What is Preimplantation Genetic Diagnosis / Screening or Testing (PGD, PGS or PGD)?
- Definition of PGD or what is the meaning of PGD?
- PGD in an IVF program, whom is it made for?
- How are genetic disease inherited?
- The innovative features of the NGS method in the preimplantation genetic diagnosis
- Benefits of the NGS method in preimplantation genetic diagnosis
- Why is it recommended to use NGS in an IVF program?
- Why should you do NGS in the NGC clinic?
At least half of the IVF programs end in disappointment, only a third of the excellent quality embryos survive and even fewer end up in a birth of a healthy baby. Why does this happen? That is the most frequent question of the patients at IVF clinics.
Preimplantation genetic screening / preimplantation genetic diagnosis (PGS / PGD) - is a technique that allows you to increase the effectiveness of ART programs (IVF) due to the selection of embryos free of the genetic disease.
NEXT GENERATION SEQUENCING, NGS - is a method of direct analysis of the genomes of the embryos.
- maternal age> 35 years;
- habitual miscarriage;
- multiple attempts of IVF failed;
- some forms of male infertility that are associated with chromosomal abnormalities;
- carriage of chromosomal rearrangements, translocations, inversions and other chromosomal abnormalities.
In the diagrams below, D or d represents a defective gene, and n or N represents a normal gene. Mutations do not always lead to disease.
One of the parents has a defective gene that dominates over its normal pair. Since the children inherit half of the genetic material from each parent, there is a 50% risk of inheriting a defective gene, and hence the disease.
Both the parents are carriers of defective genes, but have a pair of normal genes. It requires two defective copies of the gene, to inherit the disease . Each descendant has a 50% chance of becoming a carrier, and a 25% chance of inheriting the disease.
Normal females have XX chromosomes, while XY is normal for males. Women who have a normal gene on one of the X chromosomes are protected from the faulty gene on their other X chromosome. However, the man has no such protection, because he has only one X chromosome. Every male child from a mother, who carries the defect, has a 50% chance of inheriting the defective gene and the disease. Each female descendant has a 50% chance of becoming a carrier, like her mother. (In the picture below, X is a normal gene and the other X is the defective one.)
If before we learned a letter from each chapter of the book (using the FISH technique), moving on, we began to read a full sentence from each chapter (aCGH), now, we can read the full book letter by letter(NGS). This way we can roughly interpret the possibilities of the new method, which requires a very high intellectual tolerance threshold.
- Large authenticity of the research.
- Accuracy of the research: analysis of all the 24 chromosomes at the same time with an accuracy of more than 99.9% (higher fidelity compared to the aCGH method).
- Sensitivity of the research: direct reading (decoding) of the genetic information encoded in the DNA of the embryo.
- Big opportunities for the analysis of the genome of the embryo - the possibility of combining the study of the chromosomal and the monogenic diseases in a single analysis.
- Safety of the embryo - embryo biopsy is done only once, for diagnosis of the chromosomal and the monogenic diseases.
- Most of the process is automated - additional opportunities to avoid any mistakes starting from the reception of the material from the embryo.
- An analysis of all the 24 chromosomes simultaneously, with the highest accuracy if compared to the other methods.
- Increased accuracy in the diagnosis of mosaic aneuploidies.
- The possibility to distinguish a balanced set of chromosomes from a normal one.
- The possibility to detect uniparental disomy (in the analysis of the parental samples).
- Identification of haploid and triploid.
- The possibility to identify micro and macro rearrangements (5 bp).
- Simultaneous diagnosis of chromosomal and monogenic diseases as well as other mutations.
- Prospects of the exception of a variety of pathogenic mutations in the future of the children, which includes screening couples with infertility, sperm and oocyte donors, and perhaps in all people (for example cystic fibrosis, autism, intellectual disabilities, spinal-muscular atrophy and so on to infinity).
- The trend in the long term is to reduce the initial cost, thus approximately repeating the the law of Murr for semiconductors.
Any doctor can explain that the main and the most common cause of failure in an IVF program is incorrect chromosome segregation in the transferred embryo, ie, the reasons are usually only genetic. Even if the embryologist evaluates the quality (morphology - "external" data) of the embryo as excellent, on the fifth day of development (blastocyst), we understand that half contains a modified chromosome set and thus is not implanted, or it is implanted but stops giving a biochemical pregnancy, or leads to an abortion before 9 weeks of pregnancy, or will lead to the birth of a child with Down's syndrome, Turner, Klinefelter, and others.
Preimplantation genetic screening / diagnosis (PGS / PGD): is an evolutionary progress from the microscope and fluorescence immuno hybridization(FISH) through microarrays and comparative genomic hybridization (aCGH) to the sequencing of the genome of the embryo (NGS).
Who is at risk of having numerical chromosomal abnormalities?
Any one of us. In their life, almost all women have a miscarriage in the early stages. Many people do not even know about the termination of the pregnancy, which is expressed as a small menstruation delay or a preclinical abortion. Almost everyone, in their lifetime, with a small exception, have had a genetically abnormal embryo formed. "Nature" does not allow such fetuses to develop, interrupting them at different stages, only making mistakes in the cases of the Down syndrome, Patau, Turner, etc. Even if someone uses the oocyte donation program with perfectly healthy, fully examined genetic donor, a third of the ideal blastocysts will have chromosomal abnormalities. Yes, without a doubt, a woman's age increases the risk of that happening, thus after 40 years, more than 80% of the ideal embryos carry a chromosomal anomaly. In addition, patients with infertility may have a higher risk than the general population. Patients with severe male factor of infertility or habitual miscarriage - are at a higher risk. Also, the risk is maybe higher in patients with a reduced ovarian reserve.
- Our specialists were the first in the country to use the PGS and have evolved from the FISH diagnostic method to the diagnosis by the aCGH method
- In the three years, we have done over 400 diagnostics
- More than 1,000 embryos have been analyzed by the comparative genomic hybridization on chips
- We were coming long way from PGD by FISH and aCGH to NGS
Continuing the tradition,we were the first in the country and in the CIS countries from 2015 launched the most modern and precise method of preimplantation genetic diagnosis - a method of sequencing a new / next-generation (Next Generation Sequencing, NGS).
Here at NGC Clinic the preimplantation genetic diagnosis by the NGS method is performed on the world's first registered in the FDA new generation MiSeqDx sequencer (Illumina, USA), designed specifically for the clinical laboratories. This is the first such machine in Russia and we are the first who began to use sequencing (the NGS) in Russia and the CIS countries for preimplantation genetic diagnosis (PGS). We are happy and pleased that we have a new opportunity to be able to qualitatively help many people and we are delighted by the fact that as a result of our work, there will be less sick children.