Ovarian Diseases
Conditions
Keywords
estradiol, testosterone, combined oral contraceptive, low responders, ICSI
Brief summary
The aim of this study is to compare the effectiveness of testosterone,estradiol and a combined treatment with estrogens/progestagens prior to IVF-ICSI in previously diagnosed low responder patients.
Detailed description
During controlled ovarian hyperstimulation (COH), most of the early antral follicles are required to grow coordinately. Marked follicular size discrepancies during COH imply that an important number of follicles undergo unsatisfactory maturation. It has been proved that follicular priming with estradiol during the luteal phase of the cycle prior to COH or testosterone treatment during the early follicular phase of the COH cycle may increase the amount of oocytes and embryos retrieved. Nevertheless there are no prospective studies comparing such approaches. The present study consist of two phases: The present study consists of two different phases: * Phase I: (Non randomized) Identification of confirmed low responder patients. Potential low responder patients will be subjected to an standardized ovarian hyperstimulation protocol * Phase II: (Randomized) those patients, once confirmed as low responders, will be offered the opportunity to enter the interventional part of the study, being randomized to three different treatment groups: estradiol, testosterone or combined progestagens and estrogens prior to the IVF-ICSI cycle. The previous cycle (phase I) will be used as a self-control for each patient.
Interventions
DRUGTestosterone
Transdermal testosterone (20µg/kg/day)from day 24 of the previous cycle to day 2 of the ICSI cycle
DRUGEstradiol
Transdermal estradiol (200µg/day)from day 20 of the previous cycle to day 3 of the ICSI cycle
DRUGCombEq
(150µg Desogestrel + 30µg Ethinylestradiol)/day during the luteal phase of the two cycles prior to the ICSI. Valerate estradiol 4mg/day during 10 days, starting the second day of the cycle prios to the ICSI cycle.
Sponsors
Instituto de Investigacion Sanitaria La Fe
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 41 Years
Healthy volunteers
No
Inclusion criteria
1. Phase 1 (Non randomized. The patient must fit the first plus at least other 2 criteria) * Infertility requiring an IVF/ICSI treatment * Age ≥ 38 years * Basal FSH ≥ 10 mUI/ml (day 3 of the cycle) * Serum AMH ≤ 5 pmol/l * Antral follicular count ≤ 6 (day 3 of the cycle) 2. Phase 2 (Randomized. The patient must fit at least one criterion regarding the day of GNRH analogue administration during the cycle performed in Phase 1) * Less than 4 follicles which mean diameter measuring more than 16mm * Serum estradiol levels ≤ 500 pg/ml * 4 MII or less than 4 MII oocytes retrieved
Exclusion criteria
* Patients suffering of endometriosis * Patients having progesterone levels ≤ 4 ng/ml (day 21 of the cycle) * Patients having a partner affected by severe oligo/astheno/teratozoospermia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of MII oocytes retrieved | 36h after GnRH analogue administration |
Secondary
| Measure | Time frame |
|---|---|
| Total number of oocytes retrieved | 36h after GnRH analogue administration |
| Total number of viable embryos | 48h after follicular puncture |
| Serum and Follicular hormonal levels (testosterone, androstenedione, estradiol) | 36h after GnRH analogue administration |
| Total number of follicles punctured | 36h after GnRH analogue administration |
| Implantation rate | 15 days after embryo transfer |
| Pregnancy rate | 15 days after embryo transfer |
| Clinical pregnancy rate | 5 weeks after embryo transfer |
| Granulosa cells genetic expression profile | 36h after GnRH analogue administration |
Countries
Spain
Outcome results
None listed