10 November 2014
Embryos are carefully evaluated in the lab for reporting purposes and in order to select those with the highest implantation potential. The limitations of evaluating embryos, based on development rate and morphological criteria alone, are well recognised.
Correlations between gross morphology and implantation are weak and inaccurate and embryo grading is not necessarily a predictor of pregnancy. We often get pregnancies from “poorer quality” embryos.
When we look at embryos in the laboratory, notes are taken on the quality and rate of development of each individual embryo. Quality is assessed by examining how well the embryos appear to be developing in the petri dish, and at Medfem Fertility Clinic are scored on a 3 point scale (with a 3 being the best and a 1 being the worst). For embryos being scored on the third day in the lab, grade 3 embryos have round and symmetrical cells, look “textbook” perfect in every way and give high pregnancy rates when transferred. Only about 20% of all embryos get this top perfect score. The more common situation is that when the cells of an embryo divide, the resulting cells are not quite even in size or shape. Also, human embryos have a tendency to lose tiny pieces or fragments of their cells during cell division, and the severity of this fragmentation is largely what grades are based on. Fragmentation may be the result of stimulation protocol or culture conditions. Often these fragments disappear or are reabsorbed back into the cells in the next round of division. Fragmented embryos can implant and often go to full term.
A grade “2+” embryo would likely have a small amount of cell fragmentation, but otherwise look relatively normal. Since the embryo is contained within a shell, the fragments remain in close association with the cells and are readily visible under the microscope. A small amount of fragmentation is normal however, and can be expected in most human embryos. If the fragmentation becomes severe, then the cells will likely get smaller and more uneven, and the embryo will get a worse grade. A grade “1” embryo is the lowest or poorest point on the scale and usually represents embryos that have almost entirely disintegrated into fragments or have degenerative qualities. Chances of pregnancy from these embryos will be marginal at best.
For embryos being scored on the 5th or 6th day in the laboratory, we expect further development and progression of the embryos to the blastocyst stage. While an embryo is usually composed of 6-10 loosely associated cells on day 3, by day 5 the cells should have compacted together and begun to differentiate. Late on day 3, as the cells continue to divide, they compact tightly together to form a ball of cells that we call a “morula.” The outer cells in the morula immediately begin to pump fluid into the centre of the ball, opening up a small cavity (or cyst) in the centre. As early as the afternoon of day 4, this little cavity can be observed, and it continues to enlarge in size as the embryo develops. In line with cavity formation, the cells of the embryo begin to organise into 2 distinct groups. One group of cells, usually about 2/3 of the total remains on the outside of the ball, surrounding the growing cavity. These outer cells will eventually become the placenta allowing the embryo to implant in the uterus. The remaining 1/3 of cells stay on the inside of the embryo and these will develop into the fetus and some of the extraembryonic membranes (such as the yolk sac).
Grading embryos at the blastocyst stage is a little more complicated than grading day 3 embryos. The stage which the embryo has developed to is first assessed, and more advanced embryos are considered better with higher chances of achieving pregnancy. A morula would be considered less developed and therefore graded lower than an early blastocyst, which would in turn be less developed compared to a more expanded blastocyst. In general, the embryo at the most advanced stage among a cohort, will be the one selected for transfer. However, in addition to looking at the stage that the embryo has reached, the embryologist will also assess the quality of the inner and outer cells, zona thickness and the degree of expansion. These features are given a grade from A (best) to B (absent) and then an overall grade is assigned to the embryo. An embryo with nice distinct populations of outer and inner cells (A and B scores) would be a grade 3 or a perfect embryo. If either cell population has fewer and/or less compact cells, the grade might drop to a 2. If an embryo has little or no outer or inner cells, a grade 1 will be assigned. Blastocysts remaining after transfer can be frozen for later use provided that they are grade 3 or 2+.
At Medfem Fertility Clinic our embryologists are always available to talk with you and explain the results of your embryo grading. Please feel free to contact us with any questions that you may have.