'Blastocyst' is a word that is guaranteed to come up at some point in every IVF cycle. This is a key stage in embryo development and in many ways it is the ultimate goal in IVF, since an embryo must reach the blastocyst stage to implant. Whether this is in the laboratory or in your body, blastocysts are an essential prerequisite to making a baby.

Blastocyst development timeline

An embryo will usually form a blastocyst on day 5 or 6 after fertilisation, but the process can start as early as day 4. Although the embryo has moved on significantly since fertilisation, it is still smaller than a dot and can not quite be seen with the naked eye. By this stage, the embryo is made up of several hundred cells which have begun to organise themselves into two equally important structures: the trophectoderm and the inner cell mass.

Trophectoderm

The trophectoderm is the name given to the outer cells of the blastocyst. This is the portion that will go on to form the placenta and other supporting structures around the baby.

The cells of the trophectoderm have a cobbled appearance. They line the outside of the embryo and press up against the protective shell (zona pellucida). As the blastocyst gets larger, the trophectoderm expands while the zona pellucida gets thinner. Eventually the trophectoderm breaks through the shell and the rest of the embryo hatches out with it as it prepares to implant into the lining of the uterus.

hatched blastocyst
Inner Cell Mass

The inner cell mass is the part of the blastocyst which will go on to form the actual baby.

As the name suggests, the inner cell mass is a ball of cells which sits more centrally in the embryo, inside the trophectoderm layer. Although it doesn't look like much, the inner cell mass is particularly fascinating as the cells are described as 'pluripotent' meaning that they have the potential to turn into any type of cell in the body. If successful, this small, insignificant-looking ball of cells may go on to form the trillions of cells making up a human body.

labelled blastocyst
The Blastocoel

The blastocoel is a cavity of fluid which forms in the centre of the blastocyst.

The appearance of the blastocoel is the earliest sign that the embryo has started forming a blastocyst. It begins as small cracks appear in the centre of a compacted embryo (morula) and fill with fluid. These pockets of fluid then begin to merge together until they form a single cavity which gradually expands until the blastocyst reaches full size.

Blastocysts actually rely heavily on the blastocoel as it provides structure and support to the embryo. It will also form the basis of the yolk sac during pregnancy. However, it is common for blastocysts to collapse and re-expand again as the fluid is lost and replenished, particularly if the embryo is frozen and thawed.

 

Blastocyst Grading

Although embryos at the blastocyst stage are still relatively early in development in terms of forming a baby, they are already very complicated biological structures. They are all genetically unique and have undergone many changes in gene expression and metabolism. The potential of a blastocyst to form a successful pregnancy is heavily dependent on these subcellular changes which cannot be seen with the naked eye. Basic blastocyst grading is usually based only on the appearance of the cells as they are seen down the microscope. More advanced methods of blastocyst grading can also take into account criteria such as developmental timings and how well the embryo developed on previous days. For example, did the cells divide evenly? Were there many signs of fragmentation? Did the embryo reach each milestone at the correct time? Are some cells showing signs of degeneration?

In the early days of IVF, it was unclear which factors were most important in embryo grading. Many years of research and analysis of patient outcomes has now given embryologists a huge amount of insight into the key aspects of blastocyst formation. Although there are still many unknowns, it is now clear what differentiates a good quality blastocyst from a poor quality blastocyst.

blastocyst quote
What makes a blastocyst top quality?

Blastocyst grading is typically based on three features:

  1. How well the blastocyst has expanded (graded as 1-6 with 1 being the least expanded and 6 the most)
  2. Quality of the inner cell mass (graded A-C with A being top quality and C being poor quality)
  3. Quality of the trophectoderm (graded A-C with A being top quality and C being poor quality)

If an embryo reaches the blastocyst stage, that is immediately a good sign for its potential regardless of the quality of the cells. However, developmental timings are very important and embryos which reach the later stages of development more quickly are often considered better quality. This means that a blastocyst which is more expanded will score higher than an embryo which is only just showing the first signs of expansion.

blastocyst quality

As the the inner cell mass is the portion forming the baby, it makes sense that the quality of these cells is key to the potential to achieve a pregnancy. The inner cell mass should be a large, well-defined group of cells that are tightly packed together. You should be able to clearly see where the inner cell mass is and it shouldn't have any areas of degeneration.

Finally, the trophectoderm should be made up of many evenly-spaced cells which look cobbled. There should not be any gaps or dark, patchy areas and the cells should look uniform across the embryo.

It's not all about looks

When grading a blastocyst it is important to consider the whole developmental process of the embryo because one snapshot doesn't necessarily tell the whole story. Most importantly, the appearance of the cells does not always correspond to activity inside the cells. Beautiful, top-quality blastocysts often fail to implant and equally, blastocysts graded as poor quality can go on to make beautiful healthy babies. The quality of the DNA and the health of the cells are absolutely vital in determining the potential of an embryo. Although these factors can be linked to the appearance of the embryo, there is a wealth of information below the surface that we cannot see and will ultimately determine its fate.

More tools for embryo selection are emerging which can help to identify the blastocyst with the greatest potential to form a healthy pregnancy. These are still considered 'add-on treatments' and are not widely accepted. In particular, there has been much research based around genetic analysis of the blastocyst to determine whether it has the correct number of chromosomes, therefore eliminating embryos which are abnormal and would be never been able to make a baby. This is called preimplantation genetic screening (PGS) and can provide more information about the quality of the embryo. You can read more about this and other add-on treatments here.