IVF and Embryo Grading

Throughout the years, different in vitro fertilization (IVF) techniques have been developed. One of these techniques was how to choose the embryo that would result in the delivery of a healthy baby.

Sperm, eggs and embryos all undergo a grading system during IVF. Embryologists determine the best quality embryo based on morphology (appearance). This grading is a complex process that begins at the time of the egg retrieval and continues throughout early embryonic development. 

The Day of Egg Retrieval (Day 0)
During the IVF process, approximately 80 percent of eggs that are retrieved will be mature. Only mature eggs will successfully fertilize.

There are two ways to fertilize the egg:

  • The first method is called microdroplet, in which approximately one hundred thousand sperm are dropped onto the egg. It is impossible in this situation to determine ahead of time if the egg is mature. We only know if the egg was mature once the egg is fertilized.
  • Another fertilization option is ICSI (intracytoplasmic sperm injection). During ICSI, a normal sperm is chosen and injected directly into the egg. The embryologist prepares the egg by denuding, or stripping, the egg of its supporting cells. She then can tell if the egg is mature and has the potential to fertilize.

Regardless of the fertilization method, the average fertilization rate with IVF is 70 to 75 percent.

Day 1
The next morning the embryologist determines which eggs have fertilized. The score is based on the number, position and size of the pronuclei. There should be two nuclei, one from the sperm and one from the egg. They should be equal in size and located in the center of the egg. Inside each pronucleus are several smaller structures called nucleolar precursor bodies (NPB’s) which should line up with one another. A “halo” forms around the two nuclei which is composed of fluid (cytoplasm).

Day 2
Two days after the egg retrieval the embryologist will score the embryos based on the number of cells, number of nuclei and evenness of cell size. Ideally, the embryo should be made of 4 cells. Each cell should only have one nucleus. Cells that have multiple nuclei are more likely to arise from an abnormal embryo. Finally, the embryologist will score the embryo based on how even in size the cells are. The more equal they are in size, the higher the score.

Day 3
On day 3, the embryologist continues to score the embryo based on the number of cells and the evenness of cell size. She will also consider the three dimensional distribution of cells, the degree of fragmentation and rate of development. Fragmentation has to do with the integrity of the membrane surrounding the cell.  Embryos that grow too quickly or too slowly are more likely to be abnormal.

Day 4
Our embryologists do not evaluate embryos on day 4. Many changes are happening to the embryos at this stage which make it difficult for them to score. Most normal embryos are at the morula stage on day 4. This looks like a big ball of cells rapidly dividing.

Day 5
Ideally, embryos on day 5 have made it to the blastocyst stage. In order to have made it to this stage, the embryo has to undergo “compaction” or a fusion of cells to form the blastocoel that began around day 3 or 4 when the embryo was in 8-16 cell stage. The blastocoel is a fluid filled structure that helps separate the trophectoderm and the inner cell mass.

The best quality blastocyst has an adequate number of cells making up the trophectoderm, the inner cell mass and the blastocoel. The cells that make up the trophectoderm should be evenly sized and spaced. These cells become the placenta. The cells that make up the inner cell mass should be compact and equally sized as well. These cells become the embryo.  

Your physician or embryologist should review the embryo quality with you on the day of your transfer. This is a good time to ask questions as to how they decided which embryo or embryos to transfer.

Dr. Colleen Casey is a reproductive endocrinologist at the Center for Reproductive Medicine in Minnesota. She received her medical degree from the University of Minnesota, is a Fellow of the American College of Obstetrics and Gynecology and is board certified in Reproductive Endocrinology and OB/GYN. She completed her OB/GYN residency at the University of Michigan, where she received the resident of the year teaching award from medical students. She completed her reproductive endocrinology fellowship at the University of Vermont in 2008. Dr. Casey's main research has focused on how hormones relating to obesity alter reproductive potential. Dr. Casey specializes in the evaluation and treatment of complex infertility problems. This includes all aspects of female and male infertility, Polycystic Ovarian Syndrome (PCOS), endometriosis, diminished ovarian reserve and recurrent pregnancy loss.

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