<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/NCT03795220</url>
  </required_header>
  <id_info>
    <org_study_id>63569</org_study_id>
    <secondary_id>2018-002207-34</secondary_id>
    <nct_id>NCT03795220</nct_id>
  </id_info>
  <brief_title>Preparing and Timing of the Endometrium in Modified Natural Cycle Frozen-thawed Embryo Transfers</brief_title>
  <official_title>Preparing and Timing of the Endometrium in Modified Natural Cycle Frozen-thawed Embryo Transfers (mNC-FET) - a Randomized Controlled Multicenter Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anja Bisgaard Pinborg</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Copenhagen University Hospital, Hvidovre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regionshospitalet Horsens</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Copenhagen University Hospital at Herlev</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aalborg University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hillerod Hospital, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regionshospitalet Viborg, Skive</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The increasing use of FET emphasizes the importance of preparing and timing the endometrium&#xD;
      in FET cycles, however there is no consensus on luteal phase progesterone supplementation in&#xD;
      mNC-FET and the optimal day of blastocyst warming and transfer. The aim of this multicenter&#xD;
      RCT is to assess the effect of progesterone supplementation in hCG-triggered mNC-FET and the&#xD;
      effect of embryo thawing and transfer at hCG+6 or hCG+7 days, respectively. In total 604&#xD;
      patients will be included with n=151 in each of the four study arms. The primary outcome is&#xD;
      live birth rate per transfer (LBR) and the goal is to show a 10% increase in LBR after&#xD;
      progesterone supplementation and to assess whether blastocyst warming+transfer 6 days after&#xD;
      hCG trigger is superior to 7 days after hCG trigger in mNC-FET.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Single embryo transfer and freezing of surplus embryos has lowered twin birth rates after in&#xD;
      vitro fertilization (IVF) to a level of less than 5% in Denmark. However, several treatments&#xD;
      with repeated frozen embryo transfers (FET) before a viable pregnancy is confirmed are&#xD;
      burdensome to the patients. New freezing techniques has optimized the quality of the embryo&#xD;
      transferred in FET cycles, but optimization of the endometrium in the luteal phase is still&#xD;
      lacking behind. In a mNC-FET, which is the routine in many clinics, ovulation is induced with&#xD;
      an hCG injection when the leading follicle is ≥17 mm. The hCG trigger is important for&#xD;
      controlling the time of ovulation, but triggering an unhealthy follicle at an inappropriate&#xD;
      time may cause luteal phase insufficiency and thus suboptimal function of the endometrium.&#xD;
      Danish public fertility clinics are not routinely using progesterone supplementation in&#xD;
      mNC-FET, but there may be a rationale to do so, and some implantations may be rescued. In&#xD;
      this study we will compare live birth rates in mNC-FET with and without progesterone&#xD;
      supplementation in the luteal phase, and further we will explore the optimal timing of&#xD;
      blastocyst warming and transfer by comparing embryo transfer at hCG trigger +6 days versus +7&#xD;
      days. This is a superiority study with the aim to detect an increase in live birth rates of&#xD;
      10%. Hence, this adequately powered RCT may make a major contribution to knowledge on mNC-FET&#xD;
      to the benefits of patients. We will include 604 patients divided 1:1 (302:302) in each arm&#xD;
      +/- progesterone and these will further be divided 1:1 in blastocyst warming and transfer +6&#xD;
      and +7 days after hCG injection. The primary endpoint is live birth rate per transfer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 6, 2019</start_date>
  <completion_date type="Anticipated">January 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2024</primary_completion_date>
  <phase>Phase 4</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 multicenter trial with inclusion of 604 mNC-FET cycles. We will include 604 patients divided 1:1 (302:302) in each arm +/- progesterone supplementation and these will further be divided 1:1 in blastocyst warming and transfer +6 and +7 days after hCG injection. Patients randomised to progesterone supplementation will start administering medicine four days after the ovulation trigger up til the day of the pregnancy test. If the pregnancy test is positive, medication will continue for 30 days more.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>The study is a single blinded study; therefore, the study medication will be blinded for the treating doctors, but not for the patients, the non-treating doctors or the study nurses. Patients will only be seen by a treating doctor at the day of blastocyst transfer and at the day of the pregnancy scan. The participants will not take progesterone the morning of the blastocyst transfer, but immediately after to keep the treating doctors blinded. Patients will be instructed in not disclosing their study group to the treating doctor.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Live birth rates per transfer</measure>
