Chromosome Analysis and Fertility

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Chromosome Analysis and Fertility

Common Sex Chromosome Abnormalities

A sex chromosome abnormality is any difference in the X or Y chromosome. There may be an extra X or Y chromosome, a missing sex chromosome, or problems with how the X or Y chromosome is formed. Some of these conditions are common enough that they have a specific name and we know what symptoms to expect. These most common sex chromosome abnormalities are described here, but there are others.

Klinefelter Syndrome
Turner Syndrome

Klinefelter Syndrome

Klinefelter syndrome happens when a male inherits an extra X chromosome. This means they have two X chromosomes and one Y (written 47,XXY), rather than one X and one Y. All individuals with Klinefelter syndrome are male because they have at least one copy of the Y chromosome.  A drawing of the chromosomes from a man with Klinefelter syndrome is shown here.

About 1 in 500 to 1 in 1000 males is born with XXY chromosomes. It is the most common chromosome change in men with very low or absent sperm counts. The symptoms of Klinefelter syndrome are variable, but usually mild.  Many males with an extra X chromosome have no obvious differences and may never know that they have the condition.  In fact, only about one-third of males with Klinefelter syndrome have been diagnosed, and less than 10% (1 in 10) of affected boys are identified before puberty. The most common symptom is infertility. In many cases, a man is discovered to have Klinefelter syndrome when he undergoes an evaluation to determine why he is experiencing fertility problems.

Because boys with Klinefelter syndrome usually produce lower than average levels of the male hormone testosterone, some have physical characteristics such as small testicles and a smaller amount of facial and body hair.  Men with Klinefelter syndrome tend to be either tall and lanky or more rounded with mildly enlarged breast tissue (called gynecomastia). Klinefelter syndrome does not seem to affect sexual orientation or gender identity.

Klinefelter syndrome can occur in males regardless of ethnic background or family history.  It is caused by a genetic change that happens by chance, and is usually not passed down through generations of a family.

About 1 in 5 (20%) men with Klinefelter syndrome, have chromosome results that aren't simply one extra X chromosome. Other possible results include:

  • Mosaic Klinefelter syndrome (46,XY/47,XXY), which happens when some cells have an extra X chromosome and some cells do not.
  • More than one extra X or Y chromosome (48, XXXY;  48,XXYY; or 49,XXYY)
  •  Extra X chromosomes that have an abnormal structure

While there is no cure for Klinefelter syndrome, treatments like testosterone supplements can help lessen symptoms, especially when started at puberty. Most men with Klinefelter syndrome will need help from intracytoplasmic sperm injection (ICSI) to become a biological father. This technique is successful in over half of men with Klinefelter syndrome.  Most children born to men with Klinefelter syndrome have had normal chromosomes, but there may be a higher chance to have a child with a chromosome disorder. If a man with Klinefelter syndrome is not able to have a biological child, other options (including sperm donor, adoption, and remaining childfree) can be considered.

Turner Syndrome

Turner syndrome usually happens when a female inherits just one X chromosome and no second sex chromosome. This means she has a total of 45 chromosomes instead of the usual 46 (written as 45,X). A drawing of the chromosomes from a female with Turner syndrome is shown here.

About 1 in 2500 female babies has Turner syndrome. Intelligence is usually normal. Turner syndrome is often recognized by puberty because of physical signs like:

  • Shorter than expected height
  • Extra skin on the sides of the neck called webbing
  • A hairline that is lower on the neck than usual
  • Puffy hands or feet
  • Birth defects of the heart, kidneys, or bones 
Women with Turner syndrome have ovaries that stop working at a young age. This usually causes absent periods and infertility. However, about 5% to 10% of females with Turner syndrome will start their period naturally.  In rare cases, a woman with Turner syndrome may conceive without help.

About half (50%) of females with Turner syndrome have chromosome results that aren't simply one X chromosome. Other possible results include:

  • Mosaic Turner syndrome (45,X/46,XX), which happens when some cells have an extra X chromosome and some cells do not. Mosaic Turner syndrome may be milder than full Turner syndrome. The picture below shows the chromosomes from a person with mosaic Turner syndrome.
  • A second sex chromosome is there, but part of it is missing or it isn't formed correctly. The second sex chromosome could be an X or a Y chromosome. If it is part of a Y chromosome, there is an increased risk for ovarian cancer. Doctors usually recommend removing the ovaries at an early age.  

Turner Mosaicism

click to enlarge

While there is no cure for Turner syndrome, treatments like estrogen and growth hormone supplements can help lessen symptoms, especially when started at puberty. Most women with Turner syndrome need help to become pregnant, usually through egg donation. However, women with Turner syndrome have an increased risk for life-threatening heart problems during pregnancy. Women considering pregnancy need to have heart testing before pregnancy. If there are signs of a heart problem, pregnancy is probably too risky. If the results are normal, it doesn't guarantee there will be no problems and the risks must be carefully considered.

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Why are you considering chromosome analysis?

Options for Women           Show options for men »

I have never had menstrual periods.

I stopped having periods (or had very irregular periods) at a young age.

I have a birth defect of my uterus, vagina, or external genitalia.

I have other signs that make my doctor or I think I might have a chromosome abnormality.

I think I have infertility or reproductive health issues, but I haven't seen a doctor and/or had any testing yet.

Medical guidelines say men with very low or absent sperm counts that aren't caused by a blockage should consider chromosome analysis. Men with very low sperm counts (less than 5 to 10 million sperm per milliliter) have about a 5% chance to have a chromosome abnormality. Men with no sperm in their semen analysis have about a 10% to 15% chance to have a chromosome abnormality.

