<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/NCT03298750</url>
  </required_header>
  <id_info>
    <org_study_id>SHEBA-15-2289-AK-CTIL</org_study_id>
    <nct_id>NCT03298750</nct_id>
  </id_info>
  <brief_title>Mechanical Stimulation of the Ovary for Infertility Treatment in Patients With Very Low Ovarian Reserve</brief_title>
  <official_title>Mechanical Stimulation of the Ovary for Infertility Treatment in Patients With Very Low Ovarian Reserve</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheba Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sheba Medical Center</source>
  <oversight_info>
    <has_dmc>No</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>
      Examine the possibility that mechanical stimulation and ovarian fragmentation in women with&#xD;
      premature ovarian failure or low ovarian reserve intended for egg donation may cause early&#xD;
      follicular recruitment and increase chances of achieving pregnancy through IVF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The women will undergo a surgical laparoscopy during which one of the two technique will&#xD;
      ensue.&#xD;
&#xD;
        1. One of the ovaries will be scratched ( 2 mm depth) with a knife. Simultaneously, a piece&#xD;
           of the ovary will be preserved for further histologic analysis and research in the&#xD;
           laboratory.&#xD;
&#xD;
        2. A piece of one ovary will be resected (up to one third of the ovary's volume, without&#xD;
           harming the other ovary.&#xD;
&#xD;
      The resected ovarian tissue will be transferred immediately to the laboratory where the&#xD;
      cortex will be divided from the medulla and sliced to small pieces of 1-2 square millimeters.&#xD;
&#xD;
      These pieces will be transferred back to the operation room in order for them to be&#xD;
      transplanted under the serosa layer of the remaining ovary.&#xD;
&#xD;
      Any bleeding would be stopped using a stiches or hemostatic mesh (diathermy will not be&#xD;
      used).&#xD;
&#xD;
      Simultaneously, a piece of the ovary will be preserved for further histologic analysis and&#xD;
      research in the laboratory.&#xD;
&#xD;
      Post operational follow up ( up to two years) including: menstrual cycle surveillance,&#xD;
      hormonal profile, AMH level, US of the pelvis and Antral Follicles Count (AFC).&#xD;
&#xD;
      A month after the surgery, an ovarian stimulation will commence following IVF while close&#xD;
      monitoring the ovarian response and comparing the pre and post operation response.&#xD;
&#xD;
      Moreover, the treated ovary will be compared to the untreated one: using the US the ovarian&#xD;
      volume and antral follicles size and count will be evaluated.&#xD;
&#xD;
      The preserved pieces of ovary will be histologically evaluated for ovarian reserve analysis.&#xD;
&#xD;
      Additionally, these pieces will be used for experiments for the evaluation of various methods&#xD;
      for primordial follicles stimulation including mechanical stimulation like the laser or using&#xD;
      substances like Akt Stimulators.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 20, 2017</start_date>
  <completion_date type="Anticipated">September 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Menstrual cycle surveillance</measure>
    <time_frame>2 years</time_frame>
    <description>Duration of the menstrual period (days)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AMH</measure>
    <time_frame>2 years</time_frame>
    <description>Ovarian reserve measurements. AMH levels ng/ml</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Estradiol</measure>
    <time_frame>2 years</time_frame>
    <description>Estradiol levels at day of HCG in Pmol/L</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Antral follicular count</measure>
    <time_frame>2 years</time_frame>
    <description>measurement of. any antral follicles at day 3-5 with ultrasound</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IVF outcomes</measure>
    <time_frame>2 years</time_frame>
    <description>Number of oocytes at OPU</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FSH levels</measure>
    <time_frame>2 years</time_frame>
    <description>FSH levels at. day 2-3 of menstruation IU/L</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IVF outcomes fertilization rates</measure>
    <time_frame>2 years</time_frame>
    <description>fertilization rate. - number of fertilized oocytes relatively to total number of oocytes</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IVF outcomes</measure>
    <time_frame>2 years</time_frame>
    <description>pregnancy rates</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Ovarian Stimulation</condition>
  <arm_group>
    <arm_group_label>Mechanical stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mechanical stimulation of ovarian tissue</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Resection of ovarian tissue and mechanical stimulation</intervention_name>
    <description>he women will undergo a surgical laparoscopy during which one of the two technique will ensue.&#xD;
One of the ovaries will be scratched ( 2 mm depth) with a knife. Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.&#xD;
A piece of one ovary will be resected (up to one third of the ovary's volume, without harming the other ovary.&#xD;
The resected ovarian tissue will be transferred immediately to the laboratory where the cortex will be divided from the medulla and sliced to small pieces of 1-2 square millimeters.&#xD;
These pieces will be transferred back to the operation room in order for them to be transplanted under the serosa layer of the remaining ovary.&#xD;
Any bleeding would be stopped using a stiches or hemostatic mesh (diathermy will not be used).&#xD;
Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.</description>
    <arm_group_label>Mechanical stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy women, aged 21-40. with premature ovarian failure.&#xD;
&#xD;
          -  Healthy women, with poor ovarian reserve, aged 38-45, undergoing IVF Low ovarian&#xD;
             response: recruitment of up to three eggs in previous treatments.&#xD;
&#xD;
          -  After the failure of at least 4 cycles.&#xD;
&#xD;
          -  Two functioning ovaries, follicular and hormonal response of both ovaries in prior&#xD;
             therapies.&#xD;
&#xD;
          -  Women candidates for egg donation, and seeking further treatment before switching to&#xD;
             egg donation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with kidney disease.&#xD;
&#xD;
          -  Women with infertility factors other than ovarian failure, such as endometriosis,&#xD;
             PCOS, male factor.&#xD;
&#xD;
          -  Women with one non-functioning ovary, or that was removed.&#xD;
&#xD;
          -  Women with an intrauterine or pelvic pathology.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alon Kedem, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheba Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alon Kedem, MD</last_name>
    <phone>972543456953</phone>
    <email>kedem2001@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Noam Domniz, MD</last_name>
    <phone>972528899242</phone>
    <email>domniz@gmail.com</email>
  </overall_contact_backup>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>June 26, 2016</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>October 9, 2017</last_update_submitted>
  <last_update_submitted_qc>October 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mechanical Laboratory Ovarian Stimulation Poor responders</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/NCT03298750
org study id: SHEBA-15-2289-AK-CTIL
nct id: NCT03298750
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Examine the possibility that mechanical stimulation and ovarian fragmentation in women with
      premature ovarian failure or low ovarian reserve intended for egg donation may cause early
      follicular recruitment and increase chances of achieving pregnancy through IVF.
The women will undergo a surgical laparoscopy during which one of the two technique will
      ensue.

