Genetic Screening & Testing
Every couple who is trying to conceive should have at least one partner tested for chromosomal mutations which could lead to rare disorders. Patients should also consider preimplantation genetic testing (PGT) if they have known hereditary disorders, multiple IVF cycle failures, or recurrent miscarriage.
At a Glance
- Genetic defects in embryos are the main reason embryos do not implant after in-vitro fertilization
- After preimplantation genetic testing, only embryos with normal numbers of chromosomes will be implanted
- Genetic testing may be used for specific genetic defects, which are in the family or detected on genetic carrier screen testing
- Due to the improved implantation rate, patients may be more inclined to do a single embryo transfer, reducing the risk of twins or triplets
- The gender of the embryo is known so patients can elect to transfer the embryo of the desired gender
What is preimplantation genetic testing (PGT) in IVF?
Preimplantation genetic testing (PGT) is divided into two main categories. The first and most common of these is PGT-A (formerly known as PGS) tests for aneuploidy, the abnormal number of chromosomes in the genetic analysis of an embryo. If there is an incorrect amount of genetic material in an embryo, it can prevent implantation, result in miscarriage, or lead to severe and fatal birth defects, the most common of which is called trisomy-21, commonly known as Down syndrome. When embryos are identified with abnormal numbers of chromosomes, they simply are not replaced. They are discarded with the permission of the patient.
The second category of preimplantation testing called PGT-M (formerly called PGD) looks for monogenic/single gene defects. If a patient has had carrier screening or is aware from her family history that her child or children would be at risk for a disorder, then all the embryos can be screened first for aneuploidy, then for this genetic abnormality. Common situations are when both the husband and wife are known to be carriers for sickle cell disease or cystic fibrosis.
How is PGT done?
The steps to do PGT are below:
- At approximately day 5 of embryo development, the embryos, now called blastocysts, have several cells removed microsurgically.
- The embryos are frozen.
- The DNA of the biopsied cells is analyzed for chromosomal errors or problematic genes. This complicated process takes at least one week.
- The embryos that are euploid (correct number of chromosomes) and free from genetic defects are available for transfer into the woman.
- The embryos that are not transferred remain cryopreserved until the patient is ready to transfer them.
- The embryos that are not safe for transfer are discarded with the patient’s permission.
Who should consider preimplantation genetic testing (PGT) in IVF?
Patients should consider preimplantation genetic testing (PGT) if they have known hereditary disorders, multiple IVF cycle failures, or recurrent miscarriage. Also, women undergoing IVF at an advanced age should consider this testing since it is more common for their embryos to have genetic abnormalities.
Can preimplantation genetic testing predict all possible abnormalities?
There are abnormalities, such as mosaicism, which cannot be detected by preimplantation genetic diagnosis. Mosaicism results from mitotic errors that occur after fertilization. About half of the embryos which exhibit mosaicism have normal chromosomes and the embryo and the baby can be normal. Putting mosaic embryos back has led to approximately half the normal implantation rate per embryo and the miscarriage rate is higher than normal. However, if no other embryos are available, transfer of mosaic embryos is a reasonable choice.
Prenatal screening blood test
A safety valve after preimplantation genetic testing is the prenatal screening blood test, a noninvasive blood test to detect several major chromosomal abnormalities. The screening assay is used for singleton and twin pregnancies with a gestational age at least 10 weeks to rule out aneuploidies or abnormal chromosomal number combinations which can lead to Down syndrome or other anomalies, or miscarriages. Fetal chromosome mosaicism cannot be distinguished by that method, however. If patients have a mosaic embryo replaced, an invasive test of the pregnancy must be performed. Negative test results do not eliminate the possibility of fetal chromosomal abnormalities of other chromosomes or of tiny errors called subchromosomal abnormalities.
This test is not 100% accurate because the test results may reflect the chromosomal changes of the placenta and not the fetus. The test does not identify pregnancies at risk for open neural tube defects such as spina bifida.
Every couple who is trying to conceive should have at least one partner tested for chromosomal mutations which could lead to rare disorders. The most common of these single gene recessive disorders is cystic fibrosis. This and at least 100 other disorders can be avoided in babies by doing a simple saliva test that is submitted to a laboratory. This screening is offered to everyone who is trying to conceive through our infertility practice.
Everyone has mutations in our chromosomes; they are part of evolution. Some mutations make us faster, smarter, and stronger, but other mutations can lead to a disease. If one of the partners is tested and has a mutation, then the other partner is tested to make sure that they do not also have this mutation. Very uncommonly, they do. In those cases, IVF with preimplantation genetic testing (PGT-M) can avoid the risk of having a baby with an uncommon serious or fatal illness.
Do I need a carrier screen if I have already had a healthy baby?
Yes, we recommend it. The risk of having an abnormal baby if you and your partner or donor have the same mutations is 1:4. So couples could have one or more babies which are normal and then have an affected child. A carrier screen is important for everyone to make sure that they do not have a baby with cystic fibrosis or other avoidable disorders.