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PGS is Harmful for Women with Low Ovarian Reserve

The Center for Human Reproduction’s Dr. David H. Barad explains why attempting pre-implantation genetic screening (PGS) actually does more harm than good for women with low functional ovarian reserve (LFOR).

When you try the one-size-fits-all approach to the typical patient who comes to CHR (who may or may not produce more than 2, 3, or 4 embryos), the problem is that most of the said patients have very few embryos and may never get to a stage that could be biopsied. Then once you biopsy it – you aren’t testing the cells that are going to be the baby – you are testing the cells that are going to be the placenta. Placenta is known to be the repository of all the odd cells that pop-up in the pregnancy, so they actually get segregated. The normal ones end up being the baby – the abnormal ones are kind of being pushed out into the trophectoderm. In fact, placental cells many times have more than one nucleus, and so by definition they will have bizarre karyotypes if you are looking at their chromosomes. The other thing is, you can think of the trophectoderm as being more like a quilt than like a mosaic. Certain patches of the trophectoderm are probably descended from a particular cell. Even though you are testing four or five cells, they are probably all daughter cells of the same progenitor. Therefore there may be other cells that are normal that you are not testing, more like a patch in the mosaic, but the technical term for an embryo that has more than one set of genes, is a mosaic. What that means is that the cells that you test may not reflect the genetic health of the inner-cell mass, which is going to be the baby (many times they will). The centers that have been doing these studies have shown that when they have a normal result, they are very likely to end up with a normal baby. However, the rub comes when you get an abnormal result, because the abnormal result may not reflect what’s true of the baby. In fact, one of the centers has recently published data, where they looked carefully at the embryos that they had deemed to be abnormal. They found that 23% of the time, repeat biopsies didn’t show the same result as the original abnormal biopsy (this is that mosaic state). What happens over time is that the normal cells have a tendency to take over and to prevail. It’s very rare that the abnormal cells will grow out and actually become and ongoing pregnancy. The net effect is that when you are dealing with a group of patients – who are very likely to have some degree of genetic abnormality (where those genetic abnormalities are segregated into the area that is going to be biopsied) – you end up with a large number of people who start cycles and never have transfers. In fact, I think they have shown that 60-80% of patients in the age group that we usually take care of will never get to transfer.