The challenges for preimplantation genetic testing for aneuploidy

Published 27 May 2022

A very well organised and well attended webinar series hosted by ESHRE on the ‘Essentials in Reproductive Medicine’ was completed in mid-May with a webinar focused on ‘Management of a PGT-A cycle’. Efthymia Constantinou, Junior Deputy of the SIG Reproductive Genetics, reports.

Georgia Kakourou, immediate past co-ordinator of the SIG RG, raised many questions related to preimplantation genetic testing for aneuploidy (PGT-A) in a comprehensive presentation for this webinar. She firstly reviewed the purpose and need behind the concept of PGT-A, describing aneuploidies detected in embryos as the main reason for failed implantation and miscarriage. She discussed how PGT-A has become a debatable ART add-on, noting questions related to its invasive nature and its cost.

Focusing on the ESHRE good practice recommendations for PGT-A published in 2020, she emphasised best practice techniques related to the embryo biopsy and the genetic testing, which if not followed may often negatively affect the test result.(1,2) She highlighted the need of adequate sampling, proper transfer and storage and the necessity of technical validation of the PGT-A platform. She then referred to the two major questions related to the validity of the test: Does the trophectoderm biopsy result represent the rest of the embryo? And can the TE biopsy result predict clinical outcome?

In answer to the first question, Kakourou presented data supporting the consistency of PGT-A results derived from a TE biopsy with the rest of the embryo in cases with ‘full’ euploid or aneuploidy results. However, in the case of mosaic or intermediate copy number results, she reported that one-third were ‘resolved’ to show full euploid or aneuploid embryos.

The efficiency of PGT-A in predicting clinical outcome was acknowledged in several studies referred to by Kakourou. The recent studies of Viotti et al and of Capalbo were among those cited to support the suggestive prioritisation of low prevalence mosaics (<50%) as the second category of preference, after euploid, for embryo transfer.(3,4)

Management of PGT-A results and especially of mosaic results is a question of concern for all those involved in preimplantation genetic testing for aneuploidy: gynaecologists, embryologists, geneticists and genetic counsellors. As Kakourou pointed out, ESHRE has developed a recommendation document on this matter which is currently under review and will be officially presented at the annual meeting in Milan this summer.

Several questions were addressed to the speaker concerning the benefits of PGT-A, the ethical dilemmas related to its implementation, practical concerns for specific patient groups, the impact of PGT-A on the wellness of newborns, non-invasive PGT-A and genetic counselling. PGT-A recommendations on mosaics are much awaited as proven by the extent of the discussion on this matter.

To sum up, the webinar emphasised once again how PGT-A can be beneficial for certain ART patient groups depending on adequate technical and the scientific competence of everyone involved. Good practice recommendations and guidelines are essential to ensure an objective interpretation of the results based on verified published data.

1. ESHRE PGT Consortium Steering Committee. ESHRE PGT Consortium good practice recommendations for the organisation of PGT. Hum Reprod Open 2020; 3: hoaa021.
2. ESHRE PGT Consortium and SIG-Embryology Biopsy Working Group. ESHRE PGT Consortium and SIG Embryology good practice recommendations for polar body and embryo biopsy for PGT. Hum reprod Open 2020; 3: hoaa020.
3. Viotti M, Victor AR, Barnes FL, et al. Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use. Fertil Steril 2021; 115: 1212-1224.
4. Capalbo A, Poli M, Rienzi L, et al. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am J Hum Genet 2021; 108: 2238-2247.

Get notified of new articles with our ESHRE newsletter.

Sign up and never miss an update