    <time_frame>Registered at the one-year follow-up after a positive pregnancy test.</time_frame>
    <description>Comparison of live birth rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Chemical pregnancy rates per transfer</measure>
    <time_frame>Measured 16 days after ovulation trigger (hCG+16).</time_frame>
    <description>Comparison of chemical pregnancy rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rates per transfer</measure>
    <time_frame>Ultrasound performed at 7-8 weeks of gestation.</time_frame>
    <description>Comparison of clinical pregnancy rates (ultrasound) between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or seven after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abortion rates per transfer</measure>
    <time_frame>Registered at the one-year follow-up after a positive pregnancy test.</time_frame>
    <description>Comparison of abortion rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ASAT (U/L)</measure>
    <time_frame>Measured at baseline.</time_frame>
    <description>ALAT measured by blood sample to ensure normal liver parameters before administration of progesterone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ALAT (U/L)</measure>
    <time_frame>Measured at baseline.</time_frame>
    <description>ALAT measured by blood sample to ensure normal liver parameters before administration of progesterone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AMH (pol/L)</measure>
    <time_frame>Measured at baseline.</time_frame>
    <description>Comparison of AMH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estradiole (mmol/L)</measure>
    <time_frame>Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.</time_frame>
    <description>Comparison of estradiole measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FSH (IU/L)</measure>
    <time_frame>Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.</time_frame>
    <description>Comparison of FSH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LH (IU/L)</measure>
    <time_frame>Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.</time_frame>
    <description>Comparison of LH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progesterone (nmol/L)</measure>
    <time_frame>Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.</time_frame>
    <description>Comparison of progesterone measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OH-progesterone (nmol/L)</measure>
    <time_frame>Measured at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.</time_frame>
    <description>Comparison OH-progesterone measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>beta-hCG</measure>
    <time_frame>Measured at transfer day (hCG+6/7), hCG+11 and hCG+16.</time_frame>
    <description>Comparison of beta-hCG measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TSH (*10^3 IU/L)</measure>
    <time_frame>Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7), at hCG+11, at hCG+14 and at hCG+19.</time_frame>
    <description>Comparison of TSH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thyroglobulin antibodies (arb.units/L)</measure>
    <time_frame>Measured at baseline.</time_frame>
    <description>Comparison of thyroglobulin antibodies measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thyroid peroxidase anitbodies (arb.units/L)</measure>
    <time_frame>Measured at baseline.</time_frame>
    <description>Comparison of thyroid peroxidase antibodies measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Obstetric complication rates</measure>
    <time_frame>Registered at the one-year follow-up after a positive pregnancy test.</time_frame>
    <description>Comparison of obstetric complication rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal complication rates</measure>
    <time_frame>Registered at the one-year follow-up after a positive pregnancy test.</time_frame>
    <description>Comparison of neonatal complication rates for children of patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">604</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>Vaginal progesterone + transfer 6. day</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lutinus + blastocyst warming and transfer 6 days after hCG trigger</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vaginal progesterone + transfer 7. day</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lutinus + blastocyst warming and transfer 7 days after hCG trigger</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No progesterone + transfer 6. day</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>No Lutinus + blastocyst warming and transfer 6 days after hCG trigger</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No progesterone + transfer 7. day</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>No Lutinus + blastocyst warming and transfer 7 days after hCG trigger</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lutinus + transfer day 6</intervention_name>
    <description>Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.</description>
