Pre-implantation Genetic Diagnosis (PGD) of monogenetic diseases and chromosomal defects
FOR DETECTING MONOGENETIC DISEASES
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PROCREA HAS BEEN OPERATING FOR YEARS AND IS ONE OF THE PIONEERS IN SWITZERLAND IN THE FIELD OF PRE-IMPLANTATION DIAGNOSIS. THE CLINIC HAS A MEDICAL GENETIC LABORATORY THAT AVAILS OF THE LATEST TECHNOLOGIES FOR ENSURING THE UTMOST DIAGNOSTIC EFFECTIVENESS AND ACCURACY. IN ADDITION, THE PROXIMITY AND ONGOING INTERACTION BETWEEN THE EMBRYOLOGY LABORATORY OF THE PROCREA CENTRE AND THE GENETIC LABORATORY MAKE IT POSSIBLE TO INCREASE THE CHANCES OF SUCCESS, BOTH IN TERMS OF ANALYSES AND THE THERAPIES.
Pre-implantation Genetic Diagnosis (PGD) makes allows for ruling to rule out the presence of serious genetic diseases of which one or both parents are carriers
This analysis is proposed if there is a serious genetic disease in the family, to allow for transferring only embryos that are not affected by the disease into the mother’s body.
PGD has been carried out in the large centres since 1992 and has allowed numerous couples who are carriers of genetic diseases to have healthy children.
Which cells are analysed
In line with the latest international recommendations, the Centre proposes two type of embryonic biopsy:
► Analysis of the polar globules of the oocyte
► Analysis of the trophectoderm cells of the blastocysts
Biopsy of the polar globules of the oocyte
This allows for analysing the genetic material coming from the mother’s side of the family and is therefore indicated in case of:
► Dominant autosomal diseases of maternal origin
► Chromosome X-linked diseases of which the woman is a healthy carrier
► Recessive diseases, of which both parents are healthy carriers
► Structural anomalies in the chromosomes
However, with this analysis it is not possible to evaluate the dominant diseases of paternal origin.
Trophectoderm cells (TE) of the blastocysts
This allows for analysing the genetic material from both partners.
The test is therefore suitable for the diseases indicated above as well as those of paternal origin.
► Dominant autosomal diseases of maternal and paternal origin (e.g. Neurofibromatosis)
► Chromosome X-linked diseases of which the woman is a healthy carrier (e.g. Duchenne Muscular Dystrophy or Haemophilia)
► Recessive diseases, of which both parents are healthy carriers (e.g. Thalassemia or Cystic Fibrosis)
► Structural anomalies in the chromosomes.
WHAT ARE TROPHECTODERM CELLS
Trophectoderm cells are the ones that make up the outer layer of the blasocysts. At this stage, the embryo consists of a few hundred cells. The trophectoderm forms the placenta while the embryo will be formed by the internal mass. The biopsy of several cells for the genetic analysis is carried out on the trophectoderm. In this way, the internal mass that will form the embryo is not touched.
WHAT ARE POLAR GLOBULES
Polar globules are produced during the maturation of the oocyte and contain the supplementary chromosomal structure of the oocyte. They do not serve any purpose and are not future constituents of the embryo, instead representing a so-called “derivative product” that can be extracted for the genetic analysis. In this way, the embryo is not touched or damaged.
THE PGS PROCEDURE
Pre-implantation genetic diagnosis (PGD) requires that the couple undergo an assisted reproduction cycle in order to be able to recover the oocytes or embryos, analyse them and transfer only those embryos without any family diseases.
The molecular technique used is extremely sophisticated and requires a setup time of the analysis for all patients. This is to allow the optimisation of the analysis, which is adapted to the genome and specific genetic mutation present in the patient.
The polar globules or cells of the trophectoderm are recovered by practicing a small hole with the laser and aspirating the cells.
The genetic material is then analysed by means of a procedure that minimises the risk of diagnostic errors (less than 1%). The genetic analysis of these cells provides very accurate results and therefore only transfers healthy embryos to the uterus the third and sixth day after fertilisation.
THE PERCENTAGE OF PREGNANCIES
The couples who are referred to an assisted reproduction centre in order to access the PGD technique are generally fertile couples who have a good probability of a successful pregnancy.
