Infertility
Conditions
Keywords
ovarian stimulation, random, egg donation, antagonist, gnrh agonist trigger
Brief summary
The purpose of this prospective single-center study is to evaluate the laboratory outcome after random start ovarian stimulation in oocyte donors. The study will be performed in egg-donors but this type of treatment has the potential to be implemented in general infertility population.
Detailed description
The study group will start ovarian stimulation randomly in different moments throughout the menstrual cycle. Randomization will take place on day 2-3 of the menstrual cycle, according to a list of random allocation of treatments and egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase starting at luteinizing hormone (LH) peak +3,+5,+7,+9 or +11. Egg-donors will receive urinary follicle stimulating hormone (FSH) 150-225 IU/d in gonadotropin-releasing hormone (GnRH) antagonist protocol with cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation and a GnRH agonist trigger with triptorelin 0,2 mg to induce the final follicular maturation. Transvaginal ultrasound and serum analysis (estradiol, progesterone, LH and FSH) will be included for cycle monitoring.
Interventions
OTHERRandom start ovarian stimulation
Egg-donors will start ovarian stimulation randomly at different moments throughout the menstrual cycle.
DRUGGonadotrophins
Urinary FSH 150-225 IU/d
DRUGGnRH antagonist
Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation
DRUGGnRH agonist
GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation.
Sponsors
Instituto Bernabeu
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Premenopausal women * 18-35 years old * FSH levels \< 10 IU/liter * Antral follicle count (AFC) \> 10 * Regular cycles * Body Mass Index (BMI) \< 28 * Signed informed consent
Exclusion criteria
* Polycystic ovary syndrome (PCOS) patients * Allergy to gonadotrophins * Concomitant participation in other trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Mature Eggs | Up to 24 hours from the oocyte collection | When collected, eggs retain numerous cells (granulosa or cumulus cells) surrounding the oocyte; this structure is termed as the cumulus oocyte complex (COC). Few hours later (2-4 hs), the oocyte is denuded from these cumulus cells, allowing for a clearer observation of the maturity status (presence or absence of a metaphase II) of the oocyte. The percentage of mature eggs represents the proportion resulting from dividing the total number of COCs collected by the number of metaphase II oocytes and multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fertilization Rate | 24 hours after day of oocyte collection | Percentage of properly fertilized eggs after microinjection (ICSI) method |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Random Start Ovarian Stimulation Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at LH peak +3,+5,+7,+9 or +11. They will receive urinary FSH 150-225 IU/d and five days later cetrorelix acetate 0,25 mg/d will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later.
Interventions:
* Random start ovarian stimulation
* Gonadotrophins: Urinary FSH 150-225 IU/d
* GnRH antagonists: Cetrorelix 0,25 mg/d
* GnRH agonist for triggering: Triptorelin 0,2 mg single dose
Gonadotrophins: Urinary FSH 150-225 IU/d
GnRH antagonist: Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation
GnRH agonist: GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Random Start Ovarian Stimulation | — |
|---|---|---|
| Age, Continuous | 25.2 years STANDARD_DEVIATION 4.2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 14 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Percentage of Mature Eggs
When collected, eggs retain numerous cells (granulosa or cumulus cells) surrounding the oocyte; this structure is termed as the cumulus oocyte complex (COC). Few hours later (2-4 hs), the oocyte is denuded from these cumulus cells, allowing for a clearer observation of the maturity status (presence or absence of a metaphase II) of the oocyte. The percentage of mature eggs represents the proportion resulting from dividing the total number of COCs collected by the number of metaphase II oocytes and multiplied by 100.
Time frame: Up to 24 hours from the oocyte collection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Random Start Ovarian Stimulation | Percentage of Mature Eggs | 82 Percentage of mature eggs | Standard Deviation 10 |
Comparison: The sample size was calculated assuming a non-inferiority margin of 5 eggs and a standard deviation (SD) of 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60).p-value: 0.8t-test, 1 sided
Comparison: The sample size was calculated assuming a non-inferiority margin of 5 eggs SD 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60). Statistical analysis used t-student test for continuous variables and chi-square test for categorical parameters.p-value: 0.8Chi-squared
Secondary
Fertilization Rate
Percentage of properly fertilized eggs after microinjection (ICSI) method
Time frame: 24 hours after day of oocyte collection
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Random Start Ovarian Stimulation | Fertilization Rate | 71 Percentage of properly fertilized eggs | Standard Deviation 7.8 |
p-value: <0.05Chi-squared