No Sperm and Its Link to Genetic Factors: An Exploratory Guide

Azoospermia, a leading cause of male infertility, occurs when a man’s ejaculate (semen) does not contain sperm. The testicles, located in the scrotum, are responsible for sperm production. These sperm cells then pass through the male reproductive system, where they combine with fluid to create semen. Semen, a thick and white fluid, is released from the penis during ejaculation. Azoospermia is detected in approximately five to ten percent of men undergoing infertility evaluations. This condition may occur either from birth or develop at a later stage in life.

 Types of azoospermia

Azoospermia can be classified into two types.

Obstructive azoospermia: In this case, the production of sperm is unaffected; however, there is an obstruction in the reproductive tract of both testicles. As a result, no quantifiable sperm can be found in the semen.

Nonobstructive azoospermia: This specific type is associated with inadequate/absent sperm production. In certain men, the quantity of sperm produced is insufficient to be noticeable in their semen.

Azoospermia, a condition influenced by numerous factors, necessitates a thorough understanding of its genetic causes for effective management. Below, we will explore diverse genetic factors associated with azoospermia, including:

Y chromosome microdeletions: Y chromosome microdeletions (the loss of small segments on the Y chromosome), plays a significant role in spermatogenesis (the origin and development of sperm cells within the testes). These deletions can disrupt the normal course of sperm production, ultimately leading to azoospermia.

Klinefelter syndrome: Individuals diagnosed with Klinefelter syndrome exhibit an additional X chromosome (47, XXY), which has an impact on the development of the testes and the process of spermatogenesis. This genetic abnormality plays a significant role in causing azoospermia.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations: Mutations occurring in the CFTR gene associated with cystic fibrosis, have the potential to cause obstructive azoospermia. These genetic alterations have a direct influence on the movement of ions and water through cell membranes, which can ultimately result in the absence of sperm in the ejaculate due to blockage within the reproductive system.

Androgen Receptor (AR) mutations: Genetic mutations occurring in the androgen receptor gene disrupt the normal response to male sex hormones, thereby influencing spermatogenesis. These genetic aberrations underscore the intricate relationship between hormonal signalling and reproductive function.

Candidate genes: Various candidate genes are implicated in non-obstructive azoospermia. Mutations in genes such as NR5A1, TEX11, etc. have been found to be associated with disrupted spermatogenesis.

Chromosomal aberrations: Azoospermia may also rarely be caused due to structural abnormalities in autosomes, which are chromosomes other than the sex chromosomes. The disruption of normal sperm production can occur due to chromosomal translocations, inversions, or deletions.

 Diagnosis of azoospermia

The diagnosis of azoospermia involves a detailed medical history and a comprehensive physical examination. Semen analysis, an essential diagnostic tool, is used to evaluate the presence and quality of sperm.

Blood tests are utilized to measure hormone levels, specifically follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. These tests are valuable in distinguishing between obstructive and non-obstructive azoospermia.

In case of obstruction, imaging studies such as scrotal ultrasound / transrectal ultrasound (TRUS) are conducted to assess the testicles and ejaculatory duct for any structural abnormalities, blockages of the vas deferens. Additionally, genetic testing may be done to identify specific genetic factors that influence spermatogenesis.

To accurately diagnose azoospermia, a comprehensive approach is necessary, which involves considering the patient’s clinical history, conducting laboratory tests, and performing imaging studies. This approach aids in guiding appropriate management and provides valuable insights into potential underlying causes.

 Treatment for azoospermia

For each individual patient, the most effective treatment will vary, depending on the underlying cause. A personalized approach is essential, considering various factors including the age and reproductive function of the partner, findings from physical examinations, and results from blood tests. 

The available treatments will also depend on the suspected causes of infertility.

In cases where there is a blockage or a history of vasectomy, reconstruction surgery may be the optimal treatment for certain men. 

On the other hand, for some individuals, the first step may involve discontinuing medications that could be contributing to the problem. Hormonal abnormalities may need to be addressed in certain cases, and treatment could potentially increase sperm production in a fraction of men. Surgical intervention to correct structural abnormalities or varicoceles may be recommended in some men, while others may benefit from a direct testicular approach to retrieve sperm for assisted reproductive techniques.

Men diagnosed with obstructive azoospermia often have an excess of sperm present in their reproductive structures. There are various techniques available to retrieve sperm in such cases, including testicular sperm extraction, testicular sperm aspiration, percutaneous epididymal sperm aspiration, etc.

There are several options available for men with nonobstructive azoospermia, microscopic testicular sperm extraction (microTESE) is the most suitable procedure for identifying sperm for in-vitro fertilization and intracytoplasmic sperm injection procedures. This method involves a careful dissection of the testicular tubules to locate the tissue that is most likely to be actively generating sperm. 

By employing this approach, it maximizes the quantity of sperm obtained while safeguarding the integrity of other testicular tissues, including the Leydig cells responsible for testosterone synthesis. 

To summarize, azoospermia exhibits a wide range of genetic origins, ranging from chromosomal aberrations and specific gene mutations. It is absolutely necessary to clear up these genetic complexities in order to achieve accurate diagnosis and develop personalized treatment approaches. 

As scientific understanding deepens, targeted interventions may provide hope for individuals affected by azoospermia, ultimately leading to improved fertility outcomes.

AndroNeo in Bangalore offers state-of-the-art azoospermia treatment and procedures for sperm retrieval. The team of experienced specialists in reproductive health ensures utmost precision and expertise in handling intricate cases. By tailoring a highly personalized treatment plan, they strive to help patients regain their fertility.

References:

1. O’Flynn O’Brien, K. L., Varghese, A. C., & Agarwal, A. (2010). The genetic causes of male factor infertility: a review. Fertility and sterility. https://www.sciencedirect.com/science/article/pii/S001502820903965X
2. Cioppi, F., Rosta, V., & Krausz, C. (2021). Genetics of Azoospermia. International journal of molecular sciences. https://doi.org/10.3390/ijms22063264
3. Azoospermia. JOHNS HOPKINS MEDICINE. https://www.hopkinsmedicine.org/health/conditions-and-diseases/azoospermia
4.  Azoospermia. Stanford MEDICINE. https://stanfordhealthcare.org/medical-conditions/mens-health/azoospermia.html