What Diseases Are Associated with Azoospermia?

By BSc, MSc (embryologist), (embryologist), MD (gynecologist) and (invitra staff).
Last Update: 10/16/2020

It is common for azoospermia to be associated with other diseases. As a matter of fact, obstructive and non-obstructive azoospermia typically appears as a consequence of other genetic or anatomical diseases.

Although there exist many diseases that can cause azoospermia, we are going to introduce you to the most common ones in the following sections.

Genetic abnormalities

There exist different chromosomal and genetic abnormalities that can lead to male infertility, whether it is caused by obstructive or non-obstructive/secretory azoospermia. Some of the most common ones are:

Klinefelter syndrome

Klinefelter is a chromosomal alteration characterized by an extra X chromosome. Therefore, males with Klinefelter syndrome have a karyotype 47, XXY instead of the normal 46, XY.

Most males with this abnormality have secretory azoospermia, as this chromosomal abnormality causes a hormonal imbalance that affects spermatogenesis (sperm production) negatively. Moreover, in case sperm are produced, they are likely to be aneuploid, that is, there are higher chances for them to have chromosomal alterations.

Depending on the level of severity, the effects of this sperm disorder on fertility can be more or less serious. However, some men affected by this pathology have managed to become fathers through assisted reproduction techniques.

You can get more information about this genetic disease here: Klinefelter Syndrome (XXY Syndrome) - Symptoms, Causes & Fertility.

Y chromosome microdeletion

Chromosome Y, responsible of male sex differentiation, contains unique genes that are involved in sperm production. The loss of small portions of the area containing these genes, known as AZF region, can lead to a lack of some of these genes, thereby affecting spermatogenesis directly.

Between 10-15% of the cases of non-obstructive azoospermia are due to Y chromosome microdeletion.

In addition, Y chromosome microdeletions in men have an incidence of 1 in 4,000 men and is the second most common genetic cause of male infertility after Klinefelter syndrome.

Kallman syndrome

It is a Y-linked genetic disease that alters the function of the hypothalamus, leading to hormonal irregularities. As a result, spermatogenesis is compromised.

The main characteristic of men affected by this syndrome is the lack of testosterone. For this reason, men with this abnormality suffer, among other symptoms, infertility.

If you want to continue reading on this topic, we recommend this post: What is Kallmann Syndrome? Symptoms, Causes & Treatment.

Cystic fibrosis

Cystic fibrosis (CF) is a hereditary genetic disease that affects the pancreas and the lungs. Moreover, CF can cause infertility issues.

Considering undergoing a fertility treatment? By getting your individual Fertility Report your will see different clinics especially selected for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

CF is one of the most common genetic diseases in Caucasian people. In fact, 1 out of every 25 persons is a carrier of the CFTR gene mutation, the causal agent of this disease.

About 10% of men with obstructive azoospermia present congenital bilateral absence of the vas deferens, that is, they do not have the ducts in charge of transporting the sperm from the testicles to the urethra. Of these patients, approximately 70% have cystic fibrosis or are carriers of the genetic mutation responsible for the disease.

Being a carrier of a genetic disease does not mean the person is sick. However, it is likely that offspring inherits it.

Chronic renal insufficiency

Chronic renal insufficiency (CRI), also known as chronic kidney disease (CKD), is defined as the progressive and permanent loss of renal activity. It can affect the hormones that cause sperm production severely.

Increased prolactin, FSH, and LH levels, along with decreased testosterone levels, affect spermatogenesis directly, which can cause azoospermia in the most severe cases.

Varicocele

A varicocele is a dilation of the spermatic veins, the set of vessels that nourish the testicles so they are able to produce sperm.

In the most severe cases of varicocele, it can have a negative impact on spermatogenesis and even prevent their production, which causes non-obstructive azoospermia. However, a varicocele can cause obstructive azoospermia, too.

The main consequence of varicocele is a reflux that raises the temperature in the testicular area, causing a negative effect on spermatogenesis. In milder cases of varicocele, men show a low sperm concentration. In contrast, those men diagnosed with a severe varicocele present azoospermia and must resort to assisted reproduction techniques to achieve their dream of parenthood.

More on this article: What Is a Testicular Varicocele?

Mumps

There exist certain childhood diseases than can compromise the adequate development of the male reproductive tract, causing non-obstructive azoospermia during adulthood due to an inflammation of the testicles (i.e. orchitis).

A good example of this type of diseases is epidemic parotitis, commonly known as mumps. This condition causes mumps orchitis (testicular infection caused by the mumps virus).

Other childhood diseases that can cause diseases in the male reproductive tract are orchitis and meningitis, high fever or certain severe infections (for example, the one caused by the Chlamydia trachomatis bacterium).

Cryptorchidism

Cryptorchidism is an anomaly of the male reproductive tract that prevents the testes from descending from the scrotum. As a result, they can remain trapped in the abdominal cavity or the inguinal canal.

