Pre-implantation Genetic Diagnosis (PGD)
When a person has a heritable RB1 mutation, pre-implantation genetic diagnosis can be used with In vitro fertilization (IVF) to avoid passing the genetic mutation to the children.
This information page focuses specifically on PGD in relation to retinoblastoma. Many websites provide extensive IVF resources, and fertility clinics will provide detailed information about the process at that specific clinic.
What Is PGD?
PGD is a genetic testing process that takes place during fertility treatment. It’s similar to the genetic testing process in relatives after your mutation has been identified. But instead of looking for your mutation in a blood sample, PGD examines a sample of cells taken from the outer layer of an embryo before it is transferred to the uterus. Results of testing are discussed and the couple/individual select embryos for transfer with guidance and support from the multidisciplinary team, hopefully leading to a successful pregnancy.
How Is PGD Different From Pre Implantation Genetic Screening?
Pre-implantation Genetic Diagnosis (PGD) is used to test for a specific genetic disease or chromosomal disorder known to be present in the family. Testing aims to identify affected and unaffected embryos so the family can have a healthy child, free from the specific medical condition.
Pre-implantation Genetic Screening (PGS) harnesses PGD technology to help people who have repeated implantation failure or miscarriage. An embryo should have 46 chromosomes. Too few or too many chromosomes (aneuploidy) is a leading cause of embryos failing to implant in the womb, or later miscarriage. PGS screens embryos to determine which are aneuploid and which are euploid (have the correct number of chromosomes). This increases the chances of successful pregnancy.
Who Can Have PGD?
PGD may be an option for you if
- You had bilateral or unilateral retinoblastoma.
- A relative had retinoblastoma, and genetic testing starting with that individual identifies that you carry an RB1
PGD can only take place after genetic testing has been done and a constitutional RB1 mutation is identified in you. PGD is not possible without first securing this genetic information – even if you had bilateral retinoblastoma or you have a family history of retinoblastoma.
Can PGD Test For Other Conditions?
Theoretically, PGD can be used to test for any condition, disease or syndrome for which the causative gene is known. However, many countries regulate the specific gene and chromosome changes that can be tested for, based on the severity of its impacts to the child. Check with your country’s appropriate regulators or ask your medical care providers for guidance.
How Does PGD Happen During IVF?
The specific protocol may differ slightly according to the clinic providing fertility care, but the process will be similar to the following. Once embryos are created in the laboratory, they are cultured (grown) for five to six days, until they reach blastocyst. At this stage, the embryo’s inner cell mass is surrounded by an outer layer called the trophoblast that will form the placenta.
A tiny sample of cells is removed (biopsied) from the trophoblast. Genetic testing of these samples takes around four weeks, so the embryos are frozen at this time. If multiple IVF stimulation cycles are planned, the biopsies may be stored and tested at the same time after all the stimulation cycles are complete.
The couple/individual will discuss results with their fertility doctor or genetic counsellor, and the next steps in the IVF plan. Decisions about which embryo(s) to transfer into the uterus will be made with advice and support of the fertility, medical and genetics team. A frozen embryo transfer cycle will then be planned to transfer the selected embryo(s) into the uterus.
Is PGD Safe?
PGD is itself considered to be very safe. Cells are biopsied from the trophoblast that becomes the placenta, not from the embryo that becomes the baby. Biopsy does not change the embryo’s ability to develop and function as expected, nor does it reduce the chance of a normal, healthy pregnancy.
Health and developmental issues are no more common in babies born following PGD than babies born using IVF alone. IVF itself does have risks, some of which can be very serious, and these should be considered when deciding whether PGD is the right option for your family. Major concerns are:
- Multiple pregnancy (twins, triplets etc.) – this risk is reduced by having an elective Single Embryo Transfer rather than multiple embryos transferred at the same time. Even with eSET, a risk remains of a single embryo separating into identical twins (or more), due to the IVF and PGD process.
- Ovarian Hyperstimulation Syndrome (a severe reaction to fertility drugs).
- Ectopic pregnancy (the embryo travels to the fallopian tube instead of implanting in the womb).
- Possible increased risk of birth defects (research is ongoing to establish if very rare instances are statistically significant, and if so, whether this is related to fertility treatment or to fertility issues that precipitate IVF treatment).
When PGS is used in addition to PGD, fewer babies will be born with chromosomal disorders since most are identified before embryo transfer.
An embryo can be damaged by the biopsy process, meaning it can no longer grow. Genetic tests may also be unsuccessful or give inaccurate results. Genetic testing of the baby at birth is strongly advised to confirm the PGD results. When staff follow strict protocols within the embryology and genetics labs, risk of human error that can lead to these failures during the PGD process is significantly reduced.
There is a very small risk a frozen embryo will not survive the thawing process necessary before a Frozen Embryo Transfer. Embryos cultured to blastocyst are considered more likely to survive the thawing process than very early stage embryos.
Fertility clinics typically document their success rates for biopsy and thawing procedures, and should be able to provide this data to clients when requested.
Does PGD Increase The Chance Of A Successful Pregnancy?
PGD itself does not increase the chance of successful IVF treatment. If PGS is used in combination with PGD, this may increase the chance of success. However, success depends on multiple factors, such as the woman’s age and health, fertility issues, and experience of the fertility clinic and genetics lab providing care. Talk to your fertility care provider about your specific circumstances.
What Causes PGD To Fail?
Sometimes, despite multiple IVF stimulation cycles, there may be no suitable embryos to transfer to the uterus. There are multiple reasons for this, including:
- not enough eggs were produced or fertilised
- embryos were damaged during the biopsy process
- all embryos have the genetic mutation identified during PGD or have aneuploidy identified during PGS
- suitable embryos did not thaw effectively for planned Frozen Embryo Transfer
What Should I Consider When Thinking About / Planning PGD?
What Should I Consider When Thinking About / Planning PGD?
Talk to your Primary Care Provider / GP, retinoblastoma doctor, lifelong care provider, genetic counsellor or another appropriate medical professional about your concerns and options. Ask for referral to a genetic counsellor if you have not yet had genetic testing for retinoblastoma.
Find out what your country’s funding options are for PGD. We cannot monitor and list them all here. Many US medical insurance companies will cover some or all of the costs for multiple cycles. In the UK, NHS guidelines advise that 3 cycles of PGD should be made available to individuals who have a known constitutional RB1 mutation – there are additional criteria, so it is important to clarify eligibility with your doctor.
When you research IVF clinic options, consider these PGD specific items:
- Are they licenced to perform PGD / PGS?
- What experience do they have in PGD / PGS, specifically retinoblastoma?
- Are the embryology and genetics labs on site? If not, where are they located?
- What support do they offer during PGD? This may be distinct from general fertility support provided.
- Do they have a named PGD co-ordinator and what is that person’s role in the process? Do you connect well with that individual?
- Who will you meet with to discuss PGD results and next steps?
- What support and next-step fertility options can they offer you if PGD establishes that all embryos have either RB1 mutation or are aneuploid?
- Is there a local PGD network/community you can tap into for additional support?
Where Can I Meet Other People Who Have Experienced PGD For Retinoblastoma?
Adult Retinoblastoma Survivors is a closed, moderated Facebook community uniquely for individuals aged over 18 who have had a diagnosis of retinoblastoma. A number of individuals in the community have varying experience of PGD.