The process of investigating an individual or group of persons to detect the presence of disease or defective genes that can be transmitted to offsprings. Women are routinely offered a variety of genetic screening tests during their first three months of pregnancy to evaluate the risk for genetic disorders in their unborn baby. The first trimester screening tests are usually done between the 10th and 13th week of pregnancy. We take every care to ensure that the baby born to you is healthy and happy. The role of genetics in assisted reproductive technology (ART) is to optimize a couple’s chance of having a healthy baby. Some forms of infertility, particularly male infertility, have a genetic basis. Couples with these forms of infertility may be at increased risk for transferring infertility to their offspring, for having a miscarriage or for having a child with a serious genetic condition. Other patients may be at increased risk for having a baby with a genetic condition based on their family history, ethnic background or age.
Preimplantation genetic diagnosis (PGD) involves testing for specific genetic conditions prior to the implantation of an embryo in the uterine wall. This form of genetic screening has been made possible by the growth of in-vitro fertilization (IVF) technology, which allows for the early stages of development to occur in a laboratory dish rather than in vivo. The purpose of PGD is to identify what are considered to be abnormal embryos in order to select the most desirable embryos for implantation. Diagnosis is comprised of two steps: extraction of one or two cells from an IVF-produced embryo, and application of the PGD test. PGD is important to embryology because it has advanced IVF results and allowed couples more opportunities to deliver a child to term; however, it has also created much controversy. Preimplantation genetic diagnosis was developed in the early 1980s as an alternative to post-implantation prenatal testing. Before this technology, the only other forms of prenatal diagnosis available involved amniocentesis and chorionic villus sampling (CVS). Both of these technologies involve the examination of embryos during later stages of development, when the embryo is already developing inside the mother. Couples who choose either of these tests must decide whether or not to terminate the pregnancy if test results come back positive for a particular genetic disease.
In October 1989, Alan H. Handyside, who later became a preimplantation genetics consultant, performed the first successful PGD test for cystic fibrosis, an X-linked disease. Initially, PGD was used as a form of gender selection to avoid having a child with a sex-linked disease. Since males are more often affected by X-linked genetic disorders, couples using PGD often choose to have only girls. PGD quickly came to be used for three main groups of inherited disease:
- Single-gene mutations such as cystic fibrosis and sickle cell anemia
- Sex-linked disorders such as hemophilia
- Chromosomal abnormalities such as Down syndrome
With PGD testing, embryos created through IVF are cultured in a laboratory for three days until they reach the 8-cell stage. At this time a blastomere biopsy is performed in which one or two of the blastomeres are removed by inserting a micropipette through the zona pellucida, which surrounds the embryo. Removing these cells does not damage the embryo, as the cells can easily multiply to replace themselves and allow for the development of a normal fetus. Once the totipotent blastomere is removed, it is prepared for genetic testing.
Blastomeres are usually examined for chromosomal abnormalities when eggs are extracted from mothers past the age of thirty-five, as these women tend to be at higher risk of having a child with abnormalities. In order to examine the genetic components of a blastomere the DNA must be removed, thereby destroying the cell. Fluorescent probes are added to the DNA, which then bind to specific chromosomes in a technique called fluorescence in situ hybridization (FISH). These fluorescent markers allow the chromosomes to become visible, enabling researchers to determine not only the sex of the embryo, but also the pairings of the chromosomes. Embryos with pairings such as “XXY” or “X” can be eliminated to avoid aneuploidy, an incorrect number of chromosomes. If a blastomere is diagnosed with aneuploidy, the embryo from which it was removed is expected to have the condition as well. In order to test for dominant and recessive disorders, a polymerase chain reaction (PCR) is used. This process allows for the examination of single-gene mutations. DNA is extracted from the blastomere, and then a particular DNA sequence is amplified by PCR to facilitate its analysis.
This is a very rapid and convenient method for technicians to test DNA. Through PCR, one molecule of DNA can be replicated into one billion molecules of DNA. Because the PCR reaction is very sensitive, it requires pure, high-quality DNA samples from only one cell. Although not very common, errors can occur and result in misdiagnosis leading to the discarding of a normal embryo, or an affected embryo being transferred into the mother. The individual blastomeres of the embryo are totipotent, meaning that they have the same developmental potential as an embryo. Therefore, isolating a blastomere involves the creation of a second, duplicate embryo, which will be destroyed during the diagnostic procedures. When the first successful blastomere separation was announced it was openly acknowledged and initiated significant controversy due to that fact that a clone was created. PGD has advanced the field of genetic testing significantly, but has also created concerns regarding eugenics and genetic discrimination. The fact that there are no present federal or state laws to regulate the use of PGD brings in even more ethical ambiguity.
Although PGD was originally thought to be a mechanism to discard embryos affected by a particular disease, some couples are now using this technology to actually choose embryos affected by a particular disease to be implanted in the uterus. Such cases have occurred with parents with dwarfism and congenital deafness. Some parents have used PGD as a means of creating siblings who can provide transplants for their older siblings, or as a means of sex selection. Because there are no governmental regulations, parents could in theory use PGD in nearly any capacity to create a child.
Preimplantation Genetic Screening (PGS) is a screening test used to determine if genetic or chromosomal disorders are present in embryos produced through In-vitro Fertilization (IVF).