We offer genetic testing for embryos created by in vitro fertilization (IVF or ICSI) for chromosomal aneuploidies, inheritable genetic disorders or structural rearrangements.
The potential risks, benefits and limitations of preimplantation genetic testing should be discussed fully with your doctor and/or a genetic counsellor prior to proceeding.
Background to chromosomes and cell development (PGT-A)
Every cell in the body has chromosomes, which are organized structures containing DNA and proteins. This information contains the genetic information (our genes) that make each human unique, and that is necessary for our growth and development.
There are 24 different types of chromosomes in humans, numbered from 1 to 22, plus the sex chromosomes X and Y. Most human cells contain a total of 46 chromosomes: 22 pairs and an XX pair in a female, or an XY pair for a male. One chromosome in each pair is inherited from the egg and the other is inherited from the sperm. Both the sperm and the egg must have 23 chromosomes to produce an embryo with the correct number of chromosomes, meaning that, when a sperm fertilizes an egg, the resulting embryo has 46 chromosomes in total.
Aneuploidy is the presence of an abnormal number of chromosomes in a cell. Any female can produce chromosomally abnormal eggs and any male chromosomally abnormal sperm. For example, if an egg with 24 chromosomes (one extra) is fertilized by a sperm with 23 chromosomes, the resulting embryo has 47 chromosomes (one extra). A common example of a chromosomal abnormality is Down’s syndrome, which is caused by the presence of three copies of chromosome 21, instead of two.
Embryo aneuploidy (either extra or missing chromosomes) may develop as a result of an abnormal egg, an abnormal sperm, individuals with balanced structural rearrangements (translocations and inversions), or due to a subsequent error during embryo cell division. Chromosome abnormalities can occur spontaneously during the maturation of the egg, maturation of the sperm, or during the process of embryo division after fertilization. Chromosomal abnormalities can give rise to implantation failure and prevent assisted reproductive treatment from resulting in pregnancy. They can also be responsible for miscarriages in the first trimester, fetal death or the birth of a child with chromosomal abnormalities or a genetically-influenced condition.
Most abnormal embryos are not distinguishable from normal embryos when assessed using a microscope in the IVF clinic. This means that assessment of embryo development and structure cannot be used to detect the presence of chromosomal abnormalities.
We offer Pre-implantation Genetic Testing for Aneuploidies (PGT-A), previously known as Pre-implantation Genetic Screening (PGS), to check embryos for abnormalities in the number of chromosomes. This can be carried out on a fresh embryo, or frozen embryos that you have in storage. The process detects extra or missing copies of the 23 pairs of chromosomes or large chromosomal imbalances. Embryos where chromosomal abnormalities are detected as a result of PGT-A will not be recommended for transfer. By identifying abnormal embryos, it is hoped to reduce the risk of miscarriages, increase the implantation rate per embryo transferred and increase the probability of having a healthy baby.
It should be noted that not all pregnancies with chromosomal abnormalities lead to implantation failure or miscarriage. However, embryos with chromosomal alterations that do successfully implant can result in the birth of a baby with serious abnormalities (such as Down’s syndrome). These conditions can be detected during the pregnancy via other types of invasive tests such as chorionic villus biopsy and amniocentesis. However, these procedures involve a risk of miscarriage and cannot be performed until after the pregnancy is achieved.
Background to genetic disorders (PGT-M)
Not all genetic abnormalities are due to chromosomal abnormalities. For example, to detect the presence of alterations in individual genes, such as cystic fibrosis, sickle cell anaemia or haemophilia, targeted tests must be performed to detect the particular change in that specific familial gene (mutation). Any known familial genetic alteration should be discussed with your clinician.
In addition, physical birth defects may appear, such as heart abnormalities, which are not related to chromosomal alterations. For this reason, ultrasound monitoring is recommended if pregnancy is achieved. Also, some illnesses are multifactorial, which means that they occur due to a combination of genetic and environmental influences. Currently, studies on embryos or on fetuses during pregnancy are not possible for the majority of these conditions as the exact cause is unknown. Some examples of these conditions are autism, schizophrenia and diabetes.
How is genetic testing performed?
Cells from an embryo(s) are required for analysis, so an IVF/ICSI cycle is required regardless of fertility history. Preimplantation genetic testing on an embryo sample is a multi-step procedure, which involves both the embryology laboratory at King’s Fertility and an off-site genetics testing laboratory. The first three phases are carried out at King’s Fertility: the in vitro fertilization, embryo biopsy and cell preparation. The biopsied cells are then transferred to the genetics laboratory for subsequent analysis.
Genetic testing for aneuploidy (PGT-A) has typically been offered to women over 37, to couples who had had several miscarriages or failed IVF cycles, to people with a family history of chromosome problems, and to men whose sperm may carry abnormal chromosomes. However, to date there is little evidence showing it improves success rates for these groups.
Genetic testing for heritable genetic diseases and structural chromosomal rearrangements are offered to any patient with a genetic diagnosis and after consultation with their doctor and genetic counsellor.
Summary
Genetic testing in the form of PGT-A is not an essential treatment and is therefore described as a treatment ‘add-on’. The HFEA (Human Fertilisation and Embryology Authority), our regulatory body, have devised a system of ‘traffic light rating’. The traffic light rating system consists of three colours that indicate whether the evidence, in the form of high-quality randomised control trials (RCTs), shows that a treatment add-on is effective at improving the chances of having a baby for someone undergoing fertility treatment. A red symbol is given for an add-on where there is no evidence from RCTs to show that it is effective at improving the chances of having a baby for most fertility patients. The HFEA have concluded that the traffic light rating for PGT-A for day five embryos is red.
For specific patient groups there may be reasons for the use of PGT-A, other than improving your overall chances of having a baby from a cycle of IVF. It may help to reduce the likelihood of having a miscarriage, and in some cases it may decrease the treatment time required to achieve a pregnancy, but more evidence is needed to confirm these findings. In these situations, it may be appropriate for you to be offered this as part of your treatment.
In contrast to PGT-A, PGT-M and PGT-SR are established treatments if there is a known and pre-identified genetic alteration and it has been agreed that this is medically indicated after your consultation with the doctor/genetic counsellor.
If you would like to find out more about the traffic light rating you can visit the HFEA website.