PGT – monogenic diseases

Pre-implantation genetic testing of monogenic diseases (PGT-M), formerly pre-implantation genetic diagnosis (PGD), is designed for couples with an increased risk of transferring a serious genetic disease via one gene from the parents to the offspring.

What is PGT-M?

Pre-implantation genetic testing of monogenic diseases (PGT-M) is a method that allows the selection of so-called “healthy” embryos without a specific genetic burden. This method is characterised by its close association with assisted reproduction and extra-corporeal fertilization and by the fact that only a selected embryo is transferred to the mother’s uterus. The main advantage of such a procedure is the exclusion of the risk that the foetus will have the observed genetic burden. The couple does not have to deal with any pitfalls associated with artificial interruptions of a pregnancy, which in practice lead to both ethical dilemmas and a mental burden for the couple, as well as the medical complications for the woman. Artificial interruption of pregnancy may also have a detrimental effect on the later ability of the couple to conceive again.

Monogenic diseases

Scientific databases contain reports of over 5,000 rare hereditary diseases that are potentially detectable by pre-implantation testing. Monogenic hereditary diseases are caused by the malfunction of one of our genes.

What are the most common types of rare diseases?

If we simply describe rare diseases by the type of heredity, we can divide them into three basic groups:

• recessive heredity
• dominant heredity
• heredity linked to the sex chromosome

The risk of transfer of the disease to the offspring is different in each group and there are also different requirements for selecting the embryo suitable for the transfer.

The most common rare diseases in our area include:

• cystic fibrosis
• spinal muscular atrophy
• metabolic disorders
• neurofibromatosis
• Marfan’s syndrome
• Huntington’s chorea
• familial hypercholesterolaemia
• fragile X syndrome
• muscular dystrophy syndrome

Furthermore, hereditary dispositions to tumour diseases such as BRCA1 and BRCA2.

What diseases can we investigate?

We have a team of specialists in the genetic laboratory of REPROMEDA who are able to prepare everything so that virtually all rare inherited illness can be excluded via pre-implantation testing.

We do not want any borders and we are ready to overcome all obstacles. Each family has its own specific genetic problem, so we seek optimal solutions individually for each of them.

How do the partners find out that there is a high risk of a certain hereditary disease in their family?

Unfortunately, the most common case is that the partners learn about the genetic burden in their family by conceiving a child with a serious illness of a hereditary nature.

In the best case, one or both partners can learn about their burden in advance – when a genetic examination is done preventively, when the disease is diagnosed in another family member, possibly from the so-called predictive panel,

PGT-M principle

The method enables us to diagnose developmental defects or hereditary diseases before the embryo is introduced into the uterus. This is the only prophylactic method that can prevent conceiving an affected child before the pregnancy itself. On the other hand, it can help select an embryo that will not be affected by the defect or disease in question. PGT-M is the only reliable method for families with a genetic burden to prevent the transfer of serious defects and hereditary diseases to offspring.

PGT-M procedure

Before PGT-M … 

Each couple must complete a set of various examinations before they are included in the assisted reproduction program. A clinical expert will perform a comprehensive diagnosis to decide on the stimulation protocol suitable for the female partner and on specific methods and procedures to be used for the IVF cycle. If partners are found to be suitable candidates for an IVF cycle with a pre-implantation embryo examination, a clinical genetic specialist will be consulted with the focus on pre-implantation testing. Partners learn all the necessary information to successfully complete the treatment and have the opportunity to discuss it with our experts repeatedly.

Basic conditions for successful completion of PGT-M

Generally, it is necessary to obtain a sufficient number of high-quality embryos. We have to consider the fact that a certain group of embryos will be excluded due to the detected high risk of a hereditary illness. If we do not get enough embryos in one cycle to have a good chance of finding a healthy embryo, all embryos can be frozen and stimulation, egg collection and fertilization can be performed again in the next cycle. Embryos from both cycles are then pooled for the examination. This procedure is called “pooling cycle”. This allows for a much higher probability of detecting a healthy embryo and avoiding an unnecessary financial burden on the couple.

Course of PGT-M itself

During PGT-M, eggs are collected from the woman after hormonal stimulation, fertilized, and a group of about seven cells is collected from the developing embryo using a micromanipulator after a five-day embryo culture. This method is very gentle to the embryo and does not pose any risk to the future foetus.

Material for examination

A group of blastocyst cells

• (5- or 6-day old embryo) is most commonly used for the analysis – the so-called trofectoderm
• a 3-day old embryo cell – blastomera
• ovum poles – polocytes

The current trends are based on the examination of blastocyst material. This allows us to judge the complete genome of the future foetus (maternal and paternal part).

