Embryo Grading in IVF
Embryo grading is a method used in IVF (in vitro fertilization) treatments to evaluate the quality of the embryos. During IVF in Cyprus, a woman’s ovaries are stimulated using fertility drugs to produce more eggs. When ready, these eggs are collected in a procedure called egg retrieval. After the egg retrieval, the mature eggs are fertilized with the father’s (or donor) sperm in our state-of-the-art lab using an ICSI (intracytoplasmic sperm injection) method. The fertilized eggs, now called embryos, are graded for quality each day during the grading cycle.
Depending on their quality, embryos are usually transferred on day 3 or day 5 after the egg retrieval. On day 5, embryos reach the blastocyst stage. This is the developmental stage that naturally occurs just before the embryo implants into the wall of a woman’s uterus.
Multiple factors will influence the final decision regarding the date of the embryo transfer including quality and development stage of embryos as well as maternal age. Embryo grading in IVF cycles is a powerful tool that helps our fertility team choose the good-looking embryos with the best prospects for implantation.
What is Embryo Quality
Embryo quality is the ability of an embryo to produce a positive outcome and result in a healthy person. It is a key factor in predicting pregnancy success in IVF cycles. Embryo grading in IVF treatments is a very helpful tool that indicates the embryos that have the best prospects for implantation. Transferring the best-quality embryos increases your chance of a successful pregnancy and a healthy baby.
Understanding Embryo Grading in IVF cycles
The lab team at the EuroCARE IVF clinic grades embryos to determine which ones have the best chance of implantation. Embryo grading in IVF is a non-invasive method of assessing the quality of embryos and selecting only the best one(s) for transfer. In addition to grading, our embryologists assess the growth rate of embryos. A rate that is described as too fast or too slow may indicate that there is an internal problem (chromosomal abnormality) within the embryo. Such embryos may not implant into the uterine lining after the transfer, leading to implantation failure and miscarriage.
Embryo grading in IVF cycles is usually performed at the cleavage stage (day-3 stage) or blastocyst stage (day-5 stage) of embryo development. Embryo grading carried out at the cleavage stage focuses on the number and appearance of the cells. The degree of DNA fragmentation, which may be caused due to an abnormal cell division is another consideration at this stage of embryo development.
Embryo Grading System
Here at EuroCARE IVF, we provide patients with a report of the quality of their embryos using a number and a letter grade. The scale from 1 to 6 describes the stage of embryo development. Letters, on the other hand, indicate the quality of the cells, with A suggesting excellent-quality and D meaning poor-quality. Our grading system in IVF treatments helps us determine which embryos to transfer and/or freeze.
We perform embryo transfers either on day 3 or day 5 after the egg retrieval. Because embryos are developmentally different on these two days, we use different grading systems for day 3 (cleavage stage) embryos and day 5 (blastocyst stage) embryos.
In blastocyst embryos (day-5 embryos), a number grade is used to identify when hatching is likely to happen. Embryo hatching happens when the embryo breaks out of the zona pellucida (covering membrane) before implantation in the womb.
At this point, our IVF specialist may decide to use a technique called assisted hatching to facilitate the implantation of the embryo. Assisted hatching is used to improve pregnancy rates for certain groups of patients including women with multiple failed IVF cycles and patients with a poor prognosis of implantation.
Letters (A-D) are used to measure the quality of two different parts of blastocyst embryos, i.e. inner layer cells (fetus) and outer layer cells (placenta).
Day 3 Embryo Grading
Day 3 embryos are also known as cleavage stage embryos. The embryo is dividing but its size remains the same. Indeed, cleavage stage embryos have the same volume as that of an unfertilized egg.
Embryos may not divide synchronously. As a result, there may be 2-, 4- and 8-cell embryos at the cleavage stage along with with 3-, 5- and 6-cell embryos. This may not be an indication of poor embryo quality as long as the growing rate is steady.