    <arm_group_label>Vaginal progesterone + transfer 6. day</arm_group_label>
    <other_name>Lutinus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lutinus + transfer day 7</intervention_name>
    <description>Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.</description>
    <arm_group_label>Vaginal progesterone + transfer 7. day</arm_group_label>
    <other_name>Lutinus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>No Lutinus + transfer day 6</intervention_name>
    <description>Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.</description>
    <arm_group_label>No progesterone + transfer 6. day</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>No Lutinus + transfer day 7</intervention_name>
    <description>Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.</description>
    <arm_group_label>No progesterone + transfer 7. day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female age 18-41 years, regular menstrual cycle (23-35 days), vitrified blastocysts&#xD;
             derived from 1.-3. IVF/ICSI cycle in a public hospital and undergoing single&#xD;
             blastocyst transfer.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Previous participation in the study, uterine malformations, intrauterine polyps or&#xD;
        submucosal myomas, breast feeding, oocyte donation, preimplantation genetic testing,&#xD;
        blastocyst conceived with sperm from testicular sperm aspiration, HIV (woman), hepatitis B&#xD;
        and C (woman), known luteal phase insufficiency or if patients are not fulfilling the&#xD;
        inclusion criteria. Further exclusion criteria are the following contraindications to&#xD;
        progesterone; allergy to the study medication, undiagnosed vaginal bleeding, current missed&#xD;
        abortion or ectopic pregnancy, hepatic insufficiency or severe hepatic disease, genital or&#xD;
        breast cancer, arterial or venous thromboembolism, thrombophlebitis or porphyria. For&#xD;
        patients participating in the sub-study, thyroid disease is an exclusion criterion.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>41 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anja B. Pinborg, Prof., DMSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fertility Clinic Rigshospitalet</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anja B. Pinborg, Prof., DMSC</last_name>
    <phone>0045 35 45 64 30</phone>
    <email>anja.bisgaard.pinborg@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marte Saupstad, MD</last_name>
    <email>marte.saupstad@regionh.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fertility Clinic, Rigshospitalet, Copenhagen University Hospital</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anja B. Pinborg, Prof., DMSc</last_name>
      <phone>004535456430</phone>
      <email>anja.bisgaard.pinborg@regionh.dk</email>
    </contact>
    <contact_backup>
      <last_name>Marte Saupstad, MD</last_name>
      <phone>004535455289</phone>
      <email>marte.saupstad@regionh.dk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Anja Bisgaard Pinborg</investigator_full_name>
    <investigator_title>Professor, chief consultant, DMSC</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>On request the study protocol and deidentified individual study data collected during the trial, including stored biobank samples, can be shared with research groups with relevant aims and a methodologically sound proposal. Approvals by necessary ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Further no data can be shared until 3 months after publication of first papers on the primary and secondary outcomes in this study. Biobank samples cannot be shared with research groups outside Denmark. Proposals of data sharing should be directed to anja.bisgaard.pinborg@regionh.dk. To gain access, data requestors will need to sign a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Data will be available from 3 months after publication of first papers on the primary and secondary outcomes in this study.</ipd_time_frame>
    <ipd_access_criteria>Approvals by necessary relevant ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Biobank samples cannot be shared with research groups outside Denmark.</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/NCT03795220
org study id: 63569
secondary id: 2018-002207-34
nct id: NCT03795220
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The increasing use of FET emphasizes the importance of preparing and timing the endometrium
      in FET cycles, however there is no consensus on luteal phase progesterone supplementation in
      mNC-FET and the optimal day of blastocyst warming and transfer. The aim of this multicenter
      RCT is to assess the effect of progesterone supplementation in hCG-triggered mNC-FET and the
      effect of embryo thawing and transfer at hCG+6 or hCG+7 days, respectively. In total 604
      patients will be included with n=151 in each of the four study arms. The primary outcome is
      live birth rate per transfer (LBR) and the goal is to show a 10% increase in LBR after
      progesterone supplementation and to assess whether blastocyst warming+transfer 6 days after
      hCG trigger is superior to 7 days after hCG trigger in mNC-FET.
