<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/NCT03798886</url>
  </required_header>
  <id_info>
    <org_study_id>ATADEK-2018/20</org_study_id>
    <nct_id>NCT03798886</nct_id>
  </id_info>
  <brief_title>Success Rate Natural Cycles Versus Modified Natural Cycles in Frozen Embryos</brief_title>
  <official_title>Comparison of Clinical Results of Frozen Embryo Transfer in Natural and Modified Natural Cycles</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acibadem University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Acibadem 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>
      There has been a recent significant increase in the frozen embryo replacement (FER) cycles&#xD;
      due to freeze-all cycles to decrease the risk of ovarian hyperstimulation syndrome. Now a&#xD;
      days making frozen embryo transfers (FETs) a viable alternative to fresh embryo transfer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There has been a recent significant increase in the frozen embryo replacement (FER) cycles&#xD;
      due to freeze-all cycles to decrease the risk of ovarian hyperstimulation syndrome. Now a&#xD;
      days making frozen embryo transfers (FETs) a viable alternative to fresh embryo transfer,&#xD;
      with reports from observational studies and randomized controlled trials suggesting that:&#xD;
&#xD;
        1. The endometrium in stimulated cycles is not optimal for implantation&#xD;
&#xD;
        2. Pregnancy rates are increased following FET&#xD;
&#xD;
        3. Perinatal outcomes are less affected after FET&#xD;
&#xD;
        4. Preimplantation genetic screening We will follow only natural and modified natural&#xD;
           cycles patients. Spontaneous ovulation will documented with hormonal and sonographic&#xD;
           monitoring. Hormonal monitoring are including estradiol and luteinizing hormone (LH).&#xD;
           Sonographic monitoring is including follicule diameter (16-20 mm). At modified natural&#xD;
           cycles we will use hCG triggering for ovulation approximately 16-20 mm diameter.&#xD;
&#xD;
      We will compare success rate between natural and modified natural cycles&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>birth</measure>
    <time_frame>bigger than 24 weeks pregnancy</time_frame>
    <description>live birth</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pregnancy rate</measure>
    <time_frame>10th day after embryo transfer</time_frame>
    <description>hcg blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical pregnancy rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>positive fetal cardiac activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>abortion rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>abortion after visualization of fetal cardiac activity</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Infertility, Female</condition>
  <arm_group>
    <arm_group_label>Natural frozen embryo transfer group</arm_group_label>
    <description>In this group all embryos will be frozen when transfer planned sonographic follicle diameter measured. After spontaneous ovulation, embryo transfer will be planned. Luteal phase support will not be used.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>modified natural embryo transfer group</arm_group_label>
    <description>In this group all embryos will be frozen when transfer planned sonographic follicle diameter measured. When follicle diameter is 16-17 mm we will apply hCG (recombinant hCG). After ovulation, embryo transfer will be done. Luteal phase support will not be used.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>natural cycle</intervention_name>
    <description>When follicle is ready for ovulation, we will use this injection by intra-dermal route</description>
    <arm_group_label>Natural frozen embryo transfer group</arm_group_label>
    <arm_group_label>modified natural embryo transfer group</arm_group_label>
    <other_name>natural LH surge</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>modified natural cycle</intervention_name>
    <description>we will use that drug in the natural modified transfer group after embryo transfer</description>
    <arm_group_label>Natural frozen embryo transfer group</arm_group_label>
    <arm_group_label>modified natural embryo transfer group</arm_group_label>
    <other_name>recombinant hcg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>embryo transfer</intervention_name>
    <description>we will do transfer when the endometrium is ready</description>
    <arm_group_label>Natural frozen embryo transfer group</arm_group_label>
    <arm_group_label>modified natural embryo transfer group</arm_group_label>
    <other_name>frozen embryo transfer</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Patient blood sample for hormonal assay&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This study will bw carried out as a prospective randomized clinical trial on regular&#xD;
        menstruating patients arriving for transfer of frozen embryo to the center in a single IVF&#xD;
        center. Results will collected and recorded daily during the study. With 80% power analysis&#xD;
        minimum number of patients 0.05% significance level is 240.&#xD;
&#xD;
        Study will be designed in 1 year.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient who are admitted to the IVF center and who will be transferred to frozen&#xD;
             embryos.&#xD;
&#xD;
          -  Infertile women under 40 years of age who accepted this study.&#xD;
&#xD;
          -  Unexplained infertilite couple.&#xD;
&#xD;
          -  All ovulatory patient.&#xD;
&#xD;
          -  Male factor.&#xD;
&#xD;
          -  Tubal factor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who made intrauterin surgery.&#xD;
&#xD;
          -  Over 40 years of age women.&#xD;
&#xD;
          -  Patients with preimplantation genetic diagnosis.&#xD;
&#xD;
          -  Anovulatory patient.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>woman who is infertile at reproductive age</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Turgut Aydın</last_name>
    <role>Study Director</role>
    <affiliation>acıbadem university atakent hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elif Ganime Aydeniz</last_name>
    <role>Study Chair</role>
    <affiliation>acıbadem university atakent hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emine Karabük</last_name>
    <role>Study Chair</role>
    <affiliation>acıbadem university atakent hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Burak Yücel</last_name>
    <role>Study Chair</role>
    <affiliation>Kanuni Sultan SüleymanHospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Acibadem MAA University Atakent Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34457</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <reference>
    <citation>Weissman A, Horowitz E, Ravhon A, Steinfeld Z, Mutzafi R, Golan A, Levran D. Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen-thawed embryo transfer: a randomized study. Reprod Biomed Online. 2011 Oct;23(4):484-9. doi: 10.1016/j.rbmo.2011.06.004. Epub 2011 Jun 15.</citation>
    <PMID>21840758</PMID>
  </reference>
  <reference>
    <citation>Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261.</citation>
    <PMID>23820515</PMID>
  </reference>
  <results_reference>
    <citation>Kupka MS, Ferraretti AP, de Mouzon J, Erb K, D'Hooghe T, Castilla JA, Calhaz-Jorge C, De Geyter C, Goossens V; European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014 Oct 10;29(10):2099-113. doi: 10.1093/humrep/deu175. Epub 2014 Jul 27.</citation>
    <PMID>25069504</PMID>
  </results_reference>
  <results_reference>
    <citation>Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.</citation>
    <PMID>20097333</PMID>
  </results_reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>March 12, 2019</last_update_submitted>
  <last_update_submitted_qc>March 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Frozen embryo replacement, IVF success, ovarian stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>We did not decide for this but if they need any information we can support all</ipd_description>
  </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/NCT03798886
org study id: ATADEK-2018/20
nct id: NCT03798886
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
There has been a recent significant increase in the frozen embryo replacement (FER) cycles
      due to freeze-all cycles to decrease the risk of ovarian hyperstimulation syndrome. Now a
      days making frozen embryo transfers (FETs) a viable alternative to fresh embryo transfer
There has been a recent significant increase in the frozen embryo replacement (FER) cycles
      due to freeze-all cycles to decrease the risk of ovarian hyperstimulation syndrome. Now a
      days making frozen embryo transfers (FETs) a viable alternative to fresh embryo transfer,
      with reports from observational studies and randomized controlled trials suggesting that:

