Embryo Grading Improves Your IVF Success
Egg meet sperm. Why, hello, embryo.
Not too far in the distant past, scientists knew very little about how this medical magic occurred. The process was certainly not transparent, taking place inside the woman’s uterus and in steps that are far too small to be seen with the human eye.
But much has changed.
In the more than 26 years since our founding, we have observed countless numbers of embryos and seen over 100,000 babies born as a result of our efforts in reproductive technology.
Thanks to the advancements of reproductive science and strides we’ve made in embryo grading at Shady Grove Fertility, we are now acutely aware of how embryos develop. We use this knowledge every day to improve outcomes for patients by monitoring embryos as they develop and grading them before transfer or vitrification.
If you’re considering fertility support from SGF, it’s important to understand how your embryos will be assessed so that you can better prepare to play a more active role in your IVF or elective egg freezing process.
Internationally renowned Scientific Director of IVF and Embryology Laboratories, Dr. Michael Tucker, one of the world’s top scientists in early human reproduction, and board certified reproductive endocrinologist, Dr. Eugene Katz takes us on a journey through the development of an embryo and explain how each embryo produced at Shady Grove Fertility is graded.
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On day 0, we retrieve eggs from the woman’s body.
Approximately 3 to 4 hours after retrieval, the lab team examines the eggs to assess:
- Quality – What is the egg’s morphology (how is it shaped)? Normally shaped, rounded eggs are considered higher quality than abnormally shaped ones. And how homogenous is the cytoplasm? That is, more even looking internal structure of the egg correlates with better quality.
- Maturity – Is the egg mature? If the egg is not mature, preferably it should not be inseminated and therefore cannot be used. On average, 70 percent of all retrieved eggs are mature.
After an initial assessment, we inseminate all mature, quality eggs in one of two ways:
- Intracytoplasmic sperm injection (ICSI) – A procedure in which one sperm cell is injected into an egg—the most common form of insemination, as it gives embryologists the most control over the insemination process.
- Conventional insemination – A procedure that places the egg into a culture medium containing between 5,000 and 10,000 sperm to facilitate fertilization. Immature eggs are routinely added into the insemination medium in this process, because they have the potential to mature during incubation overnight.
After insemination, our lab team places eggs into the incubator to begin their development.
Your eggs will remain tucked in the incubator for 15 to 18 hours after the insemination procedure. An embryologist will then remove the eggs to determine if normal fertilization has occurred.
On average, 75 to 80 percent of all inseminated eggs will be fertilized.
When we check for fertilization, we will also perform a basic chromosomal assessment. We expect to see two pronuclei in the center of the embryo, which, at this stage, is called a zygote. One of these pronuclei will be from the sperm and the other from the egg, and they represent each half of the chromosomes provided by the sperm and egg.
The presence of two pronuclei within the cell tells us that the embryo is normal. Anything more or less than two pronuclei indicates a chromosomal abnormality that prevents the embryo from use.
All normal, fertilized embryos will then go back into the incubator where they will remain between checks until they are transferred or vitrified.
On day 2, an embryologist will look for signs of embryonic cleavage. Embryonic cleavage tells us that the fertilized egg is dividing into multiple cells, and continuing to mature as an embryo.
By this time in the developmental process, we ideally want to see that the embryo has divided into at least 2 to 4 cells.
Interestingly, during this stage of the process, the embryo doesn’t actually grow in size, it simply subdivides into smaller cells.
An embryo check on day 3 is only performed if deemed necessary. Whether we check in on developing embryos on day 3 will be determined by how healthy they looked on day 2. Because it’s generally better to leave developing embryos undisturbed as much as possible, we may elect not to check on embryos that looked healthy on day 2 during day 3.
If we check on day 3, we are looking to see that the cells have continued to divide. Ideally, we should see between 5 and 10 cells in development.
We will also assess the symmetry of any cell divisions.
Because symmetry is closely correlated with greater viability, seeing optimal normal symmetry is promising.
On day 4, the embryo begins a process called compaction, and we expect the embryo to be anywhere between 12 and 50 cells. During this stage, it becomes more difficult to differentiate between the different cells that make up the embryo.
As compaction occurs, the embryo stops looking like a ball of cells and forms a shape similar to that of a raspberry or mulberry, technically known as a morula—derived from the Latin word for mulberry
Day 5 or even later on day-4 brings the transformation of the ugly duckling—the morula—into a swan—a blastocyst, consisting of anywhere from 30 to 200+ cells.
