Follicular Steroid Genesis in Controlled Ovarian Stimulation (ESTEFOL)

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.

Study Overview

• Status: Completed
• Conditions: Infertility; Controlled Ovarian Hyperstimulation
• Intervention / Treatment: Drug: COS with GnRH antagonists and rFSH; Drug: COS with GnRH antagonists and HP-HMG

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46015
    • IVI Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rFSH; Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.	Drug: COS with GnRH antagonists and rFSH; Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women with normal ovarian function.; Other Names: GnRH antagonists and rFSH
Active Comparator: HP-HMG; Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG with normal ovarian function.	Drug: COS with GnRH antagonists and HP-HMG; Controlled ovarian hyperstimulation with GnRH antagonists and HP-HMG in women with normal ovarian function.; Other Names: GnRH antagonists and HP-HMG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	21 days
OVARIAN RESPONSE	NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION	21 days

Collaborators and Investigators

• Sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Ernesto Bosch, MDPhD, IVI Valencia

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2016
• Primary Completion (Actual): June 15, 2018
• Study Completion (Actual): June 15, 2018

Study Registration Dates

• First Submitted: April 8, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (Estimate): April 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 3, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 1512-VLC-066-EB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO