InfertilityPhase 4ESTEFOLNCT02738580
Follicular Steroid Genesis in Controlled Ovarian Stimulation
A Phase 4 study testing COS with GnRH antagonists and rFSH and COS with GnRH antagonists and HP-HMG in people with Infertility and Controlled Ovarian Hyperstimulation, run by Instituto Valenciano de Infertilidad, IVI VALENCIA at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, Controlled Ovarian Hyperstimulation
- What is being tested?
- COS with GnRH antagonists and rFSH and COS with GnRH antagonists and HP-HMG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteSpain
- Study dates
- 18 Oct 2016to 15 Jun 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Analysis of Follicular Steroid Synthesis During Controlled Ovarian Stimulation With Recombinant FSH vs HMG in GnRH Antagonist Cycles
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.
- Conditions
- Infertility, Controlled Ovarian Hyperstimulation
- Being tested
- COS with GnRH antagonists and rFSH, COS with GnRH antagonists and HP-HMG
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COS with GnRH antagonists and rFSHDrug
Also called GnRH antagonists and rFSH
Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.
COS with GnRH antagonists and HP-HMGDrug
Also called GnRH antagonists and HP-HMG
Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function.
| Study group | Role | What they receive |
|---|---|---|
| rFSH | Active comparator | Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function. Receives: Drug: COS with GnRH antagonists and rFSH |
| HP-HMG | Active comparator | Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function. Receives: Drug: COS with GnRH antagonists and HP-HMG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 21 days
OVARIAN RESPONSE
NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2016 (estimated)
- Study start18 Oct 2016
- Primary completion15 Jun 2018
- Study completion15 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Valenciano de Infertilidad, IVI VALENCIA
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Ernesto Bosch, MDPhD, Principal investigator, IVI VALENCIA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02738580
- Sponsor's protocol ID
- 1512-VLC-066-EB
- Acronym
- ESTEFOL
- Status last verified
- Feb 2020
- First submitted
- 8 Apr 2016
- Last updated
- 3 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Bosch E, Alama P, Romero JL, Mari M, Labarta E, Pellicer A. Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial. Hum Reprod. 2024 Feb 1;39(2):393-402. doi: 10.1093/humrep/dead251.
PubMed 38037188
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Follicular Steroid Synthesis During Controlled Ovarian Stimulation With Recombinant FSH vs HMG in GnRH Antagonist Cycles
- ClinicalTrials.gov ID
- NCT02738580
- Acronym / sponsor ID
- ESTEFOL / 1512-VLC-066-EB
- Conditions
- Infertility, Controlled Ovarian Hyperstimulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Instituto Valenciano de Infertilidad, IVI VALENCIAUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- 18 Oct 2016 (actual)
- Primary completion
- 15 Jun 2018 (actual)
- Study completion
- 15 Jun 2018 (actual)
- First posted
- 14 Apr 2016 (estimated)
- Results
- Posted 3 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rFSH | Active comparator | Drug: COS with GnRH antagonists and rFSHControlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function. |
| HP-HMG | Active comparator | Drug: COS with GnRH antagonists and HP-HMGControlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| COS with GnRH antagonists and rFSHAlso: GnRH antagonists and rFSHControlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function. | Drug | rFSH |
| COS with GnRH antagonists and HP-HMGAlso: GnRH antagonists and HP-HMGControlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function. | Drug | HP-HMG |
Primary outcome
SERUM PROGSTERONE CONCENTRATION
Time frame: 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
Time frame: 21 days
NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38037188Bosch E, Alama P, Romero JL, Mari M, Labarta E, Pellicer A. Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial. Hum Reprod. 2024 Feb 1;39(2):393-402. doi: 10.1093/humrep/dead251.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernesto Bosch, MDPhD principal investigator
IVI VALENCIA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing COS with GnRH antagonists and rFSH and COS with GnRH antagonists and HP-HMG in people with Infertility and Controlled Ovarian Hyperstimulation, run by Instituto Valenciano de Infertilidad, IVI VALENCIA at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SERUM PROGSTERONE CONCENTRATION (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02738580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2020.