Aneuploidy & PGS

Aneuploidy

A normal embryo cell contains 46 chromosomes, including the sex chromosomes X and Y. These normal embryos are called euploid. When an embryo forms with cells that have an extra or missing chromosome, this is called aneuploidy. There is now clinical evidence that abnormal aneuploid embryos, which can look morphologically normal, have a 96% chance of NOT implanting1.

It’s therefore important to identify and ONLY transfer euploid embryos to improve chances of a successful IVF cycle.

As this graph shows, the incidence of embryo aneuploidy increases with age. This is a major reason for the decreasing expectation of live birth per treatment cycle associated with increasing maternal age2

More than 40% of healthy looking IVF embryos are aneuploid in women older than 35 years.

Harton et al, Fert Steril Dec 2013 100 (6): 1695-703

Pre-implantation Genetic Screening 

The most significant recent advance to improve IVF success rates has been the introduction of 24 chromosome pre-implantation genetic screening (PGS).

The purpose of PGS is to identify embryos with the correct number of chromosomes for IVF transfer. PGS cannot correct aneuploid embryos; it can only identify those embryos that are not suitable for transfer.

Selecting only euploid embryos to transfer with PGS has been demonstrated to:

  • Reduce the time to pregnancy (and baby) by reducing the number of cycles/transfers needed to become pregnant 4;
  • Reduce the risk of miscarriage 5;
  • Allow only the selection of euploid embryos 1 for freezing, avoiding the expense of storing embryos unsuitable for transfer;
  • Overcome the adverse effect of maternal age on IVF success by focussing on euploid embryos 2; and
  • Reduce the risk of multiple pregnancy from IVF 6 & 7.

PGS can increase the clinical pregnancy rate by around 50%

Yang et al, Mol Cytogenet. 2012, 5: 24.

References

  1. 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
  2. Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Harton GL, Munné 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
  3. Fertility treatment in 2012: trends and figures. Human Fertilisation and Embryology Authority (HFEA) - Download
  4. 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
  5. 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
  6. 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
  7. 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.