<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/NCT03027843</url>
  </required_header>
  <id_info>
    <org_study_id>newivf20170110</org_study_id>
    <nct_id>NCT03027843</nct_id>
  </id_info>
  <brief_title>The Effect of Growth Hormone in Assisted Reproductive Technology Clinical Outcome of Poor Responder</brief_title>
  <official_title>A Pilot Study of the Effect of Growth Hormone in Assisted Reproductive Technology Clinical Outcome of Poor Responder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</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>
      Assisted reproduction treatment in patients with low ovarian reserve is a big difficult&#xD;
      clinical problem. Growth hormone (GH) is crucial in the development of follicles since&#xD;
      preantral follicle to ovulation and can promote steroid hormones and gamete formation,&#xD;
      increase the granular cell sensitivity,and inhibition of follicular atresia. Latest research&#xD;
      shows that GH can improve egg quality through regulating mitochondrial function of the&#xD;
      oocytes and increase the rate of embryo euploid. It becomes a new argument in that promotion&#xD;
      of clinical pregnancy rate in assisted reproduction treatment. GH applied in the field of&#xD;
      assisted reproduction 30 years experience of applicable people, but drug dosage, drug&#xD;
      intervention time continue to explore. 2015 China assisted reproductive stimulate ovulation&#xD;
      medicine expert consensus recommend joint GH for poor ovarian response, repeated implantation&#xD;
      failure patients and older patients assisted fertility treatment, but not on the specific use&#xD;
      time limit, the daily dose of drugs and curative effect. How to maximize growth hormone&#xD;
      potential advantage in improving the egg quality bothers the clinical doctors. We had a&#xD;
      self-controlled retrospective analyses in growth hormone application and found that the&#xD;
      average daily injections of GH dose 2 iu for 45 days can significantly improve the embryo&#xD;
      quality in patients with low ovarian reaction. And now long-acting recombinant human growth&#xD;
      hormone is available, which make it convenient for patients. A forward-looking experimental&#xD;
      is expected to answer clinical practical problems and provide proper GH regimen for low&#xD;
      ovarian responder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a pilot study to investigate the effect of growth hormone in assisted&#xD;
      reproductive technology clinical outcome of poor responder.&#xD;
&#xD;
      Design: randomized controlled trial. Setting: Assisted reproductive technologies unit.&#xD;
      Patients: patients diagnosed poor ovarian responder who is in accordance with the inclusion&#xD;
      criteria, and not meet the exclusion criteria, who had repeated IVF treatment from Mar 2017&#xD;
      to Aug 2019.&#xD;
&#xD;
      Intervention: The comparison was made between GH group and the control group, both groups are&#xD;
      conducted with the mini-dose GnRH-a long protocol for IVF treatment. GH group use Long-acting&#xD;
      recombinant human growth hormone 14IU qw, until the day of hCG.&#xD;
&#xD;
      Main outcome measures: The primary outcome of the study is live birth rate. The secondary&#xD;
      outcomes were clinical pregnancy rate, number of oocytes retrieved, fertility rate, normal&#xD;
      fertilization rate, rate of transferable embryo and good quality embryo rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 2017</start_date>
  <completion_date type="Anticipated">April 2020</completion_date>
  <primary_completion_date type="Anticipated">August 2019</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>live birth rate</measure>
    <time_frame>1-2year</time_frame>
    <description>Live birth rate(%): number of live birth/ transferred cycle.Compare the live birth rate between the two group with SPSS 20.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>clinical pregnancy rate</measure>
    <time_frame>1-2 year</time_frame>
    <description>Clinical pregnancy means pregnancy sac is seen intrauterine under ultrasound 7 weeks after embryo transferred. Clinical pregnancy rate(%): number of clinical pregnancy/transferred cycle.Compare the clinical pregnancy rate between the two group with SPSS 20.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of oocytes retrieved</measure>
    <time_frame>1-2 year</time_frame>
    <description>Compare the number of oocytes retrieved between the two group with SPSS 20.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fertility rate</measure>
    <time_frame>1-2 year</time_frame>
    <description>Fertility rate(%): number of occyte fertilized/ number of oocytes retrieved. Compare the fertility rate between the two group with SPSS 20.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>normal fertility rate</measure>
    <time_frame>1-2 year</time_frame>
    <description>Normal fertility rate(%): number of occyte normally fertilized/ number of oocytes retrieved. Compare the normal fertility rate between the two group with SPSS 20.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>transferable embryo rate</measure>
    <time_frame>1-2 year</time_frame>
    <description>Cleavage embryo grades 1 or 2 with at least 5 blastomeres are considered as transferrable embryo.Transferable embryo rate(%): number of transferable embryo/number of feritilized oocytes. Compare the transferable embryo rate between the two group with SPSS 20.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>good quality embryo rate</measure>
    <time_frame>1-2 year</time_frame>