Sometimes, during the cleavage stage, a small portion of cytoplasm (the inside of the cell) may not be included in the new cells. These parts of an embryo are called fragments. Due to the absence of genetic material (DNA), fragments are considered not to be cells. They are often a result of an abnormal cell division. The degree of fragmentation is defined as mild (<10%), moderate (10-25%) and severe (>25%) depending on the extent and location of fragmentation. Fragmentation is used to predict the implantation potential of an embryo.
Embryo grading in IVF cycles performed at the cleavage stage (day 3) of embryo development relies on the number and appearance of the cells. The number of cells is also used to indicate the rate of embryo growth. If embryos grow at a normal pace, they will contain between 6 and 10 cells.
GOOD: 4 cells (Day 2), 7-9 cells (Day 3)
FAIR: 5-6 cells (Day 2); 6 cells; >9 cells (Day 3)
POOR: <4 cells (Day 2), <6 cells (Day 3)
Appearance is evaluated using a score from 1 to 4. For example, embryos with a grade 1 is made up of cells of equal size and do not contain any fragments. Four-point scored embryos, on the other hand, have a moderate to severe degree of fragmentation, and their cells may be of equal or unequal size.
The number of cells in a cleavage stage embryo is a far more important factor than the degree of fragmentation. For example, an 8-cell cleavage stage embryo with moderate fragmentation has a bigger potential for growth into a blastocyst than a 4-cell grade 2 embryo.
Day 5 Embryo Grading
On day 5, embryos continue to divide and the number of cells continues to increase. At the blastocyst stage, the cells start to differentiate into two groups. One cell type forms the Inner Cell Mass (ICM). This ball of cells will eventually grow into the fetus. The other cell type is the Trophectoderm Epithelium (TE). These cells will create the placenta.
TE cells are found on the outside and the ICM in the inside of the embryo. Both TE and ICM cells are necessary for a healthy pregnancy to be established. We use a letter grade for each cell type along with a grade that indicates the expansion of an embryo. Expansion grades are indicators of the embryo’s growth.
Embryo grading in IVF at the blastocyst stage is a complex system that takes into consideration different parts and aspects of the embryo. A blastocyst is assessed when we take all of its components into account. Other factors such as maternal age, fertility history, and other information are considered as well when making a decision on the optimal day of transfer, the number of embryos to transfer, and exactly which embryos to transfer.
Embryo Development in IVF
In an IVF cycle, fertilization and embryo development take place in our EuroCARE IVF specialized lab. The eggs are collected from the woman’s ovaries and are fertilized by injecting single sperm cells. This technique of fertilization is called intracytoplasmic sperm injection (ICSI) and is used in all IVF treatments at no extra cost.
Embryos that have been cultured for three days in the lab are called cleavage stage embryos. Embryos that reach the advanced stage of development on day five after fertilization are called blastocysts.
Once embryo grading is done, our fertility specialist will inform you about the quality of your embryos. You will also discuss the date of transfer and the number of embryos to transfer.
Embryo Development Stages
This is the timeline of embryo development in IVF:
- Day 0: Fertilization (ICSI)
- Day 1: Fertilization assessment
- Day 2: Cell division – the embryo is between 2-4 cells
- Day 3: Cell division – the embryo is between 6-8 cells
- Day 4: Compaction – morula formation (16-32 cells )
- Day 5: Blastocyst formation (advanced embryos)
Let’s dive into the process of embryo development:
- Day 0: Fertilization (ICSI)
On day 0, mature eggs are retrieved from the woman’s ovaries. The collected eggs are then evaluated based on:
- Quality – What is the egg’s shape? And how homogeneous is the cytoplasm?
- Maturity – What is the size of the egg? Is it mature enough to be fertilized by the sperm?
Once the quality and maturity assessment is done, we proceed with the fertilization of good-quality, mature eggs using Intracytoplasmic sperm injection (ICSI) in Cyprus. This is an advanced procedure in which single sperm cells are injected into each egg. The biggest advantage of ICSI is that it ensures a high fertilization rate and control over the fertilization process. Fertilized eggs are placed into an incubator to allow them to develop into embryos.
