Immediate Versus Postponed Single Blastocyst Transfer in Modified Natural Cycle Frozen Embryo Transfer (mNC-FET): a Multicenter Randomized Controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Rigshospitalet, Denmark
- Enrollment
- 464
- Locations
- 1
- Primary Endpoint
- Live birth rate per randomized patient
Study Overview
Brief Summary
The purpose of this randomized controlled trial is to investigate if immediate single blastocyst transfer (in the first menstrual cycle following oocyte retrieval) is non-inferior to standard postponed single blastocyst transfer (in the second or subsequent menstrual cycle following oocyte retrieval) in modified natural cycle frozen-thawed embryo transfer (mNC-FET) in terms of live birth rate.
Detailed Description
The study is a multicenter randomized non-blinded controlled trial with the purpose of investigating if immediate mNC-FET is non-inferior to standard postponed mNC-FET in terms of live birth rate and other obstetric- and neonatal outcome.
Several fertility clinics in Denmark will participate in the recruitment of patients. All clinics perform standardized treatments according to the public health care system in Denmark. Patient enrolment is expected to begin in February 2021 and continue until December 2024.
The study population will consist of 464 patients undergoing mNC-FET after a fresh IVF/ICSI cycle that did not result in a viable pregnancy, or after a freeze-all cycle. Eligible patients will be recruited if they fulfil the inclusion criteria and none of the exclusion criteria. Patients will be randomized 1:1 by simple randomization to one of the following study arms:
I. Immediate mNC-FET In the Immediate arm, patients will undergo mNC-FET in the menstrual cycle immediately following oocyte retrieval with failed fresh embryo transfer or freeze-all.
II. Postponed mNC-FET In the Postponed arm, mNC-FET is performed at least one full menstrual cycle after the fresh embryo transfer or freeze-all cycle, which means that the first FET following the fresh cycle is not started until the second menstrual bleeding or later.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients eligible for FET in a modified natural cycle
- •Regular menstrual cycle (23-35 days)
- •Vitrified day 5 or 6 blastocyst
- •Blastocyst Gardner score > or = 3BB at the day of vitrification
Exclusion Criteria
- •Uterine malformations or presence of hydrosalpinx
- •Submucosal uterine myomas
- •Uterine polyps
- •Allergy to standard fertility medication
- •Contradiction to standard fertility medication
- •Male of female HIV, hepatitis B or C
- •Preimplantation Genetic Testing (PGT) in the fresh cycle
- •Severe OHSS during the fresh cycle (defined as need for ascites drainage and/or hospital admission)
- •Oocyte donation
- •Testicular sperm aspiration (TESA)
Arms & Interventions
Immediate mNC-FET
In the immediate arm, patients undergo mNC-FET in the menstrual cycle immediately following oocyte retrieval and failed fresh embryo transfer or freeze-all.
Intervention: Immediate mNC-FET (Procedure)
Postponed mNC-FET
Standard procedure where mNC-FET is performed at least one full menstrual cycle after failed fresh embryo transfer or freeze-all cycle.
Outcomes
Primary Outcomes
Live birth rate per randomized patient
Time Frame: One-year follow-up after a positive pregnancy test
Live birth rate in patients randomized to immediate versus postponed FET
Live birth rate per protocol
Time Frame: One-year follow-up after a positive pregnancy test
Live birth rate in patients randomized to immediate versus postponed FET minus dropouts
Secondary Outcomes
- Endocrinology of the luteal phase(Baseline, day of ovulation trigger (hCG+0), early luteal phase* (hCG+4), day of transfer (hCG+6) and mid-luteal phase* (hCG+11)(*only at Rigshospitalet), within one FET cycle, up to approximately 1 month)
- Positive hCG rate per randomized patient and per blastocyst transfer(16 days after ovulation trigger (hCG+16))
- Ongoing pregnancy rate per randomized patient and per blastocyst transfer(Ultrasound at 7-8 weeks of gestation)
- Day of ovulation(From first day of FET cycle to the day of ovulation trigger (hCG+0), up to 1 month)
- Clinical pregnancy loss(Routine ultrasound at 7-8 weeks of gestation or ad hoc ultrasound before 22 weeks of gestation)
- Cycle cancellation(16 days after ovulation trigger (hCG+16) and through study completion, up to 1 year)
- Reason for cycle cancellation(16 days after ovulation trigger (hCG+16) and through study completion, up to 1 year)
- Pregnancy related complications(One-year follow-up after a positive pregnancy test)
- Live birth rate per blastocyst transfer(One-year follow-up after a positive pregnancy test)
- Biochemical pregnancy loss(16 days after ovulation trigger (hCG+16) and up to 7-8 weeks)
- Time-to-live-birth(From day of ovarian stimulation through study completion, up to 18 months)
- Neonatal outcome(One-year follow-up after a positive pregnancy test)
- Number of ovarian follicular structures >10 mm(At baseline and on day of ovulation trigger (hCG+0), up to 1 month)
- Time-to-pregnancy(From day of ovarian stimulation to day of clinical pregnancy, up to 1 year)
- Quality of life assessment(Baseline and mid-luteal phase (hCG+11), up to 1 month)
Investigators
Kristine Loessl
MD, PhD
Rigshospitalet, Denmark