<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/NCT04489147</url>
  </required_header>
  <id_info>
    <org_study_id>#FWA00015574</org_study_id>
    <nct_id>NCT04489147</nct_id>
  </id_info>
  <brief_title>Effect of Metformin on Non PCO Women Undergoing IVF/ICSI</brief_title>
  <official_title>Effect of Metformin on Non PCO Women Undergoing IVF/ICSI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kasr El Aini Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kasr El Aini 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>
      400 Patients will be randomly assigned into two groups after informed consent from every&#xD;
      patient.&#xD;
&#xD;
      They will be classified into 2 groups:&#xD;
&#xD;
      Group A ( involves 200 patients ) will receive metformin 850 mg twice daily along the cycle&#xD;
      of Intra-cytoplasmic sperm injection (ICSI) Group B ( involve 200 patients) will not receive&#xD;
      metformin. They will undergo a cycle of ICSI. Primary outcome of this trial is to detect&#xD;
      occurrence of Ovarian Hyper-stimulation Syndrome (OHSS) , while secondary outcomes include&#xD;
      quality &amp; number of retrieved&#xD;
&#xD;
      follicles fertilization rate ,ongoing pregnancy rate &amp; endometrial thickness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a prospective, single-blinded (to the outcomes assessor), randomized controlled&#xD;
      trial conducted at the In Vitro Fertilization ( IVF) centers of the Departments of Obstetrics&#xD;
      &amp; Gynecology, Kasr El-Ainy Hospital and Beni-suef hospital in Cairo University and Beni-suef&#xD;
      university,respectively, Egypt, to determine the clinical effect of metformin on ICSI&#xD;
      outcomes in non PCO patients. Ethical committee approval was obtained. The study will include&#xD;
      400 infertile patients.&#xD;
&#xD;
      Inclusion criteria :&#xD;
&#xD;
        -  Patients subjected to IVF/ICSI aged 20-35 years with long agonist protocol&#xD;
&#xD;
        -  history of infertility for at least two years (either primary or secondary)&#xD;
&#xD;
        -  normal Thyroid stimulating Hormone (TSH) and prolactin&#xD;
&#xD;
      Exclusion criteria :&#xD;
&#xD;
        -  Patients who used metformin in the past 3-months before study&#xD;
&#xD;
        -  having medical problems such as kidney or liver diseases&#xD;
&#xD;
        -  Severe endometriosis.&#xD;
&#xD;
        -  hypo-thalamic amenorrhea.&#xD;
&#xD;
        -  Severe male factor( patients with testicular biopsy or those with azoo-spermia).&#xD;
&#xD;
        -  Associated uterine factor.&#xD;
&#xD;
        -  IVF/ ICSI for sex selection. All patients are informed about the study and consent is&#xD;
           given by those who accept to participate.&#xD;
&#xD;
      Careful history taking include infertility type, duration , cause, obstetric history, medical&#xD;
      and surgical history and demographic distribution is taken. Full physical examination and 2&#xD;
      dimensional (2D) transvaginal sonography (TVS) are done on day 2 to 5 of menses to assess&#xD;
      antral follicle count, uterus and adnexa . Body mass index (BMI) and waist/hip ratio (WHR)&#xD;
      are calculated, Blood samples are taken for AntiMullerian Hormone (AMH), Basal Follicle&#xD;
      Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), thyroid stimulating&#xD;
      hormone ( TSH), Prolactin and free testosterone.&#xD;
&#xD;
      All 400 participants will be randomized by withdrawing closed envelopes for each patient into&#xD;
      group A and group B .&#xD;
&#xD;
      Group A ( involves 200 patients ) will receive metformin 850 mg twice daily along the cycle&#xD;
      of ICSI Group B ( involve 200 patients) will not receive metformin.&#xD;
&#xD;
      They will undergo a cycle of ICSI.The agonist protocol is followed.Long protocol steps:&#xD;
&#xD;
        -  Start from day 19th - 20th by GnRH agonist ;Triptorelin 0.1mg subcutaneous (Decapeptyl,&#xD;
           Ferring). -1st visit : after 2 weeks of start of GnRH agonist or day 2 of cycle, we&#xD;
           confirm down regulation by a serum level of E2to be &lt;50 pg/ml, endometrial thickness&#xD;
           &lt;5mm, no ovarian cyst by ultrasound. Then we add Gonadotropins as Intramuscular (I.M.)&#xD;
           injections of 150-300 I.U. of highly purified Human Menopausal Gonadotropins daily&#xD;
           (Merional, 75 I.U. /vial, IBSA). The dose is adjusted according to the age, BMI, AFC,&#xD;
           serum levels of anti-mullerian hormone (AMH), follicle stimulating hormone (FSH) and&#xD;
           ovarian response.&#xD;
&#xD;
        -  2nd visit : on 6th - 7 th days of Gonadotrophins and then every other day to do&#xD;
