EFA.MC.2017.“The Abnormal Embryos That Aren’t”,“Tens of thousands of women thought they couldn't have babies: But what if they could.”Dr. Norbert Gleicher Dr. Monica Halem

Preimplantation genetic screening may be misleading many women into thinking that they cannot conceive.

Key Points

Highlights:

• Preimplantation genetic screening (PGS) is not 100 percent reliable in deciding whether or not an embryo will lead to a successful pregnancy.

Importance:

• Many women whose fertility is compromised might be missing out on the chance of becoming pregnant based on the results of the preimplantation genetic screening.

Key points:

• Preimplantation genetic screening is only a hypothesis that has never been proven.
• Cells that are collected from an embryo to be tested are usually part of what will give rise to the placenta and may not reflect the health of the embryo itself.
• Aneuploidy or an abnormal number of chromosomes may be helping with the imputation of the embryo.
• An embryo can eliminate cells with an abnormal number of chromosomes and ensure that only healthy cells go on to divide and develop into a baby.

Lay Summary

The presentation started with the story of Monica Halem who had endometriosis and had been trying to conceive using in vitro fertilization VF), but was told that none of her fertilized embryos would be viable based on pre-implantation genetic screening or PGS.

PGS is a genetic test developed by Dr. Verlinsky and colleagues in 1990 and used on embryos produced by IVF that looks for aneuploidy or incorrect number of chromosomes in the cells making up the embryo. Aneuploidy is the primary cause of miscarriage, therefore not using embryos that are aneuploid increases the success rate of IVF.  

However, Halem found a fertility clinic where she was told that sometimes embryos that appear to be abnormal with PGS could actually lead to successful pregnancies. Halem decided to “give it a try,” had some of her “abnormal” embryos transferred, and became pregnant.

“I have a 20-month-old daughter from an abnormal embryo that was PG tested that would've never been here had it not been for people …who think out of the box that this PGD testing is not 100% [reliable]”, Halem added.

The second part of the presentation was by Dr. Norbert Gleicher, a fertility physician at The Centre for Human Reproduction in New York City. 

Dr. Gleicher stressed that PGS is a hypothesis that has “never been proven.” According to Gleicher, there have been three “versions” of the test since it started being used in 2000. In what Dr. Gleicher called version 1, the test used embryo biopsies, where few cells were being removed from embryos that were three days old and had just six to eight cells to test for chromosomal abnormalities. This was followed by version 2, used between 2008 and 2017 where a blastocysts biopsy was being used. A blastocyst is a five-day-old embryo made of around 200 cells. Since July 2017, the third version of PGS has been in rigor, called preimplantation genetic testing for aneuploidy (PGTA). 

According to Dr. Gleicher, “An embryo biopsy cannot determine whether or not the embryo is chromosomally normal. Therefore, the test cannot be used to decide whether to transfer or discard an embryo.” 

Dr. Gleicher then said that close to a hundred healthy pregnancies worldwide have been possible from what appeared to be chromosomally abnormal embryos from PGS. So, now embryos are grouped into one of three categories: those that are normal, those that are mosaic, and those that are abnormal or aneuploid. However, the cut off points of which group an embryo falls into depending on the percentage of aneuploidy is not very clear.  

However, because during a biopsy most of the cells to be analyzed come from the trophectoderm which will go on to form the placenta, the test does not provide information about the health of the future embryo at all, Dr. Gleicher went on to explain. In fact, he added that it is very common for the normal placenta to have genetically abnormal cell islands and that aneuploidy or mosaicism could be helping with the implantation of the embryo. Finally, the inner cell mass that will give rise to the embryo can self-correct by eliminating abnormal cells via a biological mechanism known as programmed cell death.

Dr. Gleicher concluded by reporting that in collaboration with mathematicians at the Rockefeller Institute for Medical Research they have demonstrated that it is not possible to come to a conclusion about the chromosomal abnormality of an embryo based on a biopsy from just five or six cells.