Alternative Names
reduced fertility; lack of fertility; fertility problems
Symptoms & Characteristics
Infertility can result from many different causes including genetic causes, non-genetic causes, or a combination of both. Different types of evaluations and tests are often needed to establish cause (if possible). Detailed personal and family histories are assessed in order to prioritize which evaluations and tests will likely be the most informative.
Evaluations may include different specialties such as genetics, reproductive endocrinology, and gynecology. Evaluations and tests may take time to complete, which can often be stressful for couples whom desire children. Sometimes, even after numerous tests and evaluations, a cause is still not found.
Treatment
Treatment for infertility is dependent upon the cause (if known).
How Common Is It?
It is estimated that about 11% of couples experience infertility.
Genetics & Inheritance
Both genetic and non-genetic factors play a role in infertility. Some proposed non-genetic causes may include:
- Environmental exposure to harmful toxins, chemicals, or medications
- Uterine abnormalities (like bicornate uterus and fibroids)
- Poor diet, malnutrition, being underweight (in females)
- Athletic training (in females)
- Polycystic Ovarian Syndrome (PCOS)
- Sexually transmitted diseases (STDs)
- Radiation treatment and chemotherapy for reproductive cancers
There are also various genetic causes of infertility. Some of the more common genetic causes may include:
A parental chromosome abnormality (such as Klinefelter syndrome, Turner syndrome, Y chromosome deletion or a structural rearrangement in chromosome material called a chromosome translocation)
- Klinefelter syndrome (47, XXY): Males typically have one X and one Y chromosome. Klinefelter syndrome occurs when a male has an extra X chromosome for a total of two X's and one Y. The symptoms vary and may include: small testes, enlarged breasts (called gynecomastia), lack of body hair, and sometimes, developmental delay (although many men have normal intelligence). Abnormal development of the testicles results in low or absent sperm production and possibly low testosterone leading to infertility or reduced fertility.
- Turner Syndrome (45, X): Females typically have two X chromosomes. Turner syndrome most typically occurs when a women has only one X chromosome and no other sex chromosome. The symptoms vary and may include: short stature, extra folds of skin on the neck (called webbed neck), a low hairline at the back of the neck, puffiness or swelling of the hands and feet, skeletal abnormalities, congenital heart defects, and/or kidney problems. Most affected women do not undergo puberty without the assistance of estrogen therapy. Very early loss of ovarian function (called premature ovarian failure) can occur even before an affected female is born.
- Y chromosome deletion: While there are only about 50 genes on the Y chromosome, most of these genes direct an embryo to become a male and are important for sperm production and fertility. Microdeletions are small missing regions of DNA that cannot be found by a standard chromosome analysis, and as such, require more specialized genetic testing. Microdeletions that occur in the AZF (azoospermic factor) genes may affect sperm production resulting in no sperm (called azoospermia) or few sperm (called oligospermia) depending on the amount of missing DNA and the specific missing region. About 1 in 4,000 males in the general population have a Y chromosome deletion that can contribute to infertility.
- Chromosome translocation: Sometimes a parent can have a rearrangement of genetic material in their chromosomes but no actual loss or gain of genetic material. This is called a balanced chromosome translocation. Although this parent is healthy with no physical or mental problems, they have an increased risk to have a conception with extra or missing genetic material. This can result in infertility, pregnancy losses, a stillborn child or a living child with physical and developmental problems. In about 5% of infertile couples, one of them has a chromosome translocation.
A genetic condition in a parent (such as cystic fibrosis, Fragile X syndrome, galactosemia and sickle cell anemia)
- Cystic fibrosis: Cystic fibrosis is a genetic condition caused by mutations in the CFTR gene at the location 7q31.2. Cystic fibrosis mainly affects the lungs and pancreas. However, some variations and mutations in the CFTR gene also cause a condition called congenital bilateral absence of the vas deferens (CBAVD), in which the vas deferens (the tubes that connect sperm from the testes to the penis) are missing. This leads to fertility problems in males. Of note, cystic fibrosis may also cause reduced fertility in females, but it is less common. Cystic fibrosis is most common in Caucasians.
- Fragile X syndrome: Fragile X syndrome is a genetic condition caused by a mutation in the FMR-1 gene at the location Xq27.3. Normally, this gene has three "letters" of DNA (CGG) that are repeated about 5-35 times at the beginning of the gene. Essentially, if the repeat size expands to >200 repeats, the gene is "shut off" and loses its function. Fragile X syndrome mainly causes mental retardation, some abnormal physical features, and autism. Females have two X chromosomes, while males have one X and one Y chromosome. As males have only one X, if that X has >200 repeats then they are affected. Females with one normal X and one with >200 repeats may be affected with Fragile X syndrome although their symptoms may be milder in comparison to affected males. If a female has one normal X and one X with about 59-200 repeats, they are called premutation carriers, and typically do not have Fragile X syndrome, but are at increased risk to have children with Fragile X syndrome. Regarding infertility, females who are premutation carriers are at an increased risk for premature ovarian failure (POF). Some studies have shown that females with 36-58 repeats may also be at increased risk for POF over the general population. About 1 in 240 to 1 in 460 females are believed to be Fragile X premutation carriers. This carrier frequency may be even higher in certain populations.
- People who have other genetic conditions may also have infertility or reduced fertility. As affected people are typically diagnosed by adulthood due to more significant symptoms, most of these conditions are not included in a routine infertility work-up, For example, galactosemia, is a metabolic condition that can cause premature ovarian failure in affected females, and sickle cell anemia can cause reduced fertility in both affected males and females.
There are some reproductive options for people who have chromosome abnormalities or genetic conditions that cause infertility. Some of these options may include:
- In vitro fertilization (IVF) can be used in conjunction with assisted reproductive technologies like Intracytoplasmic Sperm Injection (ICSI). ICSI refers to the process of selecting a sperm and injecting it directly into an egg in order to increase the chance of getting a fertilized embryo.
These decisions are very personal and complex and are best made with the help of a specialist who not only fully understands all of the options, but is also understanding of a couple's specific concerns. Genetic counseling with a trained genetic professional may be beneficial along with other specialist consultations.
Genetic Testing
Clinical genetic testing for infertility is often available as part of a gender-specific Infertility panel. Clinical genetic testing for infertility may include:
- Genetic testing for Y chromosome deletions (for males only)
- Genetic testing for Fragile X syndrome (for females only)
- Genetic testing for cystic fibrosis (for males especially)
Clinical genetic testing for infertility is available online (over the internet) or through an in person genetic consultation. Go to the Tests tab to link to the best providers, compare providers and read provider reviews or use our find a genetic professional directory to locate a trained genetic professional in your area.
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