Fertility Disorders
Conditions
Brief summary
The purpose of this randomized pilot study is to compare the efficacy of double oocyte retrieval vs. conventional antagonist ovarian stimulation protocol in poor prognosis patients undergoing in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI).
Interventions
DRUGCorifollitoropin alfa (CFA)-double pick up
In the study group, 225 IU of recombinant FSH (rFSH) will continue after the first oocyte retrieval (OR). Antagonist administration will be initiated when at least one follicle measuring ≥14 mm will be present in the ultrasound. If one or more follicles ≥17 mm are observed, patients will undergo a second triggering with human chorionic gonadotropin (hCG) 5000 IU and a second OR will be performed. In case of patients with no follicular development following 10 additional days of rFSH post-OR
Sponsors
CRG UZ Brussel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Age 25-40 years * Body mass index (BMI) ≤ 35 and ≥ 19 * Antimüllerian hormone (AMH) level of ≤1.5 ng/mL or antral follicular count (AFC) of ≤6 follicles or ≤5 oocytes retrieved in a previous cycle following standard conventional ovarian stimulation.
Exclusion criteria
* Testicular sperm extraction * History of \> 3 three consecutive previous unsuccessful IVF cycles * BMI \>35 or \<19 * Use of oral contraceptives \<3 months before start of the treatment * polycystic ovary syndrome (PCOS) according to the Rotterdam criteria * Ovarian stimulation for pre-implantation genetic testing (PGT-A/M) * Medical/social freezing * In vitro maturation (IVM) * History of untreated autoimmune, endocrine or metabolic disorders, * Ovarian cystectomy or oophorectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of MII Oocytes Retrieved Between the Two Arms | 1 month | number of mature (or metaphase II, MII) oocytes retrieved during oocyte retrieval |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cumulus Oocyte Complexes (COCs) Retrieved | 1 month | number of COCs retrieved at oocyte retrieval |
| Number of Oocytes Fertilized | 1 month | number of fertilized oocytes at day 1 after oocyte retrieval |
| Total Number of Available Embryos | 1 month | number of available embryos at day 3 or day 5 after oocyte retrieval, good quality and therefore transferable |
| Number of Preovulatory Follicles | 1 month | number of follicles ≥11m on the day of final oocyte maturation trigger |
| Clinical Pregnancy Rates | 4 months | clinical pregnancy rate |
| Live Birth Rates | 12 months | number of live births |
| Cumulative Live Birth Rates | 24 months | defined as the first live birth following the transfer of fresh and subsequent frozen-thawed embryos |
| Duration of Ovarian Stimulation | 1 month | number of days of ovarian stimulation |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group A single injection of 150mcg of corifollitropin alfa was administrated at day 2/3 of the cycle, followed by 225IU of recombinant FSH (rFSH) in a fixed antagonist protocol. Group A (control group) underwent conventional triggering with hCG 5000 IU and a single oocyte retrieval (OR) | 24 |
| Double Pick up Group A single injection of 150mcg of corifollitropin alfa was administrated at day 2/3 of the cycle, followed by 225IU of recombinant FSH (rFSH) in a fixed antagonist protocol. Group B (study group) underwent triggering with GnRHagonist. 225 IU of rFSH was continued after the first oocyte retrieval (OR). Antagonist administration was initiated when at least one follicle measuring ≥14 mm was present on the ultrasound. If one or more follicles ≥17 mm were observed, patients underwent a second triggering with hCG 5000 IU and a second OR was performed. In case of patients with no follicular development following 13 additional days of rFSH. | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | Double Pick up Group | Total | Control Group |
|---|---|---|---|
