<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/NCT03238807</url>
  </required_header>
  <id_info>
    <org_study_id>IntraUterine HCG Assiut</org_study_id>
    <nct_id>NCT03238807</nct_id>
  </id_info>
  <brief_title>Effect of Intrauterine Injection of Hcg Before ET on Clinical Outcomes in IVF/ICSI Cycles</brief_title>
  <official_title>Effect of Intrauterine Injection of Human Chorionic Gonadotropin Before Embryo Transfer on Clinical Outcomes in In-vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Subfertility is the inability to conceive after 12 months of regular unprotected sexual&#xD;
      intercourse. Around 15% of couples suffer from subfertility. As a treatment for subfertility,&#xD;
      Assisted Reproductive Techniques (ART) have been a choice for subfertile couples. In Egypt in&#xD;
      2010, Pregnancy Rate was calculated to be 36.2%, Live Birth Rate to be 25.7%.&#xD;
&#xD;
      Implantation is the process by which the embryo adheres to the wall of the uterus.&#xD;
      Endometrial receptivity plays the most important role for successful implantation after&#xD;
      embryo quality. It is estimated that up to 70% of early pregnancy losses are due to failure&#xD;
      of implantation.&#xD;
&#xD;
      Despite extensive research, the embryo-maternal dialogue that orchestrates the implantation&#xD;
      process is still not fully understood. Much effort has been done in the last decades to&#xD;
      detect factors affecting Implantation and improve endometrial receptivity.&#xD;
&#xD;
      Human Chorionic Gonadotropin (hCG) is a placental glycoprotein hormone that required to&#xD;
      maintain pregnancy. Recent research data demonstrates that hCG is secreted very early by the&#xD;
      embryo before implantation to facilitate it. hCG has been proved to cause attraction of&#xD;
      inflammatory cells, promote angiogenesis, regulate chemical mediators at the endometrium.&#xD;
      These effects proceed the classical role of hCG during pregnancy and could be a directly&#xD;
      involved in and facilitating the implantation process.&#xD;
&#xD;
      Studies have been conducted to study the effect of injection of different concentrations of&#xD;
      hCG inside the uterine cavity before Embryo Transfer (ET) to improve endometrial receptivity&#xD;
      and outcomes of In-Vitro Fertilization (IVF) or Intra-Cytoplasmic Sperm Injection (ICSI)&#xD;
      cycles.&#xD;
&#xD;
      A recent systematic review was conducted on 12 studies performing intrauterine injection of&#xD;
      different doses of hCG before ET. Results of this study showed that there is increased&#xD;
      pregnancy outcome after injection of intrauterine 500 IU of hCG. The study recommended a&#xD;
      definitive large clinical trial with live birth as the primary outcome. There was no evidence&#xD;
      that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo&#xD;
      stage at transfer or dose of intrauterine hCG.&#xD;
&#xD;
      Aim of the study:&#xD;
&#xD;
      To detect whether intrauterine injection of hCG before ET improves clinical outcomes in&#xD;
      IVF/ICSI cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a Randomized Controlled Trial (RCT) to be done at ART center of Women's Health&#xD;
      Hospital, Assiut university, Egypt.&#xD;
&#xD;
      All steps for IVF/ICSI procedure, from the beginning of the induction for controlled ovarian&#xD;
      stimulation until just before the procedure of ET, will be done for all enrolled patients as&#xD;
      routinely decided according to the local protocol of the ART center in Women Health Hospital,&#xD;
      Assiut University. In the day of ET, number and quality of Embryos will be decided according&#xD;
      to the routine practice guided by the local protocol.&#xD;
&#xD;
      The intervention preparation will be prepared by adding one vial of hCG containing 5000 IU to&#xD;
      1mL of tissue culture medium (Continuous Single Culture, IrvineScientific). To obtain 500 IU&#xD;
      of hCG, 0.1 milliLiter (mL) of the preparation will be injected inside the uterus before ET&#xD;
      in the study group. For the control group, 0.1 mL of the tissue culture medium without hCG&#xD;
      will be injected inside the uterus before the ET. For both groups we will use Intra-Uterine&#xD;
      Insemination (IUI) catheter (Sperm Trans, Sperm Processor) to inject the solution inside the&#xD;
      uterine cavity 4 minutes before ET.&#xD;
&#xD;
      We will standardize the procedure of ET for all women apart from the intervention versus&#xD;
      control step. All women participating in the study will be put in lithotomy position. Cusco's&#xD;
      speculum will be introduced to visualize the cervix. Guided by transabdominal ultrasound with&#xD;
      a full bladder, the ET catheter (Cook Sydney IVF Catheter) will be introduced through the&#xD;
      cervical os into the uterine cavity. After introduction of the catheter into the uterine&#xD;
      cavity loaded embryos will be injected inside the cavity 0.5 cm from the fundus.&#xD;
&#xD;
      Biochemical pregnancy test will be done 14 days after ET by measuring hCG in the woman's&#xD;
      serum. If the test result is positive (according to the standard values that is used in the&#xD;
      laboratory), a transvaginal ultrasound will be done 3 weeks following the positive&#xD;
      biochemical test, to document the visualization of gestational sac, fetal pole and cardiac&#xD;
      pulsation.&#xD;
&#xD;
