search
Back to results

Oral Versus Vaginal Progesterone for Luteal Phase Supplementation in Frozen Embryo Transfer Cycles (REMODEL)

Primary Purpose

Frozen Embryo Transfer, Hormone Replacement Therapy, Dydrogesterone

Status
Active
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Dydrogesterone 10 MG Oral Tablet
Micronized progesterone
Sponsored by
CRG UZ Brussel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Frozen Embryo Transfer

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • ≤40 years of age at the time of IVF/ICSI treatment
  • BMI ≥18 to ≤30 kg/m2 with a documented history of infertility
  • Have undergone COS as part of an ART treatment and have had an unsuccessful fresh embryo transfer in that cycle, OR, have undergone freeze all strategy
  • Scheduled to undergo FET with a standard exogenous/programmed hormonal replacement therapy (HRT) regimen
  • Have at least 1 blastocyst vitrified on the 5th or 6th day after oocyte retrieval
  • Elective single embryo (blastocyst) transfer (SET)
  • Normal ultrasound examination at enrollment (or if <12 months old)
  • Signed patient authorization for use/disclosure of data.

Exclusion Criteria:

  • Women with a history of recurrent miscarriage, defined as >2 consecutive miscarriages (biochemical pregnancy losses are not included)
  • Absence of implantation (serum hCG = negative) after two consecutive cycles of IVF, ICSI or FET where the cumulative number of transferred embryos was >4 cleavage-stage embryos and >2 blastocysts
  • Presence of hydrosalpinx that is not surgically treated
  • Endometrial abnormalities on scanning during ovarian stimulation, such as endometrial polyp(s), sub mucosal fibroid(s), endometrial hyperplasia, endometrial fluid accumulation, or endometrial adhesions
  • Participating in another clinical study at the same time
  • Known allergic reactions to dydrogesterone or other progestogens products
  • Any contraindication or other condition that precludes use of dydrogesterone in a particular patient, in accordance with the precautions listed in the locally approved label
  • Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects in or to complete the study
  • History of prior chemotherapy
  • Contraindication for pregnancy
  • Transfer of >1 embryo

Sites / Locations

  • Brussels IVF

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dydrogesterone

Micronized progesterone

Arm Description

Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using dydrogesterone 10 mg 3 times daily

Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using micronized progesterone 2x200 mg twice daily vaginally

Outcomes

Primary Outcome Measures

Ongoing pregnancy
visualisation of a fetal heart activity via pelvic (vaginal/abdominal) ultrasound examination at 12 weeks of gestation.

Secondary Outcome Measures

Live birth rate
as the birth of a live newborn after 22 weeks of gestation
Time of delivery
time of delivery (gestational week) will be confirmed (by calculation from date of embryo transfer)
Incidence of Treatment-Emergent Adverse Events
Tolerability and safety will be asses during the whole study period. Adverse events will be considered as unexpected if the nature, seriousness, severity or outcome of the reaction(s) is not consistent with the reference information. The expectedness of adverse events for the medications used in this study is detailed in the reference safety information in the current summary of product characteristics (SmPCs) issued in the participating countries. All serieus suspected unexpected serious adverse drug reactions (SUSARs) will be subject to expedited reporting. The investigator is responsible for submitting reports of SUSARs to the appropriate national regulatory authorities within the required reporting period. The investigator is responsible for notifying the IECs/IRBs in writing of the SUSARs within the required reporting timelines. Copies of the notification will be maintained by the investigator in the study documentation files.
Patient reported outcome
Questionnaire (using the Treatment Satisfaction Questionnaire of Medication (TSQM)) and recording information on treatment tolerability and convenience
Incidence of newborn adverse events
Newborn wellbeing and safety including congenital malformations will be evaluated after delivery via a telephonic contact with the patient
Biochemical pregnancy rate
serum hCG test (> 25 mIU/ml), without ultrasound evaluation of a pregnancy
Clinical pregnancy rate
assessed by transvaginal ultrasound and defined as the presence of ≥1 gestational sac on examination
Miscarriage rate
defined as spontaneous loss of a clinical pregnancy before 22 weeks of gestation (where embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus)
Rate of preterm birth
Delivery before 37 weeks of gestation
Rate of pre-eclampsia
Incidence of pre-eclampsia as defined by the defined as the development of hypertension after 20 weeks of gestation together with one or more new-onset conditions: proteinuria, maternal or uteroplacental dysfunctions. Univariate and multivariable regression analysis were performed to control for known or potential PE risk factors, more specifically: body mass index (BMI), African ethnicity, previous history of hypertensive disorders of pregnancy, mean arterial pressure (MAP) at the first prenatal consultation, polycystic ovary syndrome (PCOS) and ovulation disorders, endometrial thickness and oocyte recipients.
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
Implantation rate
assessed by ultrasound and defined as the number of gestational sacs per number of embryos transferred
Blastocyst development score
using the system developed by Gardner
Number of cryopreserved embryos
Number of cryopreserved embryos
Summary characteristics of the preceding controlled ovarian stimulation cycle
information on used stimulation medication, total dose of stimulation medication used, duration of stimulation medication, trigger medication

