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Genetic Disorders &
Infertility in Men

Genetic causes of male infertility

Diagnosing infertility in men due to genetic abnormalities is a complex undertaking due to the wide range of genes involved in the production and transport of healthy sperm. Infertility researchers also are constantly identifying additional genetic anomalies contributing to male infertility.

When examinations and the results of a man’s semen analysis indicate deficiencies in sperm count, presence or quality, genetic screening may be performed to determine a specific genetic cause for male infertility. These diagnostic results help us determine the best way to address the issue through treatment, such as IVF with ICSI using the man’s sperm or using donor sperm to achieve pregnancy. The results may also indicate that the male or couple may benefit from genetic counseling.

In addition to genetic disorders causing male infertility, they can also cause a child to inherit serious medical and developmental complications. To check for male genetic defects in an embryo created through IVF, preimplantation genetic testing will be performed. This testing examines embryos for a range of genetic problems that may cause implantation failure, miscarriage or birth defects.

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Genetic disorders & infertility in men at a glance
  • Genetic disorders cause infertility in men primarily by compromising the production of mature sperm, called spermatogenesis, and its transportation to the egg for fertilization.
  • According to a study published by the National Institutes of Health, genetic disorders cause 2%-8% of male infertility cases.
  • Genetic testing may be recommended if the man has a very low sperm count, no sperm in semen or physical defects such as small testicles, and if he and his partner have experienced multiple miscarriages.
  • The primary types of genetic disorders causing male infertility are cystic fibrosis gene mutation, chromosomal abnormalities in number such as Klienfelter syndrome, Y chromosome microdeletions of genes, Noonan syndrome, and chromosomal translocations.
  • A semen analysis and/or physical exam first determines that the sperm is the source of male infertility, then depending on the fertility specialist’s evaluation, genetic testing will be done to pinpoint a genetic abnormality.
  • Male infertility genetic disorders can’t be cured but in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) of the man’s sperm can help him father a child, and sperm donation can help a couple have a baby.

Genetic disorders that lead to male infertility

A fertility specialist may recommend genetic testing to see if the male has one of the genetic disorders affecting his fertility described in detail below. Additionally, if a couple has suffered multiple miscarriages, a physician may perform genetic testing to identify any abnormalities that could be preventing the pregnancy. Physical barriers such as the absence of the vas deferens or small testicles, may also indicate a genetic issue.

Spermatogenesis, azoospermia & oligospermia
  • Spermatogenesis: Disrupts the ability to produce healthy sperm cells.
  • Azoospermia: Blocks the ability to even produce sperm cells.
  • Oligospermia: Defects that result in very poor or low-quality sperm.

Other genetic disorders can impair fertility, such as malformed sperm that can’t survive long enough to fertilize the female egg. Men with azoospermia or severe oligospermia have a greater risk of a genetic abnormality than men who are infertile for other reasons.

Kleinfelter syndrome

Almost all men with Kleinfelter syndrome are infertile. An additional X chromosome in males causes Kleinfelter syndrome (47, XXY).

It is diagnosed at or before birth about 10% of the time. It is more often diagnosed at adolescence or adulthood in men with small testicles and hypogonadotropic hypogonadism, which is a failure of the testicles to produce sex hormones. Men with enlarged breasts, called gynecomastia, are also often diagnosed with the syndrome.

The syndrome affects about 1 in 1,000 boys. Kleinfelter syndrome causes about 3% of male infertility cases, and is more common in men with oligospermia or azoospermia. In addition to infertility, the condition can result in decreased facial and pubic hair, a small penis and low sex drive.

The genetic disorder can also result in osteoporosis, language and speech problems, learning disabilities and behavioral issues.

Cystic fibrosis gene mutation

Cystic fibrosis is an inherited disorder that can be life-threatening, affecting the lungs and digestive tract. Research has found that a specific genetic mutation occurs with the disease that only affects male fertility.

Abnormality in the cystic fibrosis gene called CFTR (cystic fibrosis transmembrane conductance regulator) is strongly associated with an absence of the vas deferens, the tube that transports sperm to the urethra for ejaculation. Men with this CFTR mutation usually don’t have cystic fibrosis but are carriers of the gene. However, almost all men with cystic fibrosis have congenital bilateral absence of the vas deferens (CBAVD).

Men with the CFTR mutation may also have a blockage of the ejaculatory duct or blockage of the epididymis, a coiled tube behind each testicle that transports sperm to the vas deferens. A fertility specialist may recommend genetic testing for men with low sperm count, which is an indicator of the CFTR mutation.

