Pre-Implantation Genetic Screening ("PGS"), Diagnosis ("PGD") And Sex Selection

On this page:

  1. What Is PGS?
  2. The Purpose And Benefits Of PGS?
  3. PGS Is Recommended For...
  4. What Is Involved In PGS?
  5. Risks And Limitations Of Embryo Biopsy, Frezing And PGS.
  6. What Is PGD?
  7. Sex Selection.
  8. Find Out More.

What Is PGS?

Pre-implantation Genetic Screening (“PGS”), also known as aneuploidy screening, screens for an aberration in the total number of chromosomes.

A normal embryo cell contains 46 chromosomes (22 pairs of autosomes and one pair of sex chromosomes either XX if it’s a girl or XY if it’s a boy).

Embryos with the correct number of chromosomes are called euploid.

When an embryo forms with cells that have extra or missing chromosomes (incorrect chromosome numbers) this is called aneuploidy. Clinical studies have shown that aneuploid embryos have a very small chance (approximately 4%) of implantation after In Vitro Fertilisation (“IVF”). If an aneuploid embryo does implant, it is very likely to miscarry, or if pregnancy progresses to term and results in a live birth then there is a risk that the child born may have a chromosomal abnormality such as Down syndrome. So it is important to identify embryos with the correct chromosome number. 

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The Purpose And Benefits Of PGS.

The purpose of PGS is to identify embryos with the correct number of chromosomes for embryo transfer and freezing, that is, euploid embryos.

PGS may:

  • Facilitate the selection of euploid embryos for freezing and avoiding the use or storage of aneuploid embryos that are unlikely to implant.
  • Increase the implantation rate of embryos in an IVF cycle.
  • Reduce the risk of miscarriage.
  • Reduce the average time to pregnancy by reducing the number of transfers and IVF cycles needed to become pregnant.
  • Overcome the adverse effect of age on IVF success rates.
  • Reduce the risk of multiple pregnancies from IVF by encouraging the transfer of one euploid embryo at a time. 

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PGS Is Recommended For...

PGS is recommended if you:

  • Have had a number of embryo transfers without pregnancy.
  • Have a history of early miscarriage.
  • Are 36 years or over. The number of embryos likely to have incorrect chromosome numbers increases with age.
  • Have a family history of chromosome disorders, for example Downs syndrome.
  • Have disorders that are sex-linked and want to prevent its transmission, for example Duchenne Muscular Dystrophy, Haemophilia.
  • Had a previous pregnancy or child with whole chromosomal abnormalities, for example Klinefelter or Turners syndrome.

Female age and the likelihood of success.
IVF success rate decreases with increasing age; this is because the number and quality of eggs collected reduce with age.

The percentage of aneuploid embryos begins to increase after the age of 35 years. Clinical data has shown that the likelihood of aneuploid embryos in the age group between 30 to 34 years is 35%, 48% for the age group between 35 to 39 years, and 70% from 40 years and over.

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What Is Involved In PGS?

IVF treatment cycle, egg collection, fertilisation and embryo culture.
The IVF treatment cycle and the process of egg collection will be similar to the routine procedure; however for IVF with PGS, cycle fertilisation will be achieved using Intracytoplasmic Sperm Injection ("ICSI").

With ICSI only 1 sperm is injected into the egg to create an embryo, where as with IVF an egg is fertilized by adding sperm around the egg. With IVF the excess sperm will bind themselves to the egg, and stay bound to the resulting embryo.

These sperm may inadvertently be included in the biopsy sample and therefore affect the PGS result.

Obtaining the sample for PGS.
Any genetic test requires a small sample of cell(s) to be biopsied (taken out) from the embryo for PGS.

Clinical evidence has shown that it is best to perform this biopsy on Day 5 or 6 of culture that is when the embryo has reached the blastocyst stage of development. At blastocyst stage, the inner cell mass (the cell that forms the baby) is visible and the biopsy can be taken from the trophectoderm which forms the outer layer of cells, these cells go on to form the placenta. The cells that produce the placenta are easily replaced as the embryos grow but it is not vital to the make up of a baby at term.

