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

Infertility, Female Clinical Trial

— REMODEL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04758871
• Other study ID #: REMODEL
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 1, 2021
• Est. completion date: May 1, 2024

Study information

• Verified date: September 2023
• Source: CRG UZ Brussel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: May 1, 2024
• Est. primary completion date: September 11, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Dydrogesterone
• Frozen Embryo Transfer
• Hormone Replacement Therapy
• Infertility
• Infertility, Female

Intervention

Drug:
• Dydrogesterone 10 MG Oral Tablet
10 mg three times daily
• Micronized progesterone
2x 200 mg vaginal tablets two times daily

Locations

Country	Name	City	State
Belgium	Brussels IVF	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
CRG UZ Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy	visualisation of a fetal heart activity via pelvic (vaginal/abdominal) ultrasound examination at 12 weeks of gestation.	12 weeks
Secondary	Live birth rate	as the birth of a live newborn after 22 weeks of gestation	22-42 weeks
Secondary	Time of delivery	time of delivery (gestational week) will be confirmed (by calculation from date of embryo transfer)	follow-up time of 30 days after delivery
Secondary	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.	follow-up time of 30 days after delivery
Secondary	Patient reported outcome	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
Secondary	Incidence of newborn adverse events	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
Secondary	Biochemical pregnancy rate	serum hCG test (> 25 mIU/ml), without ultrasound evaluation of a pregnancy	day 12-18 of luteal phase supplementation (pregnancy test)
Secondary	Clinical pregnancy rate	assessed by transvaginal ultrasound and defined as the presence of =1 gestational sac on examination	Day 33-39 of LPS (Verification of pregnancy)
Secondary	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)	22 weeks
Secondary	Rate of preterm birth	Delivery before 37 weeks of gestation	follow-up time of 30 days after delivery
Secondary	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.	follow-up time of 30 days after delivery
Secondary	Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis	Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis	follow-up time of 30 days after delivery
Secondary	Implantation rate	assessed by ultrasound and defined as the number of gestational sacs per number of embryos transferred	Day 33-39 of LPS (Verification of pregnancy)
Secondary	Blastocyst development score	using the system developed by Gardner	at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation)
Secondary	Number of cryopreserved embryos	Number of cryopreserved embryos	day of screening and enrollment
Secondary	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	day of screening and enrollment