Controlled Ovarian Hyperstimulation, Infertility
Conditions
Brief summary
Serum concentrations of the different hormones involved in follicular steroid genesis during a cycle of controlled ovarian stimulation with recombinant FSH or HMG will be compared in this study. Serum Progesterone (P) levels at the end of Controlled Ovarian Stimulation (i.e. the day of triggering) have been related to cycle outcome, in terms of ongoing pregnancy and live birth rates. Large cohort studies show that P levels above a certain threshold are associated with poorer cycle outcome. The mechanisms behind P elevation are not well understood yet. It has been shown that P levels are positively related to ovarian response and to the dose of FSH given during COS. Furthermore, it has been well documented that P levels at the end of stimulation are significantly higher when recombinant (r) FSH is used for COS when compared to HMG, either in a GnRH agonist long protocol or in a GnRH antagonist protocol. Some authors suggest that this finding is explained by the fact that COS with rFSH provides a higher oocyte yield than when hMG is given, so the higher P levels observed would be explained by the larger number of follicles developed when rFSH is used. On the other hand, other authors explain this event by a different follicular esteroidogenesis when HMG is used for COS compared to rFSH The hypotheisis behind this assumption is that rFSH enhances P synthesis from its precursor pregnenolone in the granulosa cells. This P is unable to be further metabolized into androgens because of the lack of 17-20 lyase in the human granulosa cells, and therefore is delivered into circulation. On the other hand, when HMG is given for COS, the ∆4 pathway is promoted, and pregnenolone will be catabolized in to Dehidroepiandrostenodione (DHEA), in the theca cells, and this one to Androstenodione, which will be finally aromatized in to estrogens. This mechanism will explain the lower P and higher E2 levels observed in HMG cycles in comparison to rFSH cycles.
Interventions
DRUGCOS with GnRH antagonists and rFSH
Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.
DRUGCOS with GnRH antagonists and HP-HMG
Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function.
Sponsors
Roche Pharma AG
Instituto Valenciano de Infertilidad, IVI VALENCIA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Good physical and psychological condition * Normal menstrual cycle (25-35 days) * Normal ovarian reserve defined by serum ANH010-30 pMol/L * All other criteria to fulfill by oocyte donors
Exclusion criteria
* Kidney failure * Ovarian Polyquistic syndrome * Any systemic or metabolic disfunction that counter indicates the use of gonadotrophins * Any other reason that involves exclusion of the oocyte donation program
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SERUM PROGSTERONE CONCENTRATION | 21 days | Compare hormonal blood serum concentrations of progesterone during ovarian stimulation implied in follicular steroidogenesis during a cycle of Controlled Ovarian Stimulation with either r-FSH or HP-HMG. |
| OVARIAN RESPONSE | 21 days | NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rFSH Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.
COS with GnRH antagonists and rFSH: Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function. | 56 |
| HP-HMG Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function.
COS with GnRH antagonists and HP-HMG: Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function. | 56 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | EXCLUDED FROM DONNOR PROGRAM | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | rFSH | HP-HMG | 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 | 56 Participants | 56 Participants | 112 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 56 Participants | 56 Participants | 112 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 / 56 | 0 / 56 |
| other Total, other adverse events | 0 / 56 | 0 / 56 |
| serious Total, serious adverse events | 1 / 56 | 0 / 56 |
Outcome results
Primary
OVARIAN RESPONSE
NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION
Time frame: 21 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rFSH | OVARIAN RESPONSE | 16.5 folicles |
| HP-HMG | OVARIAN RESPONSE | 17.5 folicles |
p-value: <0.49t-test, 1 sided
Primary
SERUM PROGSTERONE CONCENTRATION
Compare hormonal blood serum concentrations of progesterone during ovarian stimulation implied in follicular steroidogenesis during a cycle of Controlled Ovarian Stimulation with either r-FSH or HP-HMG.
Time frame: 21 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rFSH | SERUM PROGSTERONE CONCENTRATION | 0.74 ng/mL |
| HP-HMG | SERUM PROGSTERONE CONCENTRATION | 0.45 ng/mL |
p-value: <0.05t-test, 2 sided