Genetic Causes of Male Infertility


Genetic anomalies can be the cause of severe sperm abnormalities in men. For most of these men to become fathers, they will need intracytoplasmic sperm injection (ICSI), a laboratory process of injecting sperm directly into an egg with a tiny needle as part of in vitro fertilization (IVF).

Men with severe sperm abnormalities are also at higher risk of fathering children who inherit serious health problems, ranging from next-generation male infertility to cystic fibrosis. As ICSI has enabled more of these men to become fathers, the need to identify genetic problems in their sperm has become crucial in order to help them have the healthiest children possible. Two tests have become widely available for such circumstances: karyotype, blood testing for detection of chromosomal abnormalities, and pre-implantation genetic diagnosis (PGD), for detection of possible abnormalities in embryos created from their sperm.

Of course, few advanced medical treatments are risk-free. Studies have shown an association between ICSI and a very small increased risk – one percent – of having a child with a chromosome abnormality. However, thus far no evidence has suggested that ICSI itself causes this risk or that it poses a risk for any other abnormalities.

Nonetheless, after conception, each couple in these circumstances should consider prenatal diagnosis. Choices include:

  1. Amniocentesis: fluid in the sac surrounding the fetus is tested for genetic problems.
  2. Chorionic villus sampling (CVS): tiny finger-like growths in the placenta are sampled and tested.
  3. Non-invasive prenatal testing (NIPT): a blood test on the mother at 10 weeks of pregnancy to evaluate the chromosomes of the fetus.
Mother kissing little baby at home

Breaking Barriers, Building Families

Since 1983, we have pioneered fertility treatment for every kind of family. We want to help you achieve your dream of having a baby.

Request appointment

Who is at risk?

Men with the following are considered to have severe male factor infertility and should undergo a karyotype chromosome blood test:

  • Sperm count: less than 10 million/cc
  • Sperm motility: less than 25 percent
  • Sperm morphology
  • Azoospermia (zero sperm count)

Types of genetic causes of male infertility

Three genetic conditions are associated with male-factor infertility:

Chromosome abnormalities

Approximately five to 16 percent of men with severe sperm abnormalities have some type of chromosome abnormality, which can be diagnosed by a karyotype. Men with a chromosome abnormality have an increased risk of fathering a child with a chromosome abnormality. Also, their sons may be at increased risk for infertility problems. These men and their female partners should consider some type of prenatal diagnosis-such as amniocentesis, CVS or NIPT- if a pregnancy results.

Y chromosome microdeletions

Ten to 20 percent of men with severe sperm abnormalities may have normal chromosomes but may be missing very tiny areas of their Y chromosome. These missing areas are called microdeletions. Routine testing will not identify microdeletions; they must be detected with detailed DNA analysis.Genes located in these areas are very important for the production and development of sperm. When these genes are missing (“deleted”), male-factor infertility occurs. Currently, it appears that the main implication of a microdeletion is that it would be passed on to all male children, making them also infertile. This testing should be considered for all men who have severe male factor infertility with a normal chromosome study.

Cystic fibrosis and congenital absence of the vas deferens (CAVD)

Congenital absence of the vas deferens is the cause of approximately one to two percent of male infertility. This is often the diagnosis in men with azoospermia . CAVD is associated with an increased chance to be a carrier for a gene that causes the lung disease known as cystic fibrosis (CF).

Cystic fibrosis is a recessive inherited condition, meaning both parents must be carriers to be at risk for passing the disease to a child. Cystic fibrosis causes various glands in the body to produce a thick, sticky mucus, which leads to breathing problems, infections, lung damage, and digestive problems. More than 80 percent of men with CAVD are carriers for at least one genetic mutation known to cause CF. Therefore, it is very important that men with azoospermia and/or known CAVD and their female partners undergo CF carrier testing. The male children of men with CAVD may also be at increased risk of having CAVD.