Clinical trial NCT04758871: Oral Versus Vaginal Progesterone for Luteal Phase Supplementation in Frozen Embryo Transfer Cycles
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Frozen Embryo Transfer
Hormone Replacement Therapy
Dydrogesterone
Infertility, Female
Lead sponsor: CRG UZ Brussel
Sponsor class: OTHER
First posted: 2021-02-17
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label randomized controlled trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Ongoing pregnancy
timeFrame: 12 weeks
Secondary outcomes:
measure: Live birth rate
timeFrame: 22-42 weeks
measure: Time of delivery
timeFrame: follow-up time of 30 days after delivery
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: follow-up time of 30 days after delivery
measure: Patient reported outcome
timeFrame: day 12-18 of luteal phase supplementation (pregnancy test) and at 12 weeks gestation
measure: Incidence of newborn adverse events
timeFrame: follow-up time of 30 days after delivery
measure: Biochemical pregnancy rate
timeFrame: day 12-18 of luteal phase supplementation (pregnancy test)
measure: Clinical pregnancy rate
timeFrame: Day 33-39 of LPS (Verification of pregnancy)
measure: Miscarriage rate
timeFrame: 22 weeks
measure: Rate of preterm birth
timeFrame: follow-up time of 30 days after delivery
measure: Rate of pre-eclampsia
timeFrame: follow-up time of 30 days after delivery
measure: Occurence of antenatal bleeding, ultrasonographic abnormalities, gestational diabetes, cholestasis
timeFrame: follow-up time of 30 days after delivery
measure: Implantation rate
timeFrame: Day 33-39 of LPS (Verification of pregnancy)
measure: Blastocyst development score
timeFrame: at the time of embryo transfer (visit 2: day 6 of luteal phase supplementation)
measure: Number of cryopreserved embryos
timeFrame: day of screening and enrollment
measure: Summary characteristics of the preceding controlled ovarian stimulation cycle
timeFrame: day of screening and enrollment
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Brussels IVF
Study officials:
affiliation: CRG UZ Brussel
name: Christophe Blockeel
role: PRINCIPAL_INVESTIGATOR
References: