<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/NCT03832894</url>
  </required_header>
  <id_info>
    <org_study_id>MD IVF</org_study_id>
    <nct_id>NCT03832894</nct_id>
  </id_info>
  <brief_title>Oestradiol Supplementation in Luteal Long Agonist Fresh In Vitro Fertilization/Intra Cytoplasmic Sperm Injection ( IVF/ICSI) Cycle .</brief_title>
  <official_title>Effects of Adding Oestradiol Supplementation in Luteal Phase in Patients Undergoing in Vitro Fertilization/ Intra Cytoplasmic Sperm Injection (IVF/ICSI ) Long Agonist Fresh Embryo Transfer Cycles</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo University</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>
      Whether oestradiol administration affects the pregnancy rate in long agonist fresh IVF/ICSI&#xD;
      cycles. Oestradiol level will be measured the day of HCG trigger to assess whether oestradiol&#xD;
      level affects cycle outcome results.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      6. Background and Rationale: Progesterone is essential for successful implantation and&#xD;
      maintenance of early pregnancy . Although the oestrogen is not essential, it is important to&#xD;
      maintain the progesterone level during the pregnancy and promote the transformation of the&#xD;
      endometrium from the secretory to proliferative phase.&#xD;
&#xD;
      Compromised granulosa cells luteinisation could cause infertility or early miscarriage. In&#xD;
      assisted reproductive technologies (ART) cycles, curettage of the granulosa cells during&#xD;
      oocyte retrieval is thought to reduce corpora lutea function and thus progesterone&#xD;
      production, resulting in a decrease in pregnancy rate.&#xD;
&#xD;
      Therefore, luteal support is routinely performed in ART cycles. Consensus has been reached on&#xD;
      the supplementation of progesterone after the day of oocyte retrieval, which was performed in&#xD;
      approximately 80% of the cycles and significantly improved clinical outcomes.However, the&#xD;
      efficacy of oestradiol supplementation in luteal support remains controversial.&#xD;
&#xD;
      Previous studies have shown that the lower the serum estrogen level was at 4, 7 and 9 days&#xD;
      following transplantation, the lower the clinical pregnancy rate. Previous studies showed&#xD;
      that in patients with long or short duration ovulation induction, luteal support with&#xD;
      oestradiol supplementation led to an increased serum estrogen level and an improved pregnancy&#xD;
      rate . It was also found that patients having luteal support with estrogen (4 mg per day) had&#xD;
      a significantly higher clinical pregnancy rate (40.6% vs 21.6%) and a significantly lower&#xD;
      abortion rate (12.8% vs 38%) than those treated with progesterone alone.&#xD;
&#xD;
      In contrast, other investigators have failed to show any benefit of oestradiol&#xD;
      supplementation during the luteal phase and a Cochrane review published in 2015 reported no&#xD;
      differences in rates of live birth or ongoing pregnancy between the progesterone group and&#xD;
      progesterone add oestrogen group. Hence, it remains unclear whether the addition of estrogen&#xD;
      to progesterone for luteal support is associated with higher pregnancy rate and live birth&#xD;
      rate.&#xD;
&#xD;
      In this study, the investigators will evaluate outcomes of patients undergoing IVF/ICSI-ET&#xD;
      with oestradiol supplementation in addition to progesterone for luteal support. The&#xD;
      investigators also report on the efficacy implications of oestradiol supplementation for&#xD;
      patients undergoing IVF/ICSI-ET.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">January 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</primary_completion_date>
  <phase>Phase 3</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Randomization will be held by using the computer generated randomization codes, which will then be placed in the sealed envelopes by a third party (nurse).&#xD;
Each patient will choose a sealed envelope containing randomization number either group A or B. Both participant and health provider will be blinded to patients grouping</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>4 weeks after embryo transfer of each enrolled patient</time_frame>
    <description>Number of gestational sacs per number of embryos transferred per cycle</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Chemical pregnancy rate</measure>
    <time_frame>Two weeks after embryo transfer of each enrolled patient</time_frame>
    <description>Quantitative Beta Human Chorionic Gonadotropin (BHCG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rate</measure>
