Follicular Steroid Genesis in Controlled Ovarian Stimulation

NCT ID: NCT02738580

Last Updated: 2020-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-18
• Study Completion Date: 2018-06-15

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.

Conditions

Infertility; Controlled Ovarian Hyperstimulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rFSH

Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.

Group Type: ACTIVE_COMPARATOR

COS with GnRH antagonists and rFSH

Intervention Type: DRUG

Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.

HP-HMG

Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function.

Group Type: ACTIVE_COMPARATOR

COS with GnRH antagonists and HP-HMG

Intervention Type: DRUG

Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function.

Interventions

COS with GnRH antagonists and rFSH

Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.

Intervention Type: DRUG

COS with GnRH antagonists and HP-HMG

Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function.

Intervention Type: DRUG

Other Intervention Names

GnRH antagonists and rFSH; GnRH antagonists and HP-HMG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Instituto Valenciano de Infertilidad, IVI VALENCIA

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ernesto Bosch, MDPhD

Role: PRINCIPAL_INVESTIGATOR

IVI VALENCIA

Locations

IVI Valencia

Valencia, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 38037188 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1512-VLC-066-EB

Identifier Type: -

Identifier Source: org_study_id