Clinical trial NCT02738580: Follicular Steroid Genesis in Controlled Ovarian Stimulation
Official title: Analysis of Follicular Steroid Synthesis During Controlled Ovarian Stimulation With Recombinant FSH vs HMG in GnRH Antagonist Cycles
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Controlled Ovarian Hyperstimulation
Lead sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2016-04-14
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: SERUM PROGSTERONE CONCENTRATION
timeFrame: 21 days
measure: OVARIAN RESPONSE
timeFrame: 21 days
Secondary outcomes:
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: IVI Valencia
Study officials:
affiliation: IVI VALENCIA
name: Ernesto Bosch, MDPhD
role: PRINCIPAL_INVESTIGATOR
References: