A Multicentre Randomized Controlled Trial of a "Freeze All and Transfer Later" Versus a Conventional "Fresh Embryo Transfer" Strategy for Assisted Reproductive Technology (ART) in Women With a Regular Menstrual Cycle
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 424
- Locations
- 2
- Primary Endpoint
- Ongoing pregnancy rates
Study Overview
Brief Summary
The purpose of this study is to compare conventional fresh embryo transfer with a "freeze all and transfer later strategy" in assisted reproductive technology in terms of ongoing pregnancy rates, live birth rates as well as perinatal outcomes.
Detailed Description
The study is a multicentre randomized controlled double-blinded trial with the purpose to investigate if pregnancy- and live birth rates can be improved by a "freeze all and transfer later"-strategy with transfer of the best quality, frozen, thawed embryo in a subsequent natural cycle compared with conventional fresh embryo transfer with transfer of the embryo in the stimulated cycle.
In total 5 clinics in Denmark and Sweden will be participating in the recruitment of patients for the study.
The patients will be screened and randomized computerized on cycle day 2 or 3 and allocated to one of the two study arms:
I: hCG (human chorion gonadotrophin) arm with traditional hCG triggering and fresh blastocyst transfer II: GnRH (gonadotropin-releasing hormone)- agonist triggering arm with blastocyst cryopreservation and subsequent transfer in a subsequent natural cycle.
The randomization will be done after the decision of gonadotrophin (rFSH/hMG) starting dose, and both doctor and patient will be blinded to the randomization until the day of hCG/agonist trigger. Both groups will be stimulated in a short GnRH antagonist protocol. The ovarian stimulation The gonadotrophin stimulation is performed according to the general standards in each of the clinics and can be altered according to the ovarian response with a maximum of 300 IU.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 39 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •AMH (Anti-Müllerian hormone) > 6.28 pmol/L (Roche Elecsys assay)
- •Female age 18 years to less than 40 years
- •1, 2 or 3 IVF/ICSI cycle with oocyte aspiration
- •Regular menstrual cycle between 24 and 35 days
- •BMI between 18 and 35
- •Two ovaries
- •Can and will sign informed consent
Exclusion Criteria
- •Women who do not fulfil the inclusion criteria
- •Endometriosis stage III to IV
- •Ovarian cysts with diameter > 30 mm at day of start of stimulation
- •Submucosal fibroids
- •Women with severe co-morbidity (IDDM, NIDDM, gastrointestinal, cardiovascular, pulmonary, liver or kidney disease)
- •Dysregulation of thyroid disease
- •Not danish or English speaking women
- •Contraindications or allergies to use of Gonadotrophins or GnRH antagonists
- •TESA (testicular sperm aspiration)
- •OD (oocyte donation)
- •Previous inclusion in the study
Arms & Interventions
Freeze all
Transfer of a frozen, thawed blastocyst in a subsequent natural menstrual cycle
Intervention: Freeze all (Procedure)
Fresh embryo transfer
Standard procedure
Outcomes
Primary Outcomes
Ongoing pregnancy rates
Time Frame: Two years
Outcome measured per transfer of the first blastocyst, per oocyte pick-up, per start of ovarian stimulation and per randomized patient.
Secondary Outcomes
- Time-to-delivery(Three years)
- Preeclampsia(Three years)
- Preterm birth(Three years)
- Low birth weight(Three years)
- Small-for-gestational age (SGA)(Three years)
- Placental rupture(Three years)
- Positive hCG 11 days post embryo transfer(Three years)
- Miscarriages, biochemical pregnancies, ectopic pregnancies(Three years)
- Quality of life for female and partner(Two years)
- Cost-effectiveness(Three years)
- Live birth rates(Two years)
- Cumulative live birth rates(Two years)
- Number of cycles with no embryo transfer(Two years)
- Time-to-pregnancy(Two years)
- Perinatal mortality(Three years)
- Large-for-gestational age (LGA)(Three years)
Investigators
Anja Bisgaard Pinborg
Professor, MD, DMSc
Hvidovre University Hospital