What are genetic causes of infertility?Note:
Each cell in the body normally has 46 chromosomes. |
|
Chromosomes are the structures in cells that pass on genetic information. Each cell in our body has 46 chromosomes which contain all the genetic information (genes) for the development and function of our body. Changes to chromosomes and genes can result in problems in sperm production.
Changes to chromosome number
Changes in the number of chromosomes in cells can result in infertility. The genetic makeup of men normally involves 46 chromosomes, two of which are the sex chromosomes, X and Y. The Y chromosome carries some genetic material that only occurs in males. The sex chromosomes in women normally consist of two X chromosomes.
Changes to chromosomes and genes can cause abnormal sperm production or blockages to sperm flow. Chromosomes are the structures in cells that pass on genetic information.
Genetic and chromosomal disorders that affect fertility include:
It is likely that other genetic disorders will be found in the future, which can help explain other sperm production problems that currently have no known cause.  Back to top
What is Klinefelter's Syndrome?Klinefelter’s Syndrome is the most common chromosomal disorder in men. About one in 650 men, have an extra X chromosome, so instead of having the normal 46XY chromosomes in their genes, there are 47XXY or similar abnormalities.
Most men with Klinefelter’s Syndrome (about 95 per cent) do not produce sperm in their ejaculate and are sterile, although there is some evidence that the first stages of sperm cells may be present in the testes around the time of puberty but then progressively disappear. However, recent evidence also suggests that in up to half of men with Klinefelter’s Syndrome, sperm can develop in small areas of the testes, which never get in to the ejaculate.
Men with Klinefelter’s syndrome have very small testes (2-6 mls, normal men >15ml). They may also have low levels of the male sex hormone, testosterone. This can result in a failure to have a normal puberty and a lowered sex drive. Other features such as increased body fat, tallness and decreased body and facial hair growth may indicate below normal testosterone production.
 More information: Klinefelter's Syndrome
Back to top
What is Down Syndrome?Down Syndrome can affect both men and women. People with this condition have an extra copy of chromosome 21 and have a range of disabilities. They have distinctive physical features and varying degrees of mental retardation. Men with Down Syndrome also have abnormal sperm production and are usually infertile. Back to top
What are Y chromosome deletions?Some men have some genetic material missing from their Y chromosome. This has recently been shown to be the cause of infertility in about one in 20 men with low sperm counts (less than 5 million sperm per millilitre). It is thought that areas on the Y chromosome that are missing are important for sperm production. Tests are now available that can pick up these changes on the Y chromosome , but the exact way in which the missing genetic material impairs sperm production is still unknown. Back to top
What is congenital absence of the vas deferens (CAVD)?Congenital absence of the vas deferens (CAVD) is a rare genetic problem that causes infertility in about one in 2500 men. Many men with CAVD have a genetic change (mutation) in the cystic fibrosis gene (cystic fibrosis transmembrane regulator, CFTR) which is the gene responsible for transportation of material across the lining of many surfaces of the body. Several parts of the reproductive tract (including the vas deferens) are missing from birth in men born with CAVD. This stops sperm from the testes passing out into the ejaculate.
In most men with cystic fibrosis, the vas deferens is absent.
More information: Absence of Vas Deferens & Seminal Vesicles Back to top
What other genetic causes of infertility are there?Abnormalities in the testosterone (androgen) receptor gene. This is a very rare condition in which the tissues of the body cannot recognise and respond to testosterone in the blood. In its most severe form, this loss of the hormone action results in a male (46XY) child being born with female genital appearance and the failure of sperm production. In mild forms, a normal appearing man may present simply with poor sperm production.
In mild forms, a normal appearing man may present simply with poor sperm production. As our knowledge of the human genes improves, it is expected that other genetic causes of infertility may begin to explain a large number of sperm production disorders that are now classified as 'unknown'. Back to top
How are genetic problems treated?At this stage there are no treatments that can fix most genetic problems that cause poor sperm production. While some men with these problems can sometimes father children naturally, in vitro fertilisation (IVF) or other forms of assisted reproduction is the most likely chance of these men having biological children.
More information: Assisted Reproductive Technologies Back to top
What are other considerations for men with genetic problems?Some genetic problems, such as Y chromosome deletions, will be passed on to any male child born through the use of sperm in ICSI/IVF procedures. The investigation of men with low sperm counts should include a Y chromosome deletion test.
Men with CAVD have a high risk of carrying a genetic change of mutation of the cystic fibrosis (cystic fibrous transmembrane regulator, CFTR) gene. About one in 25 of the general population (including females) also carry this gene mutation. As a result, it is therefore important that both the male and female partner are tested for the gene mutation if the couple decides to start IVF procedures. If both the male and female are found to carry this gene mutation, there is an increased risk that children will be born with cystic fibrosis. The couple may need to consider genetic counselling, a preimplantation genetic diagnosis (PGD) and embryo selection before starting ICSI/IVF procedures.
 Download: Male Infertility fact sheet PDF (61kb)
Back to top
|
