FCC offers both Next-Generation Sequencing (NGS) and Comparative Genomic Hybridisation (CGH). We collaborate with Reprogenetics in the USA.
It’s worth noting that deciphering DNA sequences is essential for virtually all branches of biological research. With the advent of capillary electrophoresis (CE)-based Sanger sequencing, scientists gained the ability to elucidate genetic information from any given biological system. This technology has become widely adopted in laboratories around the world, yet has always been hampered by inherent limitations in throughput, scalability, speed, and resolution that often preclude scientists from obtaining the essential information they need for their course of study. To overcome these barriers, an entirely new technology was required—Next-Generation Sequencing (NGS), a fundamentally different approach to sequencing that triggered numerous groundbreaking discoveries and ignited a revolution in genomic science.
What is PGD/PGS?
PGD (pre-implantation genetic diagnosis) is used to detect known genetic or chromosomal disorders carried by the parents. PGS (pre-implantation genetic screening) is used to detect chromosomal disorders in the embryo, the main source of embryo related In-Vitro fertilization failures. It does not help reduce miss-carriages due to insufficiencies in the endometrium. During the procedure, a number of cells are carefully biopsied from the embryo and checked for chromosome number and structure prior to embryo transfer. There are various methods of PGD/PGS available, depending on the needs of the individual patients. The embryos that have been analyzed and are found to be normal are transferred into the uterus, where they will hopefully implant and result in the birth of a healthy child.
When can PGD/PGS help?
PGD can significantly reduce the chances of having a baby affected with a known specific genetic condition (single gene disorder) or chromosomal abnormality (translocation) carried by the parents.
PGS is used as a general screen for chromosomal abnormalities (aneuploidy). In a normal embryo (euploid) there are 2 of each of 22 chromosomes and either XX or XY. An embryo is aneuploid when there are either 3 or 1 of any of the 22 pairs of chromosomes. Most aneuploidies are lethal to the embryo and either fail to implant or result in a miss-carriage. The most common aneuploidy that results in a live birth is trisomy 21, known as Downs Syndrome. The next most common is sex chromosome aneuploidies, XO, XXX, XYY. PGS has been shown to be most beneficial for patients that have:
– Recurrent Miss-carriage defined as having three consecutive miss carriages
– Implantation Failure defined as having at least 10 IVF embryos transferred without pregnancy
– Advanced Maternal Age defined as the female partner aged 38 years of age or more
– History of chromosomally abnormal child/ pregnancy
-Carriers of sex linked inherited disease
PGS can also be used to select the gender of your child.
How it works?
PGD/PGS is be performed by sampling the developing embryo at different stages. At FCC we grow the embryo to the blastocyst stage and biopsy a number of cells from the trophectoderm of the embryo. A blastocyst is a day 5/6 embryo that has developed to a specific stage. It contains two cell types – the inner cell mass, which eventually develops into fetal tissues, and the trophectoderm, which gives rise to the developing placenta and other “extra-embryonic” tissues. The embryo at this stage has at least 50 cells and up to 10 cells can be biopsied for genetic testing by one of two techniques, aCGH or NGS. Testing the embryo at this stage allows the biopsy of greater number of cells up to 10 in comparison to 1 or 2 at an earlier stage of development. This has the advantage of reduced chromosomal mosaicism (where different cells within an embryo have different numbers of chromosomes) as well as improved DNA amplification, and therefore, improved test accuracy. In order to have sufficient time to obtain test results, blastocyst testing typically requires that embryos are cryopreserved (frozen) after biopsy, and healthy embryos are thawed and transferred during a later cycle.
What’s the difference between methods of genetic diagnosis: aCGH and NGS?
aCGH and NGS are both very modern and accurate techniques. One of the principal distinctions between aCGH and NGS it is the level of sensitivity. NGS give us a higher resolution, around 10 times that of aCGH. However, aCGH will still accurately detect any chromosomal aneuploidy. NGS will more accurately detect smaller chromosomal re-arrangements. The significance of many of these is unknown. Although NGS is more sensitive and slightly reduces the risk of a miss-diagnosis, it is also more expensive and takes slightly longer to receive results. aCGH is only marginally less accurate and still provides comprehensive results. No technique is 100% accurate and a guarantee against an adverse pregnancy outcome.