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Technical limitations may be one of the largest obstacles to applying PGS.

Practice Committee of the Society for Assisted Reproductive Technology; Practice Committee of the American Society for Reproductive Medicine. Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril. 2007;88:1497-1504.

FISH probes can be chosen to reflect the nature of a given patient's risk (advanced maternal age, recurrent pregnancy loss) when performing PGS, but the technique itself is limited by the number of probe sites that can be interpreted accurately at one time. Typically, analysis of more than five chromosomes requires two cycles of hybridization, with their associated time requirement and potential for degradation of the single cell.

Alternatively, advances in the analysis of all 23 chromosomes through comparative genomic hybridization may, ultimately, provide an avenue for applying PGS. At the moment, time limitations prohibit comparative genomic hybridization without embryo cryopreservation. Further investigation of other technical limitations, such as the high rate of mosaicism, has revealed that, when two cells are examined and found to be karyotypically discordant, further analysis of the entire embryo will reveal that more than 50% of embryos are, in fact, euploid--that is, chromosomally normal. Random biopsy of the abnormal cell solely would relegate the embryo to nontransfer, despite the predominance of an underlying euploid state.

Understanding of the potential that embryos have to self-correct early mosaicism is growing; we now know that almost one half of embryos identified as aneuploid at cleavage stage correct to euploid if they survive to blastocyst stage. A karyotypic abnormality in a single cell from a day-3 embryo does not always signal an abnormal embryo.

ASRM does not support PGS to improve the live birth rate

This determination by ASRM is based on available evidence about advanced maternal age, recurrent pregnancy loss, recurrent implantation failure, and recurrent aneuploidy loss:

* In women of advanced maternal age, many day-3 embryos display aneuploidy when studied by FISH. In theory, exclusion of these embryos for transfer should improve implantation and live birth rates, but evidence does not support that premise.

* Because almost 70% of spontaneous pregnancy loss is caused by a karyotypic abnormality, and women with karyotypically recurrent pregnancy loss are more likely to experience subsequent loss with karyotype abnormalities, the premise of preimplantation screening for aneuploidy also appeared to be well founded. Studies at this time are limited to retrospective series, without randomized controlled trials published.

* Among women who experience repeated implantation failure, a finding of more than 50% abnormal embryos isn't uncommon, yet several studies have not supported an increased implantation rate or live birth rate after PGS.

FAST TRACK

We've learned that embryos have the potential to self-correct early mosaicism. With PGS, therefore, random biopsy solely of an abnormal cell would relegate a potentially euploid embryo to nontransfer

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Title Annotation:UPDATE: prenatal counseling; preimplantation genetic screening
Publication:OBG Management
Date:Jan 1, 2009
Words:447
Previous Article:PGS for women at increased risk of aneuploidy isn't supported by evidence; consider it investigational.
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