Fertility treatment is a unique opportunity to detect and prevent the transmission of genetic diseases to future children. In addition to genetic screening, embryo testing can be performed during in vitro fertilization-IVF to detect those that do not carry the disease and exclude unhealthy ones. This process is called PGD-preimplantation genetic diagnosis. Genetic concerns arise because of prior genetic or family histories or encountered during routine screening prior to fertility treatments. As technology advances, the main challenge remains identification of carriers of genetic diseases employing thorough history and screening tests by a reproductive endocrinologist and possibly genetic counseling. Be prepared, you and your partner, to tell your reproductive endocrinologist about disease history of you and other family members.
GINA-The Genetic Information Nondiscrimination Act of 2008 that took full effect in 2010, prohibits the discrimination in health coverage or employment based on genetic information
Genetic screening, who is at risk?
Routine genetic screening for each individual or couple desiring pregnancy. Screening is based on common genetic issues based on ancestry-ethnic group. Initially only one partner need to be screened and if the test is positive the other partner needs to be screened.
Everybody should be screened for Cystic fibrosis-CF and possibly Spinal muscular atrophy-SMA1.
Ashkenazi jewish ancestry should be screened to Canavan disease, CF, Tay Sch disease, familial dysautonomia. Some extend this screening to Fanconi Anemia, Bloom,Gaucher, Neiman Pick, Mucolipoidosis IV, Glycogen storage disease Ia, Maple serup urine disease and familial hyperinsulinism, Nemaline myopathy, DLD defeciency, Joubert and Usher syndromes.
Sephardic jewish ancestry should be screened for CF and Tay Sach disease. Some add Familial Mediterranean Fever, Ataxia Telangiectasia, Fanconi anemia, 11B hydroxylase defeciency, glycogen storage disease IIIa, Factor VII defeciency and other diseases.
French Canadian ancestry should be screened to Tay Sach’s disease
Mediterranean ancestry (Greek, italian, arabic..) Should be screened for Thalassemia B,
Asian descent (Japanese, pakistani, chinese..) Thalassemia a,
African Americans should be screened for Sickle cell disease
Diminished ovarian reserve. Screening of young women with diminished ovarian reserve should be considered for Fragile X syndrome pre-mutation and also for Chromosomal abnormalities e.g. mosaic Turner syndrome, using a karyotype-a test to detect the number and shape of chromosomes.
Male factor infertility. Men with very low counts less than 5 to million per mL or with no sperm in the ejaculate should be screened for CF and its variants, Kleinfelter syndrome and microdeletions of Y chromosome.
Recurrent pregnancy loss. Sometimes in couple reporting two or more losses especially early in the first trimester, one partner may carry a hidden chromosomal abnormality. One chromosome is carried on top of another, they are transmitted to the baby together increasing the risk that the newborn would have an extra chromosome-trisomy.
One parent, a prior child or family member affected with a genetic disease. If the disease is well defined, the affected individual should be tested first for the exact alteration of the DNA causing the disease-the mutation. The couple are then tested for the same mutation.
One parent or a child affected with chromosomal abnormalities. If a prior baby carried a chromosomal abnormality, both patent karyotype should be obtained to exclude that one of them carry an abnormality and to prevent its recurrence to future babies.
One parent or family members carrying an inherited predisposition to cancer. Some individuals carry an inherited predisposition for cancer due to inheriting certain mutations. Commonly multiple family members across several generations were diagnosed with specific cancers at an earlier age e.g. <50 years. Examples of these are BRCA 1 and 2 for breast and ovarian cancers, FAP gene for colon cancer...These mutations carry very high lifetime risk of cancer and can be detected. Its transmission to future children can be prevented.
Prior child diagnosed with certain cancers. Families that had a child diagnosed with cancer can consider genetic testing for Two reasons. Diagnosing a specific mutation in the child diagnosed with cancer e.g. retinoblastoma, can prevent transmission of cancer to future children. On the other hand some children diagnosed with cancer e.g. leukemia, require bone marrow transplantation from a genetically close donor. Some families select to conceive with a child that is genetically compatible with his diagnosed sibling so that the child umbilical cord blood would be used for bone marrow donor for his brother or sister.
Methods of assessment of genetic risks.
Blood tests for genetic screening. The cells in the blood are analyzed to detect the carrier status of the individual. This test can identify if the individual carry a defective gene for the disease in question. If screening tests are positive couple are better served with genetic counseling. This will often inform them of the risk of transmission to offspring so that they can make an informed decision about further testing or treatments.
Embryo biopsy and DNA testing. One or two cells of a day 3-cleavage stage embryo is removed and its DNA analyzed for one or more specific mutation. The affected embryos are excluded from uterine replacement while healthy ones are used for transfer. Results are obtained in 1-2 days and healthy embryos are transferred to the uterus.
Because the amount of genetic material available for testing is small these are considered screening not diagnostic methods. Prenatal diagnosis during the first or early second trimester of pregnancy is commonly recommended. This usually entails blood tests for the mother, amniocentesis or chorion villous sampling-CVS to test genetic material from the fetus.
Management of genetic risk during fertility treatment
Genetic abnormalities that does not require change in infertility treatment plan. If 1. Only one parent carry the genetic mutation and the other does not carry the mutation for an autosomal recessive disease (disease that require two abnormal copies to manifest) or 2. The couple do not wish to undergo any genetic tests or PGD or 3. prefer to perform these tests after establishing pregnancy, then the treatment plan does not need to be altered for a well informed couple.
Genetic abnormalities requiring change of the infertility treatment plan. For couple carrying a genetic mutation with significant risk of transmission to children and desiring to avoid or minimize this risk, the plan need to be changed. Fertility treatment should be switched to IVF to allow for testing of the embryos. After ovarian stimulation, the eggs via polar body biopsy or the embryos via embryo biopsy are tested. When the results are obtained, healthy embryos are transferred to the uterus. In some genetic diseases that preferentially manifest in certain sex as in case of Hemophilia or Duchenne myopathy that affect boys more than girls, avoiding the disease can be accomplished by transferring embryos of the opposite sex.
Routine evaluation of genetic risk starting with a thorough genetic and family history by a reproductive endocrinologist-infertility specialist or a genetic counselor can avoid transmission of genetic disease to future children and can contribute significantly to their health and well-being. Many ethical and social issues in addition entangle the application of genetic testing and PGD programs and were not discussed here. This a general overview and does not replace consultation with a qualified physician-counselor.