This project explores the implication of the telomere pathway in ovarian premature and regular aging. Telomere length and maintenance underlie several biological processes such cancer, aging, human diseases and the biology of stem cells. The reactivation of telomerase should lead to a rejuvenation of the ovarian tissue and the improvement of fertility.

The correlation of telomeric factors in blood and granulosa cells will be studied with the aim of finding telomeric biomarkers of ovarian aging.

This is a pilot study, randomized, controled, blind, parallelo arm clinical trial with inactive substance and medicine.

A pilot study will be developed with a total of 45 individuals from 30 to 45 years old, who represent the most frequent population of women seeking for ART.

A control group composed of women with normal ovarian reserve (30 to 45 years old) is needed to compare telomeric and fertility parameters with the group of women with compromised ovarian reserve. Women in the control group irrespective of their age, will have a greater number of follicles compared to women belonging to the group with compromised ovarian reserve.

A group of women with diminished ovarian reserve that will take an inactive substance has been incluided to avoid biases and to set the fertility base line for women with compromised ovarian reserve. The use of an inactive substance or placebo will help obtain better quality results. For instance, if Danazol happened to improve the fertility outcome, then, there could be a possibility that the IVF improvement might be due to other components of the pill. Using placebo, this possibility would be eliminated, since the placebo will contain all components of the pill, except Danazol.

The development of a pilot study will help us understand the statisticl behavior or the telomeric factors as well as to determine the appropriate number of individuals that shoyuld be recruited in a clinical trial to have results with statistical significance. In addition, a pilot study will help us learn errors or undesired events that may happen during the clinical trial. For instance, if patients cannot follow the indications of their doctors and why, or what proportion of patients will drop the study and the reasons for it. Furthermore, it will also help us understand if there exist a tendency, an indication or even a clear beneficial effect for patients without harming them.

The number of participants selected for the study is considered adequate for each group, since each group will be measured in an independent manner.

Inclusion Criteria:

• Provide signed and dated informed consent form.
• Willing to comply with all study procedures and be available for the duration of the study. This include the decisión to use contraception methods different to sexual hormones, such as the use of condoms, during the treatment with Danazol.
• In good general health as evidenced by medical history or diagnosed with body mass index between 18 and 30 kg/m2.
• Women with normal (AMH valued must be equal or higher tan 2ng/ml) or compromised ovarian reserve (defined as AMH < 2 ng/ml)
• Not having had any steroid hormones for one month.

Exclusion Criteria:

• Pregnancy o lactation.
• Taking other sexual hormones.
• Women with diseases in heart, liver or kidney or tumors which depend on male sexual hormones or hormone-dependent tumour.
• Women taking anticonvulsants, medicaments for diabetes, anticoagulants and anti-hypertension: ciclosporin and tacrolimus and other steroids and statins.
• Women suffering irregular genital bleeding or with thrombus or thromboembolicdiseases.
• Known allergic reactions to components of the study product (cornstarch and lactose).
• Having received ovulation induction drugs within one month before the inclusión in the study.
• Anything that would place the individual at increased risk or preclude the individual´s full compliance with or completion of the study.
• Simultaneous participation in another clinical trial or previous participation in this study.
• Participation in another clinical study 2 months before inclusión in the present study that could affect its objectives.

Most frequent population of women seeking for ART

During the first visist to the doctor, women will be selected according to the selection criteria. Those who seem to have a low ovarian reserve by ultrasound will be informed of the trial, and if they decide to participate, blood will be taken to analyze AMH values. On the second visit, women with low ovarian reserve will be randomized 1:1 for either inactive substance or Danazo, accordint to a computer-generated randomization list prepared by associated statistic. This way, the assigned group will be blind until the momento of executing the randomization procedure. Moment in which, the assigned group will be revealed.

Those with normal ovarian reserve will not be randomized and will just be included as controls.

To maintain the blinding of the trial, Danazol and placebo will be provided in boxs with blisters (PVC opaque and aluminium sealed).

Only the trial medication delegate(s) at the site will dispense the IMP and will know the treatment allocation.