Since testing methods cannot always detect the CFTR mutation, it is assumed that men missing the vas deferens (CBAVD) do have the CFTR mutation. To work around the problem of no vas deferens or blockages, sperm can be extracted from the testicles and used during IVF to fertilize the female egg.

Genetic counseling may also be recommended for the male and his female partner to determine the risks of having a child with cystic fibrosis. Also, men with obstructive azoospermia of unknown cause are at an increased risk of having a child with cystic fibrosis.

Y chromosome microdeletions

This condition affects the production of sperm and results in genetic information needed for producing healthy sperm to be missing from areas of the Y chromosome. The American Society for Reproductive Medicine estimates that these microdeletions account for 16% of the infertility cases in men with azoospermia or severe oligospermia.

The location of the microdeletion on the Y chromosome indicates the type of impact it has on sperm production. Most microdeletions causing azoospermia or oligospermia occur in the Azoospermia Factor (AZF) region on the long arm of the Y chromosome. Where the microdeletion is detected can influence the approach to possible fertility treatment.

Genetic counseling is recommended for couples when the man has Y chromosome microdeletions. Sons of these men will inherit the deletion and may be infertile.

Chromosomal translocation

A chromosomal translocation is an unusual rearrangement of a chromosome, the two main types being a reciprocal translocation and a Robertsonian translocation. Men with these translocations experience degrees of low sperm count and no sperm in semen. One study showed that chromosomal translocations cause 2.1% of male infertility cases.

The chromosomal translocations do not appear to affect semen volume but do show a much lower than normal sperm concentration. Measurements of testicular volume in men with translocations appear to be lower than in fertile men.

Noonan syndrome

Noonan syndrome is caused by mutations in more than eight genes. It is generally evident at birth and can include a variety of physical effects that vary from person to person.

These can include several abnormalities in the facial structure, head, sternum, elbows and spine. Heart defects are also possible in a child with Noonan syndrome, as are blood disorders and intellectual difficulty.

Boys with Noonan syndrome may also experience infertility. This is particularly the case if one or both of their testicles did not drop into the scrotum (cryptorchidism) before birth or during their first year.

According to the National Association of Rare Disorders, 60%-75% of males with Noonan syndrome have some form of cryptorchidism. If not surgically corrected, mature sperm may not develop properly, resulting in infertility for some men. Men with Noonan syndrome who did not experience problems with undescended testicles may still experience decreased fertility.

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Types of genetic testing for infertility in men

Genetic tests for male infertility identify changes in chromosomes or genes. In general, a genetic test usually finds no abnormality in men, but about 15% of men with low sperm count or azoospermia do test positive for a genetic disorder.

There are more than 1,000 types of genetic tests, but for male infertility, there are three common types of tests: karyotype, cystic fibrosis gene mutation, and Y chromosome microdeletion.


A karyotype is essentially a picture of the chromosome. A cytogeneticist stains the chromosome and takes a picture of it under a microscope. The picture is cut up, rearranged by chromosome size and examined by the cytogeneticist looking for extra or missing pieces.

This test analyzes blood chromosomes, called karyotypes, for number and overall set up of the chromosome. It can detect if the man has extra copies of a chromosome or a missing chromosome, and if the chromosome is either missing large pieces of genetic code or has extra sections of genetic code.

Cystic fibrosis gene mutation testing

Cystic fibrosis genetic testing looks for mutations in cystic fibrosis genes that can cause infertility in men. Cells from a blood draw or from being gently scraped from the mouth contain the man’s DNA, which the lab analyzes.

Most men with congenital absence of the vas deferens (CAVD) have at least one mutation that can cause cystic fibrosis. These men and those who produce no sperm, along with their female partners, should undergo genetic testing for cystic fibrosis genes to make sure an offspring would not inherit the disease. Male children of men with CAVD have an increased risk of having CAVD.

Y chromosome microdeletion test

This test looks at the Y chromosome for missing genetic information necessary for healthy sperm production. Y chromosome microdeletions aren’t big enough for a normal karyotype test to detect. Genetics labs use polymerase chain reaction methods to analyze sites on the length of the Y chromosome. Most deletions causing no sperm or low sperm production are in the AZF region.

The exact location can indicate what treatment a fertility specialist may recommend. Y chromosome microdeletion testing may be suggested before performing ICSI using the sperm of men with nonobstructive azoospermia or very low sperm count.

No known health risks other than infertility are indicated by microdeletions of the Y chromosome.

A negative result on a Y chromosome microdeletion test does not guarantee that a genetic abnormality isn’t present. Other gene sequences that are currently unknown to researchers may also affect the production of healthy sperm.