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When researching in-vitro fertilization (IVF), there are plenty of primers available on the numerous steps involved, like ovarian stimulation, egg retrieval, and embryo transfers. One of the steps of the IVF protocol that fertility patients may feel less familiar with, however, is what happens after egg retrieval but before the embryo transfer.
Once the sperm fertilizes the egg, an IVF specialist called an embryologist will select the best embryo for transfer. The embryologist makes this decision via a process called embryo grading. “[This] assesses the quality and potential viability of embryos,” explains Zsolt Peter Nagy, Ph.D., HCLD, Laboratory Director at Reproductive Biology Associates in Atlanta. Embryo grading “involves evaluating various characteristics of the embryo under a microscope to estimate its chance of successful implantation and pregnancy.”
While embryo grading can be a valuable tool for fertility specialists, Dr. Nagy offers a caveat, advising patients to also “rely on the expertise of [their] doctor for making informed treatment decisions.”
Read on for more on how embryo grading works, and its role in IVF protocols.
Why do we need embryo grading?
The purpose of embryo grading is, according to Dr. Nagy, to “identify embryos with higher implantation potential and pregnancy success rates.” During this process, which usually takes place either on Day 3 or Day 5/6 after fertilization, the embryologist will do the following:
- Choose the most suitable embryos for transfer to the uterus
- Decide on the number of embryos to transfer (minimizing the risk of multiple pregnancies)
- Determine which embryos are eligible for cryo-preservation (aka frozen embryos for future use)
- Determine if further genetic testing might be beneficial
Although “a higher grade generally indicates better development and higher potential for successful implantation,” Dr. Nagy emphasizes that “grading is not an absolute guarantee of success.” Embryo grading is only one detail of the IVF protocol that “should be interpreted alongside other factors like the patient’s age and medical history.”
How are embryos graded?
Dr. Nagy says that grading systems can vary by clinic, but in general, “they typically involve a letter and number combination to represent the embryo quality according to the evaluated factors.” For example, a grade of “A” or “1” usually signifies the best quality, while “B” or “C” (or “2” or “3”) indicates lower quality.
Embryo evaluation criteria
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Embryos graded on Day 3 “are evaluated based on the number of cells and the degree of cell division,” says Dr. Nagy. “The number of cells in the embryo is an indicator of its development stage and division rate.” Other factors taken into consideration are cell morphology, which is an assessment of “the size, shape, and uniformity of the cells,” and “the presence and extent of any fragmentation (broken pieces of a cell) in the embryo.”
Embryos graded on Day 5 (or 6 or 7) that have reached the blastocyst stage , and are graded on the following, according to Dr. Nagy:
- Inner cell mass (ICM): This is the group of cells that will develop into the fetus. It’s evaluated for compactness, number, and size of cells.
- Trophectoderm: This is the outer layer of cells that will form the placenta. It’s evaluated for the number and appearance of cells.
- Expansion: The degree of development and expansion of the blastocoel cavity, a fluid-filled space within the embryo.
What is considered a “good” embryo grade?
Dr. Nagy is quick to point out that a “good” embryo grade is “nuanced and depends on several factors,” but here’s an overview of how the grading system works:
- Day 3 embryos: A good embryo at this stage might have 8-10 equally sized cells with minimal fragmentation (cell breakdown).
- Day 5/6 blastocysts: A good blastocyst would have many, tightly packed cells, indicating potential for fetal development. It would also contain a well-defined trophectoderm, with a sufficient number of cells suggesting a potential for proper placental formation. Finally, a good blastocyst would have a fully expanded blastocoel cavity, signifying active development.
What is considered a “bad” embryo grade?
Don’t fret if your embryo receives a less-than-stellar grade. “Even embryos with lower grades can still lead to healthy pregnancies,” assures Dr. Nagy. Here’s his breakdown of how “bad” embryo grades occur:
- Day 3 embryos: If the embryo has fewer than six cells or uneven cell division, this could suggest slower development or potential chromosomal abnormalities. Lower grades can also result from significant fragmentation or cell breakdown.
- Day 5/6 blastocysts: If the blastocyst’s inner cell mass shows few, loosely packed cells, this could indicate potential developmental issues. If the trophectoderm shows unevenly distributed or an insufficient number of cells, it could suggest possible challenges with implantation. Also, a poorly or partially expanded blastocoel cavity could suggest delayed development.
Why lower embryo grades are not an indication of failure
Receiving a low grade on your embryos can certainly feel like you’re back in school again, but it’s important to remember that fertility is an entirely different beast than, say, calculus class. “Embryo development is a dynamic process,” explains Dr. Nagy, “and lower grades at one stage might not necessarily translate to failure later.” He reiterates that embryo grading is just one factor among a much larger set of criteria: “The decision to use an embryo for transfer depends on various factors like the patient’s age, medical history, available options, and individual circumstances.”
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Above all, says Dr. Nagy, it’s critical to consult with your fertility specialist during the embryo grading process so you can understand how it applies to your individual case.
But can embryo grading contribute to IVF success rates?
“While embryo grading is not a perfect predictor of success in IVF,” says Dr. Nagy, this process can contribute to IVF success rates. He says grading can help identify embryos with higher developmental potential, which in turn can increase the likelihood of successful implantation and pregnancy. Embryo grading can also help clinicians optimize their transfer strategy, as well as provide crucial information about the embryos that will help patients make the most informed decisions possible.
How much should patients rely on embryo grading?
“Patients undergoing IVF shouldn't rely solely on embryo grading to determine their chances of success,” says Dr. Nagy. “It is one of several factors to consider and should be interpreted in the context of individual circumstances, and in consultation with a fertility specialist.”
Embryo grading, like any other scientific process, has its limitations. First of all, grading is subjective: “Different embryologists might assign slightly different grades, affecting the interpretation of embryo quality,” says Dr. Nagy. Also, embryo grading only assesses the visual characteristics of the embryo, “not its full genetic potential or ability to implant and develop successfully.” And just because you have a “high-grade” embryo, there’s no guarantee it will implant. “Conversely,” says Dr. Nagy, “some lower-grade embryos can still lead to healthy pregnancies.”
Other factors to consider in the IVF process are sperm quality and the uterine environment. “Healthy sperm is crucial for fertilization and successful embryo development,” says Dr. Nagy, while “a healthy uterine environment is essential for implantation and carrying a pregnancy.”
As you would in any other stage of IVF, the best thing you can do during the embryo grading process is to have open lines of communication with your fertility team. “Don’t hesitate to ask your fertility specialist about any concerns or uncertainties regarding grading and its implications for your treatment plan,” advises Dr. Nagy. “A comprehensive approach considering various factors and personalized guidance from a fertility specialist is crucial for maximizing the chances of a successful IVF journey."
Sarene Leeds holds an M.S. in Professional Writing from NYU, and is a seasoned journalist, having written and reported on subjects ranging from TV and pop culture to health, wellness, and parenting over the course of her career. Her work has appeared in Rolling Stone, The Wall Street Journal, Vulture, SheKnows, and numerous other outlets. A staunch mental health advocate, Sarene also hosts the podcast “Emotional Abuse Is Real.” Visit her website here, or follow her on Instagram or Twitter.