Treatments & Procedures

Genetic Testing and Male Factor Infertility

What is a genetic test?

A genetic test is a blood test that looks at a person’s DNA, or genetic information. Some types of genetic tests look at the number and “setup” of a person’s chromosomes, while other types look for changes (mutations) in certain parts of the person’s genetic code.

Chromosomes are tiny structures that contain the DNA that regulates the way the human body grows and functions. Chromosomes are normally found in pairs. Usually, there are 46 chromosomes per cell: 22 pairs of “somatic” chromosomes and one pair of sex chromosomes. The sex chromosomes are the genetic material that determines if a human is a man or a woman. In most cases, women have two X chromosomes, and men have one X and one Y chromosome.

It is important to know that most genetic tests do not examine all of a person’s genetic material. There are different ways to examine genetic material. Your healthcare provider can explain the type of genetic test that is being considered for you, and why.

Who should undergo genetic testing for male factor infertility?

“Male factor infertility” is the name for any condition in the man that may be a reason why a couple cannot have a baby. A male factor is found in half of all couples seeking treatment for infertility.

A large number of couples have male factor infertility. Unfortunately, the overall chances of actually finding a genetic cause for male factor infertility are very low. Certain conditions, however, can increase these chances. Your fertility specialist may recommend genetic testing if you have one or more of the following conditions:

  • very low sperm count, or no sperm seen in the semen;
  • physical features that suggest a genetic cause (for example, small testicle size, or if the doctor cannot feel the sperm tube called the vas deferens);
  • several miscarriages (unexpected end of a pregnancy).

What are the chances of finding a genetic abnormality for male factor infertility?

The chances of identifying a genetic cause for male factor infertility depends on the man’s laboratory results, physical exam findings, ethnic and racial background, and family history. Overall, the chances of finding a genetic abnormality are very low; however, in men who have very low sperm count or no sperm in the ejaculate, the chance of a successful abnormal genetic test may be as high as 15%.

What genetic tests are recommended for men with male factor infertility?

The three most common genetic tests are:

  • Karyotype (also known as a chromosome analysis). This test examines the number and “set-up” of the chromosomes, and can detect if a person is missing or has extra copies of entire chromosomes, or very large pieces of the genetic code.
  • Cystic fibrosis (CF) gene test. Cystic fibrosis is a genetic (inherited) condition that mainly affects the lungs. Recent research has uncovered “variant” forms of cystic fibrosis that affect male fertility only. Cystic fibrosis gene testing looks for misspellings (mutations) in the cystic fibrosis genes that can cause male infertility. (Please see the discussion below for more information about cystic fibrosis mutations.)

The results of genetic testing may help your fertility specialist learn how likely it is to find sperm in the testicles. Healthcare providers in the genetic disorders specialty can also give people their genetic test results and advise them if they are likely to pass along a genetic abnormality to future children.

What conditions are found by genetic tests for male factor infertility?

  • Klinefelter syndrome is a common genetic cause for male infertility. Klinefelter syndrome occurs when a man inherits an extra “X” chromosome, giving him XXY sex chromosomes instead of the XY seen in the typical male. Approximately 1 out of every 500 to 1,000 males have Klinefelter syndrome. In men who have who have a very low sperm count or no sperm in their ejaculate, however, the chances of finding Klinefelter syndrome may be as high as 10%. Men with Klinefelter syndrome typically have small testicles and infertility, may be tall, and can have larger breasts than expected. A lower-than-expected testosterone level is common in men with Klinefelter syndrome. If you have Klinefelter syndrome, you may be referred to a genetic counselor and/or endocrinologist to discuss how this condition will affect your health and potential to have children. This is not a life-threatening condition, but you should follow up with your doctor to help manage this condition.
  • Y chromosome microdeletion is diagnosed when portions of the Y chromosome DNA are missing–specifically, the areas of the Y chromosome that “code” for male fertility. If areas are deleted or missing, it can affect male fertility. Which portion of the Y chromosome DNA is missing is important, as it may predict the chances of finding sperm in the testicle. This genetic abnormality can also be passed on to children.
  • Cystic fibrosis gene mutation. Cystic fibrosis is seen in about 1 in 3,200 people in the Caucasian ethnicity. Recent research has identified “variant” forms of cystic fibrosis that can affect fertility in men only. This is one reason that fertility specialist will recommend the CF gene test. If you are found to have this condition, your doctor will recommend that you meet with a genetic counselor to discuss how your child may be affected. Cystic fibrosis can cause other health issues, and follow-up with your doctor is important.
  • Other chromosome abnormalities may be found during a karyotype test. In about 2-4% of couples who have several miscarriages and/or unexplained infertility, one member will have a “balanced translocation.” A balanced translocation is a difference in chromosome setup that does not necessarily cause health problems, but can lead to miscarriage, infertility, and/or having a child with developmental difficulties/mental retardation. Because these other conditions are rare, the treatment for these conditions is decided on a case-by-case basis while seeing a genetic specialist.

What happens when a couple with a genetic cause for male factor infertility wants to have a baby?

When the man has a genetic cause for infertility, some couples will decide not to use the man’s sperm to create a pregnancy. These couples can choose a procedure called intrauterine insemination using donor sperm, adoption, or fostering. Some couples will choose to not have children.

When sperm are found in men with a genetic cause for infertility, the number of sperm is usually very small. In many cases, these sperm can be used to fertilize the woman’s eggs in the laboratory using a technique call intracytoplasmic sperm injection (ICSI).

The techniques for finding sperm are called “sperm retrieval.” The options most appropriate for the genetic causes for male infertility are the following:

  • Klinefelter syndrome: Most men with Klinefelter syndrome will not have sperm in the ejaculate. It may be possible, however, to find sperm in the testicles using a technique called microsurgical testicular sperm extraction (MTESE). In some cases, hormone medication may increase the chance of finding sperm during MTESE.
  • Y chromosome microdeletion: The chances of finding sperm in the testicles in men with a Y chromosome microdeletion depends on the part or parts of the Y chromosome that are missing. If your fertility doctor thinks that there is a chance of finding sperm in the testicle, he or she may suggest the MTESE procedure.
  • Cystic fibrosis gene mutation: Because CF gene mutations do not appear to affect sperm production, most men with this condition will make sperm normally. In many cases, sperm can be retrieved using a technique called percutaneous epididymal aspiration (PESA).

Stahl PJ, Masson P, Mielnik A, et al. A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligospermia. Fertil Steril 2010; 94: 1753-1756.

Denschlag D, Tempfer C, Kunze M, et al. Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review. Fertil Steril 2004; 82: 775-779.


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