        1. One of the ovaries will be scratched ( 2 mm depth) with a knife. Simultaneously, a piece
           of the ovary will be preserved for further histologic analysis and research in the
           laboratory.

        2. A piece of one ovary will be resected (up to one third of the ovary's volume, without
           harming the other ovary.

      The resected ovarian tissue will be transferred immediately to the laboratory where the
      cortex will be divided from the medulla and sliced to small pieces of 1-2 square millimeters.

      These pieces will be transferred back to the operation room in order for them to be
      transplanted under the serosa layer of the remaining ovary.

      Any bleeding would be stopped using a stiches or hemostatic mesh (diathermy will not be
      used).

      Simultaneously, a piece of the ovary will be preserved for further histologic analysis and
      research in the laboratory.

      Post operational follow up ( up to two years) including: menstrual cycle surveillance,
      hormonal profile, AMH level, US of the pelvis and Antral Follicles Count (AFC).

      A month after the surgery, an ovarian stimulation will commence following IVF while close
      monitoring the ovarian response and comparing the pre and post operation response.

      Moreover, the treated ovary will be compared to the untreated one: using the US the ovarian
      volume and antral follicles size and count will be evaluated.

      The preserved pieces of ovary will be histologically evaluated for ovarian reserve analysis.

      Additionally, these pieces will be used for experiments for the evaluation of various methods
      for primordial follicles stimulation including mechanical stimulation like the laser or using
      substances like Akt Stimulators.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Menstrual cycle surveillance
time frame: 2 years
description: Duration of the menstrual period (days)
measure: AMH
time frame: 2 years
description: Ovarian reserve measurements. AMH levels ng/ml
measure: Estradiol
time frame: 2 years
description: Estradiol levels at day of HCG in Pmol/L
measure: Antral follicular count
time frame: 2 years
description: measurement of. any antral follicles at day 3-5 with ultrasound
measure: IVF outcomes
time frame: 2 years
description: Number of oocytes at OPU
measure: FSH levels
time frame: 2 years
description: FSH levels at. day 2-3 of menstruation IU/L
measure: IVF outcomes fertilization rates
time frame: 2 years
description: fertilization rate. - number of fertilized oocytes relatively to total number of oocytes
measure: IVF outcomes
time frame: 2 years
description: pregnancy rates
arm group label: Mechanical stimulation
arm group type: Experimental
description: Mechanical stimulation of ovarian tissue
intervention type: Procedure
intervention name: Resection of ovarian tissue and mechanical stimulation
description: he women will undergo a surgical laparoscopy during which one of the two technique will ensue.
One of the ovaries will be scratched ( 2 mm depth) with a knife. Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.
A piece of one ovary will be resected (up to one third of the ovary's volume, without harming the other ovary.
The resected ovarian tissue will be transferred immediately to the laboratory where the cortex will be divided from the medulla and sliced to small pieces of 1-2 square millimeters.
These pieces will be transferred back to the operation room in order for them to be transplanted under the serosa layer of the remaining ovary.
Any bleeding would be stopped using a stiches or hemostatic mesh (diathermy will not be used).
Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.
arm group label: Mechanical stimulation
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alon Kedem, MD
role: Principal Investigator
affiliation: Sheba Medical Center
last name: Alon Kedem, MD
phone: 972543456953
email: kedem2001@gmail.com
last name: Noam Domniz, MD
phone: 972528899242
email: domniz@gmail.com
responsible party type: Sponsor
mesh term: Infertility
sharing ipd: No