LAUSR

“Are we there yet?”- these are the words that many parents would have heard when taking children on some sort of trip. The journey began over 30 years ago when the first PGTs were done. It was simple back then- the answers required were generally simple (or at least straightforward) and you only went looking for directed answers. PGS was for chromosomes and PGD was for a gene(s)- and generally, never the two would meet. Early chromosome testing was based on FISH and the targets were polar bodies or blastomeres from cleavage embryos- apart from some technical expertise in getting the sample, analysis was essentially down to the operator's ability to count to 1 (2nd PB) or 2 (1st PB and blastomeres). Life was good- but unfortunately the results were often not so productive with implantation rates resisting change and only some groups reporting decreased miscarriage rates for some patient cohorts. The naysayers reached a crescendo around 2005 when it was proclaimed that not only was PGS not helping but it was hurting patient's chances of a pregnancy. Three years of gloom followed with claim and counter claim on the appropriateness of PGS. PGD fared a bit better with the simple logic of Mendelian genetics and obvious success in outcomes- although some mishaps in the early days led some groups to possibly over emphasize and focus on DNA contamination, ADO and recombination events- life for PGD though was generally good. The darkness of those 3 years of doubt and dispute were substantially dispelled when a British Knight led the field into the new era of comprehensive chromosome screening where every chromosome could now be seen to be both problematic and mischievous. Finally, the full impact of identifying any and all chromosome changes was seen- a dramatic increase in implantation rate and decreased miscarriage rates for most groups tested. There were still some shadowy areas of understanding but the light was again shining and things were, maybe, good again. Was it just a breakthrough in analysis that flicked the switch? No, there were some underlying bits to the puzzle that were not given the amount of the credit for the improvements that they possibly deserved. Two other steps in addition to CCS were essential for the realization of these new outcomes- vitrification with concomitant cryo-transfer and blastocyst stage biopsy. The naysayers retreated, not totally but sufficiently far to encourage the bulk of the world to adopt the new processes. “Are we there yet?”. No, but getting closer. In the meantime, PGD continued on its singular path but now it had to also face the multitude of positive findings associated with the benefits of CCS- find not only the correct genetics for an embryo but also the correct chromosome compliment. How to combine the two for the best of both world's outcomes? Approaches to improved PGS (now referred to as PGT-A, PGT-SR) and combining PGD (now PGT-M) into a single will be discussed. “Are we there yet?”