| Age, Continuous | 35.6 years STANDARD_DEVIATION 2.9 | 36 years STANDARD_DEVIATION 3.3 | 36.3 years STANDARD_DEVIATION 3.6 |
| Anti-Müllerian hormone (AMH) | 0.6 ng/ml STANDARD_DEVIATION 0.3 | 0.55 ng/ml STANDARD_DEVIATION 0.27 | 0.5 ng/ml STANDARD_DEVIATION 0.2 |
| antral follicle count (AFC) | 5.7 number of follicles STANDARD_DEVIATION 2.8 | 6.1 number of follicles STANDARD_DEVIATION 3.1 | 6.6 number of follicles STANDARD_DEVIATION 3.3 |
| basal FSH | 9.8 IU/L STANDARD_DEVIATION 3.4 | 9.8 IU/L STANDARD_DEVIATION 3.4 | 9.7 IU/L STANDARD_DEVIATION 3.6 |
| Body Mass index (BMI) | 24.5 kg/m^2 STANDARD_DEVIATION 5 | 24.4 kg/m^2 STANDARD_DEVIATION 4.3 | 24.3 kg/m^2 STANDARD_DEVIATION 3.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 24 Participants | 48 Participants | 24 Participants |
| infertility duration | 3.7 years STANDARD_DEVIATION 7 | 3.1 years STANDARD_DEVIATION 5.1 | 2.4 years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 24 Participants | 48 Participants | 24 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 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Number of MII Oocytes Retrieved Between the Two Arms
number of mature (or metaphase II, MII) oocytes retrieved during oocyte retrieval
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Number of MII Oocytes Retrieved Between the Two Arms | 4.1 number of oocytes | Standard Deviation 2.4 |
| Double Pick up Group | Number of MII Oocytes Retrieved Between the Two Arms | 3.0 number of oocytes | Standard Deviation 2.2 |
Secondary
Clinical Pregnancy Rates
clinical pregnancy rate
Time frame: 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Clinical Pregnancy Rates | 7 Participants |
| Double Pick up Group | Clinical Pregnancy Rates | 13 Participants |
Secondary
Cumulative Live Birth Rates
defined as the first live birth following the transfer of fresh and subsequent frozen-thawed embryos
Time frame: 24 months
Secondary
Duration of Ovarian Stimulation
number of days of ovarian stimulation
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Duration of Ovarian Stimulation | 9.9 days | Standard Deviation 2.7 |
| Double Pick up Group | Duration of Ovarian Stimulation | 9.9 days | Standard Deviation 3 |
Secondary
Live Birth Rates
number of live births
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Live Birth Rates | 6 Participants |
| Double Pick up Group | Live Birth Rates | 8 Participants |
Secondary
Number of Cumulus Oocyte Complexes (COCs) Retrieved
number of COCs retrieved at oocyte retrieval
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Number of Cumulus Oocyte Complexes (COCs) Retrieved | 5.3 number of oocytes | Standard Deviation 2.7 |
| Double Pick up Group | Number of Cumulus Oocyte Complexes (COCs) Retrieved | 3.3 number of oocytes | Standard Deviation 2.2 |
Secondary
Number of Oocytes Fertilized
number of fertilized oocytes at day 1 after oocyte retrieval
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Number of Oocytes Fertilized | 3.7 number of fertilized oocytes | Standard Deviation 2.4 |
| Double Pick up Group | Number of Oocytes Fertilized | 2.3 number of fertilized oocytes | Standard Deviation 2 |
Secondary
Number of Preovulatory Follicles
number of follicles ≥11m on the day of final oocyte maturation trigger
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Number of Preovulatory Follicles | 5.4 number of follicles | Standard Deviation 2.2 |
| Double Pick up Group | Number of Preovulatory Follicles | 5.0 number of follicles | Standard Deviation 1.6 |
Secondary
Total Number of Available Embryos
number of available embryos at day 3 or day 5 after oocyte retrieval, good quality and therefore transferable
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Total Number of Available Embryos | 1.5 number of embryos | Standard Deviation 0.9 |
| Double Pick up Group | Total Number of Available Embryos | 1.4 number of embryos | Standard Deviation 1.3 |