Single embryo transfer and freezing of surplus embryos has lowered twin birth rates after in
      vitro fertilization (IVF) to a level of less than 5% in Denmark. However, several treatments
      with repeated frozen embryo transfers (FET) before a viable pregnancy is confirmed are
      burdensome to the patients. New freezing techniques has optimized the quality of the embryo
      transferred in FET cycles, but optimization of the endometrium in the luteal phase is still
      lacking behind. In a mNC-FET, which is the routine in many clinics, ovulation is induced with
      an hCG injection when the leading follicle is ≥17 mm. The hCG trigger is important for
      controlling the time of ovulation, but triggering an unhealthy follicle at an inappropriate
      time may cause luteal phase insufficiency and thus suboptimal function of the endometrium.
      Danish public fertility clinics are not routinely using progesterone supplementation in
      mNC-FET, but there may be a rationale to do so, and some implantations may be rescued. In
      this study we will compare live birth rates in mNC-FET with and without progesterone
      supplementation in the luteal phase, and further we will explore the optimal timing of
      blastocyst warming and transfer by comparing embryo transfer at hCG trigger +6 days versus +7
      days. This is a superiority study with the aim to detect an increase in live birth rates of
      10%. Hence, this adequately powered RCT may make a major contribution to knowledge on mNC-FET
      to the benefits of patients. We will include 604 patients divided 1:1 (302:302) in each arm
      +/- progesterone and these will further be divided 1:1 in blastocyst warming and transfer +6
      and +7 days after hCG injection. The primary endpoint is live birth rate per transfer.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, controlled multicenter trial with inclusion of 604 mNC-FET cycles. We will include 604 patients divided 1:1 (302:302) in each arm +/- progesterone supplementation and these will further be divided 1:1 in blastocyst warming and transfer +6 and +7 days after hCG injection. Patients randomised to progesterone supplementation will start administering medicine four days after the ovulation trigger up til the day of the pregnancy test. If the pregnancy test is positive, medication will continue for 30 days more.
primary purpose: Treatment
masking: Single (Investigator)
masking description: The study is a single blinded study; therefore, the study medication will be blinded for the treating doctors, but not for the patients, the non-treating doctors or the study nurses. Patients will only be seen by a treating doctor at the day of blastocyst transfer and at the day of the pregnancy scan. The participants will not take progesterone the morning of the blastocyst transfer, but immediately after to keep the treating doctors blinded. Patients will be instructed in not disclosing their study group to the treating doctor.
measure: Live birth rates per transfer
time frame: Registered at the one-year follow-up after a positive pregnancy test.
description: Comparison of live birth rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Chemical pregnancy rates per transfer
time frame: Measured 16 days after ovulation trigger (hCG+16).
description: Comparison of chemical pregnancy rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Clinical pregnancy rates per transfer
time frame: Ultrasound performed at 7-8 weeks of gestation.
description: Comparison of clinical pregnancy rates (ultrasound) between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or seven after hCG trigger.
measure: Abortion rates per transfer
time frame: Registered at the one-year follow-up after a positive pregnancy test.
description: Comparison of abortion rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: ASAT (U/L)
time frame: Measured at baseline.
description: ALAT measured by blood sample to ensure normal liver parameters before administration of progesterone.
measure: ALAT (U/L)
time frame: Measured at baseline.
description: ALAT measured by blood sample to ensure normal liver parameters before administration of progesterone.
measure: AMH (pol/L)
time frame: Measured at baseline.
description: Comparison of AMH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Estradiole (mmol/L)
time frame: Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.
description: Comparison of estradiole measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: FSH (IU/L)
time frame: Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.
