Preimplantation Genetic Screening (PGS) / Preimplantation Genetic Testing for Aneuploidy (PGT-A)
Preimplantation Genetic Testing for Aneuploidy (chromosomal abnormality) (PGT-A), also known as Preimplantation Genetic Screening (PGS), is a very early method of screening the chromosomal make-up of embryos with the aim of increasing the pregnancy rate and reducing the risk of miscarriage for specific groups of patients. These groups include but not limited to older women, those with recurrent IVF failure or unexplained recurrent miscarriage. Patients in these groups can produce embryos with an abnormal number of chromosomes (aneuploid embryos).
In the past, PGT-A was performed at an earlier stage of embryonic development (day-3) and with now outdated technology, screening only a few chromosomes on each embryo. This approach was not found to be beneficial.
Currently, the testing is by means of a technology called next generation sequencing (NGS) which examines all of the chromosomes from a few samples of cells, which are removed (biopsied) from each embryo at the blastocyst stage. Blastocysts are embryos which have reached day 5 or 6 of development after fertilisation of the eggs. A blastocyst is formed of over 100 cells arranged in two layers. The inner cell mass will eventually form the baby. The outer cell layer (trophectoderm) develops into the placenta. Approximately, five to 10 cells will be removed from the trophectoderm. All the biopsied embryos are then frozen, by means of ‘vitrification’. Once the test results are known, you will commence preparation for a frozen thaw embryo transfer cycle, provided there is at least one embryo, which has not been found to have any chromosomal abnormalities.
For us to carry out PGT-A, you will have to go through routine in-vitro fertilisation (IVF) procedures so that we can generate several embryos. In order for the diagnosis to be done by NGS, the eggs will be fertilised by IVF or microinjected by a procedure called intra cytoplasmic sperm injection (ICSI) or other alternative methods of insemination such as by intracytoplasmic morphologically selected sperm injection (IMSI). Your consultant will discuss with you in detail the method of fertilisation. Assisted zona hatching will also be carried out. This is a procedure which involves a hole being made in the shell of the developing embryo and is usually performed on day three following egg collection. Please refer to ICSI, IMSI and assisted hatching sections of the CRGH website for further information.
You can find our latest success rates for fertility treatment with PGT-A here
What are the risks of PGT-A?
There are some risks that can occur during IVF treatment cycles for all patients. These are outlined in more detail during the consultation and in the consent form. If there are insufficient eggs, or if only a few eggs become fertilised, there is a high risk that no blastocysts will develop. In such cases, the PGS treatment cycle will be cancelled. It is also possible that the implantation capacity of a normal biopsied embryo is slightly reduced compared to a normal embryo which has not been biopsied. However, when handled by experienced embryologists, the risk of damage to the embryo is very low.
After the biopsy and diagnosis, sometimes all the embryos are found to have chromosome abnormalities, in which case there will not be any embryos suitable for transfer. Any embryo that is reported as chromosomally abnormal will be discarded. Please note that it is our policy not to transfer and discard any and all chromosomally abnormal embryos. It is quite common to find that the majority of the embryos show at least one chromosomal abnormality. The more chromosomes tested, the lower the chance of finding suitable embryos for transfer. Despite PGT-A being performed, there is no guarantee of prevention of a miscarriage or of a live birth.
We know that as women get older, there is more chance that they will have a chromosomally abnormal baby, such as Down’s syndrome, and they have an increased risk of miscarriage, which is also due to chromosome abnormalities. Studies have shown that preimplantation embryos have abnormal chromosomes in a proportion of cells within the same embryo. This is known as mosaicism i.e. the chromosomes of the embryo may not be the same in every cell. Mosaic embryos may result in failed implantation, miscarriage and pregnancy with chromosomal abnormalities. Live births have been reported following transfer of mosaic embryos1-3. It is possible that mosaic embryos may be discarded when they are capable of producing a normal pregnancy.
Although the various diagnostic methods used allow all of the chromosomes to be analysed and detect the vast majority of possible chromosome problems, it is possible that some types of abnormality might not be detected. These include rare duplications or losses affecting small pieces of a chromosome and cases where the entire set of chromosomes is duplicated (a condition called triploidy) or lost (halpoidy). Additionally, these diagnostic methods are unable to detect a problem known as uniparental disomy, where a chromosome has the correct number of copies (two), but both are derived from just one of the parents. As a result of these limitations, prenatal testing after PGT-A is advised to confirm the chromosome screening results and review the number and structure of all the chromosomes.
There is also the risk of misdiagnosis of less than 5%, which can be false positive (the embryo is reported to be chromosomally abnormal when it is not) or false negative (the embryo is reported to be chromosomally normal when it is abnormal).
PGT-A is only a screening process, we would recommend our patients, who achieve an ongoing pregnancy, consider antenatal screening tests and prenatal diagnosis tests in the same way as they would have done had they not had PGT-A.
