Single Gene PGD Testing
PGD is available for the vast majority of serious genetic conditions as long as the particular gene mutation(s) in the family have been identified through DNA testing. However, the ability to offer PGD is dependent not only on the disorder/gene itself but also on the ability to successfully offer a reliable test using available technologies.
What are the steps of the PGD process?
1. Consultation with our team.
2. Genetic testing to identify the specific disease mutation in the family (if not already done)
3. Fertility testing.
4. PGD custom test development (often referred to as “making a probe”).
5. In Vitro Fertilization: embryos are created and grown to the blastocyst stage (day 5 or 6).
6. Trophectoderm biopsy of ~5-10 cells from the future placental cells of each embryo.
7. Embryos are frozen.
8. PGD and CCS testing.
9. Results available.
10. Transfer embryos to uterus of patient or surrogate in a subsequent frozen embryo transfer cycle.
11. Extra embryos remain frozen for future use.
Is the embryo biopsy safe?
In embryos that have developed to day 5 or 6 (blastocysts), we can see the difference between the inner cell mass (cells that will make the baby) and the trophectoderm (cells that will make the placenta). We are able to safely remove cells from the future placenta without disrupting the baby-making cells. The experience and expertise of the embryologists is very important in minimizing risks to the embryos: <1% of the >10,000 embryos we have biopsied since 2010 did not survive the biopsy. We also believe the long-term risks of blastocyst biopsy to the embryo, pregnancy, and baby to be acceptably low.
Why is the day on which the biopsy is done important?
When genetic testing of embryos first became available, embryos were tested on day 3 at the “cleavage” or 8-cell stage, and only 1 cell was removed for analysis. Now, biopsy techniques and genetic testing methods have evolved to allow for testing on day 5 or 6 of embryo development. ORM only offers testing at this later stage because it is associated with better implantation rates; the ability to biopsy placental (not fetal) cells; and better reliability of genetic results.
How is genetic testing done in PGD?
Genetic testing of embryos is more complicated than genetic testing of, for example, a blood sample. Because only a very small amount of DNA is available, special genetic testing techniques are necessary in PGD. Most PGD for single-gene conditions is now done via a technique called karyomapping. Compared to older methods, this technology has improved the accuracy of PGD and has also shortened the timeline required to prepare PGD tests for patients.
In karyomapping, DNA samples from the sperm and egg providers, as well as from one or more family member(s) of known genetic status (gene carrier or non-carrier) are examined to identify a unique DNA “fingerprint” that is associated with the gene mutation(s) in the family. (If family members are not available, other special test protocols may be used). Embryos can then be tested to determine whether they carry the DNA fingerprint associated with the “normal” gene or the gene with the mutation.
How do you “make a probe?”
Prior to the IVF cycle, the PGD reference laboratory undertakes several steps to be sure that an accurate PGD test will be available for embryos. The ability to offer PGD is influenced by many factors including the particular disease gene, the family’s specific gene mutation and DNA fingerprint, and the testing technologies that are available. “Probe” is a somewhat outdated term referencing an older technology that required development of an actual, physical DNA probe that was then used to test embryos. Today, the validation of a family’s PGD test prior to IVF is more accurately referred to as the PGD test development process. During this process, the family’s DNA samples are examined to find the DNA fingerprint associated with the disease gene and to determine whether other methods of genetic testing may be necessary in addition to or instead of karyomapping. This ensures – before an IVF cycle is begun – that an accurate PGD test will be possible. The good news is that in the vast majority of cases, a PGD test can be successfully created and the planned IVF cycle can move forward.
What is the accuracy of PGD?
Generally the accuracy of PGD is >97%, but the specific accuracy may vary depending upon the particular mutation, gene, and/or family being tested. More detailed information about your particular PGD test becomes available from the PGD laboratory following the test development process.
Do you recommend CCS (chromosome screening of the embryos) along with PGD?
Yes. Due to the high rate of sporadic chromosome abnormalities in embryos (30-80%, depending on maternal age), even from healthy, young, or fertile individuals, CCS (or PGS) can provide valuable information and help us find the embryos that are most likely to result in a successful pregnancy. Therefore, ORM always performs CCS in conjunction with PGD cycles. PGD and CCS tests can be done simultaneously on the same biopsy, and adding CCS to a PGD IVF cycle does not change the overall process or the timeline for results.
Does PGD replace prenatal testing?
Not necessarily. While transferring an embryo that has tested “normal” by PGD is expected to significantly reduce the chance for the future baby/child to develop the genetic disorder in question, it does not entirely eliminate the risk. Invasive, diagnostic prenatal tests such as chorionic villus sampling (CVS) and amniocentesis are generally considered to be more accurate than PGD (often >99%) and are recommended for those who wish to confirm PGD results in the ongoing pregnancy. Whether or not to have prenatal testing is a personal decision that we recommend discussing in depth with your prenatal provider and a prenatal genetic counselor.
How do I get started with single-gene PGD?
We recommend making an appointment for a new patient consultation with one of our physicians to start. You are also more than welcome to email one of our genetic counselors with any initial questions about your specific situation prior to making an appointment.