    <description>Cleavage embryo grades 1 or 2 with 6-10 blastomeres were considered good quality embryos. Good quality embryo rate(%): number of good quality embryo/number of feritilized oocytes.Compare the good quality embryo rate between the two group with SPSS 20.0.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Low Ovarian Reserve</condition>
  <arm_group>
    <arm_group_label>GH group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients in group mini-dose GnRH-a long protocol combine with growth hormone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>patients in group mini-dose GnRH-a long protocol without growth hormone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Growth Hormone</intervention_name>
    <description>in GH group, patients have weekly injections of GH dose 14 iu, until the day of hCG.</description>
    <arm_group_label>GH group</arm_group_label>
    <other_name>somatotropin;GH;somatotrophin;somatotropic</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women age ≥35 years and ≤40 years.&#xD;
&#xD;
          2. 2≤ AFC≤6, and AMH level ≥0.5 and≤ 1.1 ng/ml.&#xD;
&#xD;
          3. Previous failed transfer cycle ≥2&#xD;
&#xD;
          4. Didn't participate in other clinical subjects in three months.&#xD;
&#xD;
          5. Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Body mass index (BMI) ≥25 kg/m2.&#xD;
&#xD;
          2. Endocrine metabolic disease, such as diabetes, insulin resistance, hyperthyroidism,&#xD;
             Cushing's syndrome, hyperprolactinemia.&#xD;
&#xD;
          3. Hypertension (systolic blood pressure ≥140mmHg and diastolic blood pressure≥90mmHg.&#xD;
&#xD;
          4. Autoimmune diseases was definitively diagnosed, such as systemic lupus erythematosus,&#xD;
             Sjogren's syndrome, Hashimoto's Thyroiditis, multiple sclerosis, rheumatoid arthritis,&#xD;
             autoimmune hemolytic anemia, recurrent miscarriage.&#xD;
&#xD;
          5. Ovarian neoplasm that ≥4 cm in diameter and has no clear pathological diagnosis by&#xD;
             surgery.&#xD;
&#xD;
          6. Complicated with adenomyosis, endometriosis confirmed by surgery, ovarian&#xD;
             endometriosis cyst ≥2 cm by ultrasound, all kind of malignant tumors or precancerous&#xD;
             disease.&#xD;
&#xD;
          7. Untreated hydrosalpinx.&#xD;
&#xD;
        Eliminate or falls off Criteria:&#xD;
&#xD;
          1. Withdraw drug and take appropriate treatment measures if serious adverse events happen&#xD;
             during the trial, and subjects will be off.&#xD;
&#xD;
          2. Patients that have bad compliance.&#xD;
&#xD;
          3. Subjects are found breach the inclusion criteria, or in accordance with exclusion&#xD;
             criteria during the test, excluded.&#xD;
&#xD;
          4. Patients request withdrawal and exit the trial because adverse events occur during the&#xD;
             trial.&#xD;
&#xD;
          5. No record about treatment.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xing Yang, M.D. &amp; Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>The Sixth Affiliated Hospital,Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xing Yang, M.D. &amp; Ph.D.</last_name>
    <phone>020-38048013</phone>
    <email>yxing_8358@126.com</email>
  </overall_contact>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>January 19, 2017</last_update_submitted>
  <last_update_submitted_qc>January 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yanhong Deng</investigator_full_name>
    <investigator_title>doctor</investigator_title>
  </responsible_party>
  <keyword>low ovarian reserve</keyword>
  <keyword>growth hormone</keyword>
  <keyword>embryo quality</keyword>
  <keyword>live birth</keyword>
  <keyword>clinical pregnancy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03027843
org study id: newivf20170110
nct id: NCT03027843
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Assisted reproduction treatment in patients with low ovarian reserve is a big difficult
      clinical problem. Growth hormone (GH) is crucial in the development of follicles since
      preantral follicle to ovulation and can promote steroid hormones and gamete formation,
      increase the granular cell sensitivity,and inhibition of follicular atresia. Latest research
      shows that GH can improve egg quality through regulating mitochondrial function of the
      oocytes and increase the rate of embryo euploid. It becomes a new argument in that promotion
      of clinical pregnancy rate in assisted reproduction treatment. GH applied in the field of
      assisted reproduction 30 years experience of applicable people, but drug dosage, drug
      intervention time continue to explore. 2015 China assisted reproductive stimulate ovulation
      medicine expert consensus recommend joint GH for poor ovarian response, repeated implantation
      failure patients and older patients assisted fertility treatment, but not on the specific use
      time limit, the daily dose of drugs and curative effect. How to maximize growth hormone
      potential advantage in improving the egg quality bothers the clinical doctors. We had a
      self-controlled retrospective analyses in growth hormone application and found that the
      average daily injections of GH dose 2 iu for 45 days can significantly improve the embryo
      quality in patients with low ovarian reaction. And now long-acting recombinant human growth
      hormone is available, which make it convenient for patients. A forward-looking experimental
      is expected to answer clinical practical problems and provide proper GH regimen for low
      ovarian responder.