Embryo biopsy.
On Day 3 of development a laser is used to precisely make a small hole in the outer shell (zona pellucida) of the embryo and by Day 5 a few trophectoderm cells begin to emerge out of the small hole in the embryo shell. This process, which is called hatching, also happens naturally, but the laser is used to encourage this natural process.

The Embryologist will collect few of these cells which are hatching (the biopsy), and these are the cells used to perform the PGS test.

Freezing the embryo.
Once the biopsy has been performed the embryos will be frozen using a process called vitrification.

Freezing of the embryo is required to allow for the PGS test to be performed. Around 5% of frozen embryos do not survive the freeze/thaw process but pregnancy rates are similar between fresh and frozen transfer cycles. Indeed, there is some emerging evidence that frozen cycles are more successful than fresh cycles because the uterus is no longer affected by the IVF drugs used for egg collection.

The PGS test.
The biopsy sample will be transferred to Adelaide-based company Reproductive Health Science Ltd (“RHS”) for PGS testing.

RHS have developed a PGS kit, EmbryoCellect™, which uses microarray technology (array Comparative Genomic Hybridisation or aCGH) to compare the number of chromosomes in a test sample cell to a known reference sample. The samples are labelled with different fluorescent dyes and the amount of fluorescence is measured and compared for each chromosome. This provides a way to count the number of chromosomes in the test cell(s) and simply determine the whole chromosome count.

RHS provide the PGS testing results to flindersfertility for clinical interpretation.

Embryo selection, thawing and transfer.
In conjunction with standard practice for embryo selection, such as appearance and development, Flinders Fertility will use the PGS test results to consider which embryos are most suitable for transfer. Only the euploid embryos (i.e. embryos with the correct chromosome number) will be considered for transfer.

The fate of the aneuploid embryos (with the incorrect number of chromosomes) will be discussed with you.

If there is more than 1 embryo determined as being suitable for transfer, 1 embryo will be thawed ready for transfer in a frozen embryo cycle and the other embryos will remain in frozen storage for use in your subsequent frozen embryo cycles, if needed.

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Risks And Limitations Of Embryo Biopsy, Freezing and PGS.

The embryo biopsy procedure may:

  • Damage the embryo.
  • Reduce the implantation potential of the embryo.

In addition, embryos:

  • May not develop to Day 5 of culture that is when the embryo has reached the blastocyst stage of development.
  • May not be suitable for biopsy.
  • May not develop to the stage that is suitable for freezing.

With embryo freezing, not all embryos may survive the freeze/thaw process.

PGS test.

  • PGS only tests for whole chromosomal number, or the loss or gain of whole chromosomes. It does not test for any other genetic conditions, including but not limited to
    • Sub-chromosomal rearrangements.
    • Single gene disorders, for example sickle cell disease, cystic fibrosis.
    • Sub-chromosomal changes.
  • The DNA in some cells may not be in a suitable condition to allow biopsies to be analysed. As such there may be no result for some embryos.
  • The biopsied cells are transferred to a tube for genetic testing. The cells may degenerate or not react and so there is a risk that PGS will not work and there will be no result for that embryo.
  • When cells biopsied from the embryo are tested, it is assumed that the results of those cells represent the whole embryo. It is well recognised clinically that some embryos are mosaic meaning they contain genetically-different cells. Mosaicism is a possible cause of an incorrect PGS result.
  • The accuracy of EmbryoCellect™ has been validated using chromosomally normal and abnormal single cells, however no genetic screen is 100% accurate and there is a small chance of an incorrect test result.

Embryo selection, thawing and transfer.

