<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/NCT04474522</url>
  </required_header>
  <id_info>
    <org_study_id>UW 20-248</org_study_id>
    <nct_id>NCT04474522</nct_id>
  </id_info>
  <brief_title>RCT of niPGT for Aneuploidy and Morphology Compared With Morphology Alone in IVF</brief_title>
  <official_title>A Randomized Double Blind Controlled Trial of Non-invasive Preimplantation Genetic Testing for Aneuploidy and Morphology Compared With Morphology Alone in in Vitro Fertilisation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      This study is to compare the efficacy in embryo selection based on morphology alone compared&#xD;
      to morphology and non-invasive preimplantation genetic testing for aneuploidy (NIPGT-A) in&#xD;
      infertile women undergoing in vitro fertilization (IVF). We supposed the embryo selection&#xD;
      based on morphology and NIPGT-A results in a higher live birth rate and a lower miscarriage&#xD;
      rate in IVF as compared with that based on morphology alone. Therefore we would like to&#xD;
      conduct a double-blind randomized controlled trial.&#xD;
&#xD;
      Infertile women undergoing IVF will be enrolled. The spent culture medium (SCM) of each&#xD;
      blastocyst will be frozen individually. They will be randomized into two groups: (1) the&#xD;
      intervention group based on morphology and NIPGT-A and (2) the control group based on&#xD;
      morphology alone. In the control group, blastocysts with the best quality morphology will be&#xD;
      replaced first. In the intervention group, blastocysts with the best morphology and euploid&#xD;
      result of SCM will be replaced first.The primary outcome is a live birth per the first embryo&#xD;
      transfer. We would like to compare live birth rates and miscarriage rates between the two&#xD;
      groups.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2021</start_date>
  <completion_date type="Anticipated">September 1, 2024</completion_date>
  <primary_completion_date type="Actual">May 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>Screening</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Live birth</measure>
    <time_frame>Number of live births beyond 22 weeks of gestation</time_frame>
    <description>Birth beyond 22 weeks of gestation per the first FET</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative live birth rate</measure>
    <time_frame>Number of pregnancies leading to live birth within 6 months of randomization</time_frame>
    <description>Number of pregnancies leading to live birth within 6 months of randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to pregnancy</measure>
    <time_frame>1 year</time_frame>
    <description>between time of IVF and pregnancy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive urine pregnancy test</measure>
    <time_frame>Positive urine pregnancy test 14 days after embryo transfer</time_frame>
    <description>Urine pregnancy test positive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy</measure>
    <time_frame>6 weeks</time_frame>
    <description>Presence of intrauterine gestational sac on scanning at gestational week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy</measure>
    <time_frame>10 weeks</time_frame>
    <description>Presence of a fetal pole with pulsation at 8-10 weeks of gestation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Miscarriage defined</measure>
    <time_frame>Pregnancy loss up to 22 weeks</time_frame>
    <description>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</measure>
    <time_frame>more than one intrauterine sac at 6 weeks</time_frame>
    <description>presence of more than one intrauterine sac at 6 weeks of gestation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ectopic pregnancy</measure>
    <time_frame>12 weeks</time_frame>
    <description>Pregnancy not in the uterus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Birth weight</measure>
    <time_frame>1 year</time_frame>
    <description>Pregnancy outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apgar score</measure>
    <time_frame>1 year</time_frame>
    <description>Pregnancy outcome</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Preimplantation Diagnosis</condition>
  <arm_group>
    <arm_group_label>intervention group using morphology and NIPGT-A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Both morphology and NIPGT-A result will be used to prioritize the sequence of embryo transfer in the intervention group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group based on morphology alone</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Morphology only will be used to prioritize the sequence of embryo transfer in the intervention arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Non-invasive Preimplantation genetic testing for aneuploidy status</intervention_name>
