In what cases is it indicated?

• Couples at risk of transmitting chromosomal alterations or monogenic diseases.
• Couples with a medical history of repeated miscarriages.
• Implantation failure after several attempts with IVF.
• Abnormalities in spermatozoa meiosis.
• Women of advanced age.

Results

In 2006, in a world first, IVI achieved the birth of a baby to a couple in which one partner was a carrier of lymphohistiocytosis, thanks to the technique of assisted reproduction with PGD.

PGD allowed the chain to be broken in chromosomal hereditary diseases carried by 72% of the embryos analysed in 2001. As such, thanks to the study of chromosomal abnormalities through the FISH and arrays techniques, around 50% of the embryos transferred resulted in pregnancy. PCR analysis of monogenic diseases led to a 54% pregnancy rate per transfer.

PGD Techniques

For couples who have been referred due to a monogenic disease, molecular diagnosis can identify whether embryos are genetically normal or whether they will be affected by the disease which has prompted the study. For couples for whom a chromosomal study is recommended, cytogenetic molecular diagnosis allows normal or balanced embryos to be identified in terms of the chromosomes which are included in the study. In order to test for numerical chromosome abnormalities two techniques can be used: the FISH technique (fluorescence in situ hybridisation) and the Array CGH technique.

Until just a few years ago, genetic diagnosis of the embryo only allowed 9 of the 23 pairs of chromosomes to be studied. Thanks to array CGH, all 23 pairs of chromosomes can be examined in order to rule out any aneuploidies before implantation takes place. Aneuploidies are abnormalities in the number of chromosomes that can cause repetition faults in assisted reproduction cycles, spontaneous miscarriage and chromosomal anomalies in new-born babies. This technology makes it possible to identify which pre-embryos are healthy and which are not in the laboratory. CGH is recommended for patients who have suffered from repeated miscarriage, couples who risk presenting chromosomal abnormalities in their offspring, and also for female patients over the age of 40 who are planning to become pregnant using their own ova.

Fluorescence in situ hybridisation (FISH) consists of marking specific chromosomes in the nucleus of the spermatozoa with fluorescent DNA probes in order to determine whether or not a chromosomal abnormality is present. The FISH test is extremely useful for advising couples who consult a specialist because of an infertility problem.

Procedure

The purpose of PGD is to analyse pre-embryos in the laboratory following in vitro fertilisation and before they are transferred to the maternal uterus. A biopsy is performed and the pre-embryos are analysed, allowing us to distinguish between the healthy ones and those which are affected. The doctor can therefore transfer only those which will result in a pregnancy with a completely healthy baby.

The technique of assisted reproduction with PGD is the result of combining in vitro fertilisation with a biopsy of pre-embryo cells by means of micromanipulation and cytogenetic molecular diagnosis techniques.

1. Preliminary phase. In this phase genetic characterisation tests are carried out on the carrier parents for the diseases to be diagnosed, with the objective of gaining as much information as possible prior to applying PGD.
2. Obtaining pre-embryos. This involves obtaining the pre-embryos which will undergo diagnosis. They must be generated “in vitro” using assisted reproduction techniques, even if the couple do not present any kind of reproductive problem that would prevent natural procreation. This is due to the fact that obtaining pre-embryos through uterine lavage is expressly prohibited.
3. Pre-embryo biopsy. The pre-embryo biopsy is performed on the third day after fertilisation, when the pre-embryo has 6 – 8 cells. It consists of extracting one or two cells from the pre-embryo, without compromising its normal development as a result. Once the biopsy has been performed the pre-embryos are put back into the incubator and they stay there until the results of the diagnosis are obtained and the possibility of transferring them is assessed.
4. Genetic diagnosis and pre-embryo transfer. The biopsy obtained is processed for analysis and a genetic study is carried out. Using the results of the genetic analysis the medical team at the Centre decides, jointly with the couple, which pre-embryos will be transferred.

What are chromosomes and genes?

Every single cell in the human body has in its nucleus 46 chromosomes (23 from the father and 23 from the mother).

These chromosomes are formed of a substance called DNA which contains our genetic information. This information is distributed over thousands of tiny fragments known as genes. As such, there are two copies of every gene, one of which has come from the mother and the other from the father.

What abnormalities of the chromosomes and genes can cause diseases?

• Numerical alterations: this is an anomaly that affects the number of copies of a chromosome, in other words instead of there being two copies of a chromosome there are three or just one. The most well-known example is Down’s syndrome, in which there are three copies of chromosome 21 instead of two.
• Structural alterations: this is an anomaly in the contents of a chromosome, that is to say a section is out of place or missing
• Monogenic diseases: these are genetic diseases caused by a fault or mutation in a single gene. Known examples of this type of disease are Cystic Fibrosis, Haemophilia, Fragile X Syndrome, Myotonic dystrophy, and Huntington’s disease, among others.