After 25 years of controversy, and as the protagonists of a debate at our Best of ASRM & ESHRE meeting implied, consensus on the applicability of PGT-A for everyone seems as remote as ever. Efthymia Constantinou, Junior Deputy of ESHRE’s SIG Reproductive Genetics, offers her opinion from the IVF lab.
It was not until the final discussion of this entertaining debate that the two presenters revealed their true feelings. And it was clear, despite their officially divergent positions, that they were both agreed that PGT-A is certainly NOT for everyone. This was also the result of the poll held both before and after the debate: 85% against PGT-A for all, and 15% in favour.
Luca Gianaroli, speaking against the motion, acknowledged in a preview interview with Focus On Reproduction that PGT-A, even after 30 years of its first application, is still a matter of debate, mainly because of the continuing improvement in technique.(1) However, for the Pro side Richard Paulson from the USA asked: Why would you NOT want to know everything possible about an embryo before transferring it to a patient? He went on to support his opinion with five arguments. PGT-A is:
* Cost effective, by reducing costs related to multiple pregnancies, failed implantation and miscarriage.
* Accurate and it does not harm embryo viability.
* The future, and we are all now awaiting PGT 3.0.
* Logical and appealing, because patients want to check everything before embryo transfer.
* And an integrated part of fertility care.
Gianaroli had four arguments against the motion.
* The WHEN story: publications show that even after almost 30 years there are still doubts about PGT-A efficacy.
* The HOW story: there are minimal or no improvements in pregnancy and live birth rate reported in some patient categories.
* The WHY story: there are still reports of potential damage related to embryo biopsy and mosaicism (pregnancy hypertension, no embryo-transfer from false positives).
* The FOR WHOM story: PGT-A is not for everybody!
During the many questions following the debate, Paulson answered that around 20-30% of samples analysed with PGT-A might have a misdiagnosis (because of mosaicism and other technical problems), and unfortunately in such cases implantation is lost.
In the absence of euploid embryos Gianaroli said that the final transfer decision depends on the patient group. In general, the priority scale for embryo transfer is euploid, mosaic and lastly aneuploid. Paulson responded (with later agreement from Gianaroli): ‘We should stop calling them mosaic!’ If that was the case, he argued, they would produce mosaic babies, but the literature suggests that mosaic embryos can often lead to the birth of normal babies.
So once again the question of ‘who can benefit from PGT-A?’ arose. Paulson responded that PGT-A certainly is beneficial for patients with a large number of embryos, for patients of advanced maternal age, and it may also have advantages for egg donors. However, it should be avoided in cases of poor responders and patients who have very few eggs frozen (for example, cancer patients having fertility preservation).
Both, however, were forward looking with regards to non-invasive methods of PGT-A, agreeing that other markers than chromosome number should be explored in spent culture medium and blastocelic fluid in order to confirm an embryo’s viability and ploidy status.
My own conclusion from the cytogenetics lab is that PGT-A remains a valid technique and does benefit pregnancy outcomes, as long as it is used in the right patient categories. Indeed, all of us working in the field of reproductive sciences are awaiting the wider introduction of PGT 3.0 to enable a better embryo selection – a greater help for couples to fulfil their dreams of parenthood and the birth of healthy babies.
1. See https://www.focusonreproduction.eu/article/ESHRE-News-Best-of-ASRM-ESHRE-2021-Gianaroli