What genetic problems affect sperm production (or sperm transport)?

Some changes to chromosomes or gene mutations cause abnormal sperm production or blockages to sperm flow that lead to male infertility.

The most common genetic causes of infertility are chromosomal conditions that affect sperm production. These include:

  • Klinefelter’s syndrome
  • Y chromosome deletions
  • other genetic problems, such as Down syndrome.

Infertility due to mutations in single genes are less common. Congenital absence of the vas deferens, where there is a blockage to sperm flow, is caused by mutations in the cystic fibrosis gene.

It is likely that other genetic disorders will be found in the future that will help explain other sperm production problems that currently have no known cause.

What are chromosomes?

Chromosomes are found in each cell in the human body. They carry the genetic material (genes) that determines all human characteristics, including hair colour, eye colour, height and sex. Each cell in the human body normally has 23 pairs of chromosomes (a total of 46). Chromosomes are made up of long strands of a chemical substance called deoxyribonucleic acid (DNA).

Of the 23 pairs of chromosomes, one pair is called the sex chromosomes because they determine a person’s sex. The sex chromosomes in a female are called XX and in a male are called XY. One sex chromosome is inherited from the mother and one from the father. Mothers always pass on an X chromosome, but fathers can pass on an X or a Y chromosome to their children.

The number and structure of chromosomes can be checked with a blood test called a karyotype.

What are genes?

Genes are made up of DNA and are located at specific places on the chromosomes. Genes determine our physical characteristics and influence some behavioural characteristics, such as intelligence.

Sometimes genes contain variations in the DNA that causes the gene to not work properly. These gene variations, called mutations, can lead to a range of physical and health conditions and/or intellectual disabilities.

What are Y chromosome deletions?

Some men have genetic material missing from their Y chromosome that is important for sperm production. Deletions on the Y chromosome are the cause of poor sperm production in about one in 20 men with low sperm counts (less than 5 million sperm per mL). Y chromosome deletions happen spontaneously during development of the embryo so usually fathers and brothers are not affected.

There are several different types of Y chromosome deletions that can be found with a blood test.

How are Y chromosome
deletions treated?

About half of men with Y chromosome deletions have enough sperm to use for ICSI; however, their male offspring will also have the Y chromosome deletion and fertility problems.


What is congenital absence of
the vas deferens?

Congenital absence of the vas deferens (CAVD) is a rare genetic problem that causes infertility. Several parts of the reproductive tract (including the vas deferens, most of the epididymis and seminal vesicles) are missing from birth (congenital). Sperm production occurs normally but the sperm cannot move from the testes into the ejaculate.

Most men with CAVD have a mutation in the cystic fibrosis (CFTR) gene. However, in most men with CAVD, the type of mutation they have means they do not have the serious lung and bowel problems that are a main feature of cystic fibrosis.

Cystic fibrosis is a serious condition caused by certain mutations in the CFTR gene, with symptoms from early life. Most men with cystic fibrosis also have absence of the vas deferens.

How is congenital absence of the vas deferens (CAVD) treated?

There are no surgical treatments for CAVD but it is usually possible to collect sperm directly from the testis or epididymis that can be used in assisted reproduction treatments such as ICSI when a man wishes to have a child.

What should men with CAVD think about?

Both the man and his partner must have a blood test to check for mutations in the cystic fibrosis (CFTR) gene, before starting assisted reproduction treatments. About one in 25 of the general population (including females) carry a CFTR mutation. It is therefore important that both are tested before starting IVF treatment.

Couples where the man has CAVD should have genetic counselling. If both partners have CFTR mutations, there is a one in four chance that their child will have cystic fibrosis. If such a couple use IVF to achieve a pregnancy, it is possible to test fertilised eggs to see if the embryo has cystic fibrosis. This is called pre-implantation genetic diagnosis. Only the embryos that are not affected by cystic fibrosis will be transferred to the woman’s uterus.


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 intellectual disability. Men with Down syndrome also have abnormal sperm production and are usually infertile.

How are genetic problems treated?

At this stage there are no treatments that can fix the genetic problems that cause poor sperm production or transport. While some men with genetic problems can father children naturally, IVF, ICSI or other forms of assisted reproduction offer the best chance for these men to have biological children.

What should men with genetic problems think about?

Some genetic problems, such as Y chromosome deletions, will be passed on to any male child born through the use of sperm in IVF or ICSI procedures. However, for most men with presumed genetic causes of infertility, we don’t yet know whether their children will be affected.

The investigation of men with unexplained low sperm counts (less than 10 million sperm/mL) should include a karyotype and, when less than 5 million sperm/mL, also a Y chromosome deletion test.

Couples where the man has CAVD should have genetic counselling to discuss the risk of cystic fibrosis in their children, and the possibility of pre-implantation genetic diagnosis and embryo selection in IVF.