Infertility and Genetic Conditions

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Background on Genetics & Infertility

Types of Genetic Tests

Congenital Absence of Vas Deferens

Other Genetic Causes

Klinefelter's Syndrome

Y-chromosome Microdeletion

Genetic Counseling


Background on Genetic Causes of Infertility in Males

Chromosomes are microscopic structures which contain the genetic material used to construct and maintain the body. They can be though of as a combination of blueprints and instruction manual. Genes contain basic instructions which direct the cells in the body. Just as missing parts of a blueprint or instructions for a house might mean that the kitchen does not get build or the dishwasher does not work properly, genetic conditions can result in malfunction of the body. A wide variety of genetic abnormalities can result in problems with fertility.


Humans normally have 46 chromosomes. There are 22 types of somatic chromosome of which 2 copies exist (for a total of 44) and 1 pair of sex chromosomes (for a total of 2). The sex chromosomes in males are an X chromosome and a Y chromosome (XY), whereas females have 2 X chromosomes (XX). Males are genetically described as 46 XY and females as 46 XX.


The causes of infertility can be categorized in a number of ways:

  1. Genetic vs. Non-genetic
  2. Reversible vs. Irreversible
  3. Treatable or non-treatable

Whlle genetic conditions are not 'reversible' with current technology, identifying a genetic condition is critical in infertile males because:

  1. A genetic cause may be transmitted to offspring.
  2. Identifying the specific genetic cause can provide important information on the chances that sperm production is present in the testis even if there are no sperm in the ejaculate.
  3. Some genetic diseases are associated with health problems in addition to infertility. Preventing those problems is important.


Which men with infertility should be evaluated for genetic causes?

Genetic abnormalities are very uncommon in men with sperm concentrations >5 million/ml - in fact, the chances of a genetic abnormality if the sperm count is > 5 million/ml is the same as in the general population.


Testing for genetic abnormalities is useful only if there are < 5 million sperm per ml.


What are the genetic abnormalities that can be present?

Despite the large number of genetic abnormalities associated with infertility, there are 4 major types of genetic problems which constitute the bulk of diagnoses.


  1. Klinefelter's Syndrome
  2. Y-chromosome microdeletions
  3. Congenital Absence of the Vas Deferens (CAVD) and Cystic Fibrosis
  4. Other: aneuploidy, translocations, inversions, etc.


Chances of a Genetic Abnormality

    Infertile Men    
  Gen Pop All < 5 million/ml No Sperm
Overall 0.5% 6% 5% 15%
47XXY (KS)
0.2% 1%   7-14%
Y-microdeletion 0.02%   7% 3-13%
47XYY 0.1% 1%   1%
CBAVD 0.1%     1%

With increasing genetic testing, Y-chromosome microdeletion is increasingly recognized as the most common identifiable cause of non-obstructive azospermia.


How are Genetic Abnormalities Diagnosed?

While there may be clinical features that suggest one cause or another, a precise diagnosis requires genetic testing. All genetic tests are done with a blood sample. A sperm is a complex DNA transport vehicle and virtually all of the chromosomes are involved in sperm production. Note that there are many genetic causes that are currently unknown and that cannot be tested for at this time. The frequently used genetic tests used in infertile men are:

  1. Karyotype: determines the number and type of chromosomes. Large defects in chromosoms can sometimes be tested, but specific genes are not identified. Analogous to checking that all of the volumes of an encyclopedia are present and that the order of the books is correct.
  2. Y-chromosome microdeletion: checks the distal arm of the Y-chromosome which is important in sperm production. See more below
  3. Cystic fibrosis testing: checks for the absence or presence of genes commonly involved in cystic fibrosis and absence of the vas deferens.


It is important to recognize that virtually every genetic abnormality will have a spectrum of severity in terms of clinical presentation. Quite frequently, men who are diagnosed later in life as a result of infertility fall into the milder range of the disease.

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Genetic Counseling

The approach to managing males with genetic problems causing infertility, the entire family including the partner and the potential offspring must be considered. Implications regarding transmission of genes to the offspring and the long-term implications is important. The ultimate goal is a healthy, happy family. Genetic counseling is recommended for all individuals. The fertility labs may offer genetic counseling as does the Provincial Medical Genetics Program. Unfortunately, it can take a long time to obtain an appointment at BC Women's Hospital.

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Author(s): K Poon  Major Revision/Review: January 2011