    <time_frame>4 weeks after embryo transfer of each enrolled patient with positive pregnancy test or 6 weeks from IVF cycle beginning in pregnant patients</time_frame>
    <description>Intrauterine gestational sac with fetal pole with positive pulsation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate</measure>
    <time_frame>10 weeks after embryo transfer of each enrolled patient or 12 weeks from starting IVF cycle in pregnant patients</time_frame>
    <description>12 weeks gestation and more</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">2</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Group receiving oestradiol tablets in addition to progesterone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A :Will receive 400mg progesterone in the form of vaginal or rectal suppositories in addition to estradiol valerate oral tablets in a dose of 4mg/day(2x2), for luteal phase support. Starting from the day of ovum pickup and for 14 days after embryo transfer.&#xD;
Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group not receiving oestradiol tablets.</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol Valerate</intervention_name>
    <description>Oestradiol supplementation starting from day of trigger through out the luteal phase</description>
    <arm_group_label>Group not receiving oestradiol tablets.</arm_group_label>
    <arm_group_label>Group receiving oestradiol tablets in addition to progesterone</arm_group_label>
    <other_name>Progynova</other_name>
    <other_name>Progesterone vaginal suppositories</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Age group 20-38 years old.&#xD;
&#xD;
          2. Patients Undergoing gonadotropin Releasing Hormone (Gn RH) long agonist protocol, with&#xD;
             fresh embryo transfer.&#xD;
&#xD;
          3. Day 3 Grade 1 embryos.&#xD;
&#xD;
          4. Trilamellar endometrium with ranging endometrial thickness from 8 mm to 14 mm.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Karyotypic abnormalities in either partner.&#xD;
&#xD;
          2. Patients with uterine abnormalities.&#xD;
&#xD;
          3. G3-G4 quality embryos.&#xD;
&#xD;
          4. Estradiol level 10,000 or more at time of trigger.&#xD;
&#xD;
          5. Cases of egg donation/sperm donation/embryo donation.&#xD;
&#xD;
          6. Polycystic ovary syndrome (PCOS )patients.&#xD;
&#xD;
          7. Poor responders (maternal age &gt;40, Antral follicle counts (AFC )&lt;5, Anti Mullerian&#xD;
             Hormone (AMH )&lt;1 and previous trial &lt;5 oocyte retrieved ) (bologna criteria 2011)&#xD;
&#xD;
          8. Those with 3 or more implantation failure.&#xD;
&#xD;
          9. Endometrial thickness &lt;8 or &gt;14mm.&#xD;
&#xD;
         10. Severe male factor.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>38 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>SHERINE HOSNY</last_name>
    <phone>01097665573</phone>
    <email>sherinehosny@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Art Unit/ Obatetrics and Gynecology Department</name>
      <address>
        <city>Cairo</city>
        <state>Cair0</state>
        <zip>11542</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sherine H Hosny</last_name>
      <phone>01097665573</phone>
    </contact>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>February 5, 2019</last_update_submitted>
  <last_update_submitted_qc>February 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>sherine Hosny Mohamed Gad Allah</investigator_full_name>
    <investigator_title>Assistant professor</investigator_title>
  </responsible_party>
  <keyword>IVF</keyword>
  <keyword>ICSI</keyword>
  <keyword>oestradiol</keyword>
  <keyword>long protocol</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>Estradiol 17 beta-cypionate</mesh_term>
    <mesh_term>Estradiol 3-benzoate</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Polyestradiol phosphate</mesh_term>
    <mesh_term>Progesterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03832894
org study id: MD IVF
nct id: NCT03832894
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Whether oestradiol administration affects the pregnancy rate in long agonist fresh IVF/ICSI
      cycles. Oestradiol level will be measured the day of HCG trigger to assess whether oestradiol
      level affects cycle outcome results.
6. Background and Rationale: Progesterone is essential for successful implantation and
      maintenance of early pregnancy . Although the oestrogen is not essential, it is important to
      maintain the progesterone level during the pregnancy and promote the transformation of the
      endometrium from the secretory to proliferative phase.

