<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/NCT02223221</url>
  </required_header>
  <id_info>
    <org_study_id>JIAI E2014-02</org_study_id>
    <nct_id>NCT02223221</nct_id>
  </id_info>
  <brief_title>Effects of PGS in Infertile Female Patients With RPL</brief_title>
  <official_title>Effects of Preimplantation Genetic Screening for Aneuploidies in Infertile Female Patients With Recurrent Spontaneous Abortion History</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ShangHai Ji Ai Genetics &amp; IVF Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ShangHai Ji Ai Genetics &amp; IVF Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recurrent pregnancy loss (RPL) is a multifactorial disorder which affects about 1% of all&#xD;
      couples and challenges both patients and clinicians technically and emotionally. IVF clinics&#xD;
      see higher prevalence of RPL, since many RPL patients are seeking for assist reproduction&#xD;
      treatment with or without other infertile factors. Guidelines for evaluation and treatment of&#xD;
      RPL patients include screening for uterine abnormalities, parental chromosomes, autoimmune&#xD;
      antibodies and cure gynecological infections, but there are still half of RPL patients remain&#xD;
      unexplained.&#xD;
&#xD;
      The documented high incidence of chromosomal errors in first-trimester miscarriages and an&#xD;
      increased rate of aneuploidy in patients with RPL has led to the theory that screening&#xD;
      embryos before implantation for aneuploidy may decrease the risk of a subsequent loss and&#xD;
      serve as a possible treatment. The technology, indications of use, and even terminology for&#xD;
      genetic testing of embryos have greatly changed since the first PGD(pre-implantation genetic&#xD;
      diagnosis) baby was born in 1990. The current best evidence shows blastocyst biopsy followed&#xD;
      by new rapid comprehensive chromosome screening(termed pre-implantation chromosomal screening&#xD;
      or comprehensive chromosome screening, PCS or CCS, or the investigators generally termed PGS)&#xD;
      based on array-comprehensive genome hybridization(aCGH), single nucleotide polymorphism&#xD;
      array(SNP-array) or next generation sequencing(NGS), to be the most powerful technology.&#xD;
      However, for whom this PGS technique is most suitable to achieve improved clinical outcome&#xD;
      have not yet been identified by well defined, ITT based research with carefully selected&#xD;
      control and adequate sample size.&#xD;
&#xD;
      The investigators research is to determine whether in vitro fertilization (IVF)/&#xD;
      intracytoplasmic sperm injection (ICSI) combined with SNP-array based pre-implantation&#xD;
      comprehensive chromosome screening (CCS) will improve the clinical outcome of infertile&#xD;
      female patients with recurrent spontaneous abortion history.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">April 30, 2017</completion_date>
  <primary_completion_date type="Actual">July 31, 2016</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>
  </study_design_info>
  <primary_outcome>
    <measure>Ongoing pregnancy</measure>
    <time_frame>12 weeks after embryo transfer for the patient</time_frame>
    <description>Ongoing pregnancy is defined as a viable intrauterine pregnancy after 12 weeks of embryo transfer.&#xD;
Ongoing pregnancy rate per treatment cycle will also be calculated on intend-to-treat(ITT) basis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Implantation of transferred embryo</measure>
    <time_frame>2 weeks after embryo transfer for the patient</time_frame>
    <description>Implantation rate per embryo transferred will also be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy</measure>
    <time_frame>4 weeks after embryo transfer for the patient</time_frame>
    <description>Clinical pregnancy is defined as the presence of a gestational sac confirmed by transvaginal ultrasound examination.&#xD;
Clinical pregnancy rate per treatment cycle will also be calculated based on ITT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to pregnancy</measure>
    <time_frame>from the date of the first time entering oocyte retrieval cycle until the embryo transfer day of a later assured ongoing pregnancy, accessed up to 24 months during the whole research period</time_frame>
    <description>Time to pregnancy is defined as from the first time entering oocyte retrieval cycle to the embryo transfer day of a later assured ongoing pregnancy, which is up to 24 months within the study period. If the patient fails obtain ongoing pregnancy during the study period, the &quot;time to pregnancy&quot; will not be recorded for the specific patient or be calculated for the &quot;average time to pregnancy&quot; for the arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome</measure>
    <time_frame>up to 42 days of a live birth</time_frame>
    <description>abortion, live birth, multiple births, birth defect, preterm delivery, small-for-gestational age, still birth, maternal complications will be recorded.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">189</enrollment>
  <condition>Infertility, Female</condition>
  <condition>Abortion, Habitual</condition>
  <arm_group>
    <arm_group_label>With PGS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IVF/ICSI cycles with PGS. Select embryos by SNP-array based PGS for the number of all chromosomes on day 5, only euploid embryos will be transferred.&#xD;
A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Without PGS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IVF/ICSI cycles without PGS. Selection of embryos are based on blastocyst morphology criteria on day 5.&#xD;
A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>IVF/ICSI</intervention_name>
    <description>In vitro fertilization or intracytoplasmic sperm injection.</description>
    <arm_group_label>With PGS</arm_group_label>
    <arm_group_label>Without PGS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>PGS</intervention_name>
    <description>Selection of embryos are based on SNP-array-based preimplantation genetic screening for the number of all chromosomes on the 5th day of IVF/ICSI.</description>
    <arm_group_label>With PGS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Without PGS</intervention_name>
    <description>Selection of embryos are based on morphology criteria on the 5th day of IVF/ICSI.</description>
    <arm_group_label>Without PGS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Women 18-48 years of age who are scheduled for IVF or ICSI with a history of recurrent&#xD;
        spontaneous abortion (continous miscarriage occurred earlier than 20 weeks of gestation for&#xD;
        equal or greater than 2 times) in our IVF institute while meeting the following criteria:&#xD;
&#xD;
          1. regular menstrual cycles and normal level of E2, P, FSH, LH, T, RPL in the early&#xD;
             follicular phase;&#xD;
&#xD;
          2. no history of hormone medicine application in the last 3 months;&#xD;
&#xD;
          3. no history of poison contact;&#xD;
&#xD;
          4. normal uterine and adnexal ultrasonography;&#xD;
&#xD;
          5. TORCH(-), chlamydia(-), mycoplasma(-), normal leucorrhoea routine, anti-phospholipid&#xD;
             antibody (-), antinuclear antibody(-);&#xD;
&#xD;
          6. for the couple, no blood type incompatibility or ABO antibody IgG≤1：64 and normal&#xD;
             blood chromosome analysis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. hydrosalpinx without operation; endometriosis; polycystic ovary syndrome; adenomyosis;&#xD;
             uterine leiomyomata(submucous myoma or non-submucous myoma which size was exceed 4cm&#xD;
             and/or with the compressed endometrium);uterine cavity lesions(such as uterine&#xD;
             malformation, intrauterine adhesions, the septate uterus, endometritis etc);&#xD;
&#xD;
          2. the former abortion is because of luteal phase defect without treatment;&#xD;
&#xD;
          3. thyroid dysfunction or increased CA125 level;&#xD;
&#xD;
          4. acute inflammation of genitourinary system or STD carriers;&#xD;
&#xD;
          5. unable to comply with the study procedures.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>48 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>XIAOXI SUN, MD</last_name>
    <role>Study Director</role>
    <affiliation>Shanghai Jiai Genetics &amp; IVF Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>YILUN SUI, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Jiai Genetics &amp; IVF Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shanghai Jiai Genetics &amp; IVF Institute</name>
      <address>
        <city>Shanghai</city>
        <zip>200011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>July 9, 2017</last_update_submitted>
  <last_update_submitted_qc>July 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>In Vitro Fertilization</keyword>
  <keyword>Intracytoplasmic Sperm Injections</keyword>
  <keyword>Infertility, Female</keyword>
  <keyword>Abortion, Habitual</keyword>
  <keyword>recurrent pregnancy loss</keyword>
  <keyword>comprehensive chromosome screening</keyword>
  <keyword>preimplantation genetic screening</keyword>
  <keyword>SNP array</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
    <mesh_term>Abortion, Habitual</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>January 21, 2018</submitted>
    <submission_canceled>Unknown</submission_canceled>
    <submitted>February 5, 2018</submitted>
    <returned>September 28, 2018</returned>
  </pending_results>
  <!-- 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/NCT02223221
org study id: JIAI E2014-02
nct id: NCT02223221
lead sponsor: 
has dmc: Yes
Recurrent pregnancy loss (RPL) is a multifactorial disorder which affects about 1% of all
      couples and challenges both patients and clinicians technically and emotionally. IVF clinics
      see higher prevalence of RPL, since many RPL patients are seeking for assist reproduction
      treatment with or without other infertile factors. Guidelines for evaluation and treatment of
      RPL patients include screening for uterine abnormalities, parental chromosomes, autoimmune
      antibodies and cure gynecological infections, but there are still half of RPL patients remain
      unexplained.

