Reproductive Genetic Testing

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Reproductive Genetic Testing

Reproductive genetics, a field of medical genetics integrated with reproductive medicine, assisted reproduction, and developmental genetics, involves a wide array of genetic tests that are conducted with the intent of informing individuals about the possible outcomes of current or future pregnancies. The tests themselves can include the analysis of chromosomes, DNA, RNA, genes, and/or gene products to determine whether an alteration is present that is causing or is likely to cause a specific disease or condition.

Types of Tests

In general, reproductive genetic testing involves the following categories of tests:

Carrier testing is performed to determine whether an individual carries one copy of an altered gene for a particular recessive disease. The term recessive refers to diseases that will occur only if both copies of a gene that an individual receives have a disease-associated mutation; thus, each child born to two carriers of a mutation in the same gene has a 25 percent risk of being affected with the disorder. Examples of carrier tests include those for Tay-Sachs disease, sickle cell anemia, and cystic fibrosis. Couples are likely to have carrier tests if they are at higher risk of having a child with a specific disorder because of their racial or ethnic heritage or family history. Carrier testing is often done in the context of family planning and reproductive health.

Preimplantation diagnosis is used following in vitro fertilization to diagnose a genetic disease or condition in a preimplantation embryo. Preimplantation genetic diagnosis is essentially an alternative to prenatal diagnosis, as it allows prenatal testing to occur months earlier than conventional tests such as amniocentesis ¿ even before a pregnancy begins. Doctors can test a single cell from an eight-cell embryo that is just days old to determine, among other things, whether it is a male or female. This can provide crucial information for genetic diseases that afflict just one sex. Preimplantation genetic diagnosis has been applied to patients carrying chromosomal rearrangements, such as translocations, in which it has been proven to decrease the number of spontaneous abortions and prevent the birth of children affected with chromosome imbalances. Preimplantation genetic diagnosis techniques have also been applied to increase implantation rates, reduce the incidence of spontaneous abortion, and prevent trisomic offspring in women of advanced maternal age undergoing fertility treatment. A third group of patients receiving preimplantation genetic diagnosis are those at risk of transmitting a single gene disorder to their offspring. The number of monogenic disorders that have been diagnosed in preimplantation embryos has increased each year. So far, at least 700 healthy babies have been born worldwide after undergoing the procedure, and the number is growing rapidly.

Prenatal diagnosis is used to diagnose a genetic disease or condition in a developing fetus. The techniques currently in use or under investigation for prenatal diagnosis include (1) fetal tissue sampling through amniocentesis, chorionic villi sampling (CVS), percutaneous umbilical blood sampling, percutaneous skin biopsy, and other organ biopsies, including muscle and liver biopsy; (2) fetal visualization through ultrasound, fetal echocardiography, embryoscopy, fetoscopy, magnetic resonance imaging, and radiography; (3) screening for neural tube defects by measuring maternal serum alpha-fetoprotein (MSAFP); (4) screening for fetal Down syndrome by measuring MSAFP, unconjugated estriol, and human chorionic gonadotropin; (5) separation of fetal cells from the mother¿s blood; and (6) preimplantation biopsy of blastocysts obtained by in vitro fertilization. The more common techniques are amniocentesis, performed at the 14th to 20th week of gestation, and CVS, performed between the 9th and 13th week of gestation. If the fetus is found to be affected with a disorder, the couple can plan for the birth of an affected child or opt for elective abortion.

Newborn screening is performed in newborns on a public health basis by the states to detect certain genetic diseases for which early diagnosis and treatment are available. Newborn screening is one of the largest public health activities in the United States. It is aimed at the early identification of infants who are affected by certain genetic, metabolic or infectious conditions, reaching approximately 4 million children born each year. According to the Centers for Disease Control and Prevention (CDC), approximately 3,000 babies each year in the United States are found to have severe disorders detected through screening. States test blood spots collected from newborns for 2 to over 30 metabolic and genetic diseases, such as phenylketonuria, hypothyroidism, galactosemia, sickle cell disease, and medium chain acyl CoA dehyrogenase deficiency. The goal of this screening is to identify affected newborns quickly in order to provide treatment that can prevent mental retardation, severe illness or death.

It is possible that somatic cell nuclear transfer (cloning) techniques could eventually be employed for the purposes of reproductive genetic testing. In addition, germline gene transfer is a technique that could be used to test and then alter the genetic makeup of the embryo. To date, however, these techniques have not been used in human studies.

Ethical Issues

Any procedure that provides information that could lead to a decision to terminate a pregnancy is not without controversy. Although prenatal diagnosis has been routine for nearly 20 years, some ethicists remain concerned that the ability to eliminate potential offspring with genetic defects contributes to making society overall less tolerant of disability. Others have argued that prenatal diagnosis is sometimes driven by economic concerns because as a society we have chosen not to provide affordable and accessible health care to everyone. Thus, prenatal diagnosis can save money by preventing the birth of defective and costly children. For reproductive genetic procedures that involve greater risk to the fetus, e.g., preimplantation diagnosis, concerns remain about whether the diseases being averted warrant the risks involved in the procedures themselves. These concerns are likely to escalate should cloning or germline gene transfer be undertaken as a way to genetically test and select healthy offspring.

Policy and Regulation

Because insufficient accuracy of genetic tests used for reproductive purposes could have dire consequences (i.e., unexpected birth of a critically ill child or termination of a normal pregnancy), the regulation of such tests has been the focus of several agencies. Four Department of Health and Human Services agencies participate in overseeing genetic tests: the CDC, the Centers for Medicare & Medicaid Services, the Food and Drug Administration (FDA), and the Office for Human Research Protections.

All laboratory tests performed for the purpose of providing information about the health of an individual must be conducted in laboratories certified under the Clinical Laboratory Improvements Act. CDC has a role in addressing the public health impact of advances in genetic research, furthering the collection, analysis, dissemination, and use of peer-reviewed epidemiologic information on human genes and coordinating the translation of genetic information into public health research, policy and practice. All laboratory tests and their components are subject to FDA oversight under the Federal Food, Drug and Cosmetic Act. Under this law, laboratory tests are considered to be diagnostic devices, and tests that are packaged and sold as kits to multiple laboratories require pre-market approval or clearance by FDA. However, according to the Secretary¿s Advisory Committee on Genetic Testing, most new genetic tests are being developed by laboratories and are being provided as clinical laboratory services. These tests are referred to as in-house tests or ¿home brews.¿ The current administration is examining whether FDA has authority, by law, to regulate such tests.

Prepared by Kathi E. Hanna, M.S., Ph.D., Science and Health Policy Consultant

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Last Reviewed: January 2006