Preimplantational Genetic Diagnosis

What is preimplantational genetic diagnosis?

Preimplantational genetic diagnosis (PGD) is a technique which allows the detection of chromosomal alterations, as well as hereditary genetic diseases in embryos obtained by in vitro fertilisation (IVF). In this way, through PGD, couples with a risk of transmitting some alteration or genetic disease to their descendents are able to continue with the pregnancy knowing that the embryo is not affected by this genetic alteration.

Hospital Clínics assisted reproduction unit achieved the first birh with PGD in 1998. Since then, many patients have achieved the birth of healthy children thanks to this technique. During these years, the number of diagnosed diseases with PGD has increased.

DGP Biopsia biòpsia embrionària
DGP Biopsia2 biòpsia embrionària

What is the legal framework?

The legal framework of PGD is under the Llei 14/2006 de 26 de maig (Law 14/2006 March 26), on human assisted reproduction techniques, specifically in article 12 which indicates when a cycle of PGD is allowed.

What are the current indications for performing PGD?

A PGD cycle is currently indicated in the following cases:

  1. Progenitors carrying chromosomal alterations (reciprocal translocations, Robertsonians or inversions). The aim is reducing the risk of generating chromosomally unbalanced embryos.
  2. Progenitors carrying monogenic diseases. The most frequent are: Huntington disease, cystic fibrosis, fragile-x syndrome, Steinert disease. The diagnoses of less frequent monogenic diseases may also be undertaken (see list of diseases treated in our center).
  3. In selected cases, PGD may be indicated for the study of possible alterations in the number of chromosome (aneuploidies) as in patients with repeated miscarriages or in patients with repeated implantation failure, that is, in patients who become pregnant but the gestation is repeatedly interrupted in a very early phase. In these cases, a complete study of the embryos’ chromosomes is recommended.

 

Can embryos be selected for other objectives? Will the indications for PGD be extended in the future?

Yes, it is currently possible to use PGD for other objectives too.Specifically, the new Law on assisted reproduction extends the possibility of using PGD with therapeutic aims to third parties, usually for treating siblings with very severe onocologic blood disease. In these cases, it is possible to select the histocompatible embryos, that is, those that have great immunologic similarity with the person to be treated in order to carry out the gestation. Later, at the time of birth, the blood from the umbilical cord of the fetus selected through the PGD technique is extracted and can be prepare and use in a transplant.

Moreover, the Comisión Nacional de Reproducción Humana (Human Reproduction Nacional Comission) has also allowed to use PGD in case of genetic predisposition of certain diseases such as breast and/or ovary (BRCA1,BRCA2).

An increase in PGD indication is foreseeable because of a better knowledge of genetic origin diseases.

 

What does PGD consist of?

To carry out PGD it is necessary to undergo IVF treatment for obtaining a determined number of oocytes, which are fertilised by an intracytoplasmatic spermatozoid injection technique (ICSI). The embryos obtained are cultured in the laboratory and on the third day post-fertilisation, when the embryo has six to eight cells, the embryonic biopsy is performed. The biopsy consists of the exctraction of one cell from each embryo to analyze its genetic content. Recently, PGD with embryo in blastocyt stage (fifth day of postfertilization) and embryo biopsy cells from trofoectoderm through laser have been developed.

There are different techniques so as to diagnose DGP:

  • FISH may be carried out to search for a certain number of chromosomes that are generally involved in a certain chromosomic alteration

  • aCGH may be carried out for a complete study of the 24 chromosome

  • PCR may be done to analyse if possible mutations of the genes can cause monogenic diseases

 

Once the results of PGD are obtained, the embryos, which are considered viable according to the preimplantational study and are therefore not affected by the alterations or genetic diseases studied, will be transferred.

How reliable is the technique?

The reliability is over 90%. Nevertheless, prenatal diagnosis studies are recommended during gestation with the aim to minimize the possibility of a false negative result.

Are there risks or added side effects?

No, there are not. The side effects are the same as in IVF cycles. When it comes to the biopsy, the possibility of embryo damage is very low; it is less than 0.6 %.

Monogenic diseases that have been analyzed in our center

Adrenolenkodystrophy linked to chromosome X

Idiopathic arterial calcification

Charcot-Marie-Tooth disease

2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD )

Ornithine transcarbamylase deficiency

Facioscapulohumeral Dystrophy 

Becker Muscular dystrophy

Duchenne Muscular dystrophy

Hereditary multiple exostoses

Cystic Fibrosis

GM1 gangliosidosis

Glycogen type 1ª

Hemophilia

Heterotaxy linked to chromosome X

Nonketotic hyperglycemia

Hypochondroplasia

Ceroid lipofuscinosis

Steinert disease

Huntington disease

Hypertrophic cardiomyopathy

Neurofibromatosis type 1

Imperfect osteogenesis

Pelizaeus-Merzbacher disease

Autosomal recessive polycystic kidney disease

Genetic predisposition to breast and/or ovary cancer (BRCA1, BRCA2)

Retinosis Pigmentary

Brugada Syndrome

Lynch Syndrome

Rendu-Osler-Weber Syndrome

Fragile X Syndrome