There is inconclusive evidence regarding the benefits of PGT-A on assisted conception outcome4-17. Whilst this technique is not evidence based with respect to improving live birth rates from randomised controlled trials and is optional, the clinic will only offer it when your consultant deems it appropriate for the treatment. The CRGH will offer PGT-A in order to reduce the chance of having a miscarriage and multiple pregnancy and shortens time to pregnancy by selecting the transfer of a chromosomally normal embryo.
PGT-A on blastocysts is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system.
PGT-A on blastocysts is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trial to show that it is effective at improving the chances of having a baby for most fertility patients. Please refer to the treatment add-ons page of the HFEA website18.
There is the emotional, physical and financial burden associated with assisted conception and PGT-A. Thus, counselling is offered to all our patients.
If you would like to book an appointment with one of our doctors you can:
- Speak to the booking team on +44 (0)20 7837 2905 (Mon – Fri 8.30am – 6pm)
- Email us on firstname.lastname@example.org
- Visit our Appointments page, fill out the contact form and a member of the team will be in touch
- Zhang Y, Chen J, Nabu S, Yeung Q, Li Y, Hui J et al. The pregnancy outcome of mosaic embryo transfer: a prospective multicentre study and meta-analysis. Genes 2020; 11:E973.
- Lee C, Cheng E, Lee M, Lin P, Chen Y, Chen C et al. Healthy live births from transfer of low mosaicism embryos after preimplantation genetic testing for aneuploidy. J Assist Reprod Genet. 2020; 37:2305-2313.
- Kahraman S, Cetinkaya M, Yuksel B, Yesil M, Cetinkaya C. The birth of a baby with mosaicism resulting from a known mosaic embryo transfer: case report. Hum Reprod 2020; 35: 727-33.
- Chen M, Wei S, Hu J, Quan S. Can Comprehensive Chromosome Screening Technology Improve IVF/ICSI Outcomes? A Meta-Analysis. PLoS One. 2015 Oct 15;10(10)
- Dahdouh EM, Balayla J, García-Velasco JA. Comprehensive chromosome screening improves embryo selection: a meta-analysis. Fertil Steril 2015;104(6):1503-12.
- Harton GL, Munné S, Surrey M, Grifo J, Kaplan B, McCulloh DH, Griffin DK, Wells D; PGD Practitioners Group. Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Fertil Steril 2013;100(6):1695-703.
- Forman E, Upham K, Cheng M, Zhao T, Hong K, Treff R et al. Comprehensive chromosome screening alters traditional morphology based embryo selection: a prospective study of 100 consecutive cycles of planned fresh euploid blastocyst transfer. Fertil Steril 2013; 100:718-24.
- Lee E, Illingworth P, Wilton L, Chambers GM. Comprehensive chromosome screening improves embryo selection: a meta-analysis. Hum Reprod 2015;30(2):473-83.
- Yang Z, Liu J, Salem S, Liu X, Lyle S, Peck A, Sills E, Salem R. 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. Molecular Cytogenetics 2012; 5(1): 24.
- Chang j, Boulet S, Jeng G, Flowers L, Kissin D. Outcomes of in vitro fertilization with pre-implantation genetic diagnosis: an analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011-2012 Fertil Steril 2016; 105(2) 394-400.
- Scott R, Upham K, Forman E, Hong K, Scott K, Taylor D, Tao X, Treff N. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro implantation and delivery rates: a randomized controlled trial. Fertil Steril 2013; 100(3);697-703.
- Neal S, Morin S, Franasiak J, Goodman L, Juneau C, Forman E, Werner M, Scott R Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage. Fertil Steril 2018; 110:896-904.
- Munne S, Kaplan B, Frattarelli J, Child T, Nakhuda G, Shamma N, et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicentre randomized clinical trial. Fertil Steril 2019; 112; 1071-1070.
- Ozgur K, Berkkanoglu M, Bulut H, Yoruk G, Candurmaz N, Coetzee. Single best euploid versus single best unknown-ploidy blastocyst frozen embryo transfers: a randomised controlled trial. J Assist Reprod Genet. 2019; 36:629-636.
- Somigliana E, Busnelli A, Paffoni A, Vigano P, Ribccaboni A, Rubio C et al. Cost-effectiveness of preimplantation genetic testing for aneuploidies. Fertil Steril 2019; 111:1169-76
- Tiegs A, Tao Z, Zhan Y, Whitehead C, Kim J, Hanson B et al. A multicentre, prospective, blinded non selection study evaluating the predictive value of an aneuploid diagnosis using a targeted next generation sequencing based preimplantation genetic testing for aneuploid assay and impact of biopsy. Fertil Steril 2020 August doi:10.1016/j.fertnstert.2020.07.052.onlline ahead of print
- Haviland M, Murphy L, Modest A, Fox M, Wise L, Nillni Y, Sakkas D, Hacker M. Comparison of pregnancy outcomes following preimplantation genetic testing for aneuploidy using a matched propensity score design. Hum Reprod 2020; 35:2356-2364.