        1. The endometrium in stimulated cycles is not optimal for implantation

        2. Pregnancy rates are increased following FET

        3. Perinatal outcomes are less affected after FET

        4. Preimplantation genetic screening We will follow only natural and modified natural
           cycles patients. Spontaneous ovulation will documented with hormonal and sonographic
           monitoring. Hormonal monitoring are including estradiol and luteinizing hormone (LH).
           Sonographic monitoring is including follicule diameter (16-20 mm). At modified natural
           cycles we will use hCG triggering for ovulation approximately 16-20 mm diameter.

      We will compare success rate between natural and modified natural cycles
observational model: Other
time perspective: Prospective
measure: birth
time frame: bigger than 24 weeks pregnancy
description: live birth
measure: pregnancy rate
time frame: 10th day after embryo transfer
description: hcg blood test
measure: clinical pregnancy rate
time frame: 8 weeks
description: positive fetal cardiac activity
measure: abortion rate
time frame: 8 weeks
description: abortion after visualization of fetal cardiac activity
arm group label: Natural frozen embryo transfer group
description: In this group all embryos will be frozen when transfer planned sonographic follicle diameter measured. After spontaneous ovulation, embryo transfer will be planned. Luteal phase support will not be used.
arm group label: modified natural embryo transfer group
description: In this group all embryos will be frozen when transfer planned sonographic follicle diameter measured. When follicle diameter is 16-17 mm we will apply hCG (recombinant hCG). After ovulation, embryo transfer will be done. Luteal phase support will not be used.
intervention type: Other
intervention name: natural cycle
description: When follicle is ready for ovulation, we will use this injection by intra-dermal route
arm group label: Natural frozen embryo transfer group
arm group label: modified natural embryo transfer group
other name: natural LH surge
intervention type: Other
intervention name: modified natural cycle
description: we will use that drug in the natural modified transfer group after embryo transfer
arm group label: Natural frozen embryo transfer group
arm group label: modified natural embryo transfer group
other name: recombinant hcg
intervention type: Other
intervention name: embryo transfer
description: we will do transfer when the endometrium is ready
arm group label: Natural frozen embryo transfer group
arm group label: modified natural embryo transfer group
other name: frozen embryo transfer
Patient blood sample for hormonal assay
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: woman who is infertile at reproductive age
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Turgut Aydın
role: Study Director
affiliation: acıbadem university atakent hospital
last name: Elif Ganime Aydeniz
role: Study Chair
affiliation: acıbadem university atakent hospital
last name: Emine Karabük
role: Study Chair
affiliation: acıbadem university atakent hospital
last name: Burak Yücel
role: Study Chair
affiliation: Kanuni Sultan SüleymanHospital
facility: 
country: Turkey
citation: Weissman A, Horowitz E, Ravhon A, Steinfeld Z, Mutzafi R, Golan A, Levran D. Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen-thawed embryo transfer: a randomized study. Reprod Biomed Online. 2011 Oct;23(4):484-9. doi: 10.1016/j.rbmo.2011.06.004. Epub 2011 Jun 15.
PMID: 21840758
citation: Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261.
PMID: 23820515
citation: Kupka MS, Ferraretti AP, de Mouzon J, Erb K, D'Hooghe T, Castilla JA, Calhaz-Jorge C, De Geyter C, Goossens V; European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014 Oct 10;29(10):2099-113. doi: 10.1093/humrep/deu175. Epub 2014 Jul 27.
PMID: 25069504
citation: Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
PMID: 20097333
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Female
sharing ipd: Undecided
ipd description: We did not decide for this but if they need any information we can support all