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PGD/PGS: 23 Chromosome Microarray - How is it done?

In order for the genetic makeup of an embryo to be determined prior to the time of embryo transfer there are two separate steps, which are important. The first of these is embryo biopsy. In most clinics doing PGD/PGS, the embryo is biopsied on the third day following oocyte retrieval when it is at the six to eight cell stage. The procedure used is similar to that for Assisted Hatching (AH) where an opening is made in the outer shell of the embryo. The opening is somewhat larger than the one made for Assisted Hatching because it is necessary to remove one cell from the embryo for testing. This is an extremely delicate procedure, for the removal of cells from an embryo at this stage may result in damage to the embryo that prevents it from developing further. Many clinics are still using acid to make this hole in the embryo wall. Arizona Center for Fertility Studies has done thousands of embryo biopsies without ever damaging a single embryo. It is done by state-of-the-art laser directed biopsy, not acid. If the embryo has been biopsied on day 3, there is about 48 hours for the testing to be completed before the embryo must be transferred. The embryo is allowed to develop to the blastocyst stage during this 48-hour period. There are relatively few laboratories in the United States that have the ability to do 23-chromosome microarray testing once the cells have been obtained. Therefore, it is common for the ART laboratory to transport the cells to the laboratory that it uses for testing. The 23-chromosome microarray is performed during the 48 hours that the embryo is developing to the blastocyst stage.

Laser Assisted Embryo Hatching

Picture of a day 3 eight-cell embryo about to undergo laser-assisted hatching (arrow, round marker, indicates where the laser beam will penetrate the zona pellucida)

Video of Arizona Center for Fertility Studies embryologist doing assisted hatching using the laser to remove a single cell or blastomere for chromosome testing and sex selection.

Alternatively, cells can be removed from embryos at the blastocyst stage. Arizona Center for Fertility Studies is one of a handful of clinics in the country that can safely biopsy cells from a blastocyst (TE or trophectoderm biopsy). This allows more cells to be used for testing but requires freezing of the embryos after biopsy since the results of the genetic testing could not be obtained before the embryo transfer must be performed.

Trophectoderm Biopsy of Blastocyst

TE or trophectoderm biopsy of a normal looking blastocyst at Arizona Center for Fertility Studies ART-IVF laboratory.

Video of Arizona Center for Fertility Studies embryologist doing a trophectoderm biopsy using the laser for chromosome testing and sex selection

Up to now, chromosomally abnormal embryos detected by either FISH (old technology) or 23-chromosome microarray (what Arizona Center for Fertility Studies considers to be state-of-the-art technology) are not recommended for transfer and are to be discarded. There is some speculation and early preliminary data to suggest that a chromosomally abnormal day 3 embryos may "self-correct" or normalize by the blastocyst stage.

Arizona Center for Fertility Studies was one of 4 major clinics that participated in what may be the first, or one of the first, studies to show that abnormal day 3 embryos can "self-correct" by the time they reach a blastocyst stage embryo. Arizona Center for Fertility Studies initial data and our follow-up data clearly show that embryos biopsied on day 3 that come back abnormal on day 5, but made nice looking blastocysts; when re-biopsied, using laser directed trophoectoderm (TE) biopsy, had a high percentage of "self-correction". Arizona Center for Fertility Studies has observed that there is a high percentage of "self-correction" if "abnormal" day 3 embryos developmentally make a nice looking day 5-6 blastocyst. "Self-correction" probably does not occur if day 3 embryos fail to develop normally. This makes sense since a normal complement of chromosomes is needed to direct normal morphologic development of an embryo. In summary, if abnormal day 3 embryos produce developmentally normal appearing blastocysts, Arizona Center for Fertility Studies now has evidence that the embryo may have "self-corrected" and is chromosomally competent.

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