Understanding embryo development is a key step in the IVF process.
In this post, you’ll learn:
- the 3 stages of embryonic development,
- realistic expectations on how many embryos make it to blastocyst, and
- how embryos are graded, and what it means for you.
Let’s get started.
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What are the stages of embryo development in IVF?
There are 3 main stages of human embryo development: the cleavage stage, the morula, and the blastocyst.
Ideally, this process should take 5 to 6 days, but it can take up to 7 days.
Let’s go over these stages day by day.
Day 0 is the day of the egg retrieval.
After your eggs are retrieved, the embryologist will examine the eggs and determine how many of them are mature.
The mature eggs will then be combined with sperm (either through conventional insemination or intracytoplasmic sperm injection (ICSI)) and incubated overnight in the IVF lab.
On the morning after your egg retrieval, we will check to see if your eggs have undergone successful fertilization.
This simply means that the egg and the sperm have come together.
The fertilized egg is now called a zygote and it will be left in the incubator to give it the best chances of growing and dividing.
At this point, the embryo will undergo cell division. This simply means that the one-cell zygote will divide into 2 cells.
These two cells will then divide again making 4.
4 will eventually make 8.
Each individual cell is called a blastomere, and the embryo is now in the cleavage stage.
Once the developing embryo has reached the third day, the embryologist will check on its development by physically counting the number of cells it contains.
Depending on the time at which we look at the embryo, it can have anywhere between 8-16 blastomeres on Day 3. (The earlier in the day you look, the fewer cells it will contain).
Cleavage stage embryos can be transferred on day 3, however, a blastocyst embryo transfer has become the gold standard in IVF.
There are several reasons:
- Blastocysts have “proven” themselves and demonstrated that the have the ability to grow and divide past a certain point in the IVF lab, whereas a Day 3 embryo can still arrest.
- Embryos that have reached the blastocyst stage of development have more likely to be genetically normal.
- Embryos aren’t supposed to be in the uterus on the third day after normal fertilization. Cleavage-stage embryos are still in the fallopian tube and don’t arrive at the uterine lining until Day 5 or 6.
Once the embryo contains 16 or more blastomeres, the embryo has now reached the morula stage.
In some cases, the embryo could even reach a stage known as an early blastocyst.
This is when the cells begin to differentiate. I.e, you can see two completely different types of cells forming. These are known as:
- trophectoderm cells (cells that will eventually become the placenta) and
- inner cell mass cells (cells that will eventually become the fetus).
Day 5, 6, or 7:
At this point, the embryo may have achieved blastulation. This is when you can clearly see the inner cell mass distinct from the trophectoderm.
The embryo is now called a blastocyst, and it is ready for implantation.
A blastocyst can be transferred fresh (in the same menstrual cycle in which it was created), or it can be frozen for future use.
If you are doing preimplantation genetic testing (aka embryo biopsy), it will be done at this time prior to freezing.
Sadly, not every embryo will make it to the blastocyst stage.
Many will arrest in any of the prior stages discussed above.
What percentage of embryos make it to blastocyst?
On average, 40-50% of the embryos you create in an IVF cycle will make it to the blastocyst stage.
This number varies significantly from lab to lab and from one patient to another.
Some patients will exceed the 50% mark, while others may have as few as 0-25%.
It is believed that embryos that fail to make it to blast are usually chromosomally abnormal, and would have never produced a viable fetus.
What percentage of blastocyst embryos survive and make a healthy pregnancy?
A high-quality blastocyst with a good grade can have up to a 70-80% of achieving implantation, and up to a 60% chance of achieving a live birth.
Therefore, the higher the number of eggs retrieved, the more likely you are to achieve a successful pregnancy.
Overall success rates tend to decrease with increasing maternal age and with poorer embryo grading.
How does embryo grading work?
Embryos are graded based on 3 factors:
- The degree of blastocyst cavity expansion,
- The appearance and cell number of the inner cell mass, and
- The appearance and number of cells of the trophectoderm.
In addition to these 3 factors, the rate of embryonic development (the amount of time required to achieve blastocyst) is also factored in.
Let’s go over each one.
Degree of blastocyst cavity expansion
Inside the blastocyst is an empty cavity known as the blastocoel. In other words, it will look like there is an empty space in the center of the embryo.