If cryptorchidism is not treated during childhood, it can lead to permanent infertility, increasing the risk of testicular cancer.

During embryo development, the testes descent through the inguinal canal into the scrotum. Right after childbirth, they are found in the scrotum.

This situation allows the testes to be at a temperature that is about 2 °C below the temperature of the rest of the body. These conditions are necessary for spermatogenesis to occur adequately. For this reason, undescended testicles (located in the pelvic cavity) are a cause of non-obstructive azoospermia).

Testicular cancer

This is the malignant proliferation of cells in the testicle. The damage caused at the testicular level can compromise the production of spermatozoa and, therefore, be the cause of azoospermia.

The most common symptoms in men with testicular cancer are the following:

  • Inflamed testicular area, either at the epididymis level or at the level of the testicles..
  • Appearance of a lump in the testicle.
  • Genital pain or heaviness.
  • Accumulation of fluid in the scrotal area.

Although these clinical manifestations in the male may also be related to other alterations, it is recommended that the specialist be consulted in order to establish the possible causes and the best treatment for this.

FAQs from users

What genetic causes are associated with azoospermia?

By Sergio Rogel Cayetano MD (gynecologist).

There are multiple genetic causes that can lead to azoospermia or the absence of sperm in the semen. Below are the most well known:

Alterations in the karyotype
sometimes the testicle is not formed correctly.
Y chromosome micordelections
affects the genes that code for sperm production, which can lead to azoospermia.
Cystic Fibrosis
This genetic disease is characterized by microtubule obstructions, which can lead to azoospermia.
Other problems
Multiple genes are involved in sperm generation. The failure of one or more of them, sometimes difficult to detect, can be linked to azoospermia.
Imagen: genetic causes associated with azoospermia

Can genetic azoospermia be cured?

By Andrea Rodrigo BSc, MSc (embryologist).

Genetic diseases such as Klinefelter Syndrome or Kallmann Syndrome do not have a cure, although there exist symptoms that can relieve or improve the qualify of life of these patients. For example, there are hormonal replacement therapies or surgical procedures that can help eliminate azoospermia when it is caused by any of these diseases.

Can stress cause azoospermia?

By Andrea Rodrigo BSc, MSc (embryologist).

Yes, situations that increase anxiety or stress levels can alter the hormones that regulate sperm production, causing zero sperm count. However, these are situations of temporary azoospermia that allow the affected man to recover fertility after returning to normality. In other words, as soon as increased stress levels decrease and the man is more relaxed, sperm production starts anew and azoospermia disappears.

Suggested for you

These diseases can be the cause of azoospermia, but there exist other situations like trauma or certain surgical procedures that can lead to zero sperm count. Want to learn more about the potential causes of this sperm disorder? Check them out here: What Are the Causes of Azoospermia?

Also, we have made reference to several diseases. To learn more about each one of them, you can visit this post: Testicular Disorders & Infertility – Impact on Reproductive Function.

Our editors have made great efforts to create this content for you. By sharing this post, you are helping us to keep ourselves motivated to work even harder.

References

de Souza DAS, Faucz FR, Pereira-Ferrari L, Sotomaior VS, Raskin S. Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling. Andrology. 2018 Jan;6(1):127-135.

Elzanaty S. Non-obstructive azoospermia and clinical varicocele: therapeutic options. Int Urol Nephrol. 2013 Jun;45(3):669-74.

Hagiuda J, Ishikawa H, Hagiwara M, Kono H, Nakagawa K, Oya M. Obstructive azoospermia caused by low ligation of varicocele: A case report. Syst Biol Reprod Med. 2017 Oct;63(5):338-339.

Röpke A, Tüttelmann F. MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility. Eur J Endocrinol. 2017 Nov;177(5):R249-R259.

Ramasamy R, Lipshultz LI. Cystic fibrosis transmembrane regulator mutation and congenital bilateral absence of the vas deferens: a bad combination for successful intracytoplasmic sperm injection outcomes. Fertil Steril. 2014 May;101(5):1246.

FAQs from users: 'What genetic causes are associated with azoospermia?', 'Can genetic azoospermia be cured?' and 'Can stress cause azoospermia?'.

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Authors and contributors

 Andrea Rodrigo
Andrea Rodrigo
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia. Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia along with the Valencian Infertility Institute (IVI). Postgraduate course in Medical Genetics. More information about Andrea Rodrigo
 Marta Barranquero Gómez
Marta Barranquero Gómez
Embryologist
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV
 Sergio Rogel Cayetano
Sergio Rogel Cayetano
MD
Gynecologist
Bachelor's Degree in Medicine from the Miguel Hernández University of Elche. Specialist in Obstetrics & Gynecology via M. I. R. at Hospital General de Alicante. He become an expert in Reproductive Medicine by working at different clinics of Alicante and Murcia, in Spain, until he joined the medical team of IVF Spain back in 2011. More information about Sergio Rogel Cayetano
License: 03-0309100
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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