Pre-implantation Genetic Diagnosis (PGD) allows couples who are carriers of a specific genetic hereditary disease to select embryos that are free of such a condition, thus preventing the disease from passing on to the next generation.

This type of diagnosis has the advantage, when compared to prenatal diagnosis that it is performed before the potential life of the embryo in the uterus.

PGD was first described more than twenty years by Handyside et al. In its first application, the PGD made it possible to select healthy embryos in couples affected by sex-linked genetic diseases, namely adrenoleukodystrophy and mental retardation linked to chromosome X (Handyside et al., 1990). Since then, over 500 works have been published on PGD for the detection of monogenic diseases, and ESHRE (European Society of Human Reproduction and Embryology) confirms that since 1997, there have been over 4,500 clinical applications for this type of PGD (Harper et al., 2012)

The pregnancy results for this type of PGD are the best ones according to the ESHRE article, and in addition, the results of the effectiveness of the technique are also high, as 90% of the embryos are diagnosed with an accuracy of more than 99.5%.

Nevertheless, PGD for monogenic diseases is not easy, as it requires an optimization of the patient to patient protocol, since the specific PCR reaction has to be designed to make it possible to broaden and detect the range of genes and mutations involved in the disease in question in a single cell embryo, and additionally, in a maximum time frame of 2-3 days. This involves a process that usually requires 3-4 months of prior work and biological samples (usually blood) from the patients and their first degree relatives.

PGD is not only used for the detection of single-gene disorders, but also for aneuploidy screening in embryos, that is, to detect whether the embryos analyzed contain the correct number of chromosomes (46), and therefore are euploid, or, if they have any extra chromosome or lack one, which in such case, would present as aneuploidy.

In most cases, the presence of aneuploidy in the embryos makes them highly inviable in the first stages of embryonic development. But some aneuploidies do not cause embryonic loss, and can be maintained during fetal development and give rise to abnormalities in the offspring caused by aneuploidy, leading to serious health problems and mental retardation, among others.

It has been postulated that the incidence of embryo aneuploidy may be behind the low fertility rate in the human species (Bahçe et al., 1999), and therefore, if euploid embryos are transferred, pregnancy rates (or implantation) would be much higher (Gianaroli et al., 2002, Munne et al. 2006b, Farfalli et al., 2007). From this assumption, PGS (Preimplantation Genetic Screening) came into being, that is to say, PGD focused on aneuploidy screening aimed at increasing the implantation rate of the embryos transferred.

The first studies on PGS were in 1996, six years after the first application of PGD for monogenic diseases by Handyside et al. (Munne and Weier, 1996 Verlinsky et al. 1996a Verlinsky et al. 1996b). Currently, there have been about 250 papers published in this field. Again drawing on data from ESHRE, since 1997, there have been more than 16,500 clinical applications of PGS in Europe (Harper et al., 2012).

FISH (Fluorescent in situ Hybridization) is the technique used in the vast majority of PGS. Depending on the number of probes that are used, FISH makes it possible to detect up to 13 of the 23 chromosomes (Abdelhadi et al., 2003), although customarily, only a maximum of 9 chromosomes (chromosomes 13, 15, 16, 17, 18, 21, 22, X and Y) are analyzed (Pujol et al., 2003), leaving, therefore, fourteen chromosomes unanalysed (more than half).

This fact, namely that more than half of the embryo’s chromosomes are not detected by FISH, can explain, as has been reported recently, that the PGS not only does not increase embryo implantation, but can actually go so far as to reduce it (Staessen et al., 2004, Mastenbroek et al., 2007, Hardarson et al., 2008, Staessen et al., 2008).

When these data were published, the PGS suffered a serious blow and stopped being applied in most IVF centres.

Since then, significant technical advances have been made and now there is the possibility of analyzing the entire chromosome group using CGH (Comparative Genomic Hybridization) or array-CGH.

Both techniques make it possible to detect variations in number in any of the embryo chromosomes, in a rapid and standardized way. Thus, it can be applied directly in blastomeres without needing to freeze the embryo to await the results, as these are obtained within a period of time that is enough to make it possible to perform the embryo transfer in the same IVF cycle.

Furthermore, when analyzing all the chromosomes at once, there is no need to perform any optimization of the protocol, which did happen when using FISH, where optimization of the probes work had to be carried out depending on the alterations one wanted to detect. This took time and had a high cost. However, if the array-CGH is used, no optimization is required at all, since all the chromosomes are detected directly.

This is especially interesting in patients with chromosomal abnormalities such as translocations, inversions or duplications, as there is a wide variety of possible changes, and array-CGH, allows us to analyze any of these types.

The technique was first applied clinically 5 years ago, obtaining five pregnancies in patients with multiple IVF failures (Hellani et al., 2008). And since then, several articles have been published on their use in partner carriers of chromosomal translocations (Colls et al., 2012, Rius et al., 2011).

Recently, a randomized study has been published where the usefulness of array-CGH in PGS is analyzed, in which they compare a control group on whom no intervention is performed, with a test group, on whom all the chromosomes are analyzed with array-CGH in order to transfer only the euploid embryos. The study shows an increase of more than 20 points in the pregnancy rate between the two groups, indicating the great potential for improvement that the technique has (Yang et al., 2012). It is too early to say with scientific evidence that the PGS with array-CGH significantly improves results, but so far, the results are very encouraging


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Last Updated: November 2017