By: Dr. Eric Flisser
Although not strictly a part of infertility treatment, genetic testing in advance of pregnancy is an important consideration. All of our physical characteristics are the result of the genes that we have inherited from our parents. Genes are sequences of DNA that “code” for the process that generates that physical characteristic. The DNA sequences that make up our genes are arranged into long strands of DNA called chromosomes. We don’t, by far, understand how every physical characteristic is inherited, and the mechanisms of gene expression may be more complex than we even yet suspect. That said, there are some basic principles of genetics that are well understood. Some diseases have genetic causes, meaning that they can be passed from one generation to the next.
All chromosomes are paired. We receive one of each chromosome pair from each genetic parent. There are 22 pairs of “autosomes,” which are numbered 1-22 and one pair of sex chromosomes (XY for male, XX for female.) That means there are two copies of each gene in our cells. A dominant gene is one that is expressed when at least one copy is present; a recessive gene is expressed when there are no dominant genes present.
Disease genes can be dominant or recessive. Typically, however, if a patient has a dominant gene that causes a disease, he or she will know about it, because the disease will manifest in some way that alters his or her life. However, we can be harboring recessive disease-causing genes without our knowledge, since if we also have a dominant gene that codes for normal, it will be expressed, and the recessive gene will remain hidden. When a patient is only a carrier of a recessive disease, meaning they have one normal and one abnormal gene, he/she experiences no symptoms of the disease itself and it has no effect on his/her health.
However, if two patients both carry a normal, dominant gene and a recessive, abnormal gene, there is a chance that they will both pass the recessive, abnormal gene to their child, who will then have two recessive, abnormal genes and zero normal, dominant genes, and therefore will inherit the disease, despite the fact that neither parent has any manifestations of this problem. An example of this is cystic fibrosis, and there are many such others.
The likelihood of being a carrier of some recessive, abnormal genes is related to ethnicity. Certain communities are more likely to have disease-causing genes than others. For example, Tay-Sachs Disease and Gaucher’s Disease are more common in the Ashkenazi Jewish population than in other populations. However, French Canadians are also more likely to be carriers of Tay-Sachs Disease than other populations, but they are not at increased risk for Gaucher’s Disease. A physician or geneticist can determine which disease-causing genes you should be screened for, based on family history of medical problems and ethnic background.
There is no requirement for genetic testing prior to pregnancy, but screening for these risks can prepare patients for the possibility that they will have an affected child or permit interventions to decrease the risk that a child will be affected by the disease. When a dominant gene exists or if both patients are carriers of a recessive disease, there is an opportunity for offspring to be affected.
With current technology, it is possible to biopsy embryos to determine if the embryo is affected by a specific disease. This process is called Preimplantation Genetic Diagnosis (PGD). In order to perform embryo biopsy, treatment using in vitro fertilization is needed, so that embryos can develop in a laboratory. Typically a single cell or a few cells are removed from the embryo and sent to a laboratory for genetic analysis. Biopsy results can identify the embryos that are non-carriers of the disease, non-affected carriers, or affected. Only embryos unaffected by the disease are returned to the uterus.
Unfortunately, this technique is only currently useful for patients who are known carriers of genetic disease when that disease gene has already been identified. It cannot yet be used to detect all genetic diseases, especially those that arise from new, spontaneous mutations or those diseases that are suspected to be genetic, but whose gene has not yet been located. For the most part, genetic screening of DNA has focused on mutations that occur with high frequency in specific population groups. There are many diseases whose gene has been identified, but since they do not occur frequently, general population screening is not performed.
All patients seeking pregnancy should consider genetic screening to determine if they are carriers of common disease-causing mutations, regardless of whether they have fertility problems. Some of these patients will not have fertility problems, but because they are at high risk of having offspring with genetic diseases, are candidates for treatment by in vitro fertilization so that embryo biopsy and diagnosis can be performed. When disease-causing mutations are identified, patients will then have the opportunity to discuss options with their physicians. Sometimes, consultations with a geneticist are useful to answer detailed questions. In some cases, patients will decide to wait until after a pregnancy is established to identify if the fetus is affected, and in some cases, preimplantation genetic diagnosis (PGD) is performed to identify the embryos that are abnormal.
The blog posts presented here do not intend to diagnose, treat, or cure any condition and are not a substitute for consultation with a physician. The postings are presented for educational purposes only.