description: Comparison of FSH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: LH (IU/L)
time frame: Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.
description: Comparison of LH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Progesterone (nmol/L)
time frame: Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.
description: Comparison of progesterone measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: OH-progesterone (nmol/L)
time frame: Measured at ovulation trigger day (hCG+0), at transfer day (hCG+6/7) and at hCG+11.
description: Comparison OH-progesterone measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: beta-hCG
time frame: Measured at transfer day (hCG+6/7), hCG+11 and hCG+16.
description: Comparison of beta-hCG measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: TSH (*10^3 IU/L)
time frame: Measured at baseline, at ovulation trigger day (hCG+0), at transfer day (hCG+6/7), at hCG+11, at hCG+14 and at hCG+19.
description: Comparison of TSH measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Thyroglobulin antibodies (arb.units/L)
time frame: Measured at baseline.
description: Comparison of thyroglobulin antibodies measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Thyroid peroxidase anitbodies (arb.units/L)
time frame: Measured at baseline.
description: Comparison of thyroid peroxidase antibodies measured by blood samples between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Obstetric complication rates
time frame: Registered at the one-year follow-up after a positive pregnancy test.
description: Comparison of obstetric complication rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
measure: Neonatal complication rates
time frame: Registered at the one-year follow-up after a positive pregnancy test.
description: Comparison of neonatal complication rates for children of patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.
arm group label: Vaginal progesterone + transfer 6. day
arm group type: Active Comparator
description: Lutinus + blastocyst warming and transfer 6 days after hCG trigger
arm group label: Vaginal progesterone + transfer 7. day
arm group type: Active Comparator
description: Lutinus + blastocyst warming and transfer 7 days after hCG trigger
arm group label: No progesterone + transfer 6. day
arm group type: Active Comparator
description: No Lutinus + blastocyst warming and transfer 6 days after hCG trigger
arm group label: No progesterone + transfer 7. day
arm group type: Active Comparator
description: No Lutinus + blastocyst warming and transfer 7 days after hCG trigger
intervention type: Drug
intervention name: Lutinus + transfer day 6
description: Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.
arm group label: Vaginal progesterone + transfer 6. day
other name: Lutinus
intervention type: Drug
intervention name: Lutinus + transfer day 7
description: Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.
arm group label: Vaginal progesterone + transfer 7. day
other name: Lutinus
intervention type: Drug
intervention name: No Lutinus + transfer day 6
description: Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.
arm group label: No progesterone + transfer 6. day
intervention type: Drug
intervention name: No Lutinus + transfer day 7
description: Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.
arm group label: No progesterone + transfer 7. day
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 41 Years
healthy volunteers: No
last name: Anja B. Pinborg, Prof., DMSC
role: Principal Investigator
affiliation: Fertility Clinic Rigshospitalet
last name: Anja B. Pinborg, Prof., DMSC
phone: 0045 35 45 64 30
email: anja.bisgaard.pinborg@regionh.dk
last name: Marte Saupstad, MD
email: marte.saupstad@regionh.dk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Anja Bisgaard Pinborg
investigator title: Professor, chief consultant, DMSC
mesh term: Infertility
sharing ipd: Yes
ipd description: On request the study protocol and deidentified individual study data collected during the trial, including stored biobank samples, can be shared with research groups with relevant aims and a methodologically sound proposal. Approvals by necessary ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Further no data can be shared until 3 months after publication of first papers on the primary and secondary outcomes in this study. Biobank samples cannot be shared with research groups outside Denmark. Proposals of data sharing should be directed to anja.bisgaard.pinborg@regionh.dk. To gain access, data requestors will need to sign a data sharing agreement.
ipd info type: Study Protocol
ipd time frame: Data will be available from 3 months after publication of first papers on the primary and secondary outcomes in this study.
ipd access criteria: Approvals by necessary relevant ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Biobank samples cannot be shared with research groups outside Denmark.