Pre-implantation genetic testing

Pre-implantation genetic testing (PGT) is used when a couple has a known risk of passing on a genetic abnormality and diagnostic testing is performed on an embryo to determine if it has also inherited the abnormality.

A typical treatment cycle for PGT might look like:

1. Stimulation of the ovaries

In order to create embryos for genetic testing, the ovaries have to be artificially stimulated using hormones to produce several eggs at the same time.

Because a significant number of a couple’s embryos are likely to be affected by the genetic or chromosomal abnormality, a large number of embryos need to be created for the best chances of success.

2. Collection of eggs from the ovaries

At the appropriate time, the eggs are removed during a surgical procedure known as egg retrieval. Once the eggs are removed, they are inspected to determine which are mature and normal appearing.

3. Insemination/injection of sperm

Fertilisation during PGT will be done either by:

• In Vitro Fertilisation (IVF): Sperm and eggs are placed together in a culture dish to allow fertilisation to occur.
• Intracytoplasmic Sperm Injection (ICSI): A single sperm is injected in the centre of an egg. This technique is used for conditions caused by a single faulty gene.

4. Fertilisation

The morning after injection/insemination of the sperm, the embryologist carefully examines each egg to see if fertilisation has occurred.

5. Embryo biopsy

The eggs that were successfully fertilised are grown in the laboratory for 5-6 days when the embryo forms what is called a blastocyst of about 100-150 cells. At this stage trophectoderm biopsy (the cells which will form the placenta) takes place.

This technique is highly specialised and can only be carried out by embryologists who have a special licence from the Human Fertilisation and Embryology Authority (HFEA).

The removal of these cells should not harm the embryo.

6. Embryo Testing

The cells are tested to see if the embryo from which they were removed contains the abnormality that causes the genetic condition.

7. Embryo Transfer

Only those embryos that do not have the specific genetic condition that was tested for will be transplanted into the woman’s uterus. Usually one embryo will be transferred to the uterus at any one time to avoid the possibility of multiple births (more than one baby in a pregnancy).

Any suitable remaining unaffected embryos will be frozen for later use.

Those embryos that are affected by the inherited condition are allowed to perish or couples are asked if they would consider allowing these embryos to be donated for research and training.

8. Pregnancy Test

Twelve days after the embryo transfer, the woman is given a pregnancy test. A positive pregnancy test means that an embryo has implanted.

If successful, the procedure will result in pregnancy and the child should not be affected by the condition for which it was tested.

Couples who request pre-implantation genetic testing (PGT) are at risk of passing on a serious* genetic condition to their children. Parents may have the condition themselves or be carriers of the condition. They may already have a child affected or they may have experienced the loss of a child or pregnancy affected with the condition.

Couples generally considered for PGT include:

Carriers of a serious autosomal recessive condition: For carriers of an autosomal recessive condition, there is a 1 in 4 (25%) risk of each pregnancy delivering an affected child.

Carriers of a serious autosomal dominant condition: For carriers of an autosomal dominant condition, there is a 1 in 2 (50%) risk of each pregnancy delivering an affected child.

Couples with inherited chromosome disorders.

Couples with a family history of serious sex-linked disorders: Couples with a family history of a sex-linked disorder have a 1 in 4 (25%) risk of each pregnancy delivering an affected child (half of all male children).

Therefore, PGT may be recommended if:

• you or your partner has a family history of a serious genetic condition and/or
• you and your partner already have a child with a serious genetic condition and/or
• you and your partner have had a number of pregnancy terminations because your baby had a serious genetic condition.

*In this section we have used the word ‘serious’ a lot. This is because the Human Fertilisation and Embryology Authority (HFEA) must find that a condition is ‘sufficiently serious’ to allow PGT.

PGT is available for three broad categories of conditions including:

Single gene defects for which PGT testing is available.

Chromosomal abnormalities, including inversions, deletions, aneuploidy (an abnormal number of chromosomes), and translocations (where a piece of one chromosome either becomes attached to another chromosome or swaps places with a segment from another chromosome).

Sex-linked conditions, for which it is not yet possible to test for the specific genetic mutation, in which case they test for sex rather than mutation.

The accuracy of PGT will vary, and there is the possibility that testing may not be 100% reliable or conclusive. However, testing is 98-99% accurate for most couples but may depend on the condition being tested for and the couple’s individual test results.

All patients are offered confirmatory prenatal testing (amniocentesis or chorionic villus sampling) if PGT results in a pregnancy.

It is difficult to assess success rates for PGT because there is currently little data available. As with most fertility treatments, success depends on many factors, including the woman’s age and weight.

Additionally, sometimes no embryos are suitable for transfer to the womb, for reasons including:

• Not enough eggs were produced or fertilised
• Embryos do not develop to the blastocyst stage
• Embryos do not survive the biopsy, although this is a rare event
• All the embryos were affected by the genetic condition.

Therefore, a pregnancy cannot be guaranteed using PGT.

PGT can provide:

• An alternative to prenatal diagnostic testing: Couples avoid the distress associated with diagnosis, particularly if late in an established pregnancy.
• An alternative to termination of pregnancy: If prenatal testing (through amniocentesis or chorionic villus tests reveals a genetic abnormality, the options available to parents are to have a child with a genetic condition or to undergo a pregnancy termination. This is a difficult and often traumatic decision. However, PGT is performed before pregnancy begins, thus eliminating this difficult decision.
• The opportunity to conceive a pregnancy that is biologically the parents’ own and yet unaffected by a genetic condition in the family: couples for whom the option of prenatal testing and termination is not an acceptable choice may not want to take the risk of a child having a genetic condition. In the past, potential parents with a genetic condition or those who know that they are carriers frequently chose adoption, embryo donation, or surrogacy or chose not to have children in order to avoid the risk of passing on the condition. PGT now allows these couples the opportunity to have a child not affected by the condition.

