Which Embryo Is Best to Transfer During IVF?

During IVF (in-vitro fertilization), the healthiest embryos are chosen and transferred to the woman’s uterus through a catheter. 

But how to determine which embryos to transfer? 

Embryos created in the lab during IVF are graded by the embryologist to distinguish between a good, an average, and a poor quality embryo, so that the one with the highest chance of becoming a baby is transferred.  

Embryo transfers normally occur either 3 days or 5 days after fertilization. 

In fact, there are different grading systems for day 3 embryos and day 5 embryos because embryos are developmentally different on these days.

Day 3 Embryos

Day 3 embryos are referred to as “cleavage stage” embryos because the cells in the embryos are dividing.

At this stage of development, embryos are graded based on:

• The number of cells in the embryo
• The symmetry of the cells in the embryo
• The degree of fragmentation

The number of cells in the embryo

Theoretically speaking, embryos would divide in a specific sequence: 1 cell becomes 2 cells, 2 cells become 4 cells, 4 cells become 8 cells, and so on… 

At this stage, the cells are known as blastomeres. 

However, not all good quality embryos follow this specific sequence.

Some embryos will have 3, 5, or 6 cells, and that’s because cells don’t divide synchronously. 

At day 3, a good embryo should ideally contain between 6 and 10 cells or blastomeres.

The symmetry of the cells in the embryo

The presence of blastomeres of unequal size (> 20% difference) in embryos signifies that there might be a high probability of chromosomal abnormality. 

Therefore, embryos with significantly uneven blastomeres are less likely to be selected for embryo transfer.

At day 3, a good embryo should ideally have blastomeres at equal size (or slightly uneven).

The degree of fragmentation

As embryos divide, sometimes a small portion of cytoplasm breaks off and forms fragmentation.

Think of fragmentation as crumbs when a piece of bread is broken apart.

Less than 20% fragmentation in human embryos is common and fine. 

However, embryos containing a lot of fragmentation lose too much cytoplasm and are less likely to be selected for transfer. 

At day 3, a good embryo should ideally have no fragmentation (or <20%).

Day 5 Embryos 

Day 5 embryos are referred to as “blastocyst stage embryos” because it is the stage of development that the embryo must reach before it can implant in the uterus.

A defining moment in embryonic development is when fluid starts to accumulate between cells at the morulae stage of development.

As the fluid’s volume increases, a cavity appears gradually forming the blastocoel.

This normally happens between Days 4 and 5 in human embryos in vitro and marks a new ‘era’ in the embryo’s life, the blastocyst stage.

The blastocyst differentiates into:

1. The inner cell mass (ICM)
2. The trophectoderm epithelium (TE)
3. A fluid‐filled cavity called the blastocoel

ICM are the cells that will develop into the actual fetus, the TE will eventually become the placenta, and the blastocoel will become the yolk sac.  

At this stage, embryos are graded based on:

• The degree of cavity expansion
• The appearance of ICM
• The appearance of TE

The degree of cavity expansion

Fluid starts to accumulate between the cells. 

As the fluid’s volume increases, the cavity appears gradually within the zona pellucida – the thick membrane surrounding the embryo before implantation.

The expansion of the fluid-filled cavity (blastocoel) relates to how large the blastocoel is. 

Grades range from 1 to 6, with 6 being the most developed.  

A good grade embryo will be one with a large cavity expansion.

Examples of the expansion grades are:

Early blastocyst (Grade 1) in which the cavity is less than half the volume of the embryo.

Expanded blastocyst (Grade 4) in which the cavity is greater than the original volume of the embryo and the ZP is thinned. 

Hatched blastocyst (Grade 6) in which the embryo has completely hatched from the zona pellucida. 

The appearance of ICM

The ICM can range from being very large with tightly packed cells to almost non-existent with loosely bound cells. 

Accordingly, the ICM has been categorized into three morphological categories:

Grade A: in which ICM contains many cells that are tightly packed together

Grade B: in which ICM is composed of several cells that are loosely grouped (may be grainy in appearance)

Grade C in which ICM contains very few cells that are loosely bound

A good grade embryo is one with a large ICM that has many cells tightly packed together. 

The appearance of TE

The TE cells play a key role in embryo implantation in the uterus.

They are scored in a similar way to ICM: 

Grade A in which TE contains many tightly packed cells of equal size

Grade B in which TE is composed of a loose layer of cells (irregular and grainy in appearance)

Grade C in which TE contains very few cells that struggle to form a cohesive layer

A good grade embryo is one with uniformly-sized cells in the TE. 

Conclusion:

Embryo grading is a tool that helps embryologists determine which embryos will most likely lead to a successful pregnancy after IVF. 

It is taken into account along with a host of other factors such as your age, fertility history, the day of transfer, and the number of embryos to transfer. 

If you are undergoing IVF, read our article Would You Tell People You Are Doing IVF? and always make sure you ask about the grades of your embryos to be transferred.

But stay hopeful because you may see many cycles fail after transferring 3 perfect looking embryos, and you may also see beautiful babies born after transferring only one “low grade” embryo. 

No matter the grading system, the embryo grades do not tell us what happens inside the embryo genetically. 

So in case you have had several miscarriages or you’re afraid to pass on a genetic disorder to your baby, your embryos can undergo a preimplantation genetic screening (PGS), so that only healthy embryos are transferred to the uterus for implantation.