PGT can answer important questions. It cannot promise a baby.

So, what is PGT?

PGT stands for Preimplantation Genetic Testing. It is genetic testing carried out during an IVF cycle, before an embryo is transferred to the uterus.

A few days after fertilisation, an embryo reaches the blastocyst stage. By then, two distinct groups of cells have started to emerge: the inner cell mass (which primarily gives rise to the fetus, and the outer layer) the trophectoderm (which mainly contributes to the placenta and other supporting tissues).

For PGT, an embryologist usually removes around five to ten cells from the trophectoderm. The embryo is typically frozen while that tiny sample makes its way to a genetics laboratory.

Tiny being the important word here.

The laboratory is not examining every cell in the embryo. It is looking at a small sample taken from one part of it.

And although “PGT” sounds like one neat, all-encompassing test, it really isn’t.

PGT-M, PGT-SR and PGT-A may share the same initials, but they are asking three very different questions.

PGT-M: when we already know what we are looking for

PGT-M begins with a clue. There is already a known inherited condition in the family, and the laboratory knows which genetic change it is looking for.

Perhaps both parents carry disease-causing variants in CFTR, the gene associated with cystic fibrosis. Perhaps one parent has Huntington disease caused by a pathogenic expansion in HTT. Or the family may be affected by sickle cell disease, spinal muscular atrophy or an inherited cancer-predisposition syndrome.

The lab is looking whether the embryo has inherited the familial genetic change we already know about rather than searching blindly through its DNA

The test is often designed specifically around that family and that condition.

Scientists may look directly for the known variant while also analysing nearby genetic markers (little molecular signposts that help them follow which stretch of chromosome the embryo inherited).

That preparation can take time. Depending on the condition and the laboratory, DNA samples may be needed from the couple and, occasionally, other family members before the IVF cycle even begins.

But even a reassuring result has boundaries.

If an embryo is reported as unaffected, it does not mean every gene has been examined or every possible genetic condition has been ruled out.

PGT-SR: when all the DNA is there, just not quite where expected

Some people can carry a chromosome rearrangement for years without ever knowing it.

They feel well. They have no symptoms. Nothing obvious is missing... Their chromosomes have simply been organised a little differently. Perhaps two chromosomes have exchanged pieces. Perhaps a section has broken away, flipped around and reattached in the opposite direction.

When the rearrangement is balanced, all the necessary genetic material may still be present! Which is why the person carrying it can be completely healthy.

The complication often appears later, when eggs or sperm are formed.

Chromosomes have to divide and separate, and with a structural rearrangement that process can sometimes produce eggs or sperm containing an unbalanced amount of chromosome material.

An embryo may then receive too much of one segment and too little of another.

Depending on the rearrangement involved, that can affect implantation, increase the risk of miscarriage or lead to a serious genetic condition.

This is where PGT-SR comes in.

It looks for embryos with chromosome imbalances related to the rearrangement already known in the family.

It is not asking whether the embryo is genetically flawless; this is one of the questions that no test can answer... It is asking whether this rearrangement has left the embryo with missing or additional chromosome material.

Depending on the method used, PGT-SR may not always distinguish an embryo with the usual chromosome arrangement from one carrying the same balanced rearrangement as the parent. Neither has an obvious gain or loss of genetic material, so both may potentially be considered for transfer.

That difference may never affect the child's health.

It could, however, become relevant years later if that child eventually decides to have children of their own.

Genetics has a habit of thinking several generations ahead.

PGT-A: when chromosome number becomes part of the decision

In PGT-A, we are looking at chromosome copy number.

Most human cells contain 46 chromosomes, arranged in 23 pairs (one copy of each pair inherited from the egg and one from the sperm).

Embryos, however, do not always begin with the expected number.

Sometimes a chromosome is missing. Sometimes there is an extra copy.

This is called aneuploidy, and it becomes increasingly common with maternal age.

PGT-A analyses DNA from the small group of trophectoderm cells removed during the biopsy.

If the sample shows chromosome copy numbers consistent with the expected number, the embryo is generally reported as euploid.

If additional or missing chromosome material is detected, it may be reported as aneuploid.

