Follicular Steroid Genesis in Controlled Ovarian Stimulation

Infertility Clinical Trial

— ESTEFOL  

Official title:

Analysis of Follicular Steroid Synthesis During Controlled Ovarian Stimulation With Recombinant FSH vs HMG in GnRH Antagonist Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02738580
• Other study ID #: 1512-VLC-066-EB
• Status: Completed
• Phase: Phase 4
• Start date: October 18, 2016
• Est. completion date: June 15, 2018

Study information

• Verified date: February 2020
• Source: Instituto Valenciano de Infertilidad, IVI VALENCIA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: June 15, 2018
• Est. primary completion date: June 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Controlled Ovarian Hyperstimulation
• Infertility

Intervention

Drug:
• COS with GnRH antagonists and rFSH
Controlled ovarian hyperstimulation with GnRH antagonists and rFSH in women 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.

Locations

Country	Name	City	State
Spain	IVI Valencia	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Valenciano de Infertilidad, IVI VALENCIA	Roche Pharma AG

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	21 days
Primary	OVARIAN RESPONSE	NUMBER OF FOLICLES REACHED AND PUNCTURED AFTER CONTROLED OVARIAN STIMULATION	21 days