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

Phase 4

Completed

• Conditions: Frozen Embryo Transfer; Dydrogesterone; Hormone Replacement Therapy; Infertility, Female
• Interventions: Drug: Dydrogesterone 10 MG Oral Tablet; Drug: Micronized progesterone

• Registration Number: NCT04758871
• Lead Sponsor: CRG UZ Brussel

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.

Study Timeline

• Study First Submitted: 2021-01-26
• Study First Submitted QC: 2021-02-15
• Study First Posted: 2021-02-17
• Study Start: 2021-10-01
• Primary Completion: 2023-09-11
• Status Verified: 2024-06
• Study Completion: 2024-06-13
• Last Update Submitted: 2024-06-13
• Last Update Posted: 2024-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 150

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dydrogesterone	Dydrogesterone 10 MG Oral Tablet	Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using dydrogesterone 10 mg 3 times daily
Micronized progesterone	Micronized progesterone	Luteal phase support for hormone replacement therapy frozen embryo transfer cycles using micronized progesterone 2x200 mg twice daily vaginally

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Biochemical pregnancy rate	day 12-18 of luteal phase supplementation (pregnancy test)	serum hCG test (\> 25 mIU/ml), without ultrasound evaluation of a pregnancy
Blastocyst development score	at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation)	using the system developed by Gardner
Incidence of newborn adverse events	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
Clinical pregnancy rate	Day 33-39 of LPS (Verification of pregnancy)	assessed by transvaginal ultrasound and defined as the presence of ≥1 gestational sac on examination
Rate of preterm birth	follow-up time of 30 days after delivery	Delivery before 37 weeks of gestation
Number of cryopreserved embryos	day of screening and enrollment	Number of cryopreserved embryos
Summary characteristics of the preceding controlled ovarian stimulation cycle	day of screening and enrollment	information on used stimulation medication, total dose of stimulation medication used, duration of stimulation medication, trigger medication
Live birth rate	22-42 weeks	as the birth of a live newborn after 22 weeks of gestation
Time of delivery	follow-up time of 30 days after delivery	time of delivery (gestational week) will be confirmed (by calculation from date of embryo transfer)
Incidence of Treatment-Emergent Adverse Events	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.
Patient reported outcome	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
Rate of pre-eclampsia	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.
Miscarriage rate	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)
Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis	follow-up time of 30 days after delivery	Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
Implantation rate	Day 33-39 of LPS (Verification of pregnancy)	assessed by ultrasound and defined as the number of gestational sacs per number of embryos transferred

Trial Locations

Locations (1)

Brussels IVF; 🇧🇪 Brussels, Belgium