Preimplantation Genetic Diagnosis (PGD)

What does it involve?

Preimplantation Genetic Diagnosis (PGD) is a technique with which to detect genetic anomalies in the embryo before it is transferred to the woman’s uterus. It is complementary with in vitro fertilisation (IVF), as the embryos studied are obtained by this method.

In 1990, Dr Handyside’s team published the results of the first pregnancy accomplished after having subjected the couple’s embryos to PGD. Its applications and diagnostic potential have continued to increase over time.

PGD involves the biopsy or extraction of a cell of the embryo obtained in an IVF cycle in its initial stages of development (normally the third day of culture). The extracted cell is analysed in order to evaluate the presence of specific genetic or chromosomal characteristics. While the study lasts, the biopsied embryos are kept in culture in the laboratory awaiting the result.

The embryos that are normal will be selected for transfer or freezing, while abnormal embryos are ruled out once and for all.

PGD therefore prevents the transmission of genetic and chromosomal abnormalities or diseases, reduces the risk of spontaneous miscarriages and even prevents the possible need to interrupt the pregnancy. It therefore improves the efficiency of IVF programmes.

For specific diseases, a clinical geneticist must be consulted before starting a PGD cycle. This specialist should perform exhaustive tests of the disease, determine the procedure to be followed and ensure detection, as the techniques have their limitations. Note too that the chances of successful treatment also depend on each case.

When is PGD applicable?

In current legislation it is applicable in the following circumstances:

• Serious hereditary diseases of early onset not susceptible to postnatal curative treatment such as cystic fibrosis, renal polycystosis and Huntington’s disease, or X-chromosome related diseases (haemophilia, Fragile X syndrome, etc.).
• Chromosomal abnormalities (aneuploidy) that may compromise embryo viability and appear because of unfavourable conditions (advanced maternal age, recurrent miscarriages, etc.).
• PGD for a third party, i.e. the selection of embryos to achieve pregnancy with HLA-typing identical (histocompatible) to that of a sibling affected by a serious haematological disease. The purpose is to be able to transplant cells from the umbilical cord of the newborn baby to the family member, although this requires the prior consent of the National Commission on Assisted Human Reproduction (CNRHA).
• Some predisposition to hereditary and familial cancer. This requires a compulsory report from the CNRHA.

When is PGD advisable?

This technique may be useful in different situations:

• Patients who are ill or carriers of genetically transmitted diseases caused by alteration to a specific gene (monogenic diseases). Gender-related diseases.
• Patients carrying transmissible chromosomal abnormalities.
• Patients with a high risk of genetic alteration to their gametes (eggs and spermatozoa) that could give rise to the formation of genetically abnormal embryos.

How is genetic material tested?

There are three molecular biological techniques for testing genetic material:

• Polymerase Chain Reaction (PCR): it involves the specific amplification of certain DNA sequences. By applying a specific number of amplification cycles, the amount of DNA can be increased to a detectable observable level. When amplification has taken place, different molecular biological techniques are used to analyse the desired sequence.

• Fluorescent In Situ Hybridisation (FISH): a fast, useful technique for studying the amount and general structure of chromosomes. It allows for specific zones of the chromosome to be labelled with fluorescent markers. Observation and diagnosis involve fluorescence microscopy. Up to 12 chromosomes can be studied.

• Microarray-based comparative genomic hybridisation (array-CGH): involves a technique for analysing multiple regions in each and every chromosome. It initially entails Whole Genome Amplification (WGA) and thereafter fluorescent labelling of the DNA and its hybridisation on BAC arrays. Subsequent analysis of the array yields information on excesses or deficiencies in the DNA present.

Would you like to know more?

In some cases informativity testing is necessary prior to the PGD cycle in order to evaluate possible diagnoses in each case.

Although PGD is very reliable, it is not 100% failsafe. Once pregnancy has been achieved, a prenatal diagnosis test is therefore advisable.

The response to ovarian stimulation in the IVF cycle necessary to obtain the embryos for PGD should also be evaluated. It is advisable to have several embryos available.

If the IVF response is low and there are few available embryos, these can be frozen for future IVF cycles. When an appropriate number of embryos have been obtained, they are thawed and the PGD is done on all the embryos.

There may be cases in which no normal embryo is obtained.