PGD/S involves genetic procedures performed on embryos prior to implantation. PGD/S works in conjunction with assisted reproductive technology and requires in vitro fertilisation (IVF).

PGD is the diagnosis of specific genetic and chromosome abnormalities in couples who are at high risk of transmitting these abnormalities to their children. PGS is the aneuploidy screening of as many chromosomes as possible in embryos from patients with subfertility with the aim of increasing their chances of a normal pregnancy.

Embryo biopsy remains the main approach to removing DNA for genetic analysis. Cells must be removed from the embryo and must contain a nucleus to be suitable for genetic analysis. Scientific studies thus far have shown that further development of the embryo is not impaired by the biopsy.

The techniques used for PGD/S are fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), array – Comparative Genomic Hybridisation (array-CGH) and karyomapping. FISH uses fluorescently tagged DNA probes which bind to their complementary sequence on a specific chromosome and may be visualised under a fluorescence microscope. PCR is a technique that amplifies a piece of DNA into thousands of copies of a specific DNA sequence. Single cell PCR is a technically demanding procedure. Array-CGH is a genome-wide screening tool for the detection of copy number imbalances. Karyomapping determines whether embryos have inherited gene defects by analysing DNA from the embryos and close relatives.

The success of the complete PGD/S procedure is dependent on various factors: fertilization, embryo quality, successful biopsy, genetic testing procedure and result interpretation. This whole process influences the number of healthy embryos available for transfer.

Chromosome Rearrangement PGD

Robertsonian and reciprocal translocations are the most common form of chromosome abnormality in humans, present in approximately one in 500 individuals. Couples where one partner carries a balanced translocation or other structural abnormality are at risk of having genetically unbalanced conceptions, which may result in failure to implant, miscarriage, or children with physical and/or mental disability.

In collaboration with a UK laboratory, testing for translocations can also be carried out using array-CGH, to not only identify the presence or absence of translocations but also assess all of the chromosomes. Therefore, a-CGH covers not only translocation testing but aneuploidy testing too. A theoretical work-up of two weeks is required.

Translocation PGD can only distinguish between embryos that are balanced or unbalanced, therefore, it cannot distinguish between embryos which are chromosomally normal or carry the balanced translocation.

Monogenic disorder PGD

Robertsonian and reciprocal translocations are the most common form of chromosome abnormality in humans, present in approximately one in 500 individuals. Couples where one partner carries a balanced translocation or other structural abnormality are at risk of having genetically unbalanced conceptions, which may result in failure to implant, miscarriage, or children with physical and/or mental disability.

In collaboration with a UK laboratory, testing for translocations can also be carried out using array-CGH, to not only identify the presence or absence of translocations but also assess all of the chromosomes. Therefore, a-CGH covers not only translocation testing but aneuploidy testing too. A theoretical work-up of two weeks is required.

Translocation PGD can only distinguish between embryos that are balanced or unbalanced, therefore, it cannot distinguish between embryos which are chromosomally normal or carry the balanced translocation.

PGS

Many studies have shown that the incidence of chromosome abnormalities in early embryos is high (50-70%). Data from oocyte donation shows that women of advanced maternal age (AMA) have decreased delivery rates due to poor oocyte quality. Therefore PGS for infertility has been developed to help women with AMA, recurrent implantation failure (RIF), repeated miscarriage (RM), and other indications. Selecting chromosomally normal embryos for replacement should increase the implantation rate, reduce spontaneous miscarriage rates and reduce aneuploid conceptions.

Even though the FISH method has been properly standardised, it remains limited to the amount of fluorescent colour dyes available. This limits the number of chromosome DNA probes used simultaneously on one cell; thus requiring one or more extra rounds of hybridisation to analyse more chromosomes.

PGS can also be carried out using Array-Comparative Genomic Hybridisation (a-CGH). a-CGH assesses all of the chromosomes. It is a more comprehensive technique that is hypothesized to improve the success rate of IVF.

PGS-1-300x224

An embryonic cell indicating 2 copies of chromosomes 13, 18 and 21

PGS-2-300x224

An abnormal embryonic cell indicating 2 copies of chromosomes 16 and 22, but only 1 copy of chromosome 15

Sex-linked Disease PGD

Sex-linked diseases are caused by mutations in genes carried on the sex chromosomes. X-linked diseases are far more common than Y-linked diseases due to the fact that there are many more genes on the X-chromosome than the Y-chromosome. X-linked diseases are inherited from a carrier mother or from an affected father. Each son born to a carrier mother has a 50% chance of inheriting the X chromosome carrying the mutant allele.

Sex selection for a non-medical reason is unacceptable and illegal in South Africa. (Tissue Act 2012)

The best option is to select for embryos that are genetically normal for the sex-linked disorder. In this instance, gender is not tested. The defective gene is examined using PCR or karyomapping.