What is PGT-SR, what does it examine in couples with a structural chromosome change such as a translocation, and what are its limits? Per ESHRE.
PGT-SR is a genetic test that, when one of the partners has a known structural chromosome change (for example a translocation), looks in a few cells of the embryo formed through IVF at whether this rearrangement has been passed on in an unbalanced way. It does not describe the embryo in all respects and offers no assurance about pregnancy or birth. The current recommendations prepared for Europe clearly set out the technical limits of the method; you clarify with your doctor and a genetics specialist whether the test is suitable for you.
In what ways does PGT-SR differ from PGT-A and PGT-M?
In a structural change, pieces of the chromosome have been moved or rearranged. In a numerical change, on the other hand, the chromosome number differs from what is expected. PGT-SR targets the structural kind; PGT-A, which screens chromosome number, and PGT-M, which looks for a single-gene variant, are tests with different purposes.
What is balanced carriership?
In a person who carries a balanced structural change, the genetic material has been rearranged but there is generally no missing or extra material; for this reason the person may not be aware of this situation. If the same change is passed on to the embryo in an unbalanced way, the embryo may have a missing or extra piece of chromosome. This is the distinction PGT-SR aims at.
Is PGT-SR considered if there is a structural change known in a parent?
The test is considered when a structural chromosome change is already known in one of the partners. The current recommendations on this subject recommend arranging the indications and patient selection for PGT-SR, and counselling and consent. In which changes the test can be technically applied depends on the type of change and the laboratory's method.
How is your past pregnancy history assessed?
A structural change can be noticed in some couples during genetic assessment. How your past pregnancy history will be assessed is a separate subject and is dealt with together with your doctor.
How does the process work?
First, genetic counselling is received and the parent's chromosome change is clarified. Then embryos are created in an IVF cycle; the small sample taken from each is examined for whether the rearrangement carried by the parent has been passed on in an unbalanced way. The sampling technique is a separate heading. After the report is out, which embryo will be transferred is decided by discussion within your treatment plan.
Can standard NGS distinguish a balanced from a normal embryo?
According to the current assessment on this subject, the standard NGS method used for PGT-SR cannot detect full ploidy changes, low-level mosaicism and abnormalities below a pre-determined resolution; nor can it distinguish a balanced result from a normal one. That is, the test can show whether an embryo is unbalanced, but it may not be able to separate an embryo carrying a balanced structural change from an embryo carrying no change at all. Resolution can also be a problem in small segments.
Can technical errors affect the result?
Methods based on whole-genome amplification are open to artefacts such as allele dropout and amplification bias; for this reason the methods need to be extensively validated. The FISH method used in older approaches looks only at the targeted chromosomes and cannot detect mosaicism in single-cell biopsy.
Are uninterpretable results and the possibility of no suitable embryo discussed?
The organisational recommendations on this subject expect that the restrictions of the test, the chance of a wrong result, mosaicism and the fate of uninterpretable embryos be addressed in consultations. The process is laborious and carries expectations; it should also be known from the start that there may be no embryo that can be transferred at all.
Can you also talk about options other than PGT-SR?
The current recommendations on this subject expect counselling not to push the couple in one direction and to cover all the reproductive routes available. In this framework PGT-SR is dealt with as one of the options reviewed by couples who carry a structural change. You can weigh the benefits and limits of each route together with your doctor.
What questions can you ask at the consultation?
- Is the type of change we have of a kind that can be examined given the resolution of the test?
- Can the test distinguish a balanced from a normal embryo, and how does the report show this?
- How will our plan take shape if no suitable embryo can be obtained?
- Is not having this test also an option, and what routes are there in that case?
- Is a separate payment made for the test?
Frequently Asked Questions
If a pregnancy occurs with PGT-SR, is prenatal diagnosis still needed?
The current recommendations on this subject advise that the option of prenatal diagnosis be put on the table in pregnancies established after PGT. The reasons are that the test can be wrong and the technical restrictions of the method. The doctor who follows your pregnancy chooses the suitable method and timing.
What happens if no suitable embryo is found?
This possibility exists and needs to be mentioned from the start in consultations. In the mosaicism assessment on this subject, it is stated that a new stimulation cycle can be used to obtain a correctly diagnosed embryo in PGT-SR. The next step is planned according to your situation.
What does an "inconsistent result" in the report mean?
In a sample taken from the outer layer, more than one cell may give a different result. According to the current assessment on this subject, the cause may be a technical error or true mosaicism. How inconsistent results are to be reported should be arranged by the laboratory, and couples should receive counselling. The detailed assessment of a mosaic result is a separate subject.
Could my child also be a carrier?
According to the current assessment on this subject, depending on the method used, a balanced and a normal embryo may not be able to be told apart from each other; some methods (for example SNP array) can make this distinction. Where they cannot be separated, the embryo transferred may also carry a balanced change like the parent. Talk with your doctor and your genetics specialist about what this means.
Is PGT-SR the same as PGT-A, which screens the chromosome number?
No. PGT-SR targets a known structural chromosome change. PGT-A investigates the chromosome number, and PGT-M a single-gene variant.
Might I not have noticed that I am a balanced carrier?
Yes. In a balanced change there is generally no missing or extra genetic material, so the person may not be aware of it.
Can every structural change be examined with the same method?
The technical feasibility of the test depends on the type of change and the laboratory method. You can talk with your genetics specialist about whether your change can be examined.
Does standard NGS detect all chromosome problems?
No. Full ploidy changes, low-level mosaicism and abnormalities below the resolution may not be detected. Resolution can also be a problem in small segments.
Does PGT-SR give assurance for pregnancy or birth?
No. It does not describe the embryo in all respects and offers no assurance about pregnancy or birth. The technical restrictions and the possibility of a wrong result need to be addressed in counselling.
Should we discuss before the test the possibility that no suitable embryo will be found?
Yes. It should be discussed from the start that no embryo that can be transferred may be obtained. How uninterpretable embryos will be handled is also a matter for counselling.
Are reproductive routes other than PGT-SR also discussed?
Yes. Counselling is expected not to be directive and to cover all the reproductive options available. You can weigh the benefits and limits of each route together.
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