Effect of Letrozole on Seminal Parameters in Men With Non Obstructive Azoospermia and Severe Oligozoospermia.
Condition: Azoospermia, Nonobstructive; Oligozoospermia
MeSH terms: Azoospermia; Oligospermia
Study type: Interventional
Phase: Phase 3

Summary: 
      The investigators hope to learn if Letrozole is effective and safe in improving severe male
      infertility by increasing testosterone, decreasing oestradiol and stimulating sperm
      production thereby improving sperm motility (movement) and concentration. The study is being
      conducted because Letrozole is not yet proven to be a standard treatment in subjects with
      absent or very low sperm counts. The investigators are hoping to determine whether Letrozole
      is equal or superior to no treatment.
    

Detailed description: 
      This is a pilot study with recruitment carried out in a single centre where participants will
      be assigned to receive Letrozole 2.5 mg once a day for 4 months. The following data will be
      collected: semen analyses, clinical history including smoking status, BMI, Y microdeletion,
      karyotype and FSH, LH, testosterone, E2, drug side effects and effects on libido. The
      following assessments will be performed before and 4 months after drug administration: sperm
      analyses, FSH, LH, E2 and testosterone measurements.

      Prior to recruitment, the study participant would have undergone the routine investigations
      for evaluating azoospermia or severe oligozoospermia. These would include FSH, LH,
      testosterone, karyotyping, Y chromosome microdeletion genetic studies and at least 1 seminal
      analysis. Despite the availability of biochemical techniques to differentiate non-obstructive
      azoospermia (NOA) patients from obstructive azoospermia patients, fine needle aspiration
      (FNA) has been regarded as a highly informative and a minimally invasive method often
      routinely done in the investigation of azoospermia. All patients with NOA would have a FNA
      performed as part of their routine workup which would be done before recruitment and
      initiation of Letrozole. The safety of FNA use is also regarded as being supportive for the
      researchers against any possible patient lawsuits resulting from any impaired spermatogenesis
      induced by an off-label prescription. All oligozoospermic patients will be offered to have
      their sperm cryopreserved before drug administration. The investigations must have been
      performed within a 6 month time frame prior to recruitment.

      There will be 3 clinic visits during the dosing period and 1 post dosing follow up visit.
      During the initial visit where recruitment into the study occurs, the participant will be
      prescribed the medication. One week later, a telephone interview will be conducted to review
      for side effects and arrange an early appointment at patient request. One month later, the
      participant will be reviewed in clinic and a side effect check list will be conducted.
      Telephone interviews will be conducted again at 2nd and 3rd month from administration of the
      drug. At 4th month from administration of the drug, the blood tests and semen analysis will
      be performed. It is likely that the participant will still be followed up for enrolment into
      IVF / ICSI programme should spontaneous pregnancy fail to occur. The window period for all
      clinic visits and telephone interviews is +/- 5 days.
    

Intervention name(s): Letrozole
Intervention type(s): Drug
Intervention description(s): Letrozole 2.5mg (1 tablet) once a day for 4 months
Intervention MeSH terms: Letrozole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment