Preimplantation genetic diagnosis and preimplantation genetic screening: what they are, when to do them

Source: ZEISS Microscopy

Analyze some cells of an embryo produced in vitro in its early stages of development, to find out if it is healthy or affected by any genetic disease or from abnormalities in the number of chromosomes. That's what you can do with the preimplantation genetic diagnosis as part of a medically assisted procreation (Pma) procedure. Objective: to "set aside" any diseased embryos, transferring only the healthy ones to the uterus.

Preimplantation diagnosis and preimplantation screening: what are the differences

The general definition of "preimplantation genetic diagnosis" - often abbreviated to pgd o pgt (from the English preimplantation genetic diagnosis or testing) actually includes two groups of tests:

  • those who evaluate the possible presence of genetic diseases or chromosomal alterations of which a couple, even a fertile one, is a carrier (for which they risk passing them on to their children);
  • those who evaluate the chromosomal structure of embryos produced during MAP procedures in infertile couples. In this case we speak of preimplantation genetic screening or, more properly, of preimplantation genetic diagnosis for aneuploidie (abnormalities in the number of chromosomes), or pgt-A.

"The first type of application has been used for some time all over the world and its use is now widely validated" says Edgardo Somigliana, director of the Pma operative unit of the Clinic in our city. "The use of the second type of application, on the other hand, is more controversial".

Pre-implantation diagnosis for fertile couples

Until recently, Law 40 of 2004 on PMA allowed access to this technique only to infertile couples. The situation changed with a 2022 Constitutional Court ruling, which also opened access to fertile couples who know they are at risk of transmitting a genetic disease to their children - such as thalassemia, cystic fibrosis, muscular dystrophy, haemophilia, Fragile X - or a chromosomal abnormality causing disease, such as a translocation.

Read also: Assisted reproduction, what the Del Paesena law provides

In these cases, instead of conceiving naturally with the risk of transmitting the disease to their children, couples can undertake a path of MAP. Before the embryos are transferred to the uterus, they are analyzed to assess whether or not they have inherited the disease or anomaly in question. The analysis is carried out on some cells taken from the embryos themselves: "A safe procedure, that is, with no particular consequences for the embryo, if performed in specialized centers, by experienced personnel", underlines Somigliana.

The execution of this test, which is in practice an extremely early prenatal diagnosis, allows to "set aside" the embryos with problems (which will be kept frozen in the Pma center), to transfer only the healthy ones to the uterus.

Alternatively, couples who find themselves in this situation and do not intend to run the risk of transmitting the disease they carry to their children can conceive naturally, carry out a prenatal investigation test (amniocentesis or villocentesis) and, in the event that the fetus is found to be ill, evaluate the possibility of termination of pregnancy (therapeutic abortion).

Read also: Choosing the prenatal diagnosis: screening test, fetal DNA test or amniocentesis / villocentesis

Where it can be done

To summarize: for many couples at risk of transmitting a genetic disease to their children - typically we are talking about diseases that are incompatible with life, or such as to cause serious health problems - PGD represents a precious opportunity to avoid abortions, whether spontaneous or therapeutic. And, thanks to the ruling of the Consulta, the law is on their side today. But be careful: this does not mean that it is so easy to access the technique, at least in the public sphere.

Meanwhile, as an article published on the site of the Rare Diseases Observatory recalls, the technique it is not explicitly mentioned in Lea, the essential levels of assistance (i.e. the services that must be offered free of charge or with a ticket from the National Health Service). And in any case in Del Paese the public centers that offer it are very few: of our city, microcitemic hospital of Cagliari, hospital of Cortona in Tuscany, Cervesi hospital of Cattolica, Center of health and protection of women and children Sant'Anna di of the city. Furthermore, the offer often concerns the diagnosis of a few diseases, typically thalassemia, cystic fibrosis, haemophilia. A situation that generates an inevitable discrimination against couples with other diseases, who are forced to go to private centers, in the country or abroad. With obviously much higher costs.

This is why in the spring of 2022 the Court of our city condemned - which even since 2022 had organized itself to offer free diagnosis to couples with thalassemia, haemophilia and cystic fibrosis - for having refused access to the a couple carrying a different disease, theexostosis.

In this panorama, the Pma Center of the Cortona hospital is an exception, which since January 2022 has activated a preimplantation genetic diagnosis at 360 ° C. "That is for all the genetic diseases for which it makes sense to do it, which are - according to a resolution of the Tuscany Region - those for which it makes sense to access prenatal diagnosis, and possibly the therapeutic interruption of pregnancy" says the director of the center , the gynecologist Luca Mencaglia. However, there are no precise lists of diseases to refer to, neither in Tuscany nor elsewhere: each individual case must be evaluated by the center to which the couple refers, with a multidisciplinary consultancy which also includes a meeting with a geneticist.

