Preimplantation genetic screening (PGS) or comprehensive chromosomes screening (CCS) has been renamed as preimplantation genetic testing (PGT). It has become a daily practice in many infertility worldwide. This technique allows chromosomal evaluation of the embryos, with more or less diagnostic accuracy. The biopsy procedure involves one or more cells of an embryo, in the context of an assisted reproduction treatment, the genetic analysis of the obtained cells and then the transfer pf these normal embryos.
The availability of this technology, which is growing, raises questions both to physicians and patients about the benefits and limitations of PGS/PGT.
All the variants of PGS/PGT have found a wide spectrum of results. These vary according to the day of embryo biopsy (whether cleavage stage -in day 2 or 3- or blastocyst stage -day 5 or 6), and according to the technology used for the genetic evaluation: in vitro fluorescence hybridization (FISH), microarrays, quantitative PCR (qPCR) or the more modern genome sequencing.
While there is considerable consensus on the indications of preimplantation genetic diagnosis (PGD) especially for the detection of a monogenic disorder or an already known parental balanced translocation, this is less clear for the PGS/PGT, which has several potential indications, ranging from recurrent miscarriages or repeated implantation failure to a wider use in women with advanced reproductive age or even the proposed use of the PGS in all cases.
What we aery know is that PGS/PGT reduces the time to pregnancy and decreases the risk of miscarriage. Both of them are outcomes very important for our patients.
In the early days, the preimplantation genetic tests were performed with FISH, with mixed results. Most platforms used centromeric and telomeric FISH probes, unable to differentiate normal chromosomes from balanced chromosomal rearrangements. This technology has also significant limitations that coming from errors in hybridization where fluorescent signals are underestimated or overestimated. These errors depend considerably from the experience of the operator. Another important limitation is that, in many cases, not all chromosomes are evaluated and, therefore, some chromosome aneuploidies could be ignored. For a long time, FISH was performed with biopsies on day 3, with similar or even worse outcomes then for cases without PGS. Only those centers with a large number of annual cases published favorable results. These inconsistencies between publications and results in other centers, limited the use of this technology in the past.
In recent years, there have been at least two significant changes. One related to the day of embryo biopsy, which currently takes place on blastocyst stage, at day 5 or 6. The other is related with the genetic platform used: the advent of microarrays, both as SNP microarrays or microarray hybridization comparative genomics (aCGH) and qPCR to assess unbalanced chromosomal aberrations in all the chromosomes. (4) With these changes, PGS started to be used in most infertility centers with significant increases in implantation rates, which made it a routine treatment and led to rethink which the appropriate indications should be.\nToday, a new platform that has yet to be evaluated in greater depth appears: genetic sequencing (Next-Generation Sequencing -NGS-), which is a tool that would potentially have a greater diagnostic accuracy.
The most recent systematic review about PGS, published by Dahdouh et al, found 3 randomized controlled trials (= 659) evaluating PGS with aCGH or qPCR, always with biopsies on day 5-6.
It shows that both the implementation rate (ie, number of gestational sacs over the number of embryos transferred) and ongoing pregnancy rate per embryo transfer are significantly higher (39% more, with an interval confidence between 20% and 60%). The 3 studies were conducted in good prognostic couples.
We should note that, when talking about PGS, the success rates are usually reported with a denominator (embryo transfer)that is not ideal in studies about reproductive medicine, as it might mislead the reader about the effectiveness of this technology. While it is expected to have an increased transfer effectiveness when doing a better embryo selection, we should emphasize that it is not expected that this technology increases live birth rate per cycle. This means that the available evidence shows that there would’t be more likelihood to achieve a live birth by using PGS, but rather, the result would be reached faster (shortening what is known as ”time to pregnancy”). This is not an irrelevant detail.
Let’s talk deeper on the above mentioned concept. PGS does have an economic cost and that variable should be discussed with patients. This is important because it means that any advantage should be contrasted against these and other potential disadvantages. PGS allows you to pick one or more embryos among the whole cohort. What would happen if PGS is not used? We could delay the achievement of the objective.
On the other hand, we must also say that no good quality studies have evaluated the use of PGS in other sub-populations to identify whether any particular group would be particularly beneficial.
Finally, it recognizes an additional advantage for the PGS, which is to encourage more couples to the choice of an elective single embryo transfer, given the evidence of increased implantation rates. The attached image shows how implantation rates remain the same at different ages in cases of chromosomally normal embryos, while rates significantly decrease with age when the embryos are not evaluated with PGS.
In 2015, the Canadian Society of Obstetrics and Gynecology published a report with recommendations based on published evidence: