CAN BIOPSY DURING A PGT CYCLE AFFECT EMBRYO DEVELOPMENT?

Preimplantation genetic testing (PGT) analyzes embryo genetic information. It allows stablishing the chromosomal status of the embryo and identifying those without chromosomal aberrations. Thus, avoiding the transfer of embryos at risk of chromosomal anomalies, contributing to the selection of the embryo with the greatest implantation potential. It is also possible to detect embryos affected by a genetic disease inherited from the parents. The PGT is a tool that helps to select which embryos are suitable for transfer, beyond their morphology.

What is PGT?

Embryo analysis is based on embryonic DNA. This is obtained from one or a few cells extracted, i.e. biopsied, from the embryo. If the biopsy is performed on day 3 of embryo development, when the embryo has between six and eight cells, a single cell is extracted for analysis. If the biopsy is performed between days 5 and 7 of development, when the embryo has reached the blastocyst stage (contains about 200 cells), between 5 and 10 cells are removed.

Can the biopsy affect the embryo development?

If the biopsy is performed by expert personnel and the embryo quality is good, the evolution of these embryos should not be negatively affected. It must be considered that the proportion of biopsied cells is higher on day 3 than in blastocyst (1 of 6-8 compared to 5-10 of 150-200), so the day 3 biopsy has a greater impact on the implantation potential than the blastocyst stage biopsy. In addition, the benefits of PGT in couples at genetic risk outweigh the possible impact of biopsy on the embryo’s ability to implant.

With respect to blastocyst biopsy, several studies have shown that biopsy at this stage does not affect embryonic development and subsequent implantation. In fact, the implantation potential of a blastocyst without chromosomal abnormalities (normal or euploid) is about 70% compared to about 40% of an undiagnosed embryo (Yang et al., 2012).

As with any manipulation process, a possible risk of damage during the process cannot be completely ruled out. According to Reprogenetics data, this figure is estimated to be less than 0.5%.

What is the future?

Currently, in order to carry out PGT, it is necessary to have a sample that is the maximum representative of the embryo, without compromising its viability. Embryo biopsy, although an invasive technique, is safe, and performed by experts and on good quality embryos does not adversely affect embryo development.

The challenge we have to face at is to carry out a genetic analysis of the embryo by means of a non-invasive procedure, which should make it possible to analyze the genetic information accurately without manipulating the embryo (see https://www.reprogenetics.es/es-posible-realizar-un-test-genetico-preimplantacional-sin-biopsiar-el-embrion/ ). For the time being and pending more evidence and studies, trophoectoderm biopsy continues to be the technique that provides the best results for carrying out a genetic test on the embryo.

IS IT POSSIBLE TO CARRY OUT A PREIMPLANTATION GENETIC TESTING WITHOUT BIOPSYING THE EMBRYO?

Preimplantation Genetic Testing (PGT) allows the determination of some genetic characteristics of the embryo in culture, before its transfer to the maternal womb. To do this, it is necessary to undergo an in vitro fertilization (IVF) cycle that allows a certain number of embryos from the couple to be available. The genetic determination will be made from the embryonic DNA obtained from the biopsy of one or a few cells of these embryos. The invasive nature of the biopsy, according to some authors, could diminish the embryo’s capacity to implant. However, when the biopsy is performed by expert hands, no differences have been observed in the ongoing pregnancy rates between biopsied and non-biopsied embryos.

Can another source of embryonic DNA be made available without the need for an invasive technique?

Several authors have published the possibility of making a diagnosis from the DNA found in the culture medium where the embryo grows up. The results obtained to date, although encouraging, show that it is still necessary to continue advancing in this field of non-invasive PGT.

What is the origin of the embryonic DNA found in the culture medium?

It is not known with certainty.

It may come from embryonic cells that have initiated cell death (apoptosis), or directly from lysed (broken) cells. Whether or not the DNA of these cells is representative of the entire embryo is yet to be answered.

It may be contamination by DNA of parental origin, either from spermatozoa (which adhere to the embryo after fertilization) or from granulose cells (cells that accompany the oocyte). In any case, this possibility could be excluded by carrying out an intracytoplasmic sperm injection or ICSI and an exhaustive mechanical elimination of the granulose cells.

Finally, a possible source can be also the DNA contained in extra-cellular vesicles that would function as messengers between different parts of the embryo. If this is the case, it could well be an excellent source of DNA for diagnosis.

Are the results so far reliable?

At present, there is not enough evidence that the result obtained from the analysis of embryonic free DNA in the culture medium can be used at the clinical level. The levels of concordance between the results obtained in the DNA from the embryo’s biopsied cells and that obtained from the culture medium are not sufficiently aligned. A relatively high false positive rate is observed, which means that embryos are wasted when they are diagnosed as abnormal when they are not. Considering that it is a technique used when the embryo has reached the blastocyst stage (days 5 to 7 of embryo culture) and that not many embryos reach this stage, the possibility of losing some of them due to a false positive is not very flattering.

The discussion is open between different authors regarding the possibility of using the information obtained in a non-invasive way (which would certainly be a very simple way of having embryonic DNA) even taking into consideration the possible loss of embryos due to false positives, as opposed to the possibility of reducing the implantation power of the embryo when applying an invasive procedure.

Without a doubt, if the origin of the embryonic DNA in the culture medium is known and its results are reliable, non-invasive diagnosis will open a new era in the field of PGT.

Until then, we will have to keep on walking.

Reprogenetics Team.

CAN A MATERNAL BLOOD TEST TELL IF OUR BABY HAS INHERITED OUR GENETIC DISEASE?

It is now possible to perform a Noninvasive Prenatal Diagnosis (on a blood sample from the pregnant woman) to find out if the fetus is a carrier of a serious genetic disease.