The Tuscan center has so far carried out 16 surveys (as of December 2022), for couples not only from Tuscany, but from various regions. The price? "You pay a ticket that depends on the number of embryos analyzed" explains Mencaglia. "Let's say from 600-700 euros to around 1200 euros if you analyze five or six embryos. "Of course, it is not exactly cheap - and the technique is not included in the Lea, the essential levels of assistance - but it is more or less a quarter of the cost in a private center.

Preimplantation genetic screening

In recent years, another possible use of genetic analysis of embryos has emerged: preimplantation screening (PGS), or preimplantation diagnosis for aneuploidy (PGT-A).

The procedure concerns not so much fertile couples carrying genetic diseases - which in any case can "add" this investigation to the diagnosis indicated in their case - but above all infertile couples who follow a path of Pma.

It consists in the analysis of the general chromosomal structure of the embryos produced, to identify those possibly characterized by anomalies, in order to set them aside, giving priority to the "healthy" ones for transfer to the uterus.

The anomalies analyzed are the so-called aneuploidie, which affect the total number of chromosomes. Sometimes, in fact, there may be one more than normal (trisomy), or one less (monosomy): a phenomenon that is more frequent the more the maternal age is advanced and which can lead to failure to implant the embryo itself, to spontaneous abortion or to fetal diseases and syndromes. For example Down syndrome, caused by the trisomy of chromosome 21.

Read also: Mom at 40? Here's everything you need to know

There are now many PMA centers, mostly private, that offer this service, with the aim - they say - of optimizing the chances of pregnancy, focusing on the best embryos from a genetic point of view. "In reality, some studies show that the number of pregnancies obtained in couples who carry out this screening is lower than those obtained in couples who do not" underlines Somigliana. It makes perfect sense that this is the case, because screening leads to a selection of the embryos to be transferred: it would seem a good thing, if we assume that all the "discarded" embryos actually deserved to be. However, this is not always the case.

Pre-implantation screening, when to do it

But let's go in order. To begin with: when does preimplantation screening make sense? A recent document from the Del Paesena Society of Human Genetics (Recommendations on Preimplantation Genetic Diagnosis, August 2022) mentions some particular situations, underlining however that in some cases a scientific discussion on the real usefulness of the procedure is still ongoing:

  • advanced maternal age (over 35 years, although some centers are offered over 40 years);
  • previous cycles of PMA with failure of implantation of the embryo;
  • polyabortivity;
  • abnormalities in sperm production on the part of man who require the use of techniques for taking the spermatozoa themselves from the seminal ways.

The question of mosaicism

One of the reasons why the technique is still considered controversial is that it is not always possible to establish with absolute certainty the genetic characteristics of an embryo. Or, rather, what consequences certain genetic characteristics may have on his future health. "It all depends on a rare but physiological phenomenon that takes the name of mosaicism"explains Novelli, head of the Medical Genetics Laboratory of the Bambino Gesù Children's Hospital in the city and coordinator of the work table that formulated Sigu's recommendations.

The fact is that when it comes to the chromosomes of an embryo it is not always all black or white, that is, all "healthy" (with the correct number of chromosomes) or all sick (with a few more or fewer chromosomes). It may happen that some cells of the embryo are fine and that others have a chromosomal abnormality instead. In this case we speak of embryonic mosaicism.

Until a few years ago, embryos with these characteristics were essentially discarded (i.e. frozen and not transferred to the uterus), but then it was discovered that a mosaic embryo does not necessarily develop into a diseased fetus. On the contrary: even the transfer of a mosaic embryo can lead to a vital pregnancy and the birth of a healthy child, as shown for the first time in 2022 in an article published in the New England Journal of Medicine by the research group of Francesco Fiorentino, director of the private Genome Laboratory. In fact, it has been discovered that some embryos can during their development self-correct, for example by eliminating cells with chromosomal abnormalities or confining them to the placenta.

Here, then, that if there are no alternatives - that is, there are no other embryos to be transferred, and there is no possibility of producing others - some centers offer the couple the transfer of an embryo with mosaicism. "Obviously - underlines Novelli - giving priority to the less problematic ones (because even the mosaics are not all the same), and explaining well to the couple what are the risks to which it goes. "Mainly, the fact that the fetus that will develop from that embryo may actually be affected by a chromosomal abnormality. So much so that in the event of a mosaic transfer, the International Society for Preimplantation Genetic Diagnosis suggests to perform an amniocentesis during pregnancy, to evaluate the final chromosomal structure of the fetus.

Updated on 09.05.2022

  • assisted fertilization
  • genetic diseases
  • pgd
  • pgt
  • down syndrome
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