The most common chromosome abnormality seen in men with low or absent sperm counts is Klinefelter syndrome, which is caused by having an extra X chromosome. Klinefelter syndrome frequently isn't diagnosed until men have an infertility evaluation. Learn more about Klinefelter syndrome. Many other chromosome abnormalities are possible that cause no symptoms except infertility.

Fertility treatments, like intracytoplasmic sperm injection, may be able to help men with low or absent sperm counts have biological children. However, a man with a chromosome abnormality may have an increased chance to have a child with a chromosome abnormality. These inherited chromosome abnormalities may cause infertility like the father has or more serious problems in the child. The risks depend on the specific chromosome abnormality. If a chromosome abnormality is found, your doctor or genetic counselor can explain the risks and family planning options.

Your doctor might also talk to you about a different genetic test called Y chromosome microdeletion testing. Learn more about Y chromosome microdeletions.

Chromosome analysis is not likely to be useful for you, but other genetic testing could be. There are many different reasons for an obstruction that keeps sperm from being released. Some reasons are infections, injury, previous surgery, or birth defects. Most causes are not genetic. However, a specific kind of obstruction called congenital absence of the vas deferens (CAVD) may be caused by genetic factors. CAVD can be diagnosed by a simple physical examination. If you have CAVD, see Cystic Fibrosis for Congenital Absence of the Vas Deferens for information about a genetic test that may be more useful for you.

Chromosome analysis is unlikely to be useful for you. Less than 1% of men with normal sperm counts have a chromosome abnormality.

Semen analysis can uncover other problems that might suggest different genetic tests that aren't covered here. If you have concerns about a different abnormality found in your semen analysis, you should discuss the possible causes and tests with fertility specialist.

Chromosome analysis may be part of the reproductive evaluation for some people, but it isn't the first step. This testing is only clearly useful for people with at least one of the other situations listed in this question.

There are many different causes for infertility and other reproductive problems. If you or your partner has concerns, you may consider seeing a fertility specialist. That doctor can review your history and order additional testing as needed.

Most females will start their period by age 15. If you are over 15 and haven't had a period, you should see a specialist (if you haven't already). There are many causes for absent periods, including hormone imbalances, diseases, tumors, birth defects, and genetic or chromosome disorders. Usually, your doctor will first do a physical examination and test the levels of some hormones.

Chromosome analysis is also a common test, especially if a hormone called FSH (follicle-stimulating hormone) is high or there are signs that the reproductive organs aren't formed normally. Chromosome analysis has two major uses in this case:

  • Find a sex chromosome abnormality. A missing X chromosome is the most common abnormality that causes absent periods. This condition is also called Turner syndrome (or 45,X). Other changes in how the sex chromosomes are formed are also possible.
  • Find out the chromosome sex. It is possible to be a normal woman in most ways, but have a chromosome pattern that looks like a male. Causes may include being resistant to male hormones or non-working genes that are critical to developing as a male.

Finding any of these conditions will explain why you haven't started your period. It may also give you and your doctor important information about possible health risks and reproductive options if that is a concern for you. See Common Sex Chromosome Abnormalities for more information.

When menstrual periods stop before age 40, it is unusually young for menopause. Your doctor will probably start with a detailed medical history, a physical examination, and measuring a group of hormones (most commonly FSH, prolactin, and TSH).

A large number of conditions can cause a woman to stop having regular periods. High FSH in such women is a clue that the ovaries aren't working normally. When the ovaries stop working normally before age 30, it can be a sign of a chromosome abnormality if other common causes have been ruled out. In this case, chromosome analysis is looking mostly for a sex chromosome abnormality. Examples of sex chromosome abnormalities are a missing X chromosome (called Turner syndrome or 45,X) or other changes in how the sex chromosomes are formed.

Finding a sex chromosome abnormality will explain why you stopped having periods at a young age. It may also give you and your doctor important information about possible health risks and reproductive options if that is a concern for you. See Common Sex Chromosome Abnormalities for more information.

Any woman who stops having periods before age 40 and has high FSH may also be offered a different genetic test called fragile X. See Fragile X Carrier Testing for more information.

If you have normal or low FSH, a different group of conditions is more likely. Chromosome analysis is rarely useful in these cases.

A birth defect of the uterus, vagina, or external genitalia is not usually caused by a chromosome abnormality. However, chromosome analysis can be useful to look at the chromosome sex. Two X chromosomes usually predict a girl, and an X and Y chromosome usually predict a boy.

It is possible to be a normal woman in most ways, but have a chromosome pattern that looks like a male. Causes may include being resistant to male hormones or having non-working genes that are critical to developing as a male. Examples are androgen insensitivity syndrome or Swyer syndrome. These conditions may cause reproductive organ birth defects.

These conditions need to be diagnosed because they may also cause an increased risk for other health problems, like cancer. A diagnosis may also give you information about reproductive options if that is a concern for you.

Some chromosome abnormalities that cause reproductive problems also cause certain physical features. These physical signs may help you or your doctor first recognize signs of a chromosome abnormality. A relatively common example is Turner syndrome, which is caused by a missing X chromosome. Physical signs of Turner syndrome include:

  • Short stature
  • Webbed neck
  • Low hairline
  • Heart birth defects
  • Kidney birth defects

Turner syndrome and other chromosome abnormalities are important to diagnose because they can cause other health risks. For instance, women with Turner syndrome have a higher risk for life-threatening heart problems during pregnancy.

See Turner Syndrome for more information.