      Pregnancy rate (PR) is calculated by the number of women with positive biochemical pregnancy&#xD;
      test to the number of women enrolled in each group. The clinical pregnancy was defined as a&#xD;
      viable pregnancy when there is evidence of a gestational sac, embryo and fetal heart rate at&#xD;
      the time of ultrasound evaluation. Clinical Pregnancy Rate (cPR) is calculated by the&#xD;
      percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each&#xD;
      group. Implantation rate (IR) is calculated by the number of visualized embryos by&#xD;
      transvaginal ultrasound to the number of transferred embryos. While Live Birth Rate (LBR) is&#xD;
      calculated by the number of live births to the number of transferred embryos. Miscarriage&#xD;
      rate (MR) is calculated by the ratio of miscarriages to the number of confirmed pregnancies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 8, 2018</start_date>
  <completion_date type="Actual">October 4, 2020</completion_date>
  <primary_completion_date type="Actual">October 4, 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>
    <intervention_model_description>Randomized Controlled Trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>Double-Blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Live Birth Rate (LBR)</measure>
    <time_frame>9 months</time_frame>
    <description>calculated by the number of live births to the number of transferred embryos</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Pregnancy Rate (cPR)</measure>
    <time_frame>5 weeks</time_frame>
    <description>calculated by the percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implantation Rate (IR)</measure>
    <time_frame>5 weeks</time_frame>
    <description>calculated by the number of visualized embryos by transvaginal ultrasound to the number of transferred embryos</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Miscarriage rate (MR)</measure>
    <time_frame>3 months</time_frame>
    <description>calculated by the ratio of miscarriages to the number of confirmed pregnancies.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">181</enrollment>
  <condition>Infertility</condition>
  <condition>ART</condition>
  <arm_group>
    <arm_group_label>Intervention Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group that will receive intrauterine injection of human Chorionic Gonadotropin before ET</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control Group</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Human Chorionic Gonadotropin</intervention_name>
    <description>500 IU of human Chorionic Gonadotropin</description>
    <arm_group_label>Intervention Group</arm_group_label>
    <other_name>Epifasi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  infertility, male or female factor&#xD;
&#xD;
          -  Women undergoing ICSI/IVF&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  functional azoospermia&#xD;
&#xD;
          -  submucous uterine myomas or previous myomectomy&#xD;
&#xD;
          -  endometriosis&#xD;
&#xD;
          -  hydrosalpinges without prior excision or occlusion of the tubal ostia&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>43 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmed Makhlouf, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hazem Saadeldine, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Esraa Badran, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karim Abdallah, M.Sc</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assiut University - Women's Health Hospital</name>
      <address>
        <city>Assiut</city>
        <zip>71515</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <results_reference>
    <citation>Abdallah KS, Makhlouf A, Badran E, El-Nashar IM, Al-Hussaini TK, Farghaly T, Mohamed HS, Mol BW, Abdelmagied AM. Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial. Reprod Biomed Online. 2021 Oct;43(4):663-669. doi: 10.1016/j.rbmo.2021.06.011. Epub 2021 Jun 20.</citation>
    <PMID>34412973</PMID>
  </results_reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Karim Abdallah</investigator_full_name>
    <investigator_title>Assistant Lecturer</investigator_title>
  </responsible_party>
  <keyword>hCG</keyword>
  <keyword>Intrauterine hCG</keyword>
  <keyword>IVF</keyword>
  <keyword>ICSI</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>Chorionic Gonadotropin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All of the individual participant data collected during the trial, after deidentification to Researchers who provide a methodologically sound proposal To achieve aims in the approved proposal.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Immediately after publication indefinitely.</ipd_time_frame>
    <ipd_access_criteria>Proposals should be directed to karimsayed88@hotmail.com. To gain access, data requestors will need to sign a data access agreement.</ipd_access_criteria>
  </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/NCT03238807
org study id: IntraUterine HCG Assiut
nct id: NCT03238807
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Subfertility is the inability to conceive after 12 months of regular unprotected sexual
      intercourse. Around 15% of couples suffer from subfertility. As a treatment for subfertility,
      Assisted Reproductive Techniques (ART) have been a choice for subfertile couples. In Egypt in
      2010, Pregnancy Rate was calculated to be 36.2%, Live Birth Rate to be 25.7%.