           folliculometry by TVS and E2 level in serum.&#xD;
&#xD;
        -  We do trigger by Human Chorionic Gonadotrophin (HCG)10000 IU I.M.(Pregnyl, Organon) when&#xD;
           at least 3 follicles reach 18mm in mean diameter or more and E2 level is less than 2500&#xD;
           pg/ml. Ovum pickup is done 34 hours after HCG injection and embryo transfer using&#xD;
           Wallace catheter on day 2 to 3.&#xD;
&#xD;
             -  -Luteal support: Natural Progesterone 400 mg 1x2, Folic acid once daily,&#xD;
                Amoxicillin-Clavulanic Acid 1gm 1x2x7 ,Progesterone 100mg I.M. daily for 10 days,&#xD;
                Acetylsalicylic Acid once daily&#xD;
&#xD;
             -  -Quantitative ß- HCG in serum after 14 days of embryo transfer. -TVS to detect&#xD;
                clinical pregnancy at 6-7 weeks of gestation.&#xD;
&#xD;
      Primary outcome of this trial is to detect occurrence of Ovarian Hyper-stimulation Syndrome&#xD;
      (OHSS) , while secondary outcomes include quality &amp; number of retrieved follicles&#xD;
      fertilization rate ,ongoing pregnancy rate &amp; endometrial thickness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 28, 2020</start_date>
  <completion_date type="Anticipated">November 27, 2020</completion_date>
  <primary_completion_date type="Anticipated">November 27, 2020</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 (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of OHSS</measure>
    <time_frame>4weeks</time_frame>
    <description>The number of cases of Ovarian Hyperstimulation Syndrome per cycle</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of Mature retrieved eggs ( M-I) follicles .</measure>
    <time_frame>2-4weeks</time_frame>
    <description>The number of mature retrieved eggs (M-I) and each number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fertilization rate</measure>
    <time_frame>4weeks</time_frame>
    <description>The number of fertilized eggs after injection with sperms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pregnancy rate</measure>
    <time_frame>4 weeks</time_frame>
    <description>number of pregnancies out of all ICSI cycles</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A ( involve 200 patients ) will receive metformin 850 mg twice daily along the cycle of ICSI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Metformin</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Group B ( involve 200 patients) will not receive metformin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>metformin 850 mg orally twice daily along the cycle of ICSI</description>
    <arm_group_label>metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients subjected to IVF/ICSI aged 20-35 years with long agonist protocol&#xD;
&#xD;
          -  history of infertility for at least two years (either primary or secondary)&#xD;
&#xD;
          -  normal TSH and prolactin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who used metformin in the past 3-months before study&#xD;
&#xD;
          -  having medical problems such as kidney or liver diseases&#xD;
&#xD;
          -  Severe endometriosis.&#xD;
&#xD;
          -  hypothalamic amenorrhea.&#xD;
&#xD;
          -  Severe male factor( patients with testicular biopsy or those with azoospermia).&#xD;
&#xD;
          -  Associated uterine factor.&#xD;
&#xD;
          -  IVF/ ICSI for sex selection.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amal Kotb, MD</last_name>
    <role>Study Director</role>
    <affiliation>Beni-Suef University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amir Gabr, MD</last_name>
    <phone>00223682030</phone>
    <email>dr_amirarabi@yahoo.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beni-suef university hospital</name>
      <address>
        <city>Beni-sweif</city>
        <state>Beni-suef Governorate</state>
        <zip>62515</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amal Kotb, MD</last_name>
      <phone>0020822318605</phone>
      <email>amalkotb7295@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kasr El Aini Hospital</investigator_affiliation>
    <investigator_full_name>Amira S Dieb</investigator_full_name>
    <investigator_title>Assistant professor</investigator_title>
  </responsible_party>
  <keyword>non PCO</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_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/NCT04489147
org study id: #FWA00015574
nct id: NCT04489147
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
400 Patients will be randomly assigned into two groups after informed consent from every
      patient.

