Genetic Screening & Testing
Considerations for genetic testing & PGS through IVF
There are many reasons to consider genetic testing. Here, we give an overview of the benefits of genetic testing and who should consider it. We also review the two different types of genetic testing as well as some alternatives.
One of the main goals of genetic screening is to identify the embryos that have the highest chance of pregnancy and the lowest chance of having a multiple pregnancy (twins or more). Healthy embryos can be cryopreserved and implanted in the future.
Who should consider genetic testing?
Patients should consider the genetic testing called preimplantation genetic screening (PGS) or preimplantation genetic diagnosis (PGD) if they have hereditary concerns, have experienced recurrent miscarriages, have repeated in vitro fertilization (IVF) failures, or require gender selection. Older patients are often advised to consider PGS, as older women’s embryos are more likely to have genetic defects.
While miscarriages occur in 15 percent of pregnancies, having only one early miscarriage is not a cause for alarm. Patients who have had recurrent miscarriages or even one late miscarriage with a chromosomal abnormality, either detected or suspected, can reduce their risk of miscarriage by PGS.
If the number of chromosomes is abnormal, the embryo is called aneuploid. By using PGS, only embryos with normal chromosomes are implanted. Once embryos are tested and deemed normal, the successful implantation rates per embryo are almost doubled. The unhealthy embryos are eliminated. Selecting a single embryo transfer to avoid a multiple pregnancy becomes much more attractive.
PGS does not completely reduce miscarriages since small defects in chromosomes and other errors in development can occur, which are not detectable by counting chromosomes. But it does dramatically reduce the chance to about 7 percent. Due to the technical error rate of 2.5 percent, occasionally a normal embryo will be declared abnormal and vice versa. Some estimates of this error rate exceed 10 percent.
Repeated IVF failures
If IVF fails repeatedly after healthy-looking embryos were implanted in at least two cycles, PGS in a subsequent cycle is an option. It is expected that 50–60 percent of embryos in a woman in her mid 30s would normally have aneuploidy. PGS can identify couples who have unusually high (80–90 percent) rates of aneuploidy in their embryos.
Patients who have a family history of a recessive or dominant genetic error for severe disease should consider preimplantation genetic diagnosis (PGD). This involves a special probe looking for a single genetic error. PGD (see more below) is another level of testing beyond PGS that involves counting the number of chromosomes.
Genetic tests are available that focus on identifying carriers of more commonly occurring diseases in their particular ethnicities. Populations of high focus include Ashkenazi Jewish, French Canadian, Asian, European, African American, Middle Eastern and Mediterranean.
Over 100 diseases can be evaluated now with blood or saliva tests. Several types of genetic tests are available for single gene analysis, including genome sequencing and microarrays. If one of the aforementioned tests flags a patient and his or her partner both as carriers for a disorder, the couple has the opportunity to explore further options. These options include IVF with PGD, which can test embryos for a particular disease prior to implantation.
What are the benefits of genetic testing?
- Identifies abnormal embryos and implants only those free of genetic disorders.
- Decreases the risk of passing on a serious genetic disorder from parent to child.
- Detects chromosomal abnormalities, increasing the chance of a successful pregnancy.
- Reduces instances of multiple pregnancy by identifying competent embryos prior to transfer to a woman’s uterus.
The two types of preimplantation genetic testing
Preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) are similar genetic tests conducted on embryos. They each evaluate for different genetic problems.
- Cells are removed from the embryo and screened for a specific genetic disease such as cystic fibrosis, sickle cell anemia or others.
- Embryos that are clear of the gene associated with a disease may be implanted.
- Testing may decrease the risk of genetic disease but cannot completely eliminate it. Confirmation with amniocentesis or chorionic villus sampling (CVS) is still necessary later on in a pregnancy.
- Only the biopsied sample of the embryo is sent to the lab for analyzing.
- May increase the success rates for IVF in women, particularly in women over 35 because the percentage of embryos with a chromosomal abnormality increases with female age.
- Can allow the diagnosis of an abnormal number of chromosomes, called aneuploidy.
- Decrease in the miscarriage risk, Down syndrome and other major chromosomal errors.
- All chromosomes are tested and the sex of the embryos is revealed. Chromosome abnormalities may include:
- Aneuploidy (too many or too few chromosomes, as in Down syndrome, also called trisomy 21)
- Translocations (incorrect chromosome position)
- Other structural alterations.
Alternatives to preimplantation genetic testing
At 10 to 12 weeks into a pregnancy, doctors can perform CVS. Another procedure they may perform is amniocentesis. This is performed 14 to 16 weeks into a pregnancy and involves removal and analysis of the amniotic fluid that surrounds the fetus. Either test can diagnose fetal genetic abnormalities. However, if an abnormality is detected, the only options are an abortion or carrying the fetus to term.
Also, ultrasound with or without blood tests can be done during pregnancy. If abnormal results are obtained with ultrasound and/or blood tests, CVS or amniocentesis may also be recommended.
Pre-screened donor eggs or donor sperm can be used in IVF to avoid the risk of inherited disease. One also has the option not to do prenatal testing or genetic testing.
Genetic screening counseling
After IVF, PGS can provide a wealth of information, but this test is not clinically indicated for everyone. It carries with it a considerable cost and can raise more questions than it answers.
Therefore, selecting the appropriate population and test is important. The successful use of genetic testing can improve health if the challenges and limitations are understood and thoroughly explained to the participants.
One important consideration for couples participating in genetic testing is the availability of specialized genetic counseling. Counseling ensures that the patients have an appropriate understanding of the results and possible outcomes.
Counseling is not always provided with genetic testing and can be an additional cost. Insurance and testing facilities vary in pricing and what may or may not be covered.
Egg and sperm donor genetic testing
Although it is not mandatory, Servy Institute of Reproductive Endocrinology’s (S.I.R.E.) affiliated egg banks request genetic testing before donations. Male partners are also encouraged to check their own risks with an advanced carrier screening before egg donation and IVF. Any couples considering IVF should be encouraged to undergo genetic testing regardless of risk factors and family history, as seeking out fertility assistance already classifies them in a higher risk population.