Roughly 10% of fertility cases have a genetic etiology. Some patients have a combination of symptoms that does not allow for the hypothesis to be narrowed down to one particular underlying genetic cause. Performing numerous physical tests is costly and time-consuming. Most importantly, delayed diagnosis and treatment have a dramatic impact on a patient’s quality of life.
Genetic testing identifies chromosomal abnormalities and DNA mutations that correlate with various infertility related disorders. Typically genetic abnormalities are the cause of spontaneous abortions. In other cases an abnormal tests may indicate the possibility a baby will have a specific medical condition or disease when born.
Genetic Fertility Tests & Panels
The Ashkenazi Jewish Panel
The Ashkenazi Jewish Panel screens for genetic diseases that occur more frequently in people of Eastern Europe (Ashkenazi) Jewish heritage. A positive result can help to identify if a couple has an increased chance of having a child born with one of these diseases.
These are 8 diseases commonly screened for in The Ashkenazi Jewish Panel:
Bloom syndrome – small size at birth, growth retardation, skin pigmentation (redness), increased number of respiratory tract and ear infections, immunodeficiency, predisposition to cancer and chromosomal instability.
Canavan disease – progressive loss of brain tissue characterized by increased head circumference, decreasing motor activity, progressive loss of visual responsiveness and mental retardation.
Cystic Fibrosis – recurrent lung infections, impaired absorption of nutrients from food/malnutrition and infertility.
Familial dysauonomia – abnormal function of the nervous system causing lack of coordination, decreased/inability to sense pain, excessive sweating, delays in speech and motor skills and gastrointestinal complications.
Fanconi anemia group C – deficient bone development and bone marrow function causing decreased numbers of blood cells, problems with heart or kidneys, abnormalities of arms and legs and increased risk of cancer.
Gaucher disease – an enzyme deficiency that may cause enlarged liver and spleen, an abnormally low number of platelets (blood cells involved in clotting), anemia (less than the normal number of blood cells) and bone pain, lesions, or fractures.
Niemann-Pick disease – caused by diminished enzyme activity. Type A is usually fatal within 2-3 years. Characteristics include: enlarged liver and spleen and progressive mental and physical degeneration. Type B also have enlarged liver and spleen but have little or no neurologic issues. They also tend to survive much longer.
Tay-sachs disease – a neurodegenerative disorder caused by an enzymatic deficiency. Symptoms typically include: developmental retardation followed by paralysis, dementia, seizures and blindness.
3 other less common diseases that may also be tested for include:
Maple Syrup Urine Disease (MSUD) – an inherited disorder in which the body is unable to process certain parts of proteins (called amino acids) properly. It is characterized by poor feeding, vomiting, lack of energy, seizures, and developmental delay. The urine of affected infants has a distinctive sweet odor, much like burned caramel. I f untreated it can lead to mental retardation and death in early childhood.
Mucolipidosis (type IV) – is caused by alterations to a protein believed to be involved in essential cell processes which leads to the accumulation of specific harmful substances throughout the body. Symptoms include: varying levels of motor and mental retardation, developmental delays, eye complications such as corneal clouding and retinal degeneration.
Glycogen Storage Disease (type 1a) – results from the absence of a key enzyme found in the liver, kidneys and intestines that affects the conversion of glycogen into glucose. This results in an excessive accumulation of glycogen in these organs. Symptoms include: abnormally enlarged organs, increased concentrations of lactic acid and abnormal elevation of lipids (fat) in the bloodstream.
Other Genetic Infertility Tests Explained
Chromosome Analysis Karyotyping: One or both of the parents may be the carrier of an abnormal chromosome. Karyotyping is the analysis of the number and shapes of chromosomes in individual cells. Abnormal karyotypes are a significant cause of recurrent miscarriage, or infertility. Chromosomal abnormalities include: extra or missing chromosomes, alterations to the normal structure of specific chromosomes or cases where sections of one chromosome will be relocated to another chromosome where it does not belong (translocation). A chromosome analysis can identify these abnormalities and determine the anatomical, physical and physiological problems associated with it.
Cystic Fibrosis: A recessive genetic disease that is the most common lethal defect among Caucasians. This means two parents carrying the recessive Cystic Fibrosis gene have a 25% chance of having a child with the disease. If one parent is a carrier, then the couples offspring would have a 50% of being a carrier of the gene. Approximately 1 in every 2,500 births results in a baby with Cystic Fibrosis. The frequency of being a carrier is dependant upon ethnicity with 1 in every 25 being European Caucasians or Ashkenazi Jews, 1 in 46 Hispanic Americans, 1 in 65 African Americans and 1 in 90 Asian Americans.
Fragile X Syndrome: A genetic mutation found exclusively on the X chromosome, Fragile X is the most common inherited form of mental retardation. There are various degrees of this mutation: mild (premutation) and severe (full mutation). About 20-30% of women carrying the milder premutation will have premature ovarian failure (POF). Each child of a woman carrying the premutation has a 50% chance of receiving an X chromosome with the premutation. There is also a chance a child will inherit a more severe version of the X chromosome resulting in the full mutation. The full mutation affects approximately 1 in 4,000 males and 1 in 8,000 females resulting in mental retardation ranging from borderline to severe. A DNA test can be performed to determine if a woman carries the genetic mutation and which form (permutation or full mutation).
Preimplantation Genetic Diagnosis (PGD): A test in which cells are taken from a developing embryo prior to being implanted. These cells are then screened for genetic or chromosomal abnormalities.
Y Chromosome Microdeletion: Mainly used for men who have very few (oligospermia) or no (azoospermia) sperm present in a semen sample and do not have any type of physical obstruction. This test identifies small missing segments of DNA from specific genes located on the Y chromosome. The functionality of these genes has been linked to male infertility. There are 3 basic deletions: AZFa – is rare and the most severe. There is no chance of being able to produce sperm, AZFb – there have been no documented cases of finding mature sperm with surgical procedures, AZFc – is the most common deletion. Successful extraction of sperm with surgical procedures occurs in ~ 2/3 of cases.