Most of the risks involved in PGT treatment are similar to those for conventional IVF:

• Fertility drug reaction: mild reactions may involve hot flushes, feeling down or irritable, headaches and restlessness; symptoms usually disappear after a short time.
• Multiple pregnancy: risk of complications is higher in a pregnancy with twins or multiples (although some centres reduce this risk by only transferring one embryo).
• Ovarian Hyperstimulation Syndrome (OHSS): Symptoms include abdominal pain and swelling, shortness of breath, nausea, vomiting, and a reduction in urine output; can result in mineral imbalances in the blood and clotting problems.
• Pelvic infection.
• Miscarriage: risk of a miscarriage after IVF is no higher or lower than after a natural conception.
• Ectopic pregnancy: pregnancy development in the fallopian tubes instead of the womb. This would not result in an ongoing pregnancy.
• There is currently no strong evidence to suggest that babies conceived through PGT are at any greater risk of abnormality than babies conceived through other forms of assisted reproduction.

Several studies have concluded that there do not appear to be any major side-effects to the PGT treatment. However, there is evidence that babies conceived through IVF are more likely to:

• be born prematurely
• weigh less than naturally conceived babies born at the same age

Follow-up data remains limited and long-term outcomes are unknown. It is important to continue to monitor the progress of children born following PGT, to gather information about the potential impact of the treatment.

The use of pre-implantation genetic testing in the UK is highly regulated. The Human and Fertilisation Embryology Authority (HFEA) regulates the use of PGT in the UK and there is a Statutory Approvals Committee (SAC) that decides if a condition is ‘serious’ enough to be able to use PGT. Conditions are licensed on a case by case basis as and when couples request its use.

Before requesting PGT, potential parents should consult their local clinical geneticist or genetic counsellor to evaluate the risk of having a child with the inherited condition. Tests should be performed to determine the genetic cause of the condition of the affected parent or family member. Couples considering this treatment should ask their genetic specialist to refer them for a PGT consultation. 

Clinics offering PGT must ensure that the type of testing done during PGT can actually identify that genetic change in an embryo biopsy and also confirm that a PGT licence has been issued by the Human Fertilisation and Embryology Authority (HFEA) or is suitable for making an application for that particular condition before proceeding further.

Before you can access PGT, the HFEA must have licensed the condition for PGT (full list of licences here). If the particular condition does not yet have a licence this does not mean that you will not be able to access PGT. Conditions are licensed on a condition-by-condition basis, as people apply to use PGT for specific conditions. If your condition is not yet licensed, your PGT clinic will be able to apply for a licence through the HFEA.

Preparation for PGT consists of several stages. These typically include:

• Referral to a PGT clinic by the couple’s clinical geneticist or genetic counsellor.
• An initial clinical consultation.
• Checking if NHS funding applies or if an application is required for procedural and drug costs.
• Obtaining the potential parents’ consent for treatment, biopsy, storage and use of gametes and embryos.
• Laboratory testing and preparatory investigations (including health history, ultrasound scan, blood tests, semen analysis).
• Treatment cycle.

Preparation time will vary, but on average it will take 5-12 months after the initial consultation before a couple will start treatment. Once in a treatment cycle, the process takes about 9-12 weeks.

The cost of PGT is typically split into two parts: procedural costs (consultations, laboratory testing, egg collection, embryo transfer, ultrasound scans, and blood tests) and drug costs (for ovarian stimulation and embryo transfer).

A couple can receive PGT treatment through the NHS if they meet certain criteria. There are slight differences in the criteria between the UK nations and may include the following.

Funding for PGT: England only

• The couple should be at risk of having a child with a serious genetic condition.
• There should be no living unaffected child from the current relationship.
• The female partner should be under 40 years of age at the time of treatment.
• The female partner should have a Body Mass Index of more than 19 and less than 30.
• Both prospective parents must be non-smokers.

Couples meeting the full criteria may be eligible for up to three complete cycles of PGT. The number of cycles that a couple will be able to access can depend on whether they are successful after a cycle and also whether further treatment after a cycle is medically recommended.

Funding for PGT: Scotland

A couple must have

• A known genetic condition in the family which conveys a ‘significant risk of a serious genetic condition’.
• No living, unaffected child, or untested child (for an adult-onset disorder) as a couple
• Female hormone level (anti mullerian hormone) of 7.5 pmol/l or greater (or an adequate ovarian scan).
• Female age < 39 years.
• Female body mass index < 30.
• Both partners should be non-smokers for at least 3 months, living at the same address for at least 2 years and both must be eligible for NHS treatment.
• PGT cannot be offered to patients with a ‘de novo’ dominant mutation.

Individuals with an unaffected child are not entitled to a second, NHS-funded cycle. Eligibility for self funded PGT can be considered by the PGT multi-disciplinary team.

Further information can be found on the NHS Lothian website here.

Funding for PGT: Wales

• Referral must take place before the female is 38 and 6 months old.
• Cycle of treatment must take place before the female’s 40th birthday.
• Female Body Mass Index must be between 19 and 30 (women who do not have a BMI between 19 and 30 may be placed on the waiting list, but must have reached the required BMI before treatment takes place).
• Both prospective parents must be non-smokers.

Couples meeting the full criteria may be eligible for up to three cycles of PGD.

If you are not eligible for NHS funding then a couple may be able to pay for a treatment cycle themselves. The price of this will vary between clinics.