EN
Fertility Treatment

The Basics of Preimplantation Genetic Testing

Preimplantation Genetic Testing (PGT) is an embryonic procedure done in unison with IVF where a tissue biopsy of a developing embryo is taken and tested for genetic (ab)normalities. The tissue biopsy takes place on blastocysts stage embryos. Afterwhich, the tissue is sent to a third party genetics lab for analysis.

PGT is broken into 3 main testing categories: Preimplantation genetic testing for aneuploidies (PGT-A), monogenic/single gene defects (PGT-M), and chromosomal structural rearrangements (PGT-SR)

Patient Populations
Goal
Genetic test type
Requires personalized test preparation?

PGT-A AKA PGS

Patient Populations All IVF Patients
Goal Increase chances of achieving a successful pregnancy
Genetic test type Screens for chromosome abnormalities
Requires personalized test preparation? No

PGT-M AKA PGD

Patient Populations Patients at high-risk of having a child with a specific genetic disease
Goal Reduce risk of passing on an inherited condition
Genetic test type Screens for a specific single gene disorder
Requires personalized test preparation? Yes

PGT-SR AKA PGD

Patient Populations Patients with a chromosomal rearrangement
Goal Increase chances of achieving a successful pregnancy with a normal/balanced chromosome constitution
Genetic test type Screens for specific unbalanced chromosome rearrangements
Requires personalized test preparation? Typically no, pending case review

PGT-A: Preimplantation Genetic Testing for Aneuploides

Formerly known as PGS (preimplantation genetic screening), PGT-A gives information about the number of chromosomes within IVF embryos. Those with normal results have higher odds of achieving a successful pregnancy.

normal chromosome number
abnormal chromosome number

Potential PGT-A Results

There are three potential results that can come from each embryo tested with PGT-A: Euploid (normal) Mosiac (mixed – some cells that were tested in the embryo are normal, some are abnormal), Aneuploid (all cells tested are abnormal).

Possible PGT-A results

Number of chromosomes per cell
Likelihood of producing a successful pregnancy
Transfer priority

Euploid

Number of chromosomes per cell Normal
Likelihood of producing a successful pregnancy High
Transfer priority High

Mosaic

Number of chromosomes per cell Mixed (some normal and some abnormal)
Likelihood of producing a successful pregnancy Intermediate
Transfer priority Intermediate, may be considered if no euploid embryos are available

Aneuploid

Number of chromosomes per cell Abnormal
Likelihood of producing a successful pregnancy Low
Transfer priority Not prioritized

Aneuploidy and Age

While everyone is at risk of producing aneuploid embryos, the risk goes up as women age. Aneuploid embryos are associated with increased implantation failure and miscarriage and lower live birth results.

  • Aneuploidy Frequency with Age
    Maternal Age

    Courtesy of CooperGenomics data of blastocyst biopsies tested via Next Generation Sequencing (2014-2017)

  • PGT-A reduces miscarriage rates
    Maternal Age

    Courtesy of CooperGenomics data of blastocyst biopsies tested via Next Generation Sequencing (2014-2017)

  • PGT-A increases live birth rates
    Maternal Age

    Courtesy of CooperGenomics data of blastocyst biopsies tested via Next Generation Sequencing (2014-2017)

The PGT-A Process

PGT-A is added in conjunction to an IVF treatment cycle – the only adjustment from a patient perspective is that the embryos must be frozen to await the test results; this means it requires a Frozen Embryo Transfer. Lucky, the technology around freezing, thawing and transfering has reach it’s maturity with success rates equal to fresh transfers.  So much so that people freeze and do FETs at the same rate as fresh transfers even when not doing genetic testing.

IVF

IVF: In vitro fertilization must be done in order to abtain the necessary embryos.

Embryo Biopsy

Embryo biopsy: an embryologist carefully removes a small sample of cells from each embryo’s trophectoderm

Genetics Lab

The embryos are sent to a genetics lab to perform the actual tests. Meanwhile the embryos are frozen to await results.

FET

After receiving the results and discussing them with you, we choose an embryo and thaw it for your frozen embryo transfer. Remaining embryos remain frozen indefinitely until ready for use.

Why PGT-M?

PGT-M: Preimplantation Genetic Testing for Single-gene Defects

PGT-M is performed on blastocyst stage embryos to significantly reduce the risk of having a child with a specific genetic disease. Whether you have a genetic disorder or have learned of a risk status through screening, an affected family member, a pregnancy, or a child with a known single-gene disorder, PGTM may be the solution for your family-building needs.

  • You and your partner are carriers of the same autosomal recessive condition
    • Cystic Fibrosis
    • Sickle cell anemia
    • Tay-Sachs disease
  • You are a carrier of an X-linked condition
    • Duchenne Muscular Dystrophy
    • Hemophelia B
    • Fragile X
  • You or your partner have an autosomal dominant condition
    • Huntington’s Disease
    • Neurofibromatosis
    • Marfan Syndrome
  • You or your partner have a mutation associated with hereditary cancer
    • BRACA1 & 2 MLH1
    • MSH2/6
    • PMS1/2 TP53 CHEK2
In addition to the above, PGT-M can be performed for over 6,000 other single-gene disorders.

The PGT-M Technology: Karyomapping

A genetic mapping technology that maps hundreds of thousands of data points across the entire genome and subsequently performs a linkage analysis.

Carrier father Chromosome region analyzed by PGT-M Unaffected Carrier Affected Carrier Mother Embryo 3 carrier Embryo 2 carrier Embryo 1 unaffected Embryo 4 affected

The PGT-M Process

PGT-M involves a close examination of the mutation an individual carries. Each test design is unique and specifically tailored to the individuals being tested so DNA samples from both partners (and often additional family members) will be required to design a test.

Case Review

It all starts with speaking to a genetic counselor to ensure your disorder is covered and determine if additional testing of the intended parents or family members is required.

Collection

If necessary the lab will collect DNA samples (and appropriate family members) to design a tailored test.

Embryo biopsy

After growing to blastocyst stage embryos a biopsy is taken by our embryologists and sent to the genetics lab. The embryos are frozen to await test results.

PGT-M

Testing is done and results sent back to us.

Why PGT-SR?

PGT-SR: Preimplantation Genetic Testing for Chromosomal Structural Rearrangements

Chromosomal rearrangements are changes from the normal size or arrangement of chromosomes. Chromosome rearrangements can be inherited or can happen via a spontaneous mutation. Many carriers are healthy and are unaware of their carrier status until they try to have children as they are at an increased risk of passing along that genetic mutations which often leads to an unsuccessful pregnancy.

Who it’s for

PGT-SR is for people who have a chromosome rearrangement and should thus be considered in conjunction with IVF if you had a child or pregnancy with a chromosome rearrangement or if you or your partner is a carrier of an:

  • Reciprocal Translocations
    Reciprocal translocations occur when pieces of genetic material break off from two different chromosomes and swap places.
  • Robertsonian translocations
    Occur when two chromosomes break and then join together to form one large chromosome. Most commonly occurs with chromosome numbers 13 & 14 and 14 & 21. This can result in Translocation Down syndrome, trisomy 13, or uniparental disomy (UPD).
  • Inversions
    Inversions are chromosome rearrangements that involve only one chromosome. In an inversion, a segment of a chromosome is flipped and reinserted upside down.

The PGT-SR Process

In most cases the PGT-SR process follows a more simple process similar to PGT-A and requires no additional testing. In some cases, it may be necessary to have a more extensive workup and follow a path similar to PGT-M.