      They will be classified into 2 groups:

      Group A ( involves 200 patients ) will receive metformin 850 mg twice daily along the cycle
      of Intra-cytoplasmic sperm injection (ICSI) Group B ( involve 200 patients) will not receive
      metformin. They will undergo a cycle of ICSI. Primary outcome of this trial is to detect
      occurrence of Ovarian Hyper-stimulation Syndrome (OHSS) , while secondary outcomes include
      quality & number of retrieved

      follicles fertilization rate ,ongoing pregnancy rate & endometrial thickness.
This study is a prospective, single-blinded (to the outcomes assessor), randomized controlled
      trial conducted at the In Vitro Fertilization ( IVF) centers of the Departments of Obstetrics
      & Gynecology, Kasr El-Ainy Hospital and Beni-suef hospital in Cairo University and Beni-suef
      university,respectively, Egypt, to determine the clinical effect of metformin on ICSI
      outcomes in non PCO patients. Ethical committee approval was obtained. The study will include
      400 infertile patients.

      Inclusion criteria :

        -  Patients subjected to IVF/ICSI aged 20-35 years with long agonist protocol

        -  history of infertility for at least two years (either primary or secondary)

        -  normal Thyroid stimulating Hormone (TSH) and prolactin

      Exclusion criteria :

        -  Patients who used metformin in the past 3-months before study

        -  having medical problems such as kidney or liver diseases

        -  Severe endometriosis.

        -  hypo-thalamic amenorrhea.

        -  Severe male factor( patients with testicular biopsy or those with azoo-spermia).

        -  Associated uterine factor.

        -  IVF/ ICSI for sex selection. All patients are informed about the study and consent is
           given by those who accept to participate.

      Careful history taking include infertility type, duration , cause, obstetric history, medical
      and surgical history and demographic distribution is taken. Full physical examination and 2
      dimensional (2D) transvaginal sonography (TVS) are done on day 2 to 5 of menses to assess
      antral follicle count, uterus and adnexa . Body mass index (BMI) and waist/hip ratio (WHR)
      are calculated, Blood samples are taken for AntiMullerian Hormone (AMH), Basal Follicle
      Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), thyroid stimulating
      hormone ( TSH), Prolactin and free testosterone.

      All 400 participants will be randomized by withdrawing closed envelopes for each patient into
      group A and group B .

      Group A ( involves 200 patients ) will receive metformin 850 mg twice daily along the cycle
      of ICSI Group B ( involve 200 patients) will not receive metformin.

      They will undergo a cycle of ICSI.The agonist protocol is followed.Long protocol steps:

        -  Start from day 19th - 20th by GnRH agonist ;Triptorelin 0.1mg subcutaneous (Decapeptyl,
           Ferring). -1st visit : after 2 weeks of start of GnRH agonist or day 2 of cycle, we
           confirm down regulation by a serum level of E2to be <50 pg/ml, endometrial thickness
           <5mm, no ovarian cyst by ultrasound. Then we add Gonadotropins as Intramuscular (I.M.)
           injections of 150-300 I.U. of highly purified Human Menopausal Gonadotropins daily
           (Merional, 75 I.U. /vial, IBSA). The dose is adjusted according to the age, BMI, AFC,
           serum levels of anti-mullerian hormone (AMH), follicle stimulating hormone (FSH) and
           ovarian response.

        -  2nd visit : on 6th - 7 th days of Gonadotrophins and then every other day to do
           folliculometry by TVS and E2 level in serum.

        -  We do trigger by Human Chorionic Gonadotrophin (HCG)10000 IU I.M.(Pregnyl, Organon) when
           at least 3 follicles reach 18mm in mean diameter or more and E2 level is less than 2500
           pg/ml. Ovum pickup is done 34 hours after HCG injection and embryo transfer using
           Wallace catheter on day 2 to 3.

             -  -Luteal support: Natural Progesterone 400 mg 1x2, Folic acid once daily,
                Amoxicillin-Clavulanic Acid 1gm 1x2x7 ,Progesterone 100mg I.M. daily for 10 days,
                Acetylsalicylic Acid once daily

             -  -Quantitative ß- HCG in serum after 14 days of embryo transfer. -TVS to detect
                clinical pregnancy at 6-7 weeks of gestation.

      Primary outcome of this trial is to detect occurrence of Ovarian Hyper-stimulation Syndrome
      (OHSS) , while secondary outcomes include quality & number of retrieved follicles
      fertilization rate ,ongoing pregnancy rate & endometrial thickness.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Rate of OHSS
time frame: 4weeks
description: The number of cases of Ovarian Hyperstimulation Syndrome per cycle
measure: The number of Mature retrieved eggs ( M-I) follicles .
time frame: 2-4weeks
description: The number of mature retrieved eggs (M-I) and each number
measure: fertilization rate
time frame: 4weeks
description: The number of fertilized eggs after injection with sperms
measure: pregnancy rate
time frame: 4 weeks
description: number of pregnancies out of all ICSI cycles
arm group label: metformin
arm group type: Active Comparator
description: Group A ( involve 200 patients ) will receive metformin 850 mg twice daily along the cycle of ICSI
arm group label: No Metformin
arm group type: No Intervention
description: Group B ( involve 200 patients) will not receive metformin
intervention type: Drug
intervention name: Metformin
description: metformin 850 mg orally twice daily along the cycle of ICSI
arm group label: metformin
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Amal Kotb, MD
role: Study Director
affiliation: Beni-Suef University
last name: Amir Gabr, MD
phone: 00223682030
email: dr_amirarabi@yahoo.com
facility: 
status: Recruiting
contact: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Kasr El Aini Hospital
investigator full name: Amira S Dieb
investigator title: Assistant professor
mesh term: Infertility
mesh term: Metformin
sharing ipd: No