Assessing the Efficacy of Clomiphene Citrate in Patients With Azoospermia and Hypoandrogenism

Study Overview
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Brief Summary
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Hypothesis: Prescribed clomiphene citrate to azoospermic patients with hypoandrogenism could improve the sperm retrieval in either fresh sperm or after surgical sperm extraction.

Detailed Description
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Hypogonadism (low testosterone level) is frequently observed in men presenting with non obstructive azoospermia. Controversy exists regarding the efficacy of preoperative hormonal manipulation in patients with hypogonadism. However, it is possible that hormonal therapy increases intra-testicular testosterone levels, and with a rise in serum testosterone, sperm production and surgical success with microTESE improve.

Official Title
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A Randomized, Double-blind, Placebo-controlled Trial of Clomiphene Citrate of Clomiphene Citrate in Hypoandrogenism and Azoospermia

Conditions
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Non Obstructive Azoospermia, Hypogonadism

Intervention / Treatment
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* Drug: Clomiphene
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years old. Man seeking fertility treatment. Azoospermia confirmed in at least 2 semen analyses with centrifugation. Testosterone <300 ng/dL and Bioavailable Testosterone<156 ng/dL. Exclusion Criteria: Presence of genetic disorders: Y chromosome deletions or abnormal karyotypes. Luteinizing hormone (LH) >25 IU/mL. Estradiol > 40 ng/dL. Hypogonadotropic hypogonadism (LH <2 IU/mL and Follicle Stimulating Hormone (FSH) <1 IU/mL). Obstructive azoospermia (FSH <7.6 IU/mL plus testicle longitudinally axis >4.6 cm or bilateral absence of vas deferens or surgical history of vasectomy). Clinical varicocele (palpable or visible in physical exam) Previous history of cryptorchidism. Use of chemotherapy, testosterone, or anti-androgen in the last two years. Partner >40 years or female factor infertility associated. Contraindications to clomiphene use: depression, heart and liver impairment, uncontrolled thyroid/adrenal dysfunction, organic intracranial lesions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clomiphene citrate<br>Clomiphene citrate 50 mg daily during 4-6 months | Drug: Clomiphene<br>* Clomiphene citrate 50 mg orally daily<br>* Other names: Serophene;|
| Placebo Comparator: Placebo<br>Placebo (1 pill daily) during 4-6 months | Drug: Placebo<br>* One pill every other day<br>* Other names: control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of sperm in the ejaculated or in the microsurgical testicular Sperm extraction (microTESE) |  | After four months of clomiphene treatment | 
| Epigenetic modifications |  | After four months of clomiphene treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testosterone levels and Bioavailable Testosterone levels |  | After two weeks and four months with clomiphene treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Azoospermia, Hypogonadism, Clomiphene