What are the treatment options for low or absent sperm production?

Treatment Options for Low or Absent Sperm Production

The treatment approach depends entirely on whether the cause is obstructive versus non-obstructive azoospermia, with surgical sperm retrieval combined with ICSI being the definitive option for most cases, while medical therapy is reserved for specific reversible conditions like hypogonadotropic hypogonadism or varicocele. 1

Diagnostic Classification Determines Treatment Path

The first critical step is distinguishing obstructive from non-obstructive causes, as this fundamentally changes management 1:

Obstructive azoospermia indicators:

• Normal testicular size and consistency on examination 1
• FSH levels typically <7.6 IU/L 1
• Low ejaculate volume (<1.4 mL) with acidic pH (<7.0) suggests distal obstruction 1, 2
• Dilated/indurated epididymides or absent vas deferens on exam 1

Non-obstructive azoospermia indicators:

• Testicular atrophy on physical examination 1, 3
• FSH levels >7.6 IU/L 1, 3
• Normal semen volume and pH 3

Treatment Options by Etiology

For Obstructive Azoospermia

Ejaculatory duct obstruction (EDO):

• Transurethral resection of ejaculatory ducts (TURED) is the primary surgical option to restore natural fertility 1, 4
• Confirm diagnosis with TRUS or pelvic MRI showing seminal vesicle diameter >15 mm, ejaculatory duct caliber >2.3 mm, or prostatic cysts 1, 4
• If TURED fails or is declined, proceed to testicular sperm extraction (TESE/TESA) with ICSI 1

Congenital bilateral absence of vas deferens (CBAVD):

• No medical or surgical treatment restores ejaculatory volume 2
• Proceed directly to microsurgical epididymal sperm aspiration (MESA) or TESE with ICSI 1, 2
• Critical: CFTR gene testing for the female partner is mandatory before assisted reproduction 2

Post-vasectomy or acquired obstruction:

• Microsurgical reconstruction (vasovasostomy or epididymovasostomy) is preferable when the female partner has normal fertility potential 1
• Alternatively, sperm retrieval with ICSI is an option 1
• Avoid epididymal sperm retrieval if future microsurgical reconstruction might be pursued due to scarring risk 1

Clinical varicocele:

• Varicocelectomy improves semen parameters and may restore sperm in ejaculate for men with azoospermia, particularly with hypospermatogenesis on histology 2
• Treatment is indicated only for palpable varicoceles with abnormal semen parameters 2
• Avoid this pitfall: Subclinical (non-palpable) varicoceles detected on ultrasound should not be treated—they do not improve outcomes 2

For Non-Obstructive Azoospermia

Surgical sperm retrieval:

• Microdissection TESE (micro-TESE) is 1.5 times more successful than conventional TESE and 2 times more likely to yield sperm than testicular aspiration 1
• Up to 50% of men with non-obstructive azoospermia have retrievable sperm despite elevated FSH 3
• Retrieved sperm is used with ICSI for fertilization 1

Medical therapy has extremely limited role:

• Patients with non-obstructive azoospermia should be informed of limited data supporting pharmacologic manipulation with SERMs, aromatase inhibitors, and gonadotropins prior to surgical intervention 1
• These medications are not FDA-approved for this indication and benefits are questionable 1

For Hypogonadotropic Hypogonadism

This is the one scenario where medical therapy can restore spermatogenesis:

• Evaluate to determine the etiology of the condition and treat based on diagnosis 1
• Human chorionic gonadotropin (hCG) 500-1,000 USP units three times weekly for 3 weeks, followed by the same dose twice weekly for 3 weeks 5
• Alternative regimen: 4,000 USP units three times weekly for 6-9 months, then reduce to 2,000 USP units three times weekly for 3 additional months 5
• FSH analogues may be added if sperm counts remain low after testosterone normalizes on hCG 3
• Critical warning: Never prescribe testosterone monotherapy to men desiring fertility—it suppresses spermatogenesis through negative feedback and can cause azoospermia 1, 3

For Oligospermia (Low Sperm Count)

Medical options with limited evidence:

• Aromatase inhibitors, hCG, or selective estrogen receptor modulators (SERMs) may be used for infertile men with low serum testosterone 1
• FSH analogues may improve sperm concentration, pregnancy rate, and live birth rate in idiopathic infertility, but benefits are limited 1
• Clinicians should inform men with idiopathic infertility that the use of SERMs has limited benefits relative to results of ART 1
• Supplements (antioxidants, vitamins) are of questionable clinical utility with inadequate data for specific recommendations 1

Assisted reproductive technology:

• For low total motile sperm count on repeated semen analysis, IUI success rates are reduced and IVF/ICSI should be considered 1
• IVF treatment allows for 37% live delivery rate per initiated cycle 1
• Success decreases with increasing female age (>35 years) 1

Mandatory Genetic Testing Before Treatment

Before proceeding with sperm retrieval and ICSI:

• Karyotype testing is required for primary infertility with azoospermia or sperm concentration <5 million/mL when accompanied by elevated FSH, testicular atrophy, or impaired sperm production 1
• Y-chromosome microdeletion screening is mandatory for azoospermic men with suspected impaired sperm production and severely oligospermic men with sperm concentrations <1 million/mL 1
• Complete AZFa and AZFb deletions have almost zero likelihood of sperm retrieval and contraindicate TESE 3
• Genetic counseling should precede ICSI as genetic abnormalities may be transmitted to offspring 2

Critical Pitfalls to Avoid

Do not perform routine imaging without clear indication:

• TRUS or pelvic MRI should be reserved for cases with clear clinical suspicion of EDO (low volume, acidic, azoospermic semen with normal testosterone and palpable vas) 2, 4
• Routine scrotal ultrasound to hunt for subclinical varicoceles is discouraged—only palpable varicoceles warrant treatment 1, 2

Do not delay genetic testing:

• Results impact counseling and treatment decisions before proceeding with assisted reproduction 2

Do not prescribe testosterone for fertility:

• Testosterone monotherapy completely suppresses spermatogenesis and can cause azoospermia that takes months to years to recover 1, 3