Full Information

First Posted
January 26, 2021
Last Updated
September 14, 2023
Sponsor
CRG UZ Brussel
search

1. Study Identification

Unique Protocol Identification Number
NCT04758871
Brief Title
Oral Versus Vaginal Progesterone for Luteal Phase Supplementation in Frozen Embryo Transfer Cycles
Acronym
REMODEL
Official Title
Dydrogesterone Versus Micronized Vaginal Progesterone (MVP) for Luteal Phase Support (LPS) in Hormone Replacement Therapy (HRT) Frozen Embryo Transfer (FET) Cycles.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
September 11, 2023 (Actual)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CRG UZ Brussel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To investigate the efficacy of dydrogesterone 30 mg compared to micronized vaginal progesterone 800 mg daily for luteal phase support in hormone replacement therapy frozen embryo transfer cycles, as confirmed by visualization of fetal heart activity by pelvic ultrasound assessment of ongoing pregnancy at 12 weeks of gestation.
Detailed Description
A randomized controlled trial comparing dydrogesterone 30 mg versus micronized vaginal progesterone 800 mg daily for luteal phase support in hormone replacement therapy frozen embryo transfer cycles. Patients will undergo an embryo transfer in a hormone replacement therapy cycle using Progynova 2 mg three times daily until an endometrium thickness of at least 7 mm is reached. Afterwards two different luteal phase supplementation methods will be compared. The primary outcome of the study is ongoing pregnancy at 12 weeks of gestation. We will also investigate other prenatal and neonatal outcome factors as well as patients satisfaction and safety of dydrogesterone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frozen Embryo Transfer, Hormone Replacement Therapy, Dydrogesterone, Infertility, Female