      Implantation is the process by which the embryo adheres to the wall of the uterus.
      Endometrial receptivity plays the most important role for successful implantation after
      embryo quality. It is estimated that up to 70% of early pregnancy losses are due to failure
      of implantation.

      Despite extensive research, the embryo-maternal dialogue that orchestrates the implantation
      process is still not fully understood. Much effort has been done in the last decades to
      detect factors affecting Implantation and improve endometrial receptivity.

      Human Chorionic Gonadotropin (hCG) is a placental glycoprotein hormone that required to
      maintain pregnancy. Recent research data demonstrates that hCG is secreted very early by the
      embryo before implantation to facilitate it. hCG has been proved to cause attraction of
      inflammatory cells, promote angiogenesis, regulate chemical mediators at the endometrium.
      These effects proceed the classical role of hCG during pregnancy and could be a directly
      involved in and facilitating the implantation process.

      Studies have been conducted to study the effect of injection of different concentrations of
      hCG inside the uterine cavity before Embryo Transfer (ET) to improve endometrial receptivity
      and outcomes of In-Vitro Fertilization (IVF) or Intra-Cytoplasmic Sperm Injection (ICSI)
      cycles.

      A recent systematic review was conducted on 12 studies performing intrauterine injection of
      different doses of hCG before ET. Results of this study showed that there is increased
      pregnancy outcome after injection of intrauterine 500 IU of hCG. The study recommended a
      definitive large clinical trial with live birth as the primary outcome. There was no evidence
      that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo
      stage at transfer or dose of intrauterine hCG.

      Aim of the study:

      To detect whether intrauterine injection of hCG before ET improves clinical outcomes in
      IVF/ICSI cycles.
This study is a Randomized Controlled Trial (RCT) to be done at ART center of Women's Health
      Hospital, Assiut university, Egypt.

      All steps for IVF/ICSI procedure, from the beginning of the induction for controlled ovarian
      stimulation until just before the procedure of ET, will be done for all enrolled patients as
      routinely decided according to the local protocol of the ART center in Women Health Hospital,
      Assiut University. In the day of ET, number and quality of Embryos will be decided according
      to the routine practice guided by the local protocol.

      The intervention preparation will be prepared by adding one vial of hCG containing 5000 IU to
      1mL of tissue culture medium (Continuous Single Culture, IrvineScientific). To obtain 500 IU
      of hCG, 0.1 milliLiter (mL) of the preparation will be injected inside the uterus before ET
      in the study group. For the control group, 0.1 mL of the tissue culture medium without hCG
      will be injected inside the uterus before the ET. For both groups we will use Intra-Uterine
      Insemination (IUI) catheter (Sperm Trans, Sperm Processor) to inject the solution inside the
      uterine cavity 4 minutes before ET.

