swim-up (SU) and Density Gradient (DG) are the two most commonly used
      techniques in sperm preparation for IUI. There is discussion about the effectiveness of these
      two techniques for IUI outcomes. The effectiveness of SU and DG methods on IUI success rate
      is not clearly understood and is controversial. This multicenter, randomized controlled trial
      will be conducted to determine which method (DG or SU) is better for IUI treatment.
Potentially eligible patients will be given information about the study on day 2 or day 3 of
      the menstrual cycle, when the ovarian stimulation starts. Screening for eligibility will be
      performed by treating physicians on the day of IUI, after having obtained the semen qualified
      for inclusion criteria from the husband. Eligible participants will be invited to a full
      discussion with investigators about the study and will be given the informed consent form.
      Couples will have enough time to decide if they agree to participate in the study or not.
      Written informed consent will be obtained by the investigators from all couples prior to
      enrolment. When a participant signs an informed consent, she is considered to be enrolled in
      the study.

      Eligible patients who have provided informed consent will be randomized in a 1:1 ratio to
      either SU or GD. Assignment to treatment allocation will be done via a web portal hosted by
      HOPE Research Center, Vietnam. The randomization schedule will be computer-generated at HOPE
      Research Center, with a permuted random block size of 2, 4, and 6. Blinding will not be
      possible due to the nature of interventions.

      Ovarian stimulation will be performed by using human menopausal gonadotrophins (hMG) (IVF-M,
      LG Life science, Korea) and follicular development will be monitored by transvaginal
      ultrasound every 3 - 5 days begin on day 2 or day 3 of the menstrual cycle. An injection of
      human chorionic gonadotropin (hCG) (IVF-C 5000 IU, LG Life Science, Korea) will be given to
      trigger ovulation when the mean diameter of the dominant follicle reached ≥ 18 mm. Those who
      have more than 7 follicles ≥ 14 mm will be subjected to cancel or convert to IVM. IUI will be
      scheduled 36 - 38 hours after hCG injection.

      A sperm sample will be obtained in the clinic by masturbation after 2-5 day of abstinence.
      Spoken and written instructions about the collection of the semen sample will be given in
      advance. The time between semen production and processing will be up to 1 hour. Sperm
      preparation will be performed after the patient agrees to participate in the study.

      In couples allocated to the sperm swim-up technique (SU): the normal and highly motile sperm
      will move against the gravity and separate from the dead or abnormal sperms to swim up to the
      upper media culture layer In couples allocated to the sperm density gradient centrifugation
      technique (GD): the density in which mature and normal sperms are capable of passing through
      filtration layer to be isolated from dead or abnormal sperms in semen Prepared sperms will be
      transferred into uterus by soft catheter (Gynétics, Belgium). Luteal-phase support will be
      done with vaginal progesterone 400 mg per day (Cyclogest 200 mg, Actavis, UK) until 7th week
      of gestation. In both groups, clinicians who perform insemination will be blinded to the
      intervention.

      The prepared sperms will be proceeded to medical doctor who will carry the IUI and have no
      information about the semen preparation step. After insemination, the patient will be asked
      to immobilize for 15 minutes. The patient will receive luteal phase support using vaginal
      micronized progesterone for 14 days. In both groups, blood hCG will be measured at day 14
      after insemination, and positive results indicate biochemical pregnancy. If the gestational
      sac is observed with ultrasonography at week 7 after transferring, clinical pregnancy will be
      confirmed. At the 11th and 12nd weeks of gestation, participants will be referred to the
      Outpatient clinic, OB/GYN Department at My Duc hospital or at My Duc Phu Nhuan hospital for
      prenatal care until delivery. When the participant attends for delivery, data on labor and
      delivery, any complications experienced by participant, and the neonates will be collected.
      For those who cannot participate the prenatal care program at either the two hospitals, for
      any reasons, we will contact the participants via telephone/email monthly until delivery to
      collect data. We also ask these participants to scan their profile in every contact.

      All analyses will be conducted on an intention-to-treat basis using the R statistical program
      The rate of live birth and the associated 95% confidence interval (CI) will be estimated and
      compared between groups using the exact method for binomial proportion.

      Differences between groups in secondary outcome variables will be analyzed using Student
      t-test or Wilcoxon signed-rank test for normally distributed or skewed variables, and
      Fisher's exact test for categorical variables, and reported as relative risk (RR) with 95%
      CI. Besides that, we will conduct the subgroup analysis to compare the effectiveness of DG
      and that of SU for each of criteria within the following categories including causes of
      infertility, quality of pre-washing semen, and total number of post-washing motile sperms.
      For the number of motile sperms after washing, we divide it into 5 subgroups including < 1
      million sperms, 1-5 million sperms, 5-10 million sperms, 10-20 million sperms, and > 20
      million sperms.

