Preconception Genetic Testing
The American College of Medical Genetics along with the American College of Obstetrics and Gynecology has recommended that all couples of reproductive age who are considering establishing a pregnancy be offered genetic testing for carrier status for multiple genetic diseases. Testing potential parents for carrier status of genetic diseases is not a novel concept, but with the completion of the Human Genome Project, the DNA sequence information for many single gene disorders has rapidly grown and is now allowing for the detection of multiple mutations.
Carriers of genetic disease do not manifest the disorder themselves, but if both parents are carriers of the same mutation, their child will have a significant chance of suffering from a serious genetic disease. The most common of these disorders have an autosomal recessive mode of inheritance where statistically 25% of children born to a couple who are both carriers will actually have the disease, 25% will not have the disease or even be carriers, and 50% will be carriers of the gene but will usually have no symptoms of the actual disease in question.
Without preconception genetic testing, parents can be shocked to learn that they have a child with a serious or even fatal disease because the parents themselves are healthy individuals who happen to be asymptomatic carriers of a mutant version of a critical gene. Testing of parents prior to conception is the only way to know if your pregnancy will be at increased risk of resulting in a child with one of these inherited disorders. If both partners are determined to be carriers of a specific abnormal gene, there are actions that can be taken to dramatically improve the chances of having a child without the genetic abnormality. Couples who present to an infertility clinic specifically to be evaluated for single gene abnormalities often have no barriers to conceiving. They are candidates for preimplantation genetic testing solely to eliminate the risk of having a child born with one of these serious or fatal conditions.
In the past, there was only one way to perform accurate genetic testing on prospective parents: patients have their blood drawn for a serum karyotype, or chromosome analysis. This test allows the physician to confirm that each partner has a normal number of chromosomes and that there are no obvious gross abnormalities within those chromosomes. This type of testing does not, however, enable the physician to screen for specific genetic diseases. Until recently, that could only be accomplished through the performance of individualized genetic tests, a very expensive and arduous process. In addition, this process was further complicated by the fact that only a small number of genetic diseases could actually be screened before the process became prohibitively expensive.
Due to tremendous advances in genetic science, two new types of genetic testing are now available. One involves the collection of saliva from each partner. Each sample can be screened for over 109 different autosomal recessive genetic disorders for a reasonable fee. In the event that only one partner is found to carry the gene for an autosomal recessive disorder, there is no chance that the couple’s children can actually have the disease in question; the worst outcome possible would be that a child could be an asymptomatic carrier of the abnormal gene – just like the affected parent. In the event that each partner has a genetic defect involving the same gene, i.e. they are both carriers, then there would be a one in four chance that any resulting offspring would actually have the disease in question. There would be a one in two chance that any offspring would be a carrier of the disease, and therefore asymptomatic, and there would be a one in four chance that any offspring would be totally unaffected. The primary advantages of this particular test are that it is performed on saliva, rather than blood, it screens for a large number of diseases very efficiently, and it is relatively inexpensive.
The other type of test actually looks at pieces of genes, rather than any whole gene or chromosome. Through the testing of tissue obtained from either a cheek swab or blood from each partner, 200-300,000 small DNA fragments representing pieces of each known gene can be evaluated. When an embryo resulting from in vitro fertilization is produced, the DNA from each embryo can be evaluated and screened as well. Not only can this testing determine whether each embryo has the normal number of chromosomes, but in addition the source of any identified genetic abnormality can be accurately identified. In other words, in the event that an embryo turns out to be chromosomally abnormal, this testing can determine whether the abnormality came from the egg or from the sperm. This is very helpful in cases of recurrent miscarriage or in cases of repetitive in vitro fertilization failure when couples are struggling to determine whether they should continue to proceed with treatment using their own gametes or whether they should consider using either donor sperm or donor oocytes.
An example that we commonly see at TFC is a couple with a history of recurrent miscarriage who has a completely normal basic evaluation. They decide to proceed with IVF using this new testing procedure. Although several of their embryos on Day 3 look normal, the embryo biopsies show that, in fact, each embryo is chromosomally abnormal. In the past, we would be unable to answer the basic question of what they should do next. By default, many fertility specialists would recommend the use of donor eggs – without actually knowing if that was the source of the problem. Now with this testing, our physicians can confidently determine whether the defect originates in the egg or the sperm, and using this information, they can help our couples determine the appropriate next step in their treatment.
These two new technologies represent a major advance in the field of genetics and offer our patients new hope for achieving their dream of a healthy family.