      Compromised granulosa cells luteinisation could cause infertility or early miscarriage. In
      assisted reproductive technologies (ART) cycles, curettage of the granulosa cells during
      oocyte retrieval is thought to reduce corpora lutea function and thus progesterone
      production, resulting in a decrease in pregnancy rate.

      Therefore, luteal support is routinely performed in ART cycles. Consensus has been reached on
      the supplementation of progesterone after the day of oocyte retrieval, which was performed in
      approximately 80% of the cycles and significantly improved clinical outcomes.However, the
      efficacy of oestradiol supplementation in luteal support remains controversial.

      Previous studies have shown that the lower the serum estrogen level was at 4, 7 and 9 days
      following transplantation, the lower the clinical pregnancy rate. Previous studies showed
      that in patients with long or short duration ovulation induction, luteal support with
      oestradiol supplementation led to an increased serum estrogen level and an improved pregnancy
      rate . It was also found that patients having luteal support with estrogen (4 mg per day) had
      a significantly higher clinical pregnancy rate (40.6% vs 21.6%) and a significantly lower
      abortion rate (12.8% vs 38%) than those treated with progesterone alone.

      In contrast, other investigators have failed to show any benefit of oestradiol
      supplementation during the luteal phase and a Cochrane review published in 2015 reported no
      differences in rates of live birth or ongoing pregnancy between the progesterone group and
      progesterone add oestrogen group. Hence, it remains unclear whether the addition of estrogen
      to progesterone for luteal support is associated with higher pregnancy rate and live birth
      rate.

      In this study, the investigators will evaluate outcomes of patients undergoing IVF/ICSI-ET
      with oestradiol supplementation in addition to progesterone for luteal support. The
      investigators also report on the efficacy implications of oestradiol supplementation for
      patients undergoing IVF/ICSI-ET.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
masking description: Randomization will be held by using the computer generated randomization codes, which will then be placed in the sealed envelopes by a third party (nurse).
Each patient will choose a sealed envelope containing randomization number either group A or B. Both participant and health provider will be blinded to patients grouping
measure: Implantation rate
time frame: 4 weeks after embryo transfer of each enrolled patient
description: Number of gestational sacs per number of embryos transferred per cycle
measure: Chemical pregnancy rate
time frame: Two weeks after embryo transfer of each enrolled patient
description: Quantitative Beta Human Chorionic Gonadotropin (BHCG)
measure: Clinical pregnancy rate
time frame: 4 weeks after embryo transfer of each enrolled patient with positive pregnancy test or 6 weeks from IVF cycle beginning in pregnant patients
description: Intrauterine gestational sac with fetal pole with positive pulsation
measure: Ongoing pregnancy rate
time frame: 10 weeks after embryo transfer of each enrolled patient or 12 weeks from starting IVF cycle in pregnant patients
description: 12 weeks gestation and more
arm group label: Group receiving oestradiol tablets in addition to progesterone
arm group type: Active Comparator
description: Group A :Will receive 400mg progesterone in the form of vaginal or rectal suppositories in addition to estradiol valerate oral tablets in a dose of 4mg/day(2x2), for luteal phase support. Starting from the day of ovum pickup and for 14 days after embryo transfer.
Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer.
arm group label: Group not receiving oestradiol tablets.
arm group type: Placebo Comparator
description: Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer
intervention type: Drug
intervention name: Estradiol Valerate
description: Oestradiol supplementation starting from day of trigger through out the luteal phase
arm group label: Group not receiving oestradiol tablets.
arm group label: Group receiving oestradiol tablets in addition to progesterone
other name: Progynova
other name: Progesterone vaginal suppositories
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 38 Years
healthy volunteers: Accepts Healthy Volunteers
last name: SHERINE HOSNY
phone: 01097665573
email: sherinehosny@gmail.com
facility: 
status: Recruiting
contact: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: sherine Hosny Mohamed Gad Allah
investigator title: Assistant professor
mesh term: Infertility
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Estradiol
mesh term: Polyestradiol phosphate
mesh term: Progesterone
sharing ipd: Undecided