There is a broad range of different genetic conditions that can lead to infertility, including some chromosomal abnormalities and sex-linked genetic disorders. In some cases, fertility can be negatively affected due to undescended testes in boys or undescended ovaries in girls.
In men, Klinefelter syndrome [1] is the most common chromosomal abnormality that causes male infertility. In this syndrome, a male is born with an extra X chromosome, which can lead to decreased fertility in a number of ways. For example, affected individuals are often unable to produce enough testosterone during puberty, and they also tend to be almost infertile even with fertility treatments such as hormone replacement therapy.
Some people may also be born with XXY syndrome, where they have two X chromosomes and one Y chromosome. Similarly to Klinefelter syndrome, these individuals will exhibit decreased fertility and impaired production of testosterone during puberty. However, in contrast to those with Klinefelter syndrome, men with XXY syndrome sometimes do achieve puberty and can even father children.
In women, Turner syndrome [2] is another example of a chromosomal abnormality that can cause infertility. Individuals with this condition typically have one X chromosome and no second sex chromosome at all. As in the cases of Klinefelter and XXY syndromes, fertility problems may result from impaired hormone production as well as from structural abnormalities in the reproductive tract.
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Sex-linked Genetic Disorders
In addition to chromosomal abnormalities, there are also a number of sex-linked genetic disorders that can cause infertility. One example is androgen insensitivity syndrome, which is caused by mutations in the gene that encodes the androgen receptor (AR). The AR normally allows the body to respond appropriately to male sex hormones called androgens. In this condition, however, the receptor is defective and cells are essentially “deaf” to male hormones.
As a result of this mutation, affected individuals develop with female sex characteristics because their bodies cannot respond appropriately to male sex hormones. People with this condition appear female at birth but often identify themselves as males when they reach puberty. Individuals can also have fertility problems, however, due to a lack of menstruation.
In other sex-linked genetic disorders, such as hemophilia A and Duchenne muscular dystrophy, infertility occurs because of an inability to produce certain proteins the body needs for sperm production or normal fertilization. In many cases, these gene mutations can also cause defects in the development of other body parts and organs.
People may also be born with Y-linked infertility, which is a result of mutations in the SRY gene on the Y chromosome. This condition affects only males because females have two X chromosomes while males have an X and a Y chromosome. In these individuals, there are no working copies of the SRY gene on either chromosome. As a result, affected individuals develop with female genitalia instead of male genitalia and cannot produce sperm.
Genetic Conditions that lead to Infertility
There are a number of other genetic conditions and genetic syndromes that can also impair fertility. One example is Kallmann syndrome, which can be caused by mutations in any one of several genes involved in the production or action of hormones that regulate the onset of puberty. These genes include kisspeptin, Lhx9, and GnRH.
Kallmann syndrome is associated with low testosterone levels [3], impaired production of other male sex hormones, delayed or absent puberty, and problems with the sense of smell. It also tends to affect mental function in a number of ways. Affected individuals are unable to sense pleasure in many activities, for example, and may experience abnormal behavior such as aggression. In addition to fertility problems, individuals with this disorder can sometimes experience other health issues such as mental retardation and diabetes.
Another genetic disorder that results in infertility is called septo-optic dysplasia (SOD). This condition can affect the development of the hypothalamus and the pituitary gland, two organs involved in the body’s hormonal system. When these organs are not fully formed, they produce hormones improperly and individuals lack certain secondary sexual characteristics such as pubic and underarm hair, enlarged breasts in men (called gynecomastia), and reduced bone density. People with septo-optic dysplasia can also have problems with their vision.
Multiple sclerosis (MS) can also cause fertility problems. This disorder occurs when the body’s immune system incorrectly attacks and damages myelin, a fatty substance that insulates nerve fibers in the brain and spinal cord. When this protective sheath is damaged, signals between the brain and other parts of the nervous system are disrupted or lost entirely. This can cause a wide range of neurological problems, including difficulty walking, numbness or tingling in the arms and legs, loss of vision, hearing problems, dizziness, weakness, fatigue, incontinence, depression and memory loss.