This cavity will expand considerably as the embryo continues to grow and develop.
The degree of expansion is graded from 1-6.
- 1 is the lowest grade with minimal expansion of the blastocele.
- 6 is the highest grade with the embryo actually hatching out of its egg (aka the zona).
The inner cell mass (ICM) appearance
The second thing that is used to grade an embryo is the appearance of the embryo’s ICM.
The ICM can be graded from A-C.
- A is the best grade, which indicates that there are many cells and they appear nice and uniform.
- C is a fair grade, which indicates that there are fewer cells and not as uniform in appearance.
The trophectoderm appearance
Lastly, we have the trophectoderm.
Trophectoderm cells are located on the perimeter of the embryo. These cells will eventually become the placenta.
Just like with the ICM, their appearance is graded from A-C.
- A is best and C is fair.
Speed of development (time to blastocyst development)
All other things being equal, a Day 5 blastocyst will have slightly better live birth rates than a Day 6 blastocyst.
Similarly, Day 6 blasts will have better success rates than a Day 7 blastocyst.
Do Grades Matter?
As with most things in IVF, there are data from both sides. Some studies show that embryo grading is not relevant to success, while other studies show increased implantation and ongoing pregnancy rates with higher grades.
In general, it is widely accepted that the better the grade, the better the chance of success.
Aside from preimplantation genetic testing, embryo grading is the best method we have to assess embryo quality.
What is the best grade of embryos in IVF?
The best possible grade an embryo could have is 6AA.
- 6 for the degree of blastocyst expansion
- A for the ICM appearance
- A for the trophectoderm appearance.
Of all the factors, it appears that the grade of the inner cell mass has the highest prognostic value.
This makes sense as these are the cells that will eventually form the fetus.
So for example, a 5AB embryo is “better” than a 5BA embryo.
Lastly, the timing of blastulation is important.
A Day 5, 6AA embryo would be preferred over a Day 6 6AA embryo.
Are grade B embryos good?
Embryo grading is fairly subjective. Two different embryologists can look at the same embryo and give two different grades.
With that said, B is the most common grade and has a good prognosis. Some embryologists will hardly ever give out an A.
On the flip side, we have seen plenty of healthy pregnancies come from embryos with a C grade.
There are definitely more factors to achieving a successful and healthy pregnancy than just the embryo grade!
Always speak with your doctor regarding which embryo will have the best chance of success following your IVF treatment!
What about embryo development after the transfer?
After your embryo transfer, you will have a pregnancy test in approximately 10-14 days to confirm implantation.
At this point, you will be approximately 4 weeks pregnant.
We don’t do an ultrasound at this point because it is too early to see anything.
Instead, we follow your pregnancy hormone to ensure that it is going up appropriately. If it is, we will see you for an ultrasound around 5-6 weeks to confirm the location of the pregnancy.
At this time, we expect to see:
- a gestational sac (which is what contains the fetus and the amniotic fluid)
- as well as a yolk sac (one of the earliest structures to form in the human embryo).
We may or may not see the fetus clearly yet. We also may or may not be able to hear the heartbeat just yet.
We will then bring you back in 1-2 weeks to further check on the growth of your fetus.
Human embryo development can be a bit confusing with all the stages, numbers, and letter grades.
However, the more you understand embryo growth, the better prepared you will be in managing expectations on
- how many viable embryos you can expect from your IVF cycle and
- what distinguishes the “best embryos” from “fair embryos.”
- Freezing Embryos: When Should You Do It
- PGS Testing: What Do The Results Mean
- Preparing For Your Embryo Transfer: What Not To Do
Alex Robles, MD, FACOG
Alex Robles is a Spanish-speaking Latino-American Reproductive Endocrinologist and Infertility specialist in New York City, and board-certified OBGYN in his final year of fellowship at Columbia University Medical College. He has a special interest in exercise, lifestyle, & nutrition.
- Blake DA, Farquhar CM, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002118. doi: 10.1002/14651858.CD002118.pub3. Update in: Cochrane Database Syst Rev. 2012;7:CD002118. PMID: 17943767.
- Glujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev. 2016 Jun 30;(6):CD002118. doi: 10.1002/14651858.CD002118.pub5. PMID: 27357126.