Should we do PGS testing on Day 3 embryos?

We always planned to do PGS analysis for to improve our surrogacy chances. But our clinic incubates their embryos only three days, and freezes them at Day 3. Now we’re not so sure that PGS is a good idea after just 3 days of development. – Felicia and Martin

Good morning Felicia and Martin.

Most clinics nowadays let embryos mature to Day 5 (what we hope will be their ‘blastocyst’ stage) before freezing. I have a clinic India that still likes to freeze embryos at Day 3, but it’s an outlier. Their rationale is that the embryos will develop better in their natural ‘in utero’ environment.

According to the theory, the longer the embryo stays in its natural environment, the healthier it will be. Of course it’s hard to tell if the embryos develop better or not because once transferred they are impossible to watch.

That Indian clinic had a good success rate… not bad, but not the best either. So I had no strong opinion one way or another. But there are exceptions, and PGS/PGD analysis is one of those exceptions.

PGS stands for Preimplantation Genetic Screening (or Diagnosis in the case of PGD). The test analyzes a cell from the embryo to see if it has a full set of healthy and well formed chromosomes.

Many people consider PGS to be a test for missing chromosomes (and thus for Downs Syndrome or other similar disorders).  But PGS analysis also will indicate embryos with malformed or transposed (not just missing) chromosomes. These types of transpositions are quite common and a leading cause of miscarriage or failed pregnancies. They arise spontaneously as embryos develop in the early stages and and chromosomes separate and split to form new cells.

If you remember your high-school biology, chromosomes are along strands of nucleic acids and protein that carry the information for cellular growth. Quite often those strands get tangled or damaged. Very often the chromosomes get positioned in the wrong spot (switched with another pair in the sequence), and can prevent a embryo from developing into a proper fetus.  This is true even if the embryo looks outwardly healthy and well developed.

Think of the embryo like a delivery truck… Even if the truck is running well, the cargo it’s carrying may be spoiled and useless. The only way to know if the cargo is good is to open the truck and check what’s inside. Similarly, you can’t tell if an embryo can develop into a healthy fetus just because it’s healthy and well developed. You need to check the chromosomes themselves – and that’s what PGS does.

But… To perform PGD/PGS an embryologist has to pinch off several cells of the embryo to examine them. Naturally, that type of invasive biopsy is not good for the embryo. But at Day 5 the embryo has hundreds of cells and can afford to lose a few. At Day 3 an embryo only has 6 to 10 cells – and the likelihood of doing serious damage to the embryo is greater.

Research shows that 75% or more of failed pregnancies (negative pregnancy tests or early term miscarriages) can be attributed to problems with the chromosomes of the embryo transferred.  PGS analysis will detect any of these issues, and potentially improve pregnancy rate and avoid miscarriages.

In my opinion, if the PGS is done by a reputable and skilled lab, the overall result is usually a higher probability of pregnancy — even when factoring the possible damage to an embryo. But I would request that your clinic let the embryos incubate until they reach a more advanced state, and then do the biopsy. That would limit the possible risk to the embryos from the biopsy.

I hope this is helpful.