- Day 1: Monitoring
During the incubation period, eggs are monitored to see if fertilization has occurred. At this point, a basic chromosomal assessment is also carried out to determine if there are two pronuclei (one from the father and one from the mother) present in the embryo.
- Day 2 & 3: Cleavage stage
On day 2, our embryologist will check if fertilized eggs are dividing into multiple cells. Ideally, an embryo at this stage will have 2 to 4 cells. The volume of the growing embryo doesn’t actually change, it just divides into smaller cells.
Embryos are assessed on day 3 only if we consider it necessary. At this stage, we look for ideally 5 to 10 cells. The symmetry of the cell division is also important because it predicts the likelihood of blastocyst formation.
Embryo transfer may be scheduled on day 3 after fertilization if the resulting embryos meet the quality standards for transfer. At the cleavage stage some of the factors that we take into account are:
- number of cells present
- rate of cell division
- (a)symmetrical cell division
- degree of fragmentation
Cleavage-stage embryo transfer can be as successful as a blastocyst-stage transfer.
- Day 4: Compaction (morula)
On day 4, embryos are expected to be between 12 and 50 cells. At this point, they become an indistinguishable ball of cells known as a morula.
- Day 5: Blastocyst
On day 5, a blastocyst is formed, which consists of 30 to over 200 cells. At the blastocyst stage, there are two types of cells:
- Inner cell mass – The group of cells that will become the fetus.
- Trophectoderm – The group of cells that will form the placenta.
At this stage of development, embryos will be either transferred to the woman’s uterus in a procedure known as blastocyst transfer, or they will be cryopreserved (embryo cryopreservation).
Embryo viability assessment
Throughout the grading cycle, we monitor embryos to evaluate their growth potential. Before transfer or cryopreservation, we carry out the final quality assessment.
At EuroCARE IVF, we usually transfer embryos on day 3 or day 5 after egg retrieval. Embryo grading in IVF performed at the cleavage stage uses morphological characteristics of embryos such as degree of fragmentation, (a)symmetrical cell division, multinucleation, and speed of cell division.
In the blastocyst stage embryos, we examine the inner and outer cells, grading each part from A to C.
The inner cell mass is graded depending on the cell number and size:
- A – Pronounced inner cell mass
- B – Visible inner cell mass
- C – Non-existent inner-cell mass
Trophectoderm
This part of the embryo is graded (A, B, or C) based on the number of cells it contains. Embryos with more cells score higher. Grade A suggests a higher chance of successful implantation. Grade B is also considered adequate as it indicates a high potential for implantation.
Whatever the circumstances, our highly experienced lab team has the ability to select the highest quality embryos that will give you the best chance of pregnancy.
Embryo Grades and Success Rates
Pregnancy success in IVF treatments is very personal as it depends on multiple factors such as patient age, body mass index, infertility history (causes and duration), and infertility type (primary/secondary).
Embryo grading in IVF is used to indicate the embryo’s potential for growing and development. A study published in the Fertility and Sterility Journal showed that embryo graded as an excellent, good, average and poor resulted in pregnancy rates as follows: 65.0%, 59.3%, 50.3%, and 33.3%, respectively. Pregnancy rates were higher after the transfer of a blastocyst that had an A-grade or B-grade TE, and an A-grade ICM.
Although embryo grade may not be everything for a successful IVF cycle, high-quality euploid (chromosomally normal) embryos are linked to higher pregnancy rates.
Embryo Grading in IVF at EuroCARE IVF
Embryo grading is a powerful tool that helps our fertility team to select only the best embryos for your transfer. Good-quality embryos have a higher chance of pregnancy success and live birth rate. When it is used along with a patient’s age and fertility history, it can help us determine the perfect timing for transfer and the optimal number of embryos to transfer.