As always, the probability of a pregnancy depends largely on the mother’s age and varies between 65% and 35% of term pregnancies. The average pregnancy rate for all maternal ages is around 50%..
THE QUALITY OF THE ANALYSES
The genetic analysis of a single cell is an extremely sophisticated procedure that requires highly qualified staff and an adequate infrastructure. Our laboratory is certified and accredited with international industrial standards (ISO/IEC 17025 and ISO 15189). This accreditation ensures a high quality standard and a low likelihood of error.
The ProcreaLab is the only laboratory in Switzerland and in Italy to have an accredited process of analysis for the entire pre-implant diagnosis of monogenetic diseases according to the international standard 15189..
THE PROCEDURE TO BE FOLLOWED FOR COUPLES WANTING TO UNDERGO A PGD
► Contact our centre and arrange a visit with the specialist assisted reproduction gynaecologist and geneticist
► The geneticist will advise you about the genetic tests to be conducted to identify the mutations present in the family (if you are not already aware of them)
► The geneticist will also inform you of the feasibility of a pre-implantation tests (in some cases the PGD may not be possible)
► Together with the doctor, the geneticist and the embryologist, you will decide which type of biopsy to perform (polar globules or biopsy of the blastocysts)
► the genetic laboratory will draw up and validate a personal test for your family. This period of preparation may last 2-3 months
► You will get to know the staff of the medically assisted procreation centre and begin therapy under the guidance of the gynaecologist you previously encountered up until the tie of obtaining various oocytes.
► After the pick-up, two polar globules will be extracted at different times (the first a few hours after the pick-up, and the second approximately 12-18 hours after fertilisation) otherwise it will be necessary to wait until after the formation of the blastocysts in order to withdraw some of the trophectoderm cells (about 5 days)
► The cells will be genetically analysed to exclude any embryos with genetic anomalies.
► One or two disease-free embryos will be transferred into the patient’s uterus.
The PGD procedure
These two techniques are both valid and very reliable in terms of the diagnostic result, and both constitute a very limited risk for the embryo. They have advantages and disadvantages and the choice is made together with the couple, taking into account their specific issues.
Polar globules can be extracted very soon after fertilisation (the first, a few hours after ICSI and the second about 12 hours later). This allows for having sufficient time to analyse them without the need to freeze all the embryos. There is in fact all the time necessary to make a transfer of the embryo from the third to the fifth day.
The disadvantage of this technique is mainly the fact that only diseases from the maternal branch can be analysed. It is therefore not a technique indicated if the genetic disease originates from the father's side of the family.
The cells of the trophectoderm of the blastocysts offer the advantage of containing both the maternal and paternal genomes. It is therefore possible to use them to analyse genetic diseases coming from both sides of the family. In addition, the genetic analysis is facilitated by the fact that there are more cells available to analyse.
The disadvantage of this technique is that, having to wait until the fifth day of cultivation in order to obtain the material to be analysed, it will hardly be possible to proceed with an "on the spot" embryo transfer. The embryos will have to be frozen and transferred during a subsequent cycle.
Pre-implantation diagnosis: the experience accrued by Procrea
Thanks to its remarkable know-how in the field of medical genetics, the Procrea Centre's genetics laboratory is able to propose pre-implantation for any type of monogenic disease or chromosomal anomaly. The only condition is that of having determined the genetic defect that causes the disease. Many laboratories offer a very narrow range of analyses. Our laboratory has validated and accredited a process that allows for analysing any variants in any gene causing the disease. For this reason, Procrea has become a name in the pre-implantation diagnosis of very rare diseases. In the table below are some of the diseases we have successfully analysed.
Familial reciprocal translocations
Spinal muscular atrophy -SMN1
Gaucher Disease - GBA
Fragile-X syndrome - FMR1
Cobalamin C defect - MMACHC
Cystic Fibrosis - CFTR
Duchenne muscular dystrophy - DMD
Synpolydactyly – HOXD13
Optic atrophy – OPA1
Achromatopsy - CNGB3
X-linked Mental Retardation
Familial pheochromocytoma- paragaglioma - SDHB