    <description>In the intervention group, comprehensive chromosome screening using NGS will be performed according to the recommendations of the company in all SCM samples. Sequence of replacement shall be altered by the NiPGT result after morpholgy.</description>
    <arm_group_label>intervention group using morphology and NIPGT-A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women aged less than 43 years at the time of ovarian stimulation&#xD;
&#xD;
          -  At least two blastocysts suitable for freezing on day 5 or 6 after oocyte retrieval&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Less than two blastocysts suitable for freezing on day 5 or 6 after oocyte retrieval;&#xD;
&#xD;
          -  Women undergoing PGT for monogenic diseases or structural rearrangement of&#xD;
             chromosomes;&#xD;
&#xD;
          -  Use of donor oocytes;&#xD;
&#xD;
          -  Hydrosalpinx shown on pelvic scanning and not surgically treated&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>43 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ernest HY Ng, MD</last_name>
    <role>Study Director</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Heidi Cheng, MBBS</last_name>
    <phone>852-22553657</phone>
    <email>chy610a@ha.org.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>
  <results_reference>
    <citation>Spandorfer SD, Davis OK, Barmat LI, Chung PH, Rosenwaks Z. Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss. Fertil Steril. 2004 May;81(5):1265-9. doi: 10.1016/j.fertnstert.2003.09.057.</citation>
    <PMID>15136087</PMID>
  </results_reference>
  <results_reference>
    <citation>Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R203-8. doi: 10.1093/hmg/ddm243.</citation>
    <PMID>17911163</PMID>
  </results_reference>
  <results_reference>
    <citation>Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000 Jun 24;320(7251):1708-12. doi: 10.1136/bmj.320.7251.1708.</citation>
    <PMID>10864550</PMID>
  </results_reference>
  <results_reference>
    <citation>Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update. 2011 Jul-Aug;17(4):454-66. doi: 10.1093/humupd/dmr003. Epub 2011 Apr 29. Erratum In: Hum Reprod Update. 2013 Mar-Apr;19(2):206.</citation>
    <PMID>21531751</PMID>
  </results_reference>
  <results_reference>
    <citation>Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012 May 2;5(1):24. doi: 10.1186/1755-8166-5-24.</citation>
    <PMID>22551456</PMID>
  </results_reference>
  <results_reference>
    <citation>Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013 Sep;100(3):697-703. doi: 10.1016/j.fertnstert.2013.04.035. Epub 2013 Jun 1.</citation>
    <PMID>23731996</PMID>
  </results_reference>
  <results_reference>
    <citation>Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, Treff NR, Scott RT Jr. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013 Jul;100(1):100-7.e1. doi: 10.1016/j.fertnstert.2013.02.056. Epub 2013 Mar 30.</citation>
    <PMID>23548942</PMID>
  </results_reference>
  <results_reference>
    <citation>Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E, Cottone G, Kokocinski F, Michel CE. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril. 2014 May;101(5):1375-82. doi: 10.1016/j.fertnstert.2014.01.051. Epub 2014 Mar 6.</citation>
    <PMID>24613537</PMID>
  </results_reference>
  <results_reference>
    <citation>Evans J, Hannan NJ, Edgell TA, Vollenhoven BJ, Lutjen PJ, Osianlis T, Salamonsen LA, Rombauts LJ. Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update. 2014 Nov-Dec;20(6):808-21. doi: 10.1093/humupd/dmu027. Epub 2014 Jun 10.</citation>
    <PMID>24916455</PMID>
  </results_reference>
  <results_reference>
    <citation>Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.</citation>
    <PMID>25432917</PMID>
  </results_reference>
  <results_reference>
    <citation>Munne S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M, Wells D, Gordon T, Stock-Myer S, Willman S; STAR Study Group. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019 Dec;112(6):1071-1079.e7. doi: 10.1016/j.fertnstert.2019.07.1346. Epub 2019 Sep 21.</citation>
    <PMID>31551155</PMID>
  </results_reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>August 21, 2023</last_update_submitted>
  <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal 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>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aneuploidy</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/NCT04474522
org study id: UW 20-248
nct id: NCT04474522
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is to compare the efficacy in embryo selection based on morphology alone compared
      to morphology and non-invasive preimplantation genetic testing for aneuploidy (NIPGT-A) in
      infertile women undergoing in vitro fertilization (IVF). We supposed the embryo selection
      based on morphology and NIPGT-A results in a higher live birth rate and a lower miscarriage
      rate in IVF as compared with that based on morphology alone. Therefore we would like to
      conduct a double-blind randomized controlled trial.

      Infertile women undergoing IVF will be enrolled. The spent culture medium (SCM) of each
      blastocyst will be frozen individually. They will be randomized into two groups: (1) the
      intervention group based on morphology and NIPGT-A and (2) the control group based on
      morphology alone. In the control group, blastocysts with the best quality morphology will be
      replaced first. In the intervention group, blastocysts with the best morphology and euploid
      result of SCM will be replaced first.The primary outcome is a live birth per the first embryo
      transfer. We would like to compare live birth rates and miscarriage rates between the two
      groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Live birth
time frame: Number of live births beyond 22 weeks of gestation
description: Birth beyond 22 weeks of gestation per the first FET
measure: Cumulative live birth rate
time frame: Number of pregnancies leading to live birth within 6 months of randomization
description: Number of pregnancies leading to live birth within 6 months of randomization
measure: Time to pregnancy
time frame: 1 year
description: between time of IVF and pregnancy
measure: Positive urine pregnancy test
time frame: Positive urine pregnancy test 14 days after embryo transfer
description: Urine pregnancy test positive
measure: Clinical pregnancy
time frame: 6 weeks
description: Presence of intrauterine gestational sac on scanning at gestational week 6
measure: Ongoing pregnancy
time frame: 10 weeks
description: Presence of a fetal pole with pulsation at 8-10 weeks of gestation
measure: Miscarriage defined
time frame: Pregnancy loss up to 22 weeks
description: Clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.
measure: Multiple pregnancy
time frame: more than one intrauterine sac at 6 weeks
description: presence of more than one intrauterine sac at 6 weeks of gestation
measure: Ectopic pregnancy
time frame: 12 weeks
description: Pregnancy not in the uterus
measure: Birth weight
time frame: 1 year
description: Pregnancy outcome
measure: Apgar score
time frame: 1 year
description: Pregnancy outcome
arm group label: intervention group using morphology and NIPGT-A
arm group type: Active Comparator
description: Both morphology and NIPGT-A result will be used to prioritize the sequence of embryo transfer in the intervention group.
arm group label: control group based on morphology alone
arm group type: No Intervention
description: Morphology only will be used to prioritize the sequence of embryo transfer in the intervention arm.
intervention type: Genetic
intervention name: Non-invasive Preimplantation genetic testing for aneuploidy status
description: In the intervention group, comprehensive chromosome screening using NGS will be performed according to the recommendations of the company in all SCM samples. Sequence of replacement shall be altered by the NiPGT result after morpholgy.
arm group label: intervention group using morphology and NIPGT-A
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 43 Years
healthy volunteers: No
last name: Ernest HY Ng, MD
role: Study Director
affiliation: The University of Hong Kong
last name: Heidi Cheng, MBBS
phone: 852-22553657
email: chy610a@ha.org.hk
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Spandorfer SD, Davis OK, Barmat LI, Chung PH, Rosenwaks Z. Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss. Fertil Steril. 2004 May;81(5):1265-9. doi: 10.1016/j.fertnstert.2003.09.057.
PMID: 15136087
citation: Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R203-8. doi: 10.1093/hmg/ddm243.
PMID: 17911163
citation: Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000 Jun 24;320(7251):1708-12. doi: 10.1136/bmj.320.7251.1708.
PMID: 10864550
citation: Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update. 2011 Jul-Aug;17(4):454-66. doi: 10.1093/humupd/dmr003. Epub 2011 Apr 29. Erratum In: Hum Reprod Update. 2013 Mar-Apr;19(2):206.
PMID: 21531751
citation: Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012 May 2;5(1):24. doi: 10.1186/1755-8166-5-24.
PMID: 22551456
citation: Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013 Sep;100(3):697-703. doi: 10.1016/j.fertnstert.2013.04.035. Epub 2013 Jun 1.
PMID: 23731996
citation: Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, Treff NR, Scott RT Jr. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013 Jul;100(1):100-7.e1. doi: 10.1016/j.fertnstert.2013.02.056. Epub 2013 Mar 30.
PMID: 23548942
citation: Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E, Cottone G, Kokocinski F, Michel CE. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril. 2014 May;101(5):1375-82. doi: 10.1016/j.fertnstert.2014.01.051. Epub 2014 Mar 6.
PMID: 24613537
citation: Evans J, Hannan NJ, Edgell TA, Vollenhoven BJ, Lutjen PJ, Osianlis T, Salamonsen LA, Rombauts LJ. Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update. 2014 Nov-Dec;20(6):808-21. doi: 10.1093/humupd/dmu027. Epub 2014 Jun 10.
PMID: 24916455
citation: Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.
PMID: 25432917
citation: Munne S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M, Wells D, Gordon T, Stock-Myer S, Willman S; STAR Study Group. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019 Dec;112(6):1071-1079.e7. doi: 10.1016/j.fertnstert.2019.07.1346. Epub 2019 Sep 21.
PMID: 31551155
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Professor Ernest Hung-Yu Ng
investigator title: Professor
mesh term: Aneuploidy
sharing ipd: No