      We will standardize the procedure of ET for all women apart from the intervention versus
      control step. All women participating in the study will be put in lithotomy position. Cusco's
      speculum will be introduced to visualize the cervix. Guided by transabdominal ultrasound with
      a full bladder, the ET catheter (Cook Sydney IVF Catheter) will be introduced through the
      cervical os into the uterine cavity. After introduction of the catheter into the uterine
      cavity loaded embryos will be injected inside the cavity 0.5 cm from the fundus.

      Biochemical pregnancy test will be done 14 days after ET by measuring hCG in the woman's
      serum. If the test result is positive (according to the standard values that is used in the
      laboratory), a transvaginal ultrasound will be done 3 weeks following the positive
      biochemical test, to document the visualization of gestational sac, fetal pole and cardiac
      pulsation.

      Pregnancy rate (PR) is calculated by the number of women with positive biochemical pregnancy
      test to the number of women enrolled in each group. The clinical pregnancy was defined as a
      viable pregnancy when there is evidence of a gestational sac, embryo and fetal heart rate at
      the time of ultrasound evaluation. Clinical Pregnancy Rate (cPR) is calculated by the
      percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each
      group. Implantation rate (IR) is calculated by the number of visualized embryos by
      transvaginal ultrasound to the number of transferred embryos. While Live Birth Rate (LBR) is
      calculated by the number of live births to the number of transferred embryos. Miscarriage
      rate (MR) is calculated by the ratio of miscarriages to the number of confirmed pregnancies.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized Controlled Trial
primary purpose: Prevention
masking: Double (Participant, Care Provider)
masking description: Double-Blinded
measure: Live Birth Rate (LBR)
time frame: 9 months
description: calculated by the number of live births to the number of transferred embryos
measure: Clinical Pregnancy Rate (cPR)
time frame: 5 weeks
description: calculated by the percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each group
measure: Implantation Rate (IR)
time frame: 5 weeks
description: calculated by the number of visualized embryos by transvaginal ultrasound to the number of transferred embryos
measure: Miscarriage rate (MR)
time frame: 3 months
description: calculated by the ratio of miscarriages to the number of confirmed pregnancies.
arm group label: Intervention Group
arm group type: Experimental
description: Group that will receive intrauterine injection of human Chorionic Gonadotropin before ET
arm group label: Control Group
arm group type: No Intervention
description: Control Group
intervention type: Drug
intervention name: Human Chorionic Gonadotropin
description: 500 IU of human Chorionic Gonadotropin
arm group label: Intervention Group
other name: Epifasi
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 43 Years
healthy volunteers: No
last name: Ahmed Makhlouf, MD
role: Principal Investigator
affiliation: Assiut University
last name: Hazem Saadeldine, MD
role: Study Chair
affiliation: Assiut University
last name: Esraa Badran, MD
role: Study Chair
affiliation: Assiut University
last name: Karim Abdallah, M.Sc
role: Study Director
affiliation: Assiut University
facility: 
country: Egypt
citation: Abdallah KS, Makhlouf A, Badran E, El-Nashar IM, Al-Hussaini TK, Farghaly T, Mohamed HS, Mol BW, Abdelmagied AM. Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial. Reprod Biomed Online. 2021 Oct;43(4):663-669. doi: 10.1016/j.rbmo.2021.06.011. Epub 2021 Jun 20.
PMID: 34412973
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Karim Abdallah
investigator title: Assistant Lecturer
mesh term: Infertility
mesh term: Chorionic Gonadotropin
sharing ipd: Yes
ipd description: All of the individual participant data collected during the trial, after deidentification to Researchers who provide a methodologically sound proposal To achieve aims in the approved proposal.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Analytic Code
ipd time frame: Immediately after publication indefinitely.
ipd access criteria: Proposals should be directed to karimsayed88@hotmail.com. To gain access, data requestors will need to sign a data access agreement.