Follicular Steroid Genesis in Controlled Ovarian Stimulation (ESTEFOL)
Primary Purpose
Infertility, Controlled Ovarian Hyperstimulation
Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
COS with GnRH antagonists and rFSH
COS with GnRH antagonists and HP-HMG
Sponsored by
About this trial
This is an interventional treatment trial for Infertility
Eligibility Criteria
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
Sites / Locations
- IVI Valencia
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
rFSH
HP-HMG
Arm Description
Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.
Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function.
Outcomes
Primary Outcome Measures
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.
OVARIAN RESPONSE
NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION
Secondary Outcome Measures
Full Information
NCT ID
NCT02738580
First Posted
April 8, 2016
Last Updated
February 18, 2020
Sponsor
Instituto Valenciano de Infertilidad, IVI VALENCIA
Collaborators
Roche Pharma AG
1. Study Identification
Unique Protocol Identification Number
NCT02738580
Brief Title
Follicular Steroid Genesis in Controlled Ovarian Stimulation
Acronym
ESTEFOL
Official Title
Analysis of Follicular Steroid Synthesis During Controlled Ovarian Stimulation With Recombinant FSH vs HMG in GnRH Antagonist Cycles
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
October 18, 2016 (Actual)
Primary Completion Date
June 15, 2018 (Actual)
Study Completion Date
June 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto Valenciano de Infertilidad, IVI VALENCIA
Collaborators
Roche Pharma AG
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Controlled Ovarian Hyperstimulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
112 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rFSH
Arm Type
Active Comparator
Arm Description
Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.
Arm Title
HP-HMG
Arm Type
Active Comparator
Arm Description
Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function.
Intervention Type
Drug
Intervention Name(s)
COS with GnRH antagonists and rFSH
Other Intervention Name(s)
GnRH antagonists and rFSH
Intervention Description
Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.
Intervention Type
Drug
Intervention Name(s)
COS with GnRH antagonists and HP-HMG
Other Intervention Name(s)
GnRH antagonists and HP-HMG
Intervention Description
Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function.
Primary Outcome Measure Information:
Title
SERUM PROGSTERONE CONCENTRATION
Description
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
Title
OVARIAN RESPONSE
Description
NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION
Time Frame
21 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ernesto Bosch, MDPhD
Organizational Affiliation
IVI VALENCIA
Official's Role
Principal Investigator
Facility Information:
Facility Name
IVI Valencia
City
Valencia
ZIP/Postal Code
46015
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Follicular Steroid Genesis in Controlled Ovarian Stimulation
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