This matters because many aneuploid embryos will not implant. Others stop developing or result in miscarriage. Some chromosome abnormalities can continue into pregnancy and, in certain cases, result in the birth of a child with a chromosomal condition.

PGT-A can therefore help clinicians decide which embryo may be the most appropriate to transfer first.

But then comes one deceptively reassuring word: euploid.

And it is very easy to hear more certainty in that word than the test can actually provide.

Euploid and genetically perfect are not synonyms.

An euploid PGT-A result does not mean every gene has been examined. It cannot rule out every genetic condition, developmental difference or pregnancy complication.

And it cannot promise implantation, an ongoing pregnancy or a healthy baby. What it can tells us though, is that the cells that were sampled showed chromosome copy numbers consistent with euploidy, within the limits of the test.

Does PGT-A actually improve the chance of having a baby?

And here is where things become interesting... PGT-A can help identify which embryo appears most suitable to transfer first.

By avoiding the transfer of embryos with detectable chromosome imbalances, PGT-A may reduce miscarriage and, for some patients, avoid transfers that were unlikely to result in an ongoing pregnancy.

But fewer miscarriages per transfer do not automatically mean more babies per IVF cycle.

PGT-A may also reduce the number of embryos considered suitable for transfer. And because every result begins with a small biopsy, there is a possibility that an embryo capable of resulting in a live birth could be excluded because of mosaic-range findings, technical limitations or an inaccurate result.

This is why the UK Human Fertilisation and Embryology Authority has assessed PGT-A differently depending on the outcome being measured.

It has rated the evidence positively for reducing miscarriage for most fertility patients, while not supporting the claim that PGT-A increases the chance of having a baby for most patients.

At first, that sounds contradictory but if you think about it more carefully you will realise that it isn’t.

PGT-A may help avoid certain unsuccessful transfers or miscarriages and may change which embryo is transferred first.

That does not necessarily mean it increases the total chance of a live birth from all the embryos created during that IVF cycle.

Mosaicism: when an embryo refuses to fit neatly into one box

PGT-A sounds beautifully binary on paper. Euploid and Aneuploid.

An embryo begins as a single cell and then divides again and again. If a chromosome error occurs during one of those divisions, some cells may carry the change while others do not. That mixture of cell populations is called mosaicism.

Now remember the biopsy.

PGT-A does not analyse every cell in the embryo. It analyses DNA from a small group of trophectoderm cells and those cells are assessed together.

If the combined DNA signal falls somewhere between what the laboratory expects from a euploid result and what it expects from an aneuploid one, the embryo may be reported as mosaic.

But that result does not tell us exactly how many cells in the entire embryo are euploid or aneuploid. It cannot tell us what every other region of the embryo looks like.

And because the biopsy comes from the trophectoderm which are the cells that mainly contribute to the placenta, it may not perfectly represent the inner cell mass that contributes to the fetus.

And there is another wrinkle: an intermediate signal does not always mean the embryo itself is truly mosaic. Technical factors can sometimes produce a similar pattern, which is another reason these results need careful interpretation.

Different laboratories may also use different thresholds when deciding what qualifies as a mosaic-range result.

A few cells can tell us a lot but never everything

Every PGT result begins with the same reality: the laboratory has not tested the whole embryo.

It has tested a handful of cells taken from its outer layer.

Those cells may help a family avoid passing on a serious inherited condition. They may reveal an unbalanced chromosome rearrangement. They may help decide which embryo to transfer first.

But they remain a sample.

Sometimes, even that sample does not give a clear answer. A report may come back as “inconclusive” or “no result.”

A second biopsy may sometimes be considered, but the embryo may need to be thawed, handled again, biopsied for a second time and frozen again.

Whether that makes sense depends on the embryo, the laboratory and the family’s individual circumstances.

And, as with every genetic test, PGT is not completely free from error.

False-positive and false-negative results are uncommon, but they can occur. Even after PGT-M or PGT-SR, a small possibility remains that the result may not perfectly reflect the pregnancy that follows. Which is why PGT does not replace the genetic care offered during pregnancy.

Depending on the type of PGT performed, the condition involved and the family's preferences, confirmatory prenatal diagnostic testing may also be offered.