About PGD for Translocations/Chromosome Rearrangements
Individuals that carry a balanced chromosomal translocation contain all of their genetic information; however, pieces of some chromosomes have switched places. Individuals that carry chromosomal translocations are typically healthy; however, they are at increased risk for infertility, miscarriage, stillbirth, and/or having a child with birth defects.
Other types of chromosome rearrangements include inversions (where a piece of a chromosome has reversed orientation), deletions (where a piece of a chromosome is missing), duplications (where a piece of a chromosome has duplicated itself) and insertions (where a piece of a chromosome has been inserted into the incorrect location).
How can PGD for chromosome rearrangements help me and my family?
Preimplantation genetic diagnosis is able to distinguish between embryos that have the correct amount of genetic material (balanced/normal) and embryos that are missing genetic material as a result of the translocation (unbalanced). Many couples in which one member is a translocation carrier have experienced miscarriages or have had to face difficult decisions when learning about a pregnancy with an unbalanced set of chromosomes. PGD can reduce the likelihood of having to deal with these particular circumstances by knowing prior to conception that the embryo(s) transferred are balanced for the translocation.
How does RGI test for chromosome rearrangements?
Translocation testing can be performed by two possible methods:
Fluorescence In Situ Hybridization (F.I.S.H.)
F.I.S.H. is a technology that allows our laboratory to determine the presence or absence of particular chromosomes or chromosome segments. Probes labeled with fluorescent signals are used to identify specific chromosome segments involved in a translocation, and light up or fluoresce in the presence of that chromosome region. For F.I.S.H. analysis, the laboratory typically requires blood samples from the couple in order to design a system of probes for the specific chromosome rearrangement. Once this system has been created, our laboratory tests it on the blood samples to assure that the signals are clear and all necessary chromosome segments can be identified on a single cell. F.I.S.H. analysis is typically performed on blastomeres (from the Day 3 cleavage stage embryo). F.I.S.H. can be used to test only for the known translocation or can be used to test for common chromosome abnormalities (such as Down syndrome).
Array Comparative Genomic Hybridization (Array CGH or aCGH)
Array CGH allows the laboratory to determine if the correct number of all 24 chromosomes (1-22, X and Y) are present in the egg or embryo, and can detect most known translocations. Therefore, in addition to testing for the translocation, this technology also provides information about other spontaneous chromosome abnormalities that are associated with failed implantation, miscarriage, or live births with multiple anomalies. With array CGH, the amount of DNA present for each chromosome is compared to that of a normal standard, enabling us to detect missing or extra pieces of chromosomes. Array CGH typically does not require the submission of blood samples or a set-up period, and therefore there is no wait time or penalty for cancellations. This method of testing is typically performed on blastomere (Day 3) or blastocyst/trophectoderm (Day 5/6) samples.
Can embryos that are balanced for the translocation be distinguished from embryos that do not have a translocation at all?
Most of the time, PGD for a translocation can only distinguish between embryos that are balanced or unbalanced. It does not typically allow the distinction between embryos that are normal (i.e. lacking a translocation altogether) or balanced (i.e. like a parent with a translocation, with no missing or extra genetic material). However, there is a technique called nuclear conversion that enables us to better visualize the chromosomes, and allows the distinction between embryos that are normal, balanced, or unbalanced. This technology can be utilized when translocation testing is performed by F.I.S.H. analysis. Since it is a sophisticated and time-consuming procedure, nuclear conversion requires that the biopsy procedure is performed in our laboratory.
What is the accuracy of the testing?
The accuracy of translocation testing is approximately 95-98%, depending on the stage at which the embryo is tested, but it may vary depending on the type of the chromosome rearrangements. Our genetic counselors can discuss with you whether F.I.S.H. or aCGH testing is predicted to be more accurate for your specific rearrangement.