What is aneuploidy?

January 24, 2011Carole 1 Comment »

The term aneuploidy gets thrown around a lot to explain infertility, particularly infertility associated with advanced maternal age. Wikipedia does a pretty good job of defining aneuploidy. Aneuploidy is an abnormal number of chromosomes in a cell.

This begs the question,  “What is the normal number of chromosomes in a cell?” In humans, twenty three pairs of chromosomes  or 46 total chromosomes is the correct answer for all cells EXCEPT gametes, but we’ll get to sperm and eggs in a minute. Your average non-gamete body cell has 23 pairs of chromosomes because each type of chromosome (autosomes numbered 1-22,  and gender-determining sex chromosomes  that come in X and Y flavors) are inherited in sets, one from your mom, the other one from your dad.

Gender determination. If you are female, you got two X’s, one from each parent. If you  are male, you got an X from your mom and a Y from your Dad. Any particular sperm from Dad carries EITHER an X or Y. Because of this, Dads determine the gender of their offspring because Mom can only pass on an X chromosome through her egg and Dad’s sperm can pass on EITHER an X or Y. If the egg gets fertilized by a Y-bearing sperm, it’s a boy. If the egg is fertilized by an X-bearing sperm, it’s a girl.

Aneuploidy is a cellular condition in which instead of two chromosomes, you have either a missing or extra chromosome for one of the autosomes (1-22) or sex chromosomes. A variety of genetic abnormalities that cause problems can be traced to aneuploidy. Here are some examples.

Trisomy 21, an extra (third) chromosome at location 21 causes Down’s Syndrome.

Trisomy 13, an extra (third) chromosome at location 13 cause Patau Syndrome.

Trisomy 18, as extra chromosome at location 18 causes Edwards Syndrome.

These trisomies (21, 13 and 18) are compatible with life but people with these abnormalities often suffer from multiple health conditions, which vary in their severity. Sometimes an individual will have a mixture of cell types in their bodies, some cells have a normal chromosomal number and some cells have an abnormal chromosomal number- called genetic mosaicism. The presence of genetic mosaicism and which chromosomes are affected are factors that can influence the extent of health related problems an individual may experience.

However, many other aneuploidies are not compatible with life. Embryos with aneuploidy often do not implant or if they do implant, are unable to go the distance and the pregnancies fail relatively early in the first trimester. Based on genetic analysis of tissue from miscarriages, aneuploidies are often the culprit in first trimester losses.

Aneuploidies can occur with the sex chromosomes too. For instance, if a person is missing all or part of the X chromosome (XO, instead of XX), they will be female but suffer from Turner Syndrome and may have many health conditions, including infertility. Klinefelter’s syndrome is a condition in males where they have an extra X chromosome (XXY). There is another condition in males in which two Ys and one X are present called XYY Syndrome, which has no symptoms and is often not detected unless a karyotype is done.

What causes aneuploidy? Aneuploidy can arise in gametes during the production process in either the testis or the ovary. When sperm and eggs are produced, the parental DNA is not just copied for the daughter cells but is also reshuffled and pairs of chromosomes are split and only a single chromosome of the pair is passed onto the gamete. This makes sense if you think about it, because you want the sperm and egg to have only one pair of each so when they are united, the resulting embryo has a complete pair of choromosomes for that location, one from Mom and one from Dad. Sometimes, the splitting and sorting of chromosomes into the gamete doesn’t work right and the resultant gamete gets none of that chromosome or both of that chromosome. So when fertilization does occur with that gamete, the embryo gets no chromosome from one parent or two chromosomes from one parent, instead of one from each.

You can see a  You Tube video of non-disjunction of chromotids or failure of the chromosome pairs to separate during meiosis.



As women age, the eggs they produce are more likely to be aneuploid due to mistakes in the final stages of egg production. Why are these mistakes more common? I don’t know but it seems to be an unavoidable consequence of aging. Chromosomally speaking, we should have our children in our twenties or early thirties. Unfortunately, various social and personal factors are often barriers to earlier reproduction.

Some clinics will offer perimplantation genetic screening (PGS) to their older patients. PGS involves IVF to create embryos, embryo biopsy to test a cell for aneuploidy and then removing from the transfer pool any embryos that are chromosomally abnormal.

PGS, while theoretically sound, runs into some practical problems. Sometimes the 8-12 cells of the embryo at biopsy are not identical in having or lacking aneuploidy. Just by chance, you may test the one cell that has or doesn’t have aneuploidy and report an incorrect result, resulting in transferring an abnormal embryo (false negative result) or discarding anormal embryo (false positive result). Some clinics will biopsy two cells to check for mosaicism. Taking two cells increases the potential for trauma to the embryo and may reduce pregnancy rates in some cases. Newer methods like trophectoderm biopsy on day 5 of culture and microarray analysis may alleviate some of the practical problems with the application of PGS.  Two previous posts talk about these newer technologies and PGS.

Genetic testing on embryos: current benefits from PGS less than hoped


Genetic testing part two: Microarray assays may deliver on clinical promise


As egg freezing becomes more reliable, and if the cost of egg cryopreservation and IVF goes down, we may see a time in which young women in their twenties routinely freeze some of their eggs to quiet the ticking of their biological clock while they pursue careers or wait for Mr. Right to come into their lives.

© 2011 – 2015, Carole. All rights reserved.

One response to this entry

  • Tite Says:

    Because I am 43, my husband and I illiiatny chose to use an egg donor to try to achieve a pregnancy. My biological son from a previous marriage was born 10 years ago, and I had a healthy pregnancy with him. I understand how devastating it is to be informed that you have a positive pregnancy test with a very low beta hcg level. This has happened to us twice. For our first cycle, we used donor eggs that developed into just 4 poor quality embryos. We transferred all 4, and had a positive pregnancy test with a level of 15 that decreased within a few days. We recently used a new donor, which resulted in eleven excellent quality embryos. We transferred two A quality embryos on Day 5, and put the remaining nine in storage. Again, our pregnancy test came back with another low level of 6. We were dumbfounded as to how this could have happened to us twice. My hormone levels and uterine lining were fine during both cycles, and just prior to each transfer. We would like to do a cycle with our frozen embryos, but we are totally gun-shy at this point that we will have yet another biochemical pregnancy. Perhaps we should try to transfer three or four embryos next time to see if that would produce better results. My heart goes out to all of you that have a similar experience. I understand firsthand how devastating it is. I have found very little information on the internet with regard to causes of biochemical pregnancies. I welcome feedback that anyone might have.

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