Structural Chromosome Rearrangements

Balanced structural rearrangements include reciprocal translocations, Robertsonian translocations, and inversions. Get more information about chromosomes and genes.

At least one in 1000 healthy individual carries a balanced structural chromosome rearrangement. In a reciprocal translocation, the ends of two chromosomes break off, exchange and reattach. A Robertsonian translocation involves the joining of any two of the following chromosomes: 13, 14, 15, 21 or 22. Individuals with a Roberstonian translocation have 45 chromosomes, instead of the normal 46, because the two chromosomes stuck together are counted as one. In an inversion, an interior segment of a chromosome breaks off, flips, and reinserts.

Many individuals with apparently balanced structural rearrangements are healthy because they have all of their genetic information some of it is just organized in a different way. However, When these chromosomes pair up to divide to form egg or sperm cells, they often line up improperly. Segments may break off and get lost or two copies of the same chromosome may enter a cell. For this reason, couples often experience multiple miscarriages or may have a child with birth defects and/or mental retardation due to improper chromosome division.

It is known that approximately 3 out of 4 (75%) embryos created by IVF will not be capable of producing a live born child. Some will fail to implant in the uterus, while others will implant, but are unable to carry out early embryonic development. Finally, as in natural pregnancy, approximately 15%-20% of conceptions will be lost as a clinical miscarriage. These numbers are often higher when a member of a couple carries a balanced structural rearrangement.

When does PGD happen in the IVF cycle?
After embryos are created in the laboratory, they are grown for 3 days. On day 3, the PGD biopsy is done and 1 or 2 cells are removed from the embryo. The genetic material inside these cells is tested for abnormalities. On day 5, the woman returns to Genetics & IVF Institute to discuss her PGD test results. Decisions regarding selection of embryos to transfer into the uterus are made with the advice of the medical team.

Is PGD Safe?
Yes. Data from many years of PGD in animals and approximately 1200 live births in humans indicate that PGD does not lead to an increase in birth defects or chromosomal disorders. PGD is done before the embryo’s genetic material becomes ‘active’. Since it is done so early, the cells inside the embryo are still all identical and each cell is capable of becoming any part of a baby. Removal of a few of the cells of the early embryo does not alter the ability of that embryo to develop into a complete, normal pregnancy.

How do they get the cells out of the embryo?

Embryos created in an IVF cycle are cultured in the laboratory for 3 days. By this time they contain approximately 8 cells. Each embryo at this point is called a blastomere. Embryos with normal development on Day 3 will have one or two cells removed for testing in a procedure called a biopsy. The embryos are placed under a powerful microscope and very tiny glass instruments are guided to make a small cut in the zona pellucida, (a tough outer membrane holding the embryo together). Depending on the health and size of the embryo, one or two cells are taken out. The cut then snaps shut and no cells can ‘fall out’ accidentally.

In order to obtain results of the biopsy, the 1-2 cells removed must contain a nucleus, as the nucleus contains the genetic information necessary for testing. If the cell removed has no nucleus or if the nucleus breaks open as it is being prepared, testing is unable to be performed on that cell. Additionally, since embryos are actively growing and dividing, sometimes the cell taken out contains two nuclei. This could mean the cell is abnormal or is caught in the process of division. Testing of these cells may be difficult to interpret.

How exactly is the PGD test done?
PGD testing is different than most genetic testing since it is done on only one or two embryonic cells and must be completed within 48 hours to allow embryo transfer by Day 5. Since standard chromosome analysis takes several days, a different method called fluorescence in-situ hybridization (FISH) is performed.

Each chromosome or large region of a chromosome has unique areas of DNA present only on that chromosome or in that region. A small DNA probe is used to recognize these unique patterns and fluoresce, or light up, when it attaches to the chromosome. Each probe shines light in a different color, allowing several chromosomes (or regions of chromosomes) to be tested at the same time.

A customized set of PGD probes will be selected depending on the particular balanced structural rearrangement. All possible unbalanced rearrangements will be reviewed before a couple begins the IVF process to ensure correct identification of balanced and unbalanced complements. Typically FISH probes are used for the chromosomes involved in the rearrangement. For each of the numbered chromosomes tested two signals (or lights) should appear.

An example of a normal FISH test for a balanced structural rearrangement:

Chromosome 4 telomere  = red Chromosome 22  = orange Chromosome 22 telomere  = green

How are embryos chosen for transfer?
Embryos that have both a normal test result and appearance should be transferred. Sometimes embryos that have normal genetic tests will have a physical problem that prevents them from growing normally. Sometimes embryos that have abnormal genetic tests will appear to be physically normal. The combination of normal genetic testing with normal physical appearance indicates the highest chance of becoming a healthy pregnancy.

What physical characteristics are used to determine normal appearance?
Embryologists give a “score” to the embryo based on the uniform size of the different cells, the number of cell fragments present, as well as other criteria reflecting the physical appearance of the embryo. Embryos that do not have at least 5 cells on day 3 or embryos that are given a poor score rarely go on to successfully implant. While embryo morphology is helpful in picking the best embryos for transfer, it is known that many embryos with significant chromosome abnormalities have normal morphology. Even among embryos that successfully reach an advanced developmental stage (blastocyst), 25% are still chromosomally abnormal Combined with embryo morphology, aneuploidy screening helps select the best embryos for transfer in an IVF cycle.

What if all the healthy embryos are not used?
All decisions about which embryos to transfer and how to use the remaining embryos will be made together with the couple and their doctor(s).

To make an appointment for an initial consultation with one of our reproductive specialists,
please call (800) 654-4363 or (703) 698-7355.

For more information about Genetics & IVF Institute's PGD for aneuploidy,
please call (800) 654-4363 or (703) 698-7355
and ask to speak with the PGD counselor OR email PGD@givf.com.

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