There are not yet randomized controlled studies that support the claim that PGS improves IVF outcome, particularly when outcome analysis have as reference point the cycle start.
It is well understood that the gradual decline in human natural and assisted reproduction fecundity, after the age of 35, is based on the relative gradual increase of embryo genetic abnormalities. The “natural” experiment of egg donation from donors younger than 35y characteristically depicts that fecundity rate depends on oocyte age, and can remain steadily stable at any age of embryo recipient.
These observations have led to an attractively reasonable hypothesis that if we can eliminate aneuploid embryos and transfer only euploid ones, we could improve IVF outcome, particularly in older women. This is the pivotal assumption behind the application of preimplantation genetic screening (PGS) as an add–on in IVF procedures. Although this is a very simple and logical hypothesis, when discussing with couples at an IVF decision making analysis or commenting on a failed IVF cycle, on a clinical level, it is quite complicated to be communicated, as it assumes many scientific uncertainties, still unproven at a randomized clinical trial level.
PGS following a standard IVF procedure involves many additional steps, including blastocyst culture, embryo biopsy of the outer embryonic cell mass, complicated total chromosomal number analysis in a specialized genetic lab. Meanwhile, all those blastocysts must be vitrified. Then, only those with a normal set of chromosomes, if any, are thawed and must survive in order to be transferred in a natural or artificial cycle. Therefore PGS increases the steps from egg retrieval to embryo transfer, which logically increases the probabilities for missteps and mishandling each procedure and dramatically increases the cost of the IVF. A true cost benefit analysis has not yet been seen.
Exaggerated claims of better IVF outcomes can easily generate more and persistent negative feelings
As more data about PGS is accumulated, we will address, as simply as possible, some issues regarding clinical utility of modern PGS. These are:
1. Biopsies are done on the external cell mass of the blastocyst which is dedicated for placental development, while the internal cell mass is destined for embryo formation. Nature very frequently has euploid and aneuploid cells mixed together in a term called mosaicism. Finding aneuploid cells in the external cell mass of the blastocyst, particularly at only one biopsy, does not for certain reflect that the embryo will be abnormal. Therefor we might wrongly rejected as abnormal a potentially euploid embryo.
2. Studies of multiple blastocyst biopsies have demonstrated divergence of ploidy results between multiple biopsies of the same embryo at the same laboratories, and even higher divergence between biopsies in different laboratories.
3. Another interesting feature of the embryo is its ability to self-correct as it grows beyond the blastocyst stage, meaning that the euploid cell lines may become prevalent and result in development of a genetically normal embryo.
4. Biopsy of a large number of cells of the blastocyst might impair its ability for implantation.
Risks and benefits must extensively communicate with our patients regardless of the puzzling nature of this intervention
Advances in biotechnology are very exiting. In our time, PGS is a complicated and quite expensive add-on of the IVF procedure, not showing a clear benefit for our patients, but evidence that it may be harmful in terms of live births rate per cycle initiated. Risks and benefits must extensively be communicated with our patients regardless of the puzzling nature of this intervention. We should not forget that nature eliminates the genetically abnormal embryos by either not implanting or aborting early-on. The emotional load of infertility, specifically for poor prognosis patients, can be better confronted by repeated consultations and counseling, aiming to better serve our patients interests. Exaggerated claims of better IVF outcomes can easily generate more and persistent negative feelings. The likelihood of PGS evolution in terms of precision and accuracy may be clinically useful in the future.