      The documented high incidence of chromosomal errors in first-trimester miscarriages and an
      increased rate of aneuploidy in patients with RPL has led to the theory that screening
      embryos before implantation for aneuploidy may decrease the risk of a subsequent loss and
      serve as a possible treatment. The technology, indications of use, and even terminology for
      genetic testing of embryos have greatly changed since the first PGD(pre-implantation genetic
      diagnosis) baby was born in 1990. The current best evidence shows blastocyst biopsy followed
      by new rapid comprehensive chromosome screening(termed pre-implantation chromosomal screening
      or comprehensive chromosome screening, PCS or CCS, or the investigators generally termed PGS)
      based on array-comprehensive genome hybridization(aCGH), single nucleotide polymorphism
      array(SNP-array) or next generation sequencing(NGS), to be the most powerful technology.
      However, for whom this PGS technique is most suitable to achieve improved clinical outcome
      have not yet been identified by well defined, ITT based research with carefully selected
      control and adequate sample size.

      The investigators research is to determine whether in vitro fertilization (IVF)/
      intracytoplasmic sperm injection (ICSI) combined with SNP-array based pre-implantation
      comprehensive chromosome screening (CCS) will improve the clinical outcome of infertile
      female patients with recurrent spontaneous abortion history.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
measure: Ongoing pregnancy
time frame: 12 weeks after embryo transfer for the patient
description: Ongoing pregnancy is defined as a viable intrauterine pregnancy after 12 weeks of embryo transfer.
Ongoing pregnancy rate per treatment cycle will also be calculated on intend-to-treat(ITT) basis.
measure: Implantation of transferred embryo
time frame: 2 weeks after embryo transfer for the patient
description: Implantation rate per embryo transferred will also be calculated.
measure: Clinical pregnancy
time frame: 4 weeks after embryo transfer for the patient
description: Clinical pregnancy is defined as the presence of a gestational sac confirmed by transvaginal ultrasound examination.
Clinical pregnancy rate per treatment cycle will also be calculated based on ITT.
measure: Time to pregnancy
time frame: from the date of the first time entering oocyte retrieval cycle until the embryo transfer day of a later assured ongoing pregnancy, accessed up to 24 months during the whole research period
description: Time to pregnancy is defined as from the first time entering oocyte retrieval cycle to the embryo transfer day of a later assured ongoing pregnancy, which is up to 24 months within the study period. If the patient fails obtain ongoing pregnancy during the study period, the "time to pregnancy" will not be recorded for the specific patient or be calculated for the "average time to pregnancy" for the arm.
measure: Pregnancy outcome
time frame: up to 42 days of a live birth
description: abortion, live birth, multiple births, birth defect, preterm delivery, small-for-gestational age, still birth, maternal complications will be recorded.
arm group label: With PGS
arm group type: Experimental
description: IVF/ICSI cycles with PGS. Select embryos by SNP-array based PGS for the number of all chromosomes on day 5, only euploid embryos will be transferred.
A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.
arm group label: Without PGS
arm group type: Active Comparator
description: IVF/ICSI cycles without PGS. Selection of embryos are based on blastocyst morphology criteria on day 5.
A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.
intervention type: Procedure
intervention name: IVF/ICSI
description: In vitro fertilization or intracytoplasmic sperm injection.
arm group label: With PGS
arm group label: Without PGS
intervention type: Genetic
intervention name: PGS
description: Selection of embryos are based on SNP-array-based preimplantation genetic screening for the number of all chromosomes on the 5th day of IVF/ICSI.
arm group label: With PGS
intervention type: Other
intervention name: Without PGS
description: Selection of embryos are based on morphology criteria on the 5th day of IVF/ICSI.
arm group label: Without PGS
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 48 Years
healthy volunteers: No
last name: XIAOXI SUN, MD
role: Study Director
affiliation: Shanghai Jiai Genetics & IVF Institute
last name: YILUN SUI, MD
role: Principal Investigator
affiliation: Shanghai Jiai Genetics & IVF Institute
facility: 
country: China
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Abortion, Habitual
submitted: January 21, 2018
submission canceled: Unknown
submitted: February 5, 2018
returned: September 28, 2018