The extracted DNA cells are then used to determine the gene structure of the embryo. We can then say with 100% confidence that the tested embryo is either healthy or a carrier of the disease, or has a high genetic risk for the development of the disease in the future.

An embryo that passes this test and is considered genetically appropriate is then transferred to the mother’s uterus. If a couple has more embryos suitable for transfer, such embryos can be frozen in a very gentle manner and stored in liquid nitrogen. Subsequently, they can be used for repeated transfer, or in the future, should the couple want another child.

Embryo transfer

If the examination was performed in 3-day old embryos, the transfer is most commonly performed on day 5.

However, as the examination of blastocyst material is a growing trend, blastocysts can be transferred either on day 6 or vitrified (freezing using a modern method, which is highly safe and effective) and subsequently transferred in the next cycle.

Stimulated cycles do not provide high-quality mucosa. It is better to perform vitrification and transfer later in the next cycle. It is shown that this procedure increases implantation rates, in particular for women of a higher age, and increases the ratio of born children.

How much does PGT-M cost? A great advantage for couples with genetic risks is the possibility of reimbursement of pre-implantation testing from medical insurance. If PGT-M is performed, we provide this method free of charge for the client.

The IVF/PGT-M cycle is associated with further fees related to the IVF method. These include, e.g., the injection of sperm into the egg (ICSI), prolonged embryo culture, embryo cryopreservation, and a fee for hormone therapy drugs required to collect more eggs. This procedure is the same at all centres in the Czech Republic.

For more information on payment terms and further details, contact our experts.

Why PGT-M at Repromeda? At Repromeda, we have been performing pre-implantation testing of rare hereditary diseases since 2004, the longest of all assisted reproduction centres in the Czech Republic. We always try to connect our extensive experience and knowledge in the PGT-M field with the wishes and ideas of the patient about the course of the treatment itself and the entire testing process.

As the first site in Central Europe, we have also introduced the breakthrough karyomapping method into common practice.

Karyomapping
Karyomapping is a new embryo genetic analysis technology that can prevent the transfer of a genetic burden to the next generation. This applies to couples in which both partners are carriers of the respective disease, as well as to people who suffer from a hereditary disease themselves.

How does Karyomapping work?

First, it is necessary to obtain a blood sample of the future father, mother and one close relative who we know either suffers from the disease in question or is healthy (concerning the particular disease). In most cases, this relative is a child of the given couple. A blood sample of this relative is referred to as the “reference sample”.

Using Karyomapping, it is possible to investigate the chromosomes, the formations of our DNA, and proteins that contain genes and are stored in human cells. Karyomapping is used to examine maternal, paternal and reference chromosomes at approximately 300,000 different sites. This will reliably provide the so-called “DNA profile” of the chromosome with the mutated gene. Subsequently, all embryos are examined to reliably exclude those that have the mutated gene.

If the DNA profile associated with the mutated gene is not present, it can be said that the embryo inherited the normal copy of the gene without the mutation and should be healthy (concerning this disease). Such embryos are suitable for the transfer to the uterus of the mother.

How does Karyomapping differ from other methods used in PGT-M?

Simplification and speed

In addition to DNA of the partners, there is no need to request DNA from other family members. A DNA sample from only one affected family member (child or other relative) is sufficient; in some cases, even DNA from both partners is sufficient.

Solutions for hereditary cancer

This method is suitable not only for all monogenic diseases but also for all inherited cancers such as mutations in BRCA1 and BRCA2 genes.

Two in one

The karyomapping examination also includes the screening for aneuploidy of all the chromosomes (PGT-A) from the same sample, providing all the benefits associated with this examination. Only healthy embryos with the right number of chromosomes are selected for the transfer, which increases the chances of pregnancy and at the same time eliminates the conception of a child with other developmental defects caused by the wrong number of chromosomes (Down syndrome, Edwards syndrome …).

Our recommendation

Pre-implantation genetic testing of monogenic diseases cannot guarantee the birth of an absolutely healthy child, but it can safely rule out the transfer of a specific genetic burden to the next generation.

In such a case, the couple does not have to worry any longer that they will have to consider an artificial interruption of pregnancy due to a previously known problem. This helps avoid decisions on an issue complicated from both ethical and human aspects, and, on the contrary, will enable the couple to go through the entire pregnancy in the same joyous expectation as all the other parents.

IScan, which we use for the Karyomapping method in pre-implantation genetic testing.