Preimplantation Genetic Testing

Here at Sistemas Genómicos, we are currently the only Spanish laboratory that has been certified for PGT (Preimplantational Genetic Testing): we offer a PGT programme aimed at IVF centres with the maximum level of guarantees and the best diagnostic technology.

This technique is carried out on human embryos created using in vitro fertilisation techniques, and under the strictest bioethics and legal guidelines. A biopsy is carried out on the embryos in order to analyse whether or not there are any specific genetic mutations, allowing us to select an embryo that does not have the genetic disease under analysis.

Types of Preimplantation Genetic Studies

PGT

PGT is a genetic diagnostic method combined with in vitro fertilisation techniques aimed at preventing the transmission of genetic and hereditary diseases to children.

It is conducted on human embryos created using in vitro fertilisation techniques. Biopsies are conducted on the embryos using micromanipulation techniques. The biopsy can be carried out on third day of the culture (D3) or at later stages on the blastocyst (D5). The biopsy on D3 allows us to get a unique cell, known as the blastomere, while on D5, a biopsy can be carried out on the trophectoderm, a tissue that covers in internal wall of the embryo on D5.

Blastomere (D3)

Trophectoderm (D5)

The sample from the biopsy is subject to genetic analysis to find out the genetic status of the embryo it comes from. Lastly, the embryo without the disease is transferred to the mother’s womb, thus preventing transmission.

WHO IS IT AIMED AT?

 

It is aimed at all couples with a genetic risk; in other words, those who have a family member who is suffering from or is a carrier of any genetic and hereditary disease who want make sure they have healthy children. It is important to note that the vast majority of these couple are not infertile.

Diseases Analysed

 

In each case we analyse the disease that the couple presents. Specifically, these could be monogenic diseases (dominant, recessive and connected to the X chromosome), structural chromosome abnormalities (reciprocal translocations, Robertsonian translocations, inversions and other complex rearrangements) or numerical chromosome abnormalities (Turner syndrome, Klinefelter syndrome, etc.).

When conducting a PGT for monogenic diseases, we can do this for all of them that have an identified cause (https://omim.org/). In other words, we need to have one or more mutations that cause the disease that have been identified in order to conduct the PGT.

Steps to Follow to Conduct a PGT

 

Contact an assisted conception centre of your choice. They will coordinate the entire process with us, with the maximum level of guarantees. Your centre will determine what genetic reports and family information you will need in order to assess your case.

Your assisted conception centre will inform you of all of the steps to follow according to your indications to complete a PGT cycle.

PGT-M (PGT for monogenic diseases)

WHO IS IT AIMED AT

 

PGT-M (PGT for monogenic diseases) is recommended when both members of the couple are asymptomatic carriers of a disease or when one of them is affected by a genetic disease caused by the mutation of a specific gene.

Before carrying out the cycle, it is necessary to carry out a Genetic Informativity Study.

What is involved in a Genetic Informativity Study?

What is a Genetic Informativity Study?

 At Sistemas Genómicos, we know that every couple has different needs. All of us have copies of every gene (each of them inherited from a parent).

The Informativity Study allows us to know which copy of the gene contains the mutation that causes the disease in each couple.

This information is necessary to know what genetic information will be transmitted by each parent to the future embryos and to offer all of the diagnostic guarantees in PGT.


To obtain this information, some family members need to participate in the informativity study.

Our genetics experts will determine which family members are necessary during the consultation for the case.


In some cases, the couple cannot get other members of their family to collaborate for various reasons: deaths in the family, family members that do not wish to participate, etc. This complicates the pre-IVF study.

In cases where the male is the affected part of the couple and the disease has recently appeared (the first case in the family), we can do an additional study on sperms to know which copy of the gene contains the mutation.

COMPATIBLE EMBRYO SELECTION VIA PGT-M

 

In these cases, the couple is looking to have a child that is a match for their affected child. When they are born, the new child will be a donor for their sick brother or sister using stem cells from their umbilical cord.

Such cases require special authorisation from the Health Authorities of the relevant Regional Government as stipulated in the Assisted Human Reproduction Act 14/2006. Your IVF centre must request authorisation.

The steps to follow are the same as those for a PGT for monogenic diseases and what we are analysing in this case is a coding region of the genome that controls immune response, (knows as the HLA: Human Leukocyte Antigen region).

Diseases that affect the HLA system can be hereditary (but not always). If the parents are carriers of the disease that is affecting their child, PGT allows them to find embryos that are compatible and free from the disease so that their future donor child will be born healthy.

Time Frame for Conducting a PGT-M

The PGT-M is carried out in close collaboration with the assisted conception centre.

