Understanding azoospermia, one of the most common causes of male infertility

Types of azoospermia

is classified into obstructive – occurring due to post-testicular causes – and non-obstructive, which is subclassified into pre-testicular and testicular, depending on the reasons causing it.

Obstructive azoospermia

In obstructive azoospermia, even though sperm production is normal, sperm is not present in the semen due to a blockage or disrupted connection along the reproductive tract, which could be due to a congenital or acquired reason such as infection or surgery.

Non-obstructive azoospermia

In non-obstructive azoospermia, which is considered the most severe form of male infertility, sperm production is decreased or absent due to spermatogenic failure. This is either due to endocrine abnormalities that affect spermatogenesis and are classified as pre-testicular azoospermia, or due to congenital, acquired, or idiopathic testicular abnormalities that include anorchia, cryptorchidism, and infection, and are classified as testicular azoospermia. Some causes of azoospermia, such as radiation and genetic mutations (DNA changes) can cause all three azoospermia types.

Genetics of azoospermia

Around 40 genes are linked or are suspected to be associated with azoospermia. Examples include the CFTR gene that causes cystic fibrosis and is associated with both obstructive and non-obstructive azoospermia. Additionally, the ANOS1 gene, previously known as KAL-1, causes hypogonadotropic hypogonadism – a condition in which testes produce little or no sex hormones – and is associated with pre-testicular azoospermia.

Among the most frequent genetic causes of non-obstructive testicular azoospermia and severe oligozoospermia are small deletions, known as microdeletions, on the AZF region of the Y chromosome – with the most known being AZFa, AZFb, and AZFc. Genetic testing of the Y chromosome is recommended by international guidelines, such as the American Society for Reproductive Medicine, during the diagnostic process of men with non-obstructive azoospermia or severe oligospermia, as treatment success depends on the region deleted. Between AZFa, AZFb, and AZFc microdeletions, males with AZFc microdeletions have up to a 50% chance of successful micro testicular sperm extraction. For males with AZFa and AZFb microdeletions, the chance of successful micro testicular sperm extraction is almost zero.

Symptoms of azoospermia

Although a few men with azoospermia may present symptoms such as erectile dysfunction, low sex drive, and testicular discomfort, most men with azoospermia are asymptomatic until they experience unsuccessful attempts to conceive. Symptoms may include erectile dysfunction, low sex drive, and testicular discomfort. Medical and family history, physical examination, hormone levels, and semen analysis for evaluation of sperm quality and quantity are taken into consideration for azoospermia diagnosis and classification.

Treatments for azoospermia

Treatment for azoospermia depends on the underlying cause. For men with post-testicular azoospermia, treatment to restore fertility or achieve pregnancy includes either microsurgery to repair the blockage in the reproductive tract, or sperm retrieval from the testicles, epididymis, or vas deferens.

Pre-testicular azoospermia treatment includes hormone therapy or lifestyle changes to restore spermatogenesis. Men with testicular azoospermia usually have testicular disorders for which interventions have a low success rate. Additional investigations such as genetic testing or karyotyping to identify any genetic abnormalities are strongly recommended for this type. For males with non-obstructive azoospermia, there are cases where sperm could be retrieved from the testicle through testicular sperm extraction, even when spermatogenesis cannot be restored.

Conclusion

Azoospermia is a very common condition among men, and one of the most common causes of male infertility. Many cases of azoospermia can be managed; an accurate and thorough diagnosis can lead to improved prognosis, as well as advanced and targeted medical treatments which could alleviate symptoms, and where possible, help restore fertility.

can detect genetic mutations that cause azoospermia along with Y chromosome microdeletions and many other conditions. Possible next steps and clinical management should always be discussed with your doctor.

Please note: The content of this article is intended for informational purposes only and should not be perceived as medical advice.