Understanding PGD

Preimplantation Genetic Diagnosis

Preimplantation Genetic Diagnosis (PGD) is a technique used by specialized medical laboratories to select embryos not found to carry specific genetic disorders prior their transfer into a woman’s womb.

Why is PGD used?

PGD is normally used in an attempt to eliminate the risk of passing a specific genetic disorder from the parents to their child. For example, a parent carrier of inherited pancreatic disease may be apparently normal but have greater chance of conceiving a child with the disease.

PGD should not be confused with Preimplantation Genetic Screening (PGS). Couples who seek treatment with IVF with PGD don’t necessarily suffer from infertility. In fact, many PGD candidates are perfectly fertile. PGS, unlike PGD, is a genetic screening approach used to rule out the routine chromosome abnormalities that reduce pregnancy rates and increase miscarriage rates in infertile couples.

How many types of PGD are there?

Single gene mutations

Nucleic acids (DNA) are the building blocks of our genetic material. They are represented in four different types of molecules (A, T, G, and C). Single gene mutations include substitution, for example, the replacement of an A for a G or a C for a T, deletions and insertions of at least one nucleotide. These genetic alterations can happen by chance, or they may be inherited by children from their parents. Although PGD can identify either type of mutation, it is normally used to identify those an embryo would receive from parents who are carriers of a particular genetic abnormality.

Not all genetic alterations are fatal and not all mutations cause disease. Sometime mutations are in a non-coding chromosomal region leading to no apparent clinical effect. Other mutations may be in a area of coding DNA but are not translated into an amino acid change or do not result in any negative effect. These are silent mutations.

When mutations occur in a coding region they are usually translated into a amino acid change and thus a change in the structure of a protein. The mutation may, but not always, have an impact on health. When the mutation alters a biological process, a protein function, or regulatory pathway, it can lead to a clinic effect, e.g., cancer, inherited disorders, etc.


Translocations are common chromosomal alterations that often but not always impact health. Translocations are generally divided into two types: balanced or unbalanced. Balanced translocations consist of an exchange of large chromosomal regions between two chromosomes, with no net loss or gain of DNA. These events are difficult to detect using PCR-based techniques. An unbalanced translocation, however, is generally detectable, especially when the chromosomal gain or loss is large (over 10MB).

How is PGD conducted?

The most common way to perform PGD for a single mutation is Realtime PCR, a technique that relies on two fluorescent probes to detect a single mutation, one probe for the mutant allele (gene) and second probe for non-mutated allele (gene). Realtime PCR has a considerable rate of non-conclusive results and is prone to contamination.

For the first time in the field of IVF, Progenesis brings Next Generation Sequencing (NGS) as a viable alternative to Realtime PCR. NGS can read the mutation of interest directly with a coverage and sensitivity that is unmatched by PCR because NGS quantifies the representation of each allele, eliminating the issue of allele dropout, that is the failure to “see” one of the genes.

Overview of PGD Technology

For the past few years, the use of array comparative genome hybridization (aCGH) offered a substantial improvement in preimplantation genetic screening (PGS), increasing the number of tested chromosomes from a handful to 24 chromosomes. Unfortunately, his seemingly improved technology came at a cost since aCGH is estimated to have at least 2% error rate.

What makes array CGH prone to errors?

Array CGH is an indirect measurement as it relies on hybridization signals. During the hybridization process, clinical samples are labeled with a fluorescent dye and then hybridized against an array of known chromosome regions. Signals coming from each array are then scanned and analyzed using normal male and female references.

One key limitation of array CGH and other hybridization techniques is the susceptibility to signal saturation. In the case of PGS, hybridization signals arising from multiple chromosomes are beyond the aCGH sensitivity level, thus preventing the detection of polyploidy which is the presence of more than the two normal sets of chromosomes.

A second technical limitation of aCGH is detection of sex chromosome abnormalities such as Triple X (XXX), Klinefelter (XXY), or XYY syndromes. While failure to detect Triple X is due to the saturation issue, the limited detection of XXY and XYY syndromes is a result of aCGH’s limited sensitivity in Y chromosome detection.

The Y chromosome is relatively small compared to the X chromosome and it is riddled with repetitive sequences which present challenges for probe design and detection using aCGH. Considering this, it is not surprising that gender selection by aCGH is sometimes inconclusive due to the same effect.

Impact on IVF outcome

Misdiagnosis reduces implantation and pregnancy success rates, and it is linked to the transmission of genetic disorders to newborns, not to mention a psychological and financial impact on patients. For this reason, clinicians, researchers, and IVF professionals are constantly searching for new diagnostic tools with higher accuracy and lower cost for patients.

Alternative and Future Trend

Next Generation Sequencing has revolutionized the field of genetic testing, and preimplantation genetic diagnosis is not an exception. Today, with recent technology improvements, NGS is a practical and affordable option for IVF centers that demand faster, more reliable, and more accurate testing for their clients. In contrast to aCGH, Next Generation Sequencing provides direct sequencing of actual embryo DNA at single nucleotide level, providing coverage, sensitivity, and precision superior to any existing technology.

Progenesis at Pacific Coast Reproductive Society

We at Progenesis were very exited to present Next Generation Sequencing for Embryo Testing at the 63rd Annual Meeting at Pacific Coast Reproductive Society.

ASRM Batimore 2015

We had a great time in Baltimore at ASRM 2015! It was a pleasure meeting so many wonderful people and discussing our PGS/PGD services.


Southern CA Assisted Reproductive Biologist’s (SCARB) next meeting takes places on Dec. 15 at El Adobe de Capistrano. Nabil Arrach, CEO of Progenesis, will be giving a talk on “The Significance of Mitochondrial DNA Analysis in Preimplantation Genetic Testing.”

You can RSVP to this event by visiting http://www.scarbsocal.com/#!our-next-event/cee5. Don’t miss out on this opportunity for learning, good food, and good company. We hope to see you there.

Upper Egypt Assisted Reproduction Symposium

Nabil Arrach, CEO of Progenesis, will be traveling to Egypt to participate as a speaker in the Upper Egypt Assisted

Reproduction Symposium (UEARS) on February 4-5. Dr. Arrach will be speaking on topics he is strongly passionate about:

  • The importance of Mitochondrial DNA Analysis in Preimplantation Genetic Testing
  • The Future of Next Generation Sequencing in In-Vitro Fertilization

Dr. Arrach is excited for this opportunity to discuss his research with scientists from around the world.

For more information on UEARS , visit  http://www.uears.org.

Progenesis To Launch The First NGS Test For PGS Under 12 Hours

Dr.Arrach CEO at Progenesis announced the release of the first preimplantation genetic screening test performed with next generation sequencing under 12 hours.

For the first time in IVF, Progenesis is now offering results for PGS using next generation sequencing in as little as 12 hours- faster than ever before. With the Progenesis rapid next generation sequencing test, fertility doctors are now able do fresh transfer using cutting edge technology with an extremely short turnaround time

The Fifth Annual Southwest Embryology Summit

Dr. Arrach, CEO of Progenesis, will be presenting at the Fifth Annual Southwest Embryology Summit on January 4-5, 2016 in Las Vegas, NV.

Dr. Arrach will be discussing the prospect of mitochondrial DNA analysis in in-vitro fertilization