The complete PGT-M process includes stages carried out by the Reproductive Genetics Unit (in blue) and the assisted conception centre (in green).

PGT-A (PGT for aneuploidy)

PGT-A (PGT for aneuploidy) is a chromosome analysis conducted on embryos in the preimplantation stage. The aim is to select embryos with a normal number of chromosomes for the chromosomes under analysis, detecting aneuploidy; in other words, increases or decreases of one particular chromosome in the embryo. This does not detect increases or decreases in chromosome fragments or chromosome rearrangements. The transfer of an aneuploid embryo can reduce the conception rate and increase the percentage of spontaneous miscarriage.

Who is it aimed at?

 

It is aimed at any couple who uses an IVF clinic due to infertility without any family history of hereditary diseases. The established recommendations are:

  • Couples who have suffered repeated miscarriages, normal karyotypes and trombophillia screening.
  • Couples with successive failed attempts after using assisted conception techniques.
  • Women of a late reproductive age.
  • Couples with previous aneuploid conceptions.
  • Men with high aneuploidy levels in their sperm.

diseases analysed

 

Due to the nature of the study, no specific disease is studied. Only the number of chromosomes is studied. An abnormal number of one or more chromosomes is directly linked to miscarriages in the situations listed above.

Time frame for Conducting a PGT-A

The process is simpler than that of other PGTs. It is directly scheduled in with the IVF process.

Complete Process in massive sequencing Cases
Complete Process in massive sequencing Cases

PGT Structural Chromosome Abnormalities

Analysis of structural chromosome abnormalities diagnosed in parents-to-be by karyotype.

WHO IS IT AIMED AT?

 

Couples that are carriers of structural chromosome abnormalities (such as reciprocal translocations, Robertsonian translocations or inversions) can generate abnormal embryos and, in some cases, have problems with infertility and/or subfertility. In these cases, we conduct the PGT for any kind of chromosome abnormalities that have been diagnosed in either of the parents by karyotype.

Studies Options

 

There are two diagnosis options: FISH (fluorescent in situ hybridization) and massive sequencing.

The FISH technique only allows for the analysis of the chromosomes involved in the abnormality under analysis and requires a prior informativity study.

Massive sequencing study all of the chromosomes and do not require a prior informativity study.

Structural Chromosome Abnormalities Studies

 

In most cases of PGT with Structural Chromosome Abnormalities, this is carried out using CGH array or massive sequencing techniques.

Occasionally, when the unbalanced pattern of structural rearrangement of which either member of the couple is a carrier is lower than 20 Mb, it will be necessary to study it using the FISH technique.

Your centre, along with our genetics experts, will assess which type of technique is best for your specific case.

Time frame for Structural Chromosome Abnormalities PGD

Complete process for FISH cases
Complete process for massive sequencing cases

Combined PGT-SR

Who is it aimed at?

 

Combined PGT is intended for any couple in which both members are asymptomatic carriers of a disease or if one of them is affected by a genetic disease. Furthermore, sometimes there is more than one clinical indication for the same couple.

The most common case is when a couple is a carrier of a monogenic disease and one of the indications for PGT: advanced age of the mother, abnormal sperm FISH, etc. In other cases, which are much less frequent, there is more than one disease present in the couple, for example when one partner has an abnormal karyotype as well as a monogenic disease.

Before carrying out the cycle, it is necessary to carry out a Genetic Informativity Study.

What is involved in a Genetic Informativity Study?

What is a Genetic Informativity Study?

 At Sistemas Genómicos, we know that every couple has different needs. All of us have copies of every gene (each of them inherited from a parent).

The Informativity Study allows us to know which copy of the gene contains the mutation that causes the disease in each couple.

This information is necessary to know what genetic information will be transmitted by each parent to the future embryos and to offer all of the diagnostic guarantees in PGT.


To obtain this information, some family members need to participate in the informativity study.

Our genetics experts will determine which family members are necessary during the consultation for the case.


In some cases, the couple cannot get other members of their family to collaborate for various reasons: deaths in the family, family members that do not wish to participate, etc. This complicates the pre-IVF study.

In cases where the male is the affected part of the couple and the disease has recently appeared (the first case in the family), we can do an additional study on sperms to know which copy of the gene contains the mutation.

Study with various indications in the same sample

 

With Combined PGT we can study various monogenic diseases, aneuploidies or structural chromosome abnormalities and we can even select which embryos are most histocompatible for a sick brother. All in just one embryo biopsy.

Combined PGT time frame

The best strategy is to analyse whether the embryos are free of the first monogenic disease and then study the aneuploidies in these embryos. To do this, the embryos must be frozen (vitrification).

Complete process for Combined PGT with an aneuploidy study using massive sequencing