Preimplantation genetic diagnosis (PGD / PGS) is a well-established technique in IVF and aims to transfer healthy embryos to the uterus after genetic testing. However, this technique has limitations and one of them is the invasiveness of the process.
Since the first days of the PGD / PGS implementation, it has been a dream to be able to examine the embryos non-invasively, without the need to aspire any cell. The last study of Shamonki et.al in the Fertility Sterility magazine supports that the preimplantation genetic screening for chromosomal abnormalities (PGS) at the blastocyst stage can be possible by analyzing cell free DNA in the spent culture medium where the embryos are being developped in IVF.
That procedure is called non-invasive preimplantation genetic screening in vitro or NIPGT but can it be a reality in the near future? This is an exciting prospect which would eliminate the need for the micromanipulation of the embryo and would facilitate the access for testing chromosomal abnormalities in fetuses from all IVF cycles. Ideally, the NIPGT should be completely non-invasive, accurate, efficient, of high-resolution and low cost. An attractive possibility of the NIPGT is that the automated sampling and processing of the culture material where the embryos are developed should be relatively simple and if the cost of the genetic analysis is reduced in the near future it may be incorporated into the total cost of the IVF.
Recently, Gianaroli et.al. reported that NIPGT is feasible with blastocentesis (blastocoelic fluid aspiration after penetrating the outer layer of blastocyst (trophectoderm) with a sharp pipette). This research technique used by some laboratories is definitely less invasive than the conventional biopsy currently implemented in the PGD/PGS.
However, the efficiency of NIPT should be evaluated in large series of studies before its clinical application since it has significant limitations. Initially, it is not completely non-invasive, i.e., it may affect one or more cells of the trophectoderm. Additionally, the accuracy of the genetic analysis is less than optimal, since there are many false negative and positive results mainly due to the unknown cell free DNA. Furthermore, a possible contamination of the culture medium can lead to false results, so in vitro fertilization by intracytoplasmic sperm injection (ICSI) is proposed as mandatory technique for the NIPGT process. Furthermore, it should be given thorough attention to polar bodies of the oocytes, as contamination of cell free DNA could arise from the polar body could lead to error.
In summary, the current implementation of the blastocyst biopsy is a well-established process and the use of contactless laser to help release these cells is minimally invasive and thus continues to be the golden option in the PGD / PGS implementation. Conversely, the effectiveness of the NIPGT using the remaining IVF culture medium should be evaluated in larger studies before it can be clinically applicable.
Thus, the dream may be closer to reality, but there is still a long journey before its clinical application.
Reference article from Fertility Sterilty, author Professor A.H Handyside
Dimitra Christopikou, Ph. D,
PGD Lab Director,