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.

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.

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