in Vitro Fertilization, Ovulation Induction
Conditions
Keywords
embryonic structures, sperm injections, intracytoplasmic, IVF, GnRH antagonist, ovarian stimulation, cycle day 2 versus cycle day 5
Brief summary
Background of the study: Milder stimulation protocols have the advantage of being less expensive and more patient-friendly. Moreover, recent evidence suggests that mild stimulation protocols lead to lower embryo aneuploidy rates compared to conventional treatment regimens. Although with mild stimulation protocols the expected number of oocytes retrieved will be lower, pregnancy rates have shown to be similar possibly because embryo quality outfavours embryo quantity. Objective of the study: The aim of the study is to determine whether cycle day (CD) 5 start of stimulation will lead to better quality of embryos, based on morphology, than CD 2 start, in IVF with GnRH antagonist co-treatment started on a fixed day. Study design: Prospective randomized trial comparing two different starting days of ovarium stimulation (day 2 versus day 5) for IVF treatment. Intervention: One group wil start on cycle day 2 with stimulation of the ovaries with recombinant FSH. The other group will start on cycle day 5. Both group will start suppressing the gonadotrophin production of the the pituitary gland on cycle day 6 with a GnRH antagonist. Primary study parameters/outcome of the study: Primary outcome parameter is number of top embryos per ovum pick up. Secondary study parameters/outcome of the study: Secondary outcome measures are duration of stimulation, cancellation rate, fertilization rate, number of cumulus oocyte complexes obtained, number of mature oocytes obtained, number of top embryos per started cycle, amount of IU recFSH, and clinical pregnancy rate.
Interventions
DRUGMild stimulation
Fixed daily dose of 150 IU rFSH start cycle day 5 or day 2 depending on the Arm
Sponsors
Free University Medical Center
UMC Utrecht
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 36 Years
Healthy volunteers
Yes
Inclusion criteria
* Female age \< 36 years * FSH \< 12 IU/l * BMI 18-29 kg/m2 * Regular cycle (25-35 days) * No major uterine or ovarian abnormalities * No previous IVF cycles * Written informed consent
Exclusion criteria
* Oocyte donation * Medical contra indication for pregnancy or IVF treatment * Endometriosis ≥ grade 3 * Polycystic Ovarium Syndrome (PCOS) * Endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Top Embryos Per OPU. | 1 year | Proportion of top embryos per ovum pick-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cumulus Oocyte Complexes Obtained | one year | Number of cumulus oocyte complexes obtained after ovum pick-up |
Countries
Belgium, Netherlands
Participant flow
Recruitment details
Patients were recuited between 11-9-2008 and 1-10-2010 in both centers.
Pre-assignment details
Patients who didn't completed the trial were cancelled before OPU due to low- or hyperresponse or before ET due to total fertilisation failure or no embryo to transfer.
Participants by arm
| Arm | Count |
|---|---|
| Start rFSH Cycle Day 2 Start 150IU rFSH s.c. cycle day 2 | 80 |
| Start rFSH on Cycle Day 5 Start 150IU rFSH s.c. cycle day 5 | 67 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 24 | 28 |
Baseline characteristics
| Characteristic | Start rFSH Cycle Day 2 | Start rFSH on Cycle Day 5 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 80 Participants | 67 Participants | 147 Participants |
| Age, Continuous | 31.0 years STANDARD_DEVIATION 3.5 | 31.1 years STANDARD_DEVIATION 4.4 | 31.0 years STANDARD_DEVIATION 4 |
| Region of Enrollment Belgium | 49 participants | 39 participants | 88 participants |
| Region of Enrollment Netherlands | 31 participants | 28 participants | 59 participants |
| Sex: Female, Male Female | 80 Participants | 67 Participants | 147 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 80 | 0 / 67 |
| serious Total, serious adverse events | 0 / 80 | 0 / 67 |
Outcome results
Primary
Proportion of Top Embryos Per OPU.
Proportion of top embryos per ovum pick-up
Time frame: 1 year
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Start rFSH Cycle Day 2 | Proportion of Top Embryos Per OPU. | 51.1 percentage embryos |
| Start rFSH on Cycle Day 5 | Proportion of Top Embryos Per OPU. | 41.8 percentage embryos |
Secondary
Number of Cumulus Oocyte Complexes Obtained
Number of cumulus oocyte complexes obtained after ovum pick-up
Time frame: one year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Start rFSH Cycle Day 2 | Number of Cumulus Oocyte Complexes Obtained | 9.8 oocytes | Standard Deviation 5.4 |
| Start rFSH on Cycle Day 5 | Number of Cumulus Oocyte Complexes Obtained | 8.5 oocytes | Standard Deviation 5.7 |