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Open label randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dydrogesterone
Arm Type
Experimental
Arm Description
Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using dydrogesterone 10 mg 3 times daily
Arm Title
Micronized progesterone
Arm Type
Active Comparator
Arm Description
Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using micronized progesterone 2x200 mg twice daily vaginally
Intervention Type
Drug
Intervention Name(s)
Dydrogesterone 10 MG Oral Tablet
Intervention Description
10 mg three times daily
Intervention Type
Drug
Intervention Name(s)
Micronized progesterone
Intervention Description
2x 200 mg vaginal tablets two times daily
Primary Outcome Measure Information:
Title
Ongoing pregnancy
Description
visualisation of a fetal heart activity via pelvic (vaginal/abdominal) ultrasound examination at 12 weeks of gestation.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Live birth rate
Description
as the birth of a live newborn after 22 weeks of gestation
Time Frame
22-42 weeks
Title
Time of delivery
Description
time of delivery (gestational week) will be confirmed (by calculation from date of embryo transfer)
Time Frame
follow-up time of 30 days after delivery
Title
Incidence of Treatment-Emergent Adverse Events
Description
Tolerability and safety will be asses during the whole study period. Adverse events will be considered as unexpected if the nature, seriousness, severity or outcome of the reaction(s) is not consistent with the reference information. The expectedness of adverse events for the medications used in this study is detailed in the reference safety information in the current summary of product characteristics (SmPCs) issued in the participating countries. All serieus suspected unexpected serious adverse drug reactions (SUSARs) will be subject to expedited reporting. The investigator is responsible for submitting reports of SUSARs to the appropriate national regulatory authorities within the required reporting period. The investigator is responsible for notifying the IECs/IRBs in writing of the SUSARs within the required reporting timelines. Copies of the notification will be maintained by the investigator in the study documentation files.
Time Frame
follow-up time of 30 days after delivery
Title
Patient reported outcome
Description
Questionnaire (using the Treatment Satisfaction Questionnaire of Medication (TSQM)) and recording information on treatment tolerability and convenience
Time Frame
day 12-18 of luteal phase supplementation (pregnancy test) and at 12 weeks gestation
Title
Incidence of newborn adverse events
Description
Newborn wellbeing and safety including congenital malformations will be evaluated after delivery via a telephonic contact with the patient
Time Frame
follow-up time of 30 days after delivery
Title
Biochemical pregnancy rate
Description
serum hCG test (> 25 mIU/ml), without ultrasound evaluation of a pregnancy
Time Frame
day 12-18 of luteal phase supplementation (pregnancy test)
Title
Clinical pregnancy rate
Description
assessed by transvaginal ultrasound and defined as the presence of ≥1 gestational sac on examination
Time Frame
Day 33-39 of LPS (Verification of pregnancy)
Title
Miscarriage rate
Description
defined as spontaneous loss of a clinical pregnancy before 22 weeks of gestation (where embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus)
Time Frame
22 weeks
Title
Rate of preterm birth
Description
Delivery before 37 weeks of gestation
Time Frame
follow-up time of 30 days after delivery
Title
Rate of pre-eclampsia
Description
Incidence of pre-eclampsia as defined by the defined as the development of hypertension after 20 weeks of gestation together with one or more new-onset conditions: proteinuria, maternal or uteroplacental dysfunctions. Univariate and multivariable regression analysis were performed to control for known or potential PE risk factors, more specifically: body mass index (BMI), African ethnicity, previous history of hypertensive disorders of pregnancy, mean arterial pressure (MAP) at the first prenatal consultation, polycystic ovary syndrome (PCOS) and ovulation disorders, endometrial thickness and oocyte recipients.
Time Frame
follow-up time of 30 days after delivery
Title
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
Description
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
Time Frame
follow-up time of 30 days after delivery
Title
Implantation rate
Description
assessed by ultrasound and defined as the number of gestational sacs per number of embryos transferred
Time Frame
Day 33-39 of LPS (Verification of pregnancy)
Title
Blastocyst development score
Description
using the system developed by Gardner
Time Frame
at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation)
Title
Number of cryopreserved embryos
Description
Number of cryopreserved embryos
Time Frame
day of screening and enrollment
Title
Summary characteristics of the preceding controlled ovarian stimulation cycle
Description
information on used stimulation medication, total dose of stimulation medication used, duration of stimulation medication, trigger medication
Time Frame
day of screening and enrollment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≤40 years of age at the time of IVF/ICSI treatment BMI ≥18 to ≤30 kg/m2 with a documented history of infertility Have undergone COS as part of an ART treatment and have had an unsuccessful fresh embryo transfer in that cycle, OR, have undergone freeze all strategy Scheduled to undergo FET with a standard exogenous/programmed hormonal replacement therapy (HRT) regimen Have at least 1 blastocyst vitrified on the 5th or 6th day after oocyte retrieval Elective single embryo (blastocyst) transfer (SET) Normal ultrasound examination at enrollment (or if <12 months old) Signed patient authorization for use/disclosure of data. Exclusion Criteria: Women with a history of recurrent miscarriage, defined as >2 consecutive miscarriages (biochemical pregnancy losses are not included) Absence of implantation (serum hCG = negative) after two consecutive cycles of IVF, ICSI or FET where the cumulative number of transferred embryos was >4 cleavage-stage embryos and >2 blastocysts Presence of hydrosalpinx that is not surgically treated Endometrial abnormalities on scanning during ovarian stimulation, such as endometrial polyp(s), sub mucosal fibroid(s), endometrial hyperplasia, endometrial fluid accumulation, or endometrial adhesions Participating in another clinical study at the same time Known allergic reactions to dydrogesterone or other progestogens products Any contraindication or other condition that precludes use of dydrogesterone in a particular patient, in accordance with the precautions listed in the locally approved label Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects in or to complete the study History of prior chemotherapy Contraindication for pregnancy Transfer of >1 embryo
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christophe Blockeel
Organizational Affiliation
CRG UZ Brussel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brussels IVF
City
Brussels
ZIP/Postal Code
1090
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Oral Versus Vaginal Progesterone for Luteal Phase Supplementation in Frozen Embryo Transfer Cycles

We'll reach out to this number within 24 hrs