Effect of Letrozole on Seminal Parameters in Men With Non Obstructive Azoospermia and Severe Oligozoospermia.

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.

Study Overview

• Status: Completed
• Conditions: Azoospermia, Nonobstructive; Oligozoospermia
• Intervention / Treatment: Drug: Letrozole

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria

• Patients with non-obstructive azoospermia (absence of sperm in the pellets of two centrifuged semen samples collected 30-60 days apart)
• Patients with non-obstructive azoospermia who do not yield spermatozoa with fine needle aspiration (FNA)
• Patients with severe oligozoospermia (presence of sperm concentration less than 5 million per ml in both semen samples collected 30-60 days apart)
• Normal sperm appearance, consistency, liquefaction, volume and pH
• Patient must not possess any chromosomal aberrations

Exclusion Criteria

• Possible etiology of infertility present
• Seminal white blood cell concentration more than 10 million per ml
• Positive seminal culture analysis
• Positive urethral swab for chlamydia test
• Smoker
• Drug or alcohol abuse
• Ongoing medical treatment (gonadotropins, anabolic steroids, cancer chemotherapy, non-steroidal anti-inflammatory drugs, previous cancer radiotherapy or chemotherapy)
• Palpable varicocele
• X-ray exposure in the previous 8 months
• Y chromosome microdeletion
• Karyotype abnormalities (Klinefelter syndrome)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole; Participants will be assigned to receive Letrozole 2.5 mg once a day for 4 months	Drug: Letrozole; Letrozole 2.5mg (1 tablet) once a day for 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sperm density	After 4 months dosage of Letrozole
Sperm motility	After 4 months dosage of Letrozole

Secondary Outcome Measures

Outcome Measure	Time Frame
Total serum Testosterone level	After 4 months dosage of Letrozole
Total serum Estradiol level	After 4 months dosage of Letrozole
Total serum Follicle Stimulating Hormone level	After 4 months dosage of Letrozole
Total serum Luteinizing Hormone level	After 4 months dosage of Letrozole

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Investigators: Principal Investigator: Shuling Liu, KK Women's and Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: August 30, 2016
• First Submitted That Met QC Criteria: September 8, 2016
• First Posted (Estimate): September 14, 2016

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility, Male; Infertility; Azoospermia; Oligospermia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: 2014/123/D