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Antral Follicle Priming Prior to ICSI (Intracytoplasmic Sperm Injection) in Previously Diagnosed Low Responders

Phase 2
Completed
Conditions
Ovarian Diseases
Interventions
Registration Number
NCT01310647
Lead Sponsor
Instituto de Investigacion Sanitaria La Fe
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
66
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TestosteroneTestosteroneTransdermal testosterone (20µg/day) from day 24 of the previous cycle until day 2 of the ICSI cycle
EstradiolEstradiolTransdermal estradiol (200µg/day)from day 20 of the previous cycle to day 3 of the ICSI cycle
CombEqCombEq* (150µg Desogestrel + 30µg Ethinylestradiol)/day during the luteal phase of the two cycles prior to the ICSI * Estradiol valerate 4 mg/day during 10 days, starting the second day of the cycle prior to the ICSI cycle.
Primary Outcome Measures
NameTimeMethod
Number of MII oocytes retrieved36h after GnRH analogue administration
Secondary Outcome Measures
NameTimeMethod
Clinical pregnancy rate5 weeks after embryo transfer
Total number of follicles punctured36h after GnRH analogue administration
Granulosa cells genetic expression profile36h after GnRH analogue administration
Pregnancy rate15 days after embryo transfer
Total number of viable embryos48h after follicular puncture
Serum and Follicular hormonal levels (testosterone, androstenedione, estradiol)36h after GnRH analogue administration
Implantation rate15 days after embryo transfer
Total number of oocytes retrieved36h after GnRH analogue administration

Trial Locations

Locations (1)

La Fe University Hospital. Department of Obstetrics and Gynecology

🇪🇸

Valencia, Spain

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