Have you heard of embryo grading in IVF? Ever wondered why they give fertility and hormone injections to woman and stimulate their ovaries to produce more eggs? If you want one baby, you need only one egg, right? So, what happens to the others? Come, let’s find out.
An Embryo is a fertilised egg. When a sperm successfully penetrates and fertilises an egg, it results in an embryo. The cells in the embryo then start dividing very quickly, and within the next five days, this embryo will attach itself to the uterine wall. This is known as implantation, and only if this step occurs can it lead to a pregnancy.
Embryo grading is a procedure that helps evaluate and select the best embryos for IVF treatments. After giving the woman a trigger shot, the fertility specialist retrieves the embryo 36 hours later. After retrieval, the collected sperm and these eggs are put together in a petri dish, or the sperm is injected into the eggs directly for fertilisation to occur. Once fertilisation occurs, the embryos are left undisturbed for about 3 to 5 days. During this time, the embryos develop rapidly.
Embryo grading is done in two stages – one on day 3 and one on day 5 (after formation). Day 3 is the cleavage stage, and day 5 is the blastocyst stage. These gradings help doctors identify the embryos with the best chances of converting into a successful pregnancy. The higher the grade of the embryos transferred into the uterus, the better the chances of pregnancy outcome.
When the chances of embryos reaching the blastocyst stage or thriving under clinical conditions are low, the doctor will transfer the embryos on day 3. For patients responding normally, most doctors will transfer two embryos on day 3 to increase the chances of pregnancy.
When genetic testing is required or the chances of embryos progressing to day 5 under clinical conditions are good, the doctor will wait till day 5 to do the transfer. In most clinics, only one embryo will be transferred on day 5 as the chances of these embryos converting into successful pregnancies are much higher than success with day 3 embryos.
Some clinics transfer more embryos to increase their chance of success. However, the pregnancy outcome is influenced by various factors besides embryo transfer.
On day 3, after fertilisation, the cells will be actively dividing, and the embryos will develop rapidly. This is known as the cleavage stage. The embryologist will examine the embryos under a microscope to assess their structure or morphology. They will grade the embryos based on the number of cells they see.
An ideal embryo should have 6 to 10 cells in this cleavage stage. Embryos with eight or more cells are more likely to convert into successful pregnancies. In some cases, embryos with 3 to 6 cells can also develop into healthy babies.
The embryos are graded based on more factors than the number of cells the embryologist can see under the microscope. Although the grading is standardised, it can be subjective based on each embryologist’s opinion. This is an important factor determining a fertility clinic’s success rate.
Some of the other factors an embryologist will consider for embryo grading are:
This refers to the cells' readiness to adhere tightly to one another. It starts around day 4 after fertilisation and indicates the embryo’s readiness to enter the blastocyst formation.
They will check the embryos for indentation and depressions. The fewer, the better. However, there is not much data on this grading factor, as more studies are required.
The embryos are checked for fluid pockets known as vacuoles. Vacuoles vary in size and number. A higher presence of vacuoles can negatively impact blastocyst formation. So, the more vacuoles, the lower the grading of the embryos will be.
When the cells in the embryo divide and develop, some bits and pieces of the cells do not become part of the new cells. They become separate from the cells’ nucleated portion. This is known as fragmentation.
A good embryo with high grading will have less than 20% fragmentation. The more fragmentation, the less likely the embryo will convert into a successful pregnancy. The grading based on fragmentation is as follows. This grading can vary slightly from clinic to clinic.
● Grade A – No fragmentation
● Grade B – Up to 25% fragmentation
● Grade C – Up to 50% fragmentation
● Grade D – More than 50% fragmentation.
When the embryos reach the blastocyst stage on day 5, they will have two types of cells: the inner cell mass that develops into the baby and the sheet of cells that make the placenta and other tissues needed for the pregnancy. Both these cells are crucial for a successful pregnancy. So, the embryo grading at this stage will assess both tissues in addition to grading the blastocoel—the fluid-filled cavity in the embryo.
The Gardner Blastocyst Grading System is the most commonly used grading system at the Blastocyst stage. This system uses numbers and letters to denote the grade for the three layers mentioned above.
● The blastocoel is graded from numbers 1 to 6
● The inner cell mass (ICM) is graded using letters A to C
● The Trophectoderm (TE) quality is also graded using letters A to C
The embryo grade will have one number followed by two letters, like 4AA, 2AC, etc. In the blastocoel grading, the bigger the number, the better the embryo quality. So, an embryo with grade 6 will have a better outcome than an embryo with grade 1. Remember, these gradings only help identify the embryos and do not guarantee the pregnancy outcome.
Embryo grading is an essential step in an IVF cycle. However, not all embryos with high grades result in a successful pregnancy, and not all embryos with low grades fail. The outcome of an IVF cycle is very unpredictable, but embryo grading helps significantly increase pregnancy chances.
The embryo is observed on day 3 and graded on various parameters, including appearance, stage of development, number of cells present, and expansion of the blastocoel. The embryos are graded from A to D, with A being the best and having the highest chance of converting into a successful pregnancy.
The higher the embryo grade, the better its chances of converting into a successful pregnancy. Lower the grade, lower the chances. Both high-grade and low-grade embryos are transferred to increase the chances of pregnancy. The chances are better if the high number of high-grade embryos is in the transfer.
Yes, even embryos with a D grade can sometimes convert into a successful pregnancy, just like a grade A embryo can fail. The results are unpredictable and depend on various other factors.