This stage is the first time we see the cells begin to organize themselves. Cells divide into two groups:
- Inner cell mass – The group of cells that will become the embryo proper.
- Trophectoderm – The group of cells that will establish the embryos connection with the endometrium—the membrane that lines the uterus.
Once embryos reach this stage of development, they need to be placed into a uterus or be cryopreserved, as quickly as possible.
At Shady Grove Fertility, we commonly allow all embryos to develop for at least 5 days prior to transfer, giving us the opportunity to monitor embryo development closely and better predict the likelihood of a positive outcome.
While on average an embryo takes 5 days to reach the blastocyst stage, on occasion it may take just 4 days, or it make take until day 6 or even day 7.
Blastocysts that form earlier (day 5 and occasionally day 4) have higher implantation potential; and yet those embryos that take an extended period to become a blastocyst may still result in a healthy pregnancy. There is a correlation between slower embryo development and lesser viability; nevertheless, we will generally cryopreserve any embryo that reaches the blastocyst stage by day 6 or 7 for future use if it is of adequate morphology. Interestingly ALL blastocysts that are cryopreserved are treated as if they are optimal day 5 blastocysts when timing for transfer after warming is estimated. This helps adjust for any tardiness in this initial potentially ‘stressful’ developmental period while growing in the lab in vitro.
More recently, with the shift away from embryo transfer at early stages of development, and with transfers & vitrification being principally undertaken at the blastocyst stage, we have become increasingly aware that while early stage embryo development may be useful to observe as an assessment of potential viability, nevertheless, once a zygote has been established as having undergone ‘normal fertilization’ with two pronuclei present, then pretty much all the morphological development over the next several days until the blastocyst stage is reflected in the eventual apparent quality of the blastocyst. This then has led us to consider reduction in earlier stage observations, both to reduce embryo handling and to eliminate disturbance during the embryo’s in vitro culture.
In essence, by keeping the embryo in quieter culture conditions, this in turn helps to promote healthier development of that embryo. As much as we enjoy observing the earlier stages of development from day-2 through 4 and keeping our patients informed of their embryos’ development, nonetheless we recognize that by focusing on the blastocyst stage for embryo transfer and/or vitrification, we lose nothing with respect to effective embryo grading. All that said, there are some unique exceptions to this blanket reduction in embryo development observations that we apply, and therefore each case will be judged on its particular needs as to whether we take a peek at an individual embryo’s development on any given day.
Final Embryo Grading Exam
We monitor all developing embryos and take notes as they move through the stages of their development. This documentation gives us a good idea as to the potential viability of the embryo. Before transfer or cryopreservation, however, we conduct one final assessment of the embryo.
During this process, we examine the cluster of inner cells and the outer trophectoderm, and then assign each part of the embryo a grade from A to C based on set criteria.
Inner Cell Mass
The inner cell mass receives a grade depending on how pronounced the cell number & size is:
- A – Pronounced inner cell mass
- B – Visible inner cell mass, but less pronounced
- C – Essentially non-existent inner-cell mass
The grade assigned to the outer trophectoderm layer is dependent upon how many cells it contains. The higher the number of cells, the higher the grade (A, B, or C) that is assigned.
In both cases, a grade of A is the target, as it suggests the highest likelihood of successful implantation. However, A and B grades can often be considered interchangeable given the relatively wide range of speed of development of each individual embryo—presence of a critical number of cells generally defined as grade B and above is adequate to indicate a significantly higher potential for implantation and healthy pregnancy.
It must be said that as key as embryo quality grading is to establish estimates of potential embryo viability, nonetheless, it does remain just that: “an estimate.” When an embryo continues to develop regardless of issues it may have with morphology, developmental rate (and that includes late fertilization), if it is transferred to the uterus while still developing, it may still have a small potential to be carried to term as a healthy baby. There are no absolutes in biology; however, our highly experienced laboratory staff have the ability to maximize the impact of their experience in selecting the highest potential quality embryos in every circumstance.
Information You Can Trust
We know that you’re looking forward to the day your little one proudly brings home a first report card. And to make that day possible, we rely on our wealth of experience as well as the most up-to-date advancements in reproductive science. Think of embryo grading as your kiddo’s very first science grade, and one that serves an important purpose on your path to pregnancy.
By assessing the development of embryos and assigning them a final rating, we provide patients with the most reliable indications of the likelihood that their IVF treatment will be successful. This process ensures that our patients have the knowledge they need to make informed decisions as they progress through the conception process.