One of the main causes of infertility – or just problems getting pregnant for longer than expected – are wrongly assembled chromosomes in the developing embryos. In particular in women towards the age of 40 or older, a high percentage of the oocytes available in the body tend have a wrong number of chromosomes (aneuploidies) or other alterations that will stop the embryo from developing into a healthy baby. In-vitro fertilization (IVF) can help patients through a pregnancy in many cases, but if one of these embryos is chosen for re-implantation after fertilisation, the treatment will most likely fail.
“Preimplantation Genetic Screening” (PGS), now also called “Preimplantation Genetic Testing for Aneuploidies” (PGT-A), is a test often used as part of IVF cycles. PGT-A can assess the genetic health of the embryo by looking at the the number of chromosomes and parts of the chromosomes. Unfortunately there can be many additional other underlying problems, but choosing an embryo with the genetic makeup comatible with life improves the chances of achieving a successful pregnancy – reducing costs and anxiety for the patients.
The current standard practise for performing PGT-A is through shallow short-read sequencing of the genomic DNA of a few cells extracted from the developing embryo (blastocyst), and analysed e.g. using read-counting as described in this blog post.
Alternative approaches currently being developed are using the DNA from the media the embryo is growing in as part of the IVF treatment (spent culture media or SCM). This DNA originates from the embryo, but is not compacted within cells anymore (cell-free DNA or cfDNA). As this does not involve the embryonic cells themselves this is termed Non-Invasive Preimplantation Genetic Testing (niPGT). The term is also used for methods that extract the cfDNA from the blastocoele fluid (BF).
As it should be preferable to disturb the embryonic development as little as possible, non-invasive method currently receive a lot of interest and will probably be the new standard at some point. In addition, these methods for DNA extraction are cheaper and technically easier to perform.
At the moment the results achieved are less reliable however and should only be used as part of research projects. Potentially fragmentation and degradation of DNA is influencing results; another hypothesis is that preferably unhealthy cells are released by the developing embryo and thus are not representative of the genetic health of the actual embryo.