Is PGS Testing Flawed??
"If we didn't have genetic mutations we wouldn't have us. You need error to open the door to the adjacent posssible."
As you begin to emerse yourself into everything fertility, you probably have come across PGS and PGD testing of the embryo. If you were like me your first thought was really? another set of acronyms? So what is PGS or PGD testing?
PGS, or preimplantation genetic screening, is a genetic test performed on embryos produced through IVF. PGS test for aneuploidy (Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46) is a powerful genetic test to screen for numerical chromosomal abnormalities. PGS is performed on a small embryo biopsy prior to transfer and identifies which embryos are chromosomoally normal. PGS gives information about embryos’ genetic health to help your care team select the best embryo for transfer and improve your chance of achieving a successful pregnancy.
“Information is not knowledge.”
Preimplantation genetic diagnosis (PGD) is a procedure used prior to implantation to help identify genetic defects within embryos. This serves to prevent certain genetic diseases or disorders from being passed on to the child. The embryos used in PGD are usually created during the process of in vitro fertilization (IVF).
Now that we know what both of these are how to we decide if PGS testing is worth the added cost?
The PGD and PGS forms of preimplantation genetic testing were developed to prevent transfer during in vitro fertilization (IVF) of genetically abnormal embryos into the uterus. Depending on maternal age and reproductive history (recurrent miscarriages) in approximately 35 to 85 percent of IVF cases, the embryos have flawed chromosomal composition and result in failed pregnancies.
By identifying in the embryo a condition known as aneuploidy or a specific genetic disorder the parents are at risk of carrying, preimplantation genetic testing has dramatically improved the success rates of IVF, increasing successful pregnancies and births of healthy infants.
Preimplantation genetic testing began in 1990 to evaluate embryos created through IVF for genetic traits known to exist in parental DNA. This early form of preimplantation testing expanded to include preimplantation genetic screening (PGS) for aneuploidy (also calle Comprehensive chromosomal screening), a significant reason for pregnancy failure in IVF. PGS evaluates for the same genetic problems sometimes searched for in normal pregnancies using any of three prenatal tests: chronic villus sampling, amniocentesis and cell-free DNA testing.
Both PGS and PGD are often recommended for people who have experienced infertility, have had recurrent loss of pregnancy through miscarriage, or have had unsuccessful IVF treatment.
The most damaging to many IVF patients, is the results of PGS testing. Over the years PGS testing has been improving IVF outcomes (i.e live birth rates) and decreasing miscarriage rates, providing necessary information about the health and overall egg quality. More recently, we are seeing why PGS can't deliver on the promised outcome expected. By demonstrating that the technique of trophectoderm biopsy at blastocyst stage of embryos is highly inaccurate leading to many false-positive diagnoses and therefore, to the mistaken discarding of many embryos with normal pregnancy potential.
After reporting the first chromosomally normal births from transfer of allegedly chromosomally abnormal embryos at Center for Human Reproduction, at last count 17 healthy children have so far been delivered from transfers of such embryos here in the U.S. and in Europe. More importantly, not a single chromosomally abnormal pregnancy has been reported after such transfers. There is no stronger evidence for the inadequacy of PGS and, indeed, for the potential damage to many patients who undergo PGS because, by discarding false-positive, allegedly chromosomally abnormal embryos, they may be discarding the patients’ last pregnancy chances.
Damages to such patients are further aggravated when, as is often the case, colleagues then conclude that such patients should advance into egg donation since they no longer are able to produce chromosomally normal embryos. Such patients, therefore, not only were deprived of transfers of perfectly normal embryos but, because of that false-positive PGS diagnosis, also end up prematurely being pushed into egg donation
“Miracles start to happen when you give as much energy to your dreams as you do to your fears.”
New recommendations from the PGDIS
With so many healthy children born in a number of centers around the world after transfer of allegedly chromosomally abnormal embryos, even the most ardent proponents of PGS had to acknowledge that their prior claims no longer held water. The so-called Preimplantation Genetic Diagnosis International Society (PGDIS), a “club” of PGS laboratories and PGS proponents, therefore, on July 19, 2016 issued in their newsletter a “Position Statement on Chromosome Mosaicism and Preimplantation Aneuploidy Testing at the Blastocyst Stage.” By issuing brand new “recommendations for PGS laboratories,” new “recommendations for clinicians” and “guidelines to prioritize mosaic embryo transfer,” the society basically implicitly refuted all of their own prior recommendations how PGS should be performed.
The only aspect of this announcement more surprising than that it was even published was its content. It, even more blatantly than in earlier misrepresentations from this society, demonstrated to what degree the PGS industry has been driven by economic rather than scientific considerations. And here is why: In their revised recommendations for laboratories, the society, suddenly, discovered that “only validated Next Generation Sequencing (NGS) that can quantitatively measure copy numbers should be used for measurement of mosaicism in biopsy samples. Ideally, that should be NGS methodology that can accurately and reproducibly measure 20% mosaicism in a known sample.”
Though, of course, never spelled out in the newsletter, this implies that PGS laboratories, which up to now used other platforms than NGS, or utilized NGS platforms with even higher than 20% sensitivity levels for mosaicism, have for years been reporting highly inaccurate results, likely leading to the discarding of large numbers of perfectly normal embryos. In the U.S. a majority of PGS laboratories for the longest time did not use NGS platforms, including some of the largest-volume laboratories. Some of these laboratories also generated the most widely cited papers supportive of PGS in the literature
In conclusion, even the most interested proponents of PGS in the new PGDIS recommendations acknowlege how useless and misleading their past diagnostic approaches to PGS have been. Yet, still, even with the new recommendations many fertility clinics fail to acknowledge, that in early stage embryos, as single bipsy of a few cells cannot accurately tell the chromosomal status of an embryo. Therefore, PGS is clinically a worthless procedure because a single biopsy can not determine if an embryo can be transferred or if it should be discarded.
With the new PGDIS recommendations are not going far enough, since what is know, and assuming that PGDIS considers the best interest of patients as their first priority, their new recommendations should have been just that. Until more studies can demonstrate otherwise, PGS should no longer be used in an attempt to improve live birth rates in IVF and or to reduce miscarriage rates.
It is my honest belief from experience in having only 6 embryos, 5 of those embryos made it to day five. My husband and I choose to do PGS testing due to our age and all of our embryos came back abnormal. Had I taken the time to do some research before hand, we would NOT had PGS testing done. Today we could have a beautiful healthy baby in our lives instead of being hurt not only financially, but still wanting to persue a family. I believe that any fertility clinic that offers and pushes PGS testing need to offer an acknowledgement of error in PGS testing as it is flawed. It is one thing not to know better; it is another for fertility clinics to continue on the same track with knowledge they have that PGS testing needs to be better studied and needs to be removed from the market.
Save your money for baby supplies, cribs, and things for that precious gift that you may have had disposed of due to inaccurate PGS testing!
Want new articles before they get published?
Subscribe to our Awesome Newsletter.