      For missing population characteristics, first, we will analyze by removing the missing data;
      then we perform multiple imputations of lost values and perform another analysis to estimate
      the certainty of these obtained results. In case of losing track of patients or making
      protocol mistakes, we will try performing sensitivity analysis to evaluate the effects of
      these factors in the study. A statistical analysis plan will be made and signed before
      data-lock.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
masking description: The prepared sperms will be proceeded to medical doctor who will carry the IUI and have no information about the semen preparation step.
measure: Live birth rate
time frame: At 24 weeks of gestation
description: Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilization, after 24 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown. In the analysis for the primary endpoint, twin delivery will be considered.
measure: Total motile sperm count after sperm preparation
time frame: At 5 minutes after sperm preparation for IUI
description: Total motile sperm count after sperm preparation, measured by million sperm
measure: Biochemical pregnancy rate
time frame: At 14 days after insemination
description: Biochemical pregnancy defined as a serum beta-hCG level greater than 25 mIU/ml at day 14 after insemination.
measure: Clinical pregnancy rate
time frame: At 7 weeks of gestation
description: Clinical pregnancy defined as the presence of at least one gestational sac on ultrasound at week 7 of gestation with the detection of heart beat activity, after insemination.
measure: Ongoing pregnancy rate (OPR)
time frame: At the 12 weeks of gestation
description: Ongoing pregnancy is defined as a living intrauterine fetus at the 12th week of gestation.
measure: Ectopic pregnancy rate
time frame: At 5-7 weeks of gestation
description: Ectopic pregnancy defined as a pregnancy in which implantation takes place outside the uterine cavity
measure: Multiple pregnancy rate
time frame: At 7 weeks of gestation
description: Multiple pregnancy defined as two or more gestational sacs or two or more positive heart beats by transvaginal sonography
measure: Vanishing twin rate
time frame: In the first trimester pregnancy
description: Vanishing twin defined as the spontaneous reduction of a fetus while still in uterus.
measure: Miscarriage rate
time frame: Before 22 weeks of gestational age
description: Miscarriage defined as spontaneous loss of a clinical pregnancy before week 22 of gestational age, in which the embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus.
measure: Gestational age at delivery
time frame: At birth
description: Gestational age at delivery.
measure: Stillbirth rate
time frame: After 28 completed weeks of gestational age
description: Stillbirth defined as the death of a fetus prior to the complete expulsion or extraction from its mother.
measure: Preterm labor rate
time frame: At birth
description: Preterm delivery is defined as any delivery at <24, <28, <32, <37 completed weeks' gestation
measure: Spontaneous preterm birth rate
time frame: At birth
description: Spontaneous preterm birth is defined as delivery spontaneously at <24, <28, <32, <37 completed weeks
measure: Iatrogenic preterm birth rate
time frame: At birth
description: Iatrogenic preterm birth is defined as delivery non-spontaneously at <24, <28, <32, <37 completed weeks
measure: Birth weight
time frame: At birth
description: Weight of newborn
measure: Low birth weight rate
time frame: At birth
description: Low birth weight is defined as <2500 gm
measure: Very low birth weight rate
time frame: At birth
description: Very low birth weight is defined as <1500 gm
measure: High birth weight rate
time frame: At birth
description: High birth weight is defined as >4000 gm
measure: Very high birth weight rate
time frame: At birth
description: Very high birth weight is defined as >4500 gm
measure: 1-minute Apgar score
time frame: 1 minute after delivery
description: 1-minute Apgar score (0-10 score)
measure: 5-minutes Apgar score
time frame: 5 minutes after delivery
description: 5-minutes Apgar score (0-10 score)
measure: Admission to NICU rate
time frame: 7 days after delivery
description: The admittance of the newborn to NICU
measure: Congenital abnormalities rate
time frame: At birth
description: Any congenital abnormalities detected in the newborn
arm group label: Swim-up technique (SU)
arm group type: Active Comparator
description: The SU method's principle is that the normal and highly motile sperm will move against the gravity and separate from the dead or abnormal sperms to swim up to the upper media culture layer.
arm group label: Density gradient centrifugation technique (DG)
arm group type: Active Comparator
description: The DG method is based on the density in which mature and normal sperms are capable of passing through filtration layer to be isolated from dead or abnormal sperms in semen.
intervention type: Procedure
intervention name: SU
description: Aliquot 1.2 ml Ferticult Flushing media (Fertipro, Belgium) into 14 ml tube and then gently add 1 ml semen sample to the bottom of the tube (in case of larger semen volume, use multiple 14 ml tubes). The tubes then will be hold at an angle of 45 degrees for 45-60 minutes at 37C. Collect 1 ml of supernatant and then wash with 2 ml Ferticult Flushing media by centrifugation at 1200 RPM for 10 minutes. Keeping 0.3 ml washed semen for IUI, sperm density counting. Prepared sperms will be transferred into uterus by soft catheter (Gynétics, Belgium).
arm group label: Swim-up technique (SU)
intervention type: Procedure
intervention name: DG
description: Add 1.5 ml Sil-select 90% first and then 1.5 ml Sil-select 45% (Fertipro, Belgium) into centrifuge tube, then gently add 1 - 1.5 ml semen on the top of Sil-select layer and centrifuge at 1200 RPM for 15 minutes. Discard upper layer, collect 0.5 ml lower layer into new tube and then wash with 2 ml Ferticult Flushing media at 1200 RPM for 10 minutes. Discard upper layer then collect 0.3 ml lower layer for IUI, sperm density counting. Prepared sperms will be transferred into uterus by soft catheter (Gynétics, Belgium).
arm group label: Density gradient centrifugation technique (DG)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vinh Q Dang, MD
phone: +84908225481
email: BSVINH.DQ@MYDUCHOSPITAL.VN
last name: Tuyen D Duong, MSc
phone: +8497 9369699
email: tuyen.dnd@myduchospital.com.vn
facility: 
status: Recruiting
contact: 
country: Vietnam
responsible party type: Sponsor
mesh term: Infertility
sharing ipd: No