Can you pick an embryo that is most likely to produce a live
birth simply by looking at it under a microscope? Sounds like an easy question
to answer but the reality is far more complex. Stay tuned and I will explain.
In 2021, the best IVF programs in the world, do three things. First,
they culture embryos to the blastocyst stage. This usually takes 5 to 7 days. Second, embryos that
reach the blastocyst stage are frozen so they can be placed into the uterus at a more optimal time.
Third, chromosome testing of the embryos, known as PGT, is performed for women over the age of
35. I am going to focus my discussion today about programs that use these best in class techniques.
How are blastocysts graded? Across the planet, there are many different grading systems.
This becomes a problem because a scientific study published using one system isn’t necessarily going
to have the same results as another system. In general, however, blastocyst grading looks at
three different things. First is the size of the blastocyst. A developing blastocyst
fills with fluid in the middle. This causes the blastocyst to grow larger, like a water balloon.
We call this expansion. A blastocyst that is more expanded isn’t necessarily a better
quality blastocyst but it does make it easier to see different cells developing in the embryo.
The second criteria looks at a group of cells known as the inner cell mass. These are the cells
that go on to form the fetus. The third criteria looks at the remainder of the cells. These cells
are called the trophoblast. These cells eventually develop into non fetal tissues like the placenta.
There are many problems that we run into with blastocyst grading. The first problem is timing.
The microscopic appearance of the blastocyst can change even over the course of a few hours.
What looks poor at one moment may look better at another time. The second problem is called
interobserver variability. This means that two well trained embryologists can look at the same
embryo at the same time and give it a different grade. Remember, that these assessments are
very subjective and sometimes the differences can be very subtle. A third problem is that grading
systems may not be predictive of whether a live birth occurs. In fact, if you review studies that
have looked at grading blastocysts, you will find that they have reached different conclusions. For
example, some studies found that the grade of the inner cell mass predicted pregnancy potential.
Other studies found that the inner cell mass didn’t matter but the grade of the trophoblast
was important. By the way, these different factors aren’t always similar. It is possible to have a
blastocyst with a pretty inner cell mass and a not so pretty trophoblast or just the reverse. Which
one should be prioritized? Unfortunately, there is no universal agreement on this.
Is all this confusing enough yet? Just wait, it gets worse. We know that many of the embryos
that have chromosome abnormalities will never develop to the blastocyst stage.
This is one of the reasons that doing blastocyst embryo transfers is a good idea.
Blastocysts are less likely to have chromosome abnormalities compared to earlier stage embryos.
But some of them still will. In fact, some really beautiful blastocyst embryos can have
chromosomal abnormalities. Studies show that transferring chromosomally abnormal blastocysts
have an extremely poor chance of becoming a live birth. I discuss that in this video.
What if you have an embryo that reached the blastocyst stage and looked good enough to
biopsy so you could test the chromosomes and the results were normal. Does the grade even matter at
that point? Maybe not. A few studies have looked at this. Some have found no impact of the grade.
Some others have but again, they don’t always agree which criteria are important to look at.
You may have heard that there are embryo incubators that have cameras in them
that can take pictures of the embryo every few minutes as it is developing. These are called
time lapse incubators. They can produce some really amazing videos like this. Instead of
looking at the embryo at just one point, you can look at it at hundreds of time points and do all
sorts of calculations like how long does it take the embryo to divide from 2 cells to 4 cells.
Does this sort of embryo grading help to select the most viable embryos? At this point,
there is no proof that these systems are better for selecting the embryos with the best potential
for a live birth. Many IVF centers are producing studies using these time lapse incubators so there
is hope that in the future, we may find that these systems can do more than just produce cool videos.
Another technology that we are looking at for the future of
embryo selection is artificial intelligence. I discuss that technology in this video.
Our InfertilityTV Bottom Line is this. Most IVF labs will freeze or biopsy only what they feel
are good quality blastocysts. Beyond that, the role of embryo grading in determining which embryo
will produce a live birth is really uncertain and varies significantly from one lab to another
and even from one embryologist to another. IVF is stressful enough.
Try not to get too fixated on embryo grading. Some great looking embryos
may still fail to produce a live birth and some not so great looking embryos might.