Preimplantation genetic diagnostics

PGS: Preimplantation genetic screening

Preimplantation screening, which is performed during the IVF treatment, allows a prospective embryo with a normal number of chromosomes to be introduced into the uterus. Such an embryo then has the greatest chance of hatching and leading to the birth of a healthy child.

An incorrect number of embryo chromosomes may be one of the many causes of failure of IVF cycles. The condition, where some more chromosomes occur in the embryo, or when some chromosomes are missing, is called aneuploidy.

• Most pregnancies from aneuploid embryos result in spontaneous miscarriage in the first trimester.

• Some types of aneuploidy in embryos may result in the birth of a child affected by, for example, the Down syndrome (excess chromosome 21), Edwards syndrome (excess chromosome 18), or Patau syndrome (excess chromosome 13)

• The risk of aneuploidy increases with the increasing age of the woman. Doctors are convinced that this is the main reason why women suffer a steep decline in fertility during the third and at the beginning of the fourth decade of their lives.

Examination of aneuploidy of chromosomes in embryos prior to their transfer to the mother’s body, which takes place within the IVF, allows only the embryos without an identifiable genetic abnormality to be selected for transfer. The intent of this examination is to increase the chance of a healthy baby and the success of the IVF cycle.

Preimplantation screening is particularly suitable for couples that meet the following indications:
• higher female age
• unexplained repeated miscarriages
• chromosome translocations

Preimplantation screening significantly enhances the success of the IVF cycle, so even other couples can use it, in addition to the genetic risk couples.

PGD: Preimplantation genetic diagnostics

Pre-implantation genetic diagnosis (PGD) of rare diseases is intended for couples where there is evidence of the risk of transmission of a major genetic disease that is transmitted by one gene disorder from the parents onto the offspring.

Preimplantation genetic diagnosis (PGD) is a method that allows the selection of the so-called “healthy” embryo without any specific genetic burden. What is characteristic of this method is that it always associates with Assisted Reproduction and Non-Venous Fertilization methods, and that embryos are selected prior to their transfer to the uterine. The main advantage of such a procedure is to exclude the risk that the foetus will carry the genetic burden. Couples therefore do not have to deal with the potential pitfalls associated with artificial abortions of pregnancy, which in practice mean ethical dilemma, bring mental stress and health complications for women. Artificial abortion of pregnancy may also have a detrimental effect on the later ability of the couple to have a baby in the future.

In scientific databases, there are over 5,000 rare hereditary diseases mentioned that are potentially detectable by employing the preimplantation diagnostics. Monogenic hereditary diseases are caused by the dysfunction of one of our genes.

If we are to simply describe isolated diseases by the type of heredity, we can divide them into three basic groups:
• with recessive heredity
• with hereditary dominance
• with inheritance linked to the sex chromosome

Various risks of transmission of the disease to the offspring apply to different groups, as well as the different requirements for selecting the embryo suitable for transfer.

The most common rare diseases in our zone include:
• cystic fibrosis
• spinal muscular atrophy
• metabolic disorders
• neurofibromatosis
• Marfan’s syndrome
• Huntington’s disease
• familial hypercholesterolemia
• fragile X chromosome syndrome
• muscular dystrophy syndrome

Further inherited dispositions include tumour diseases, e.g. BRCA1 and BRCA2.

The PGD is the only reliable method for families with genetic burden to exclude the transmission of serious disorders and hereditary diseases onto the offspring.

Each couple must complete a set of different examinations before entering the assisted reproduction program. The clinical expert will perform a comprehensive diagnosis to gain an idea of what stimulation protocol will be suitable for the female partner, and what specific methods and procedures should be used in the IVF cycle. If partners are shown to be suitable adepts for the IVF cycles with preimplantation embryo examination, a clinical genetics consultation will take place, specializing in preimplantation diagnostics. From the practical point of view, it is necessary to obtain a sufficient number of high-quality embryos.

With the PGD itself, the ova are collected from the woman after hormonal stimulation, then they are fertilized, and after five days of embryo cultivation, a group of about seven cells are biopsied (withdrawn) from the developing embryo by means of a micromanipulator. This method is very gentle to the embryo and does not pose any risk to the future foetus.

The following are most commonly used for the analysis:
• a group of blastocyst cells – the so-called Trofectoderm
• a three-day embryo-blastoma cell
• ovum pole bodies – polocytes
Currently, there is a trend of the blastocyst material examination.

The company REPROMEDA Biology Park Brno carries out the PGS and PGD methods for our workplace..