Embryo grading is a standardized visual assessment utilized during In Vitro Fertilization (IVF) to help embryologists determine which embryos possess the highest potential for successful implantation and development. This process involves examining the embryo’s appearance under a high-powered microscope to evaluate its quality. The resulting grade serves as a predictive tool, guiding the selection of the most viable candidate embryos for transfer into the patient’s uterus or for cryopreservation.
The Purpose and Timing of Embryo Assessment
The primary function of embryo grading is to provide a systematic method for prioritizing embryos when multiple are available, maximizing the chance of a successful single embryo transfer. This assessment is not a guarantee of viability but a crucial piece of information for managing treatment strategy and patient expectations. Embryo development is dynamic, requiring two distinct grading systems because the embryo’s structure changes significantly over the first five to six days of growth.
The first assessment point typically occurs on Day 3 following fertilization when the embryo is in the cleavage stage. The second, and generally more informative, evaluation happens on Day 5 or Day 6 when the embryo has developed into a blastocyst. Differentiating between these two stages allows embryologists to make informed decisions about which embryos to culture further, transfer immediately, or freeze for future use.
Grading the Cleavage Stage Embryo (Day 3)
The Day 3 embryo is known as the cleavage stage embryo, characterized by rapid cell division without an increase in overall size. Grading at this stage focuses on two primary criteria: cell number and the degree of fragmentation. A normally developing Day 3 embryo should ideally contain between six and ten cells, with eight cells often considered optimal.
Fragmentation refers to the small blebs of cellular debris that break off from the dividing cells, or blastomeres. It is graded based on the percentage of the embryo’s volume occupied by this debris. Embryos with less than 10% fragmentation are assigned the best grades, while those with moderate (10-25%) or severe (>25%) fragmentation are considered lower quality. Cleavage stage embryos are often given a numerical grade, such as 1 through 4, where a grade 1 embryo indicates a higher developmental potential.
Grading the Blastocyst (Day 5 and Day 6)
By Day 5 or Day 6, the embryo should have developed into a blastocyst, a more complex structure assessed using the widely adopted Gardner grading system, which utilizes a number followed by two letters. The initial number, ranging from 1 to 6, describes the degree of expansion of the fluid-filled cavity, known as the blastocoel. A grade 1 represents an early blastocyst with a small cavity, while a grade 5 signifies an expanded blastocyst beginning to hatch out of its outer shell, the zona pellucida, and a grade 6 is fully hatched.
The two letters following the expansion number are assigned independently to the two distinct cell populations that form at this stage, both graded on a scale of A (best) through C (poorest). The first letter evaluates the quality of the Inner Cell Mass (ICM), the cluster of cells that will eventually develop into the fetus. An ICM graded ‘A’ is composed of many tightly packed cells, while a ‘C’ grade indicates few or poorly defined cells.
The second letter assesses the Trophectoderm (TE), the outer layer of cells that will form the placenta and other supportive structures. A TE graded ‘A’ is a cohesive layer of numerous, healthy cells, suggesting strong potential for implantation. Conversely, a ‘C’ grade TE is characterized by a sparse or uneven cell layer.
A full grade, such as 4AA, describes an expanded blastocyst with excellent quality ICM and TE layers. Conversely, a 3BC indicates a less expanded blastocyst with lower quality cell structures.
Interpreting the Grades and Implantation Potential
The final, three-part blastocyst grade is a strong, though imperfect, predictor of an embryo’s potential to implant and result in a live birth. Higher grades correlate with higher clinical pregnancy and live birth rates. For instance, excellent grade blastocysts, such as 4AA or 5AA, have been associated with pregnancy rates around 65%, while poor grade embryos may still offer a chance of success, though rates can drop to around 33%.
This grading is a morphological assessment and does not evaluate the embryo’s genetic health, which is a significant factor in implantation success. While Day 3 grades are useful for initial selection, the Day 5/6 blastocyst grade, particularly the quality of the ICM and TE, is considered a more reliable indicator of viability. Embryos with lower grades can result in healthy pregnancies, as the grade is merely a snapshot of development and not an absolute verdict on the embryo’s future potential.