Scientists are not certain what causes MS although they believe that people are possibly born with a genetic predisposition to the disorder. In this respect, some individuals may inherit a tendency to develop the condition and only experience problems when exposed to certain environmental factors such as infection or trauma.
In many cases, people with MS have no fertility issues at all, but in others it can result from hormone problems that affect ovulation and menstruation. In addition, damage to the brain and spinal cord caused by MS can affect ejaculation and cause erectile dysfunction.
Testing for certain genetic markers that relate to infertility conditions
Testing for certain genetic markers that relate to infertility conditions can identify patients who are at risk for passing on hereditary disorders to their children. Prenatal testing, such as amniocentesis and chorionic villus sampling, can detect these problems early in fetal development.
Genetic disorders that cause problems with the reproductive system such as cystic fibrosis and Klinefelter syndrome can be diagnosed before birth.
However, you may be tested for specific genetic indicators that pertain to infertility issues, but they are markers and not necessarily disorders.
Should I get a genetic screening if I want to become a parent?
That depends on your particular situation. Your doctor can help you determine whether or not to pursue genetic testing based on factors such as your age and family history. In some cases, genetic tests are recommended for women who have been infertile in the past or who have a family history of certain disorders that cause infertility issues.
In addition, you may be advised to get tested if you are planning to become pregnant through invitro fertilization (IVF) or any other assisted reproductive technology.
Many people who undergo in vitro fertilization have already experienced some form of infertility and may have a genetic predisposition for certain fertility issues. Genetic testing can help doctors determine which embryos are most likely to produce a successful pregnancy.
For example, if you have a family history of cystic fibrosis or sickle cell anemia – both genetic diseases that cause infertility problems – your doctor may suggest that the embryos created through IVF be tested for these markers to determine which ones are free from disease.
In some cases, fertility clinics will only implant embryos that have been screened.
How are genetic tests performed?
Genetic tests can be divided into two basic categories: screening and diagnostic testing. Screening tests, which are non-invasive, look for markers in the DNA of an individual or couple. If these markers are present, it indicates a predisposition to certain conditions but does not necessarily mean that the person has developed a genetic disorder.
Diagnostic testing, which often involves blood, amniotic fluid or chorionic villus sampling (CVS), is used to determine whether someone is affected by a particular genetic disorder. For some conditions, medication or surgery may prevent transmission of the disease.
For others, it may be possible to use donor eggs or sperm if you know that you carry a genetic marker associated with an X-linked disorder.
How often does fertility testing need to be done?
A doctor will most likely perform the same fertility tests until a problem with your reproductive system is discovered or until you are successful in becoming pregnant. Your doctor may also give you additional tests if you experience any health problems, such as vaginal bleeding or unusual discharge.
Should children and adolescents get tested?
Fertility testing is not routinely done on children and adolescents because most of the reproductive system does not develop until puberty. However, if a child or adolescent experiences certain symptoms — such as delayed puberty, disorders related to sexual maturation, or infertility — he or she may need to see a doctor.
Take away from this information
In this article, we’ve discussed the role that genetics plays in fertility issues. To recap, there are a number of genetic conditions and factors that can affect your ability to have children including: Kallman Syndrome, XXY syndrome, Turner Syndrome and Mutation on Chromosome 13 or 18.
For some people with these various diagnoses who want to conceive naturally it may take longer than for those without them. The reason is because they need specific treatments tailored to their condition which will help reduce any infertility-related risks associated with the disorder itself.
Fertility issues can be a sensitive topic, but the truth is that it affects one out of six couples. And while testing for potential genetic disorders may seem like an obvious step, there are also markers and indicators which you can get tested to see if your reproductive system functions as expected.
Genetic tests should only be pursued with the guidance of a doctor based on factors such as personal history or family history; however they can sometimes help doctors determine whether or not certain embryos created through IVF will produce successful pregnancies by eliminating those who carry certain markers associated with infertility problems.
