Aneuploidy Screening | emBIO IVF Center

Aneuploidy Screening

What is PGD for aneuploidy?

Aneuploidy screening minimizes the chance that a transferred embryo has a chromosome abnormality. Learn more about chromosomes and genes.

The most common chromosome abnormalities in miscarriages include:

  • trisomy (3 copies of a chromosome) or monosomy (one copy of a chromosome) for chromosomes 13, 15, 16, 18, 21, or 22
  • triploidy (3 copies of all the chromosomes)
  • abnormalities of the sex chromosomes.

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 be unable to carry out early embryonic development. Finally, as in natural pregnancy, approximately 15%-20% of conceptions will be lost as a clinical miscarriage. While there are many reasons for the failure of an embryo to make a baby, the single most important factor is an abnormality of the chromosomes.

Similarly, for most couples, a significant number of the embryos created by IVF will have chromosome abnormalities. The exact percentage of chromosomally abnormal embryos that each couple produces is related to many factors, including maternal age, number of failed IVF cycles, and the type of sperm used. In addition, a certain percentage of abnormalities is because IVF is not a natural process, and hyperstimulation of the ovaries produces an increased percentage of chromosomally abnormal eggs.

DNA Microarray Analysis for Accurate Detection of Aneuploidy

Via the microarray technique, we can examine all 24 chromosomes. That's a great improvement compared to what we could do before. More specifically, before the DNA microarray technology, we could only examine a limited number of chromosomes.

A huge advantage of the microarray technology is that we can have the results of the microarray data analysis in just one or two days, so we can transfer fresh embryos instead of a FET (frozen embryo transfer).

Microarray testing has increased live birth rates per cycle since an aneuploid embryo may be detected in every IVF cycle.


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 EMBIO to discuss her PGD test results. Our medical team will help her decide how many embryos will be transferred into her uterus.

Is PGD Safe?

Yes. Data from many years of PGD in animals and approximately 1200 live births in humans indicate that PGD does not increase 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 early embryo cells does not alter that embryo's ability to develop into a complete, normal pregnancy.

How do they get the cells out of the embryo?

Biopsy

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.

To obtain the biopsy results, 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 cannot 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 division process. Testing of these cells may be difficult to interpret.

How exactly is the PGD test done?

PGD testing differs from 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 has unique areas of DNA present only on that chromosome. 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 a light with a different colour, allowing several chromosomes to be tested simultaneously. This technique is called FISH. EMBIO uses FISH for chromosomes 13, 15, 16, 18, 21, 22, X and Y because these are the most commonly abnormal chromosomes. A normal cell should show 2 FISH signals (or lights) for each numbered chromosome, and either 2 X signals for a female or 1 X and 1 Y signals for a male. Only five different colours can be used, so most tests are done in two parts. The first 5 chromosomes are tested, those probes are washed off, and the remaining chromosomes are tested. The washing process can affect the integrity of each chromosome; therefore, a maximum of two cycles of FISH are used per cell. For this reason, every chromosome can not be tested.

pgd3

Color / Chromosome
Red = 13
Aqua = 16
Blue = 18
Green =  21
Gold = 22

An example of a normal FISH aneuploidy test showing two copies of each of the tested chromosomes:

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 a normal physical appearance indicates the highest chance of having 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, and 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 the successful implant. While embryo morphology helps pick 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 +30 2106774104.

For more information about Genetics & IVF Institute's PGD for aneuploidy, please call +30 2106774104 and ask to speak with the PGD counsellor or email Dr Paraschos.

Karyomapping, a revolutionary genetic test

Scientists developed a revolutionary test that will allow future parents to test their embryos for almost all known genetic diseases. Karyomapping is based on the same procedure as PGD (the same doctor developed it). Still, it can detect all known genetic diseases in embryos within a few weeks (the only exceptions are those that appear suddenly due to an accidental mutation).

What would you like to ask our PGD specialist?

The following questions may help you state your problem to EmBIO's PGD specialist.

  • Are you a woman over 35?
  • Have you experienced several miscarriages?
  • Have you had a prior pregnancy with a chromosome abnormality?
  • Have you experienced several failed IVF cycles?
  • Has conceiving been difficult due to a low sperm count?
  • Do you or your partner carry a balanced structural chromosome rearrangement?
  • Do you have a family history of Huntington's disease?
  • Do you or your partner carry a recessive genetic disease such as cystic fibrosis?
  • Do you or your partner carry an X-linked genetic disease such as hemophilia or Duchenne Muscular Dystrophy?
  • Do you want to balance the gender in your family (select the gender of your embryo)?

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