This study is a pilot study to investigate the effect of growth hormone in assisted
      reproductive technology clinical outcome of poor responder.

      Design: randomized controlled trial. Setting: Assisted reproductive technologies unit.
      Patients: patients diagnosed poor ovarian responder who is in accordance with the inclusion
      criteria, and not meet the exclusion criteria, who had repeated IVF treatment from Mar 2017
      to Aug 2019.

      Intervention: The comparison was made between GH group and the control group, both groups are
      conducted with the mini-dose GnRH-a long protocol for IVF treatment. GH group use Long-acting
      recombinant human growth hormone 14IU qw, until the day of hCG.

      Main outcome measures: The primary outcome of the study is live birth rate. The secondary
      outcomes were clinical pregnancy rate, number of oocytes retrieved, fertility rate, normal
      fertilization rate, rate of transferable embryo and good quality embryo rate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: live birth rate
time frame: 1-2year
description: Live birth rate(%): number of live birth/ transferred cycle.Compare the live birth rate between the two group with SPSS 20.0.
measure: clinical pregnancy rate
time frame: 1-2 year
description: Clinical pregnancy means pregnancy sac is seen intrauterine under ultrasound 7 weeks after embryo transferred. Clinical pregnancy rate(%): number of clinical pregnancy/transferred cycle.Compare the clinical pregnancy rate between the two group with SPSS 20.0.
measure: number of oocytes retrieved
time frame: 1-2 year
description: Compare the number of oocytes retrieved between the two group with SPSS 20.0.
measure: fertility rate
time frame: 1-2 year
description: Fertility rate(%): number of occyte fertilized/ number of oocytes retrieved. Compare the fertility rate between the two group with SPSS 20.0.
measure: normal fertility rate
time frame: 1-2 year
description: Normal fertility rate(%): number of occyte normally fertilized/ number of oocytes retrieved. Compare the normal fertility rate between the two group with SPSS 20.0.
measure: transferable embryo rate
time frame: 1-2 year
description: Cleavage embryo grades 1 or 2 with at least 5 blastomeres are considered as transferrable embryo.Transferable embryo rate(%): number of transferable embryo/number of feritilized oocytes. Compare the transferable embryo rate between the two group with SPSS 20.0.
measure: good quality embryo rate
time frame: 1-2 year
description: Cleavage embryo grades 1 or 2 with 6-10 blastomeres were considered good quality embryos. Good quality embryo rate(%): number of good quality embryo/number of feritilized oocytes.Compare the good quality embryo rate between the two group with SPSS 20.0.
arm group label: GH group
arm group type: Active Comparator
description: patients in group mini-dose GnRH-a long protocol combine with growth hormone
arm group label: control group
arm group type: No Intervention
description: patients in group mini-dose GnRH-a long protocol without growth hormone
intervention type: Drug
intervention name: Growth Hormone
description: in GH group, patients have weekly injections of GH dose 14 iu, until the day of hCG.
arm group label: GH group
other name: somatotropin;GH;somatotrophin;somatotropic
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Xing Yang, M.D. & Ph.D.
role: Study Director
affiliation: The Sixth Affiliated Hospital,Sun Yat-Sen University
last name: Xing Yang, M.D. & Ph.D.
phone: 020-38048013
email: yxing_8358@126.com
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Yanhong Deng
investigator title: doctor
mesh term: Hormones