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

September 14, 2023 updated by: Caroline Roelens, CRG UZ Brussel

Dydrogesterone Versus Micronized Vaginal Progesterone (MVP) for Luteal Phase Support (LPS) in Hormone Replacement Therapy (HRT) Frozen Embryo Transfer (FET) Cycles.

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Brussels, Belgium, 1090
        • Brussels IVF

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dydrogesterone
Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using dydrogesterone 10 mg 3 times daily
10 mg three times daily
Active Comparator: Micronized progesterone
Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using micronized progesterone 2x200 mg twice daily vaginally
2x 200 mg vaginal tablets two times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing pregnancy
Time Frame: 12 weeks
visualisation of a fetal heart activity via pelvic (vaginal/abdominal) ultrasound examination at 12 weeks of gestation.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live birth rate
Time Frame: 22-42 weeks
as the birth of a live newborn after 22 weeks of gestation
22-42 weeks
Time of delivery
Time Frame: follow-up time of 30 days after delivery
time of delivery (gestational week) will be confirmed (by calculation from date of embryo transfer)
follow-up time of 30 days after delivery
Incidence of Treatment-Emergent Adverse Events
Time Frame: follow-up time of 30 days after delivery

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.

follow-up time of 30 days after delivery
Patient reported outcome
Time Frame: day 12-18 of luteal phase supplementation (pregnancy test) and at 12 weeks gestation
Questionnaire (using the Treatment Satisfaction Questionnaire of Medication (TSQM)) and recording information on treatment tolerability and convenience
day 12-18 of luteal phase supplementation (pregnancy test) and at 12 weeks gestation
Incidence of newborn adverse events
Time Frame: follow-up time of 30 days after delivery
Newborn wellbeing and safety including congenital malformations will be evaluated after delivery via a telephonic contact with the patient
follow-up time of 30 days after delivery
Biochemical pregnancy rate
Time Frame: day 12-18 of luteal phase supplementation (pregnancy test)
serum hCG test (> 25 mIU/ml), without ultrasound evaluation of a pregnancy
day 12-18 of luteal phase supplementation (pregnancy test)
Clinical pregnancy rate
Time Frame: Day 33-39 of LPS (Verification of pregnancy)
assessed by transvaginal ultrasound and defined as the presence of ≥1 gestational sac on examination
Day 33-39 of LPS (Verification of pregnancy)
Miscarriage rate
Time Frame: 22 weeks
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)
22 weeks
Rate of preterm birth
Time Frame: follow-up time of 30 days after delivery
Delivery before 37 weeks of gestation
follow-up time of 30 days after delivery
Rate of pre-eclampsia
Time Frame: follow-up time of 30 days after delivery
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.
follow-up time of 30 days after delivery
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
Time Frame: follow-up time of 30 days after delivery
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
follow-up time of 30 days after delivery
Implantation rate
Time Frame: Day 33-39 of LPS (Verification of pregnancy)
assessed by ultrasound and defined as the number of gestational sacs per number of embryos transferred
Day 33-39 of LPS (Verification of pregnancy)
Blastocyst development score
Time Frame: at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation)
using the system developed by Gardner
at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation)
Number of cryopreserved embryos
Time Frame: day of screening and enrollment
Number of cryopreserved embryos
day of screening and enrollment
Summary characteristics of the preceding controlled ovarian stimulation cycle
Time Frame: day of screening and enrollment
information on used stimulation medication, total dose of stimulation medication used, duration of stimulation medication, trigger medication
day of screening and enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Christophe Blockeel, CRG UZ Brussel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2021

Primary Completion (Actual)

September 11, 2023

Study Completion (Estimated)

May 1, 2024

Study Registration Dates

First Submitted

January 26, 2021

First Submitted That Met QC Criteria

February 15, 2021

First Posted (Actual)

February 17, 2021

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 14, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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