  • All embryo(s) tested may be found to be aneuploid, meaning that no embryos are deemed suitable for transfer.
  • Embryo(s) identified as euploid may not survive the freeze/thaw process and therefore may not be available for transfer.
  • Embryo(s) identified as euploid that may survive the freeze/thaw process may still not be suitable for IVF transfer.
  • Having a euploid embryo transfer does not guarantee pregnancy because there are a number of other factors that impact IVF success.
  • A euploid embryo may be incorrectly identified as aneuploid and that euploid embryo may be discarded.
  • An aneuploid embryo may be incorrectly identified as euploid and that embryo may be selected for thawing and transfer. In this unlikely scenario, it has been shown clinically that 96% of the time the embryo will not implant. In the less than 4% of cases where an aneuploid embryo implants, most often it will miscarry but rarely it could lead to a live birth of a child with a chromosomal disorder such as Down Syndrome. These chromosome abnormalities would normally be uncovered by routine prenatal screening which is offered to every pregnant woman. It is for this reason Flinders Fertility strongly recommends routine prenatal screening if a pregnancy is achieved.

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What Is PGD?

Pre-implantation Genetic Diagnosis ("PGD") is a technique used to screen embryos prior to pregnancy for couples who are at risk of passing on serious genetic conditions to their children.

Using PGD, embryos can be tested for specific genetic conditions or for sub-chromosomal abnormalities including inversion, deletion or translocations prior to placement in the uterus and the establishment of a pregnancy. It is the earliest form of prenatal diagnostic screening carried out on a laboratory created embryo.

Flinders Fertility currently does not offer PGD.

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Sex Selection

PGD can also be used to select the sex of the embryo as some genetic diseases are linked to sex chromosomes and to avoid the sex linked inheritance of the genetic condition. For example, "Duchenne Muscular Dystrophy" is a sex linked disorder, which affects boys but not girls, but girls may still carry the gene for the disease and not suffer from it. In this case, only female embryos are selected for transfer to the mother’s uterus. Another common sex linked disease is haemophilia.

Please refer to our "Position Statement - Sex Selection" for further information.

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Find Out More

At Flinders Fertility we recognise that a website may not cover all your information requirements.  That's why we offer a number of information options. So, if you want to find out more about PGD, PGS and sex selection, either:

  1. Call on 131 IVF (131 483) to talk to one of our Fertility Specialists.
  2. Email us at enquire@flindersfertility.com.au.
  3. Seek a referral to Flinders Fertility from your Doctor.

If you require the aid of an interpreter please let us know, as well as any specific regional dialect that you may require.


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References

  • Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study.  Scott RT Jr, Ferry K, Su J, Tao X, Scott K, Treff NR.  Fertility and Sterility 2012 Apr:97(4):870-5.
  • Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization.  Harton GL, MunnĂ© S, Surrey M, Grifo J, Kaplan B, McCulloh DH, Griffin DK, Wells D; PGD Practitioners Group.  Fertility and Sterility 2013 Dec;100(6):1695-703.
  • Fertility treatment in 2012: trends and figures.  Human Fertilisation and Embryology Authority (HFEA). http://www.hfea.gov.uk/docs/FertilityTreatment2012TrendsFigures.PDF
  • Comparative genomic hybridization selection of blastocysts for repeated implantation failure treatment: a pilot study.  Greco E, Bono S, Ruberti A, Lobascio AM, Greco P, Biricik A, Spizzichino L, Greco A, Tesarik J, Minasi MG, Fiorentino F.  BioMed Research International 2014:457913.
  • Preimplantation genetic screening (PGS) with Comparative genomic hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages.  Keltz MD, Vega M, Sirota I, Lederman M, Moshier EL, Gonzales E, Stein D.  Journal of Assisted Reproduction and Genetics 2013 Oct;30(10):1339-9.
  • Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study.  Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD.  Molecular Cytogenetics 2012 May 2;5(1):24.
  • In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial.  Forman, E.  J., Hong, K.  H., Ferry, K.  M., Tao, X., Taylor, D., Levy, B., Scott, R.  T..  Fertility and Sterility 2013, 100(1), 100–7.e1.
  • Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization.  Hu, D.  G., Webb, G., & Hussey, N.  Molecular Human Reproduction 2004, 10(4), 283–9. 
  • Gender determination and detection of aneuploidy in single cells using DNA array-based comparative genomic hybridization.  Hu, D.  G., Guan, X.  Y., & Hussey, N.  Methods in Molecular Medicine 2007, 132, 135–151.
     

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