What is Aneuploidy

Aneuploidy is a term used to describe a chromosome problem, such as Down syndrome, that is caused by an extra or missing chromosome. Chromosomes are structures in our cells that carry our genetic information or genes. Normally, we have 46 chromosomes in our cells. The chromosomes come in pairs and are numbered based on their size. The largest chromosome pair is #1 and the smallest is #22. The sex chromosomes are X and Y. Women have two X chromosomes and men have one X and one Y.

We inherit half of our chromosomes (23) from each parent in the egg and sperm. Normally, the egg and sperm come together and form a cell that has 46 chromosomes. This cell divides and forms the embryo and eventually the baby. Cells with 46 chromosomes are called euploid. If the egg or sperm is missing a chromosome (45) or has an extra chromosome (47), this situation is referred to as aneuploidy.

Our Institute is able to test for a total of 11 chromosomes including common aneuploidy conditions involving chromosomes 13, 18, 21, X and Y. Examples include the following conditions:

• Down syndrome is caused by an extra copy of chromosome 21 and is also known as trisomy 21. Down syndrome is associated with mental retardation and other birth defects, such as heart problems.
• Turner syndrome is caused by the absence of one sex chromosome, also known as 45,XO. Approximately 99% of pregnancies affected with Turner syndrome are miscarried.
• Trisomy 18 is due to the presence of an extra copy of chromosome 18 in the baby’s cells. The risk for miscarriage in the pregnancy is increased. Babies born with trisomy 18 have severe mental retardation and other birth defects. The majority of babies do not survive beyond the first few months of life.
• Trisomy 13 is due to the presence of an extra copy of chromosome 13 in the baby’s cells. This condition is similar to trisomy 18 in its severity and outcome.

What is my risk for aneuploidy?

Typically, the risk for aneuploidy increases with a woman's age, regardless of her family or medical history. The theory regarding aneuploidy risk and advancing maternal age is that over time the chromosomes in the egg are less likely to divide properly leading to the egg having an extra or missing chromosome.

The estimated chances for a woman to deliver a child with an aneuploidy condition are as follows:

• At age 30 years - 1/385
• At age 35 years - 1/179
• At age 40 years - 1/63
• At age 45 years - 1/19

However, the frequency of aneuploidy in embryos is much higher than the number of babies born with aneuploidy conditions. The difference in the risk for aneuploidy in embryos versus live borns is due to the fact that a pregnancy with aneuploidy is less likely to attach to the uterus (implant) and has a greater risk for miscarriage.

The estimated percentage of embryos that are affected with aneuploidy are as follows:

• For women between the ages of 35 to 39 years approximately 40% to 50% embryos are abnormal.
• For women 40 years and older, on average, greater than 50% of embryos are abnormal.

The majority of embryos with a missing chromosome will not result in pregnancy and only few of those carrying an extra chromosome will go to term. The lack of implantation and the loss rate of aneuploid embryos are believed to be the main reasons why the pregnancy rate in women over 40 is so low.

The purpose of preimplantation genetic diagnosis for aneuploidy is to increase the pregnancy rate, reduce the number of pregnancy losses, and reduce the number of babies born with aneuploidy conditions.

How do we test for aneuploidy?

PGD for aneuploidy condition is performed by the following two methods:

• Polar Body Analysis (Normal) (Abnormal-Chromosome 21) (Abnormal-Chromosome 18)
• Embryo Biopsy

Polar body analysis indirectly tests the eggs chromosomes. Blastomere analysis examines the embryo directly. The biopsied cells (polar body and/or blastomere) are analyzed using a technique called Fluorescent In Situ Hybridization or FISH. This technique uses probes, or small pieces of DNA labeled with a fluorescent dye, that are a match for the chromosomes we want to analyze. The probes are applied to the biopsied cell and attach to the chromosomes. The fluorescent dye lights up the chromosomes that are being analyzed, and the laboratory can determine if an extra or missing chromosome is present.

Our Institute routinely tests for chromosomes 8, 9, 13, 15, 16, 17, 18, 21, 22, X, Y. However, we are also able to test for other chromosomes, as indicated.

What is the accuracy of the testing?

F.I.S.H. technology is widely available in modern medicine and has a published accuracy rate of 95%. The highest accuracy is obtained by testing both polar bodies and a single cell from the embryo (blastomere), as one would expect the majority of problems with the chromosomes studied to be determined through this sequential testing. The accuracy of polar body analysis is approximately 95%. Testing using only a cell from the embryo (blastomere analysis) has a slightly lower rate of accuracy due to the possibility of mosaicism (more than one cell line) in the embryo. Embryo biopsy and chromosome testing via F.I.S.H. is therefore approximately 90% accurate by itself.

How can aneuploidy testing help me and my family?

We believe PGD for aneuploidy can do the following:

• Increase the implantation rate for IVF patients.
• Lower the risk for miscarriage related to an aneuploidy condition.
• Lower the risk of having a baby with an aneuploidy condition.

It is well known that the pregnancy rate after in-vitro fertilization decreases dramatically with maternal age. Aneuploid embryos have a lower survival rate than normal embryos and the majority seldom implant. It appears likely that the decrease in pregnancy rates with maternal age is in part caused by the increase in aneuploid embryos. By testing embryos for common aneuploid conditions, we may be able to increase the pregnancy rates noticeably.

Aneuploidy is the cause in 50% or more of pregnancy losses. By testing for common aneuploidy conditions, the risk for miscarriage should decrease. At our clinic, we have found that the increase in implantation rate and the decrease in miscarriages has resulted in a significant increase in ongoing pregnancies and healthy babies delivered by our patients.

Does PGD replace prenatal testing?

No, PGD does not replace prenatal testing, such as chorionic villus sampling or amniocentesis. We recommend that prenatal testing be performed in the resultant pregnancy via chorionic villus sampling or amniocentesis in order to confirm our diagnosis from PGD and to rule out other aneuploidy condition not tested by PGD, as this is the standard-of-care. Our genetic counselors can discuss what prenatal testing options are available to you.

Next Steps:

Please review our PGD information packet and pamphets and contact our
genetic counselors at 773-472-4900 or rgi@flash.net with any questions or inquiries
regarding our PGD program.

• Aneuploidy Pamphlet
• Aneuploidy Packet