Aneuploidy screening is used to detect numerical chromosomal aberrations in embryos created in vitro and intended for implantation. It is a cytogenetic test that can only detect numerical aberrations of specific chromosomes. Aneuploidy screening thus represents a form of preimplantation genetic diagnosis (PGD).
What is aneuploidy screening?
Aneuploidy screening is used only in in vitro fertilization. The main goal is to transfer only embryos without detectable chromosomal aberrations into the uterus. The term aneuploidy screening refers to cytogenetic testing procedures that can provide an indication of numerical aberrations in certain chromosomes in in vitro fertilization (IVF). In principle, aneuploidy screening can give an indication of nullosomy, monosomy and polysomy such as trisomy. In nullosomy, a chromosome pair is completely missing, in monosomy, one homologous chromosome of each chromosome pair is missing, and in polysomy, more than two homologous chromosomes are present for a given chromosome pair. The best known polysomy is trisomy 21, which leads to Down syndrome. Since most numerical chromosomal aberrations – especially monosomies – are lethal, i.e. lead to natural abortions, miscarriages or stillbirths, only embryos without detectable chromosomal aberrations are implanted into the uterus. This should improve the success rate of IVF, but certain chromosomal aberrations are not necessarily lethal, but lead to abnormalities and severe limitations later in life, as in Down syndrome or Turner syndrome. Therefore, in some countries there is a general ban or severe restrictions on this type of preimplantation genetic diagnosis (PGD) for ethical reasons.
Function, effect, and goals
Aneuploidy screening is used only in in vitro fertilization. The main goal is to transfer only embryos without detectable chromosomal aberrations into the uterus in order to get the highest possible chance of success for pregnancy in artificial insemination. In principle, two procedures can be distinguished: polar body diagnostics and examination of the preimplantation embryo. The first procedure involves the examination of the polar bodies of the unfertilized egg. Only a possible aneuploidy of the egg cell is examined. This is done on the assumption that about 90% of aneuploidies are of maternal origin. This is not PGD in the narrower sense, but rather a prefertility diagnosis, because fertilization, i.e. the fusion of an egg with a sperm cell, has not yet taken place. Aneuploidy screening of the preimplantation embryo in the early blastula stage, on the other hand, is considered PGD because the examination refers to the “real” embryonic stage – even if it is still a very early stage, only a few days old. In polar body diagnostics, the two polar bodies formed by the egg cell during the first and second maturation division before fusion with the sperm cell are removed and examined for aneuploidy. The so-called FISH test (fluorescence in situ hybridization) is used to detect any aneuploidy. Up to now, the FISH test only allows the examination of chromosomes 13, 16, 18, 21, 22 and the sex chromosomes X and Y. The chromosomes of the chromosomes that are present after maturation can be examined. The chromosomes of the double helix structure, which is split after the division of maturation, connect to chromosome-specific DNA probes with the respective complementary DNA sequence. The DNA probes are labeled with different fluorescent colors. Under the light microscope, the homologous chromosomes can be counted in a semi-automated procedure, so that numerical aberrations can be detected. Analogous to polar body diagnostics, aneuploidy screening is performed on preimplantation embryos that are still in the early blastomere stage. Now, however, we are dealing with diploid chromosome sets whose double helix must first be split in order to be able to initiate the connection of the chromosomes with the complementary DNA probes. In both procedures, the goal of aneuploidy screening remains a positive selection of the in vitro fertilized egg before transfer to the uterus in order to achieve the highest possible success rate for the desired pregnancy.A much-discussed ethical problem arises from negative selection, which is automatically associated with positive selection and which some extreme critics like to bring argumentatively close to eutanasia. Another ethical problem is seen in the use of IVF to produce the so-called savior baby. Via positive selection of embryos created in vitro, omnipotent immunocompatible stem cells can be grown that could save the lives of siblings with certain diseases by implantation.
Risks, side effects, and hazards
Aneuploidy screening itself, as well as the harvesting of the cell nuclei to be examined, takes place outside the body and therefore poses no direct risks or dangers to health and is therefore free of side effects. The actual risks and dangers lie in the fact that the benefit of anoiploidy screening on blastomeres, i.e. on pre-implantation embryos for an increase in the success rate with regard to the desired pregnancy has not yet been demonstrated. General, system-immanent problems arise due to exaggerated expectations regarding the precision of the screening results. This is true in both positive and negative results. A positive result, i.e. at least one chromosomal aberration has been found, is subject to a certain degree of uncertainty. It may happen that the positive result wrongly excludes the corresponding oocyte for transplantation although in reality there is no chromosomal defect. However, this type of misdiagnosis is less due to the procedure itself than to the fact that embryos in the blastula stage may well have a few cells with chromosomal aberrations. On the other hand, prospective parents of an IVF child cannot be sure that a negative result of the aneuploidy test will actually show no chromosomal aberration. Another danger is the removal of the necessary number of cells from the embryo. It happens that the cells taken by biopsy die and can no longer be examined. Since the biopsy cannot be repeated on the same embryo, it is no longer available for transplantation because no examination result is available. There is also debate about the extent to which the biopsy affects the embryo’s fertility, compromising the overall success rate for pregnancy.
