Hello everyone! Let’s talk about embryo development. What is normal versus abnormal embryo development? And how do we know if an embryo is suitable for transfer? Let’s find out!
Review: an embryo is created when a sperm fertilizes an egg. This creates a one-cell embryo (know as a zygote) that now has 2 sets of DNA (1 set from the egg and 1 set from the sperm). This one cell then divides into 2 cells, then 4, and so on until it as over 100 cells! At this point, the embryo can be graded to determine if it’s suitable for transfer.
Embryos follow a timeline as they develop. Here is the normal timeline for embryo development in the IVF lab:
Day 0: Egg retrieval (or thaw) insemination
The day of the egg retrieval or thaw and insemination is considered day 0 in the IVF lab. At this point, any mature eggs are inseminated and will remain in the incubator overnight.
Day 1: Fertilization check
The morning after insemination, an embryologist will check to see if fertilization has occurred. Any embryos that show signs of fertilization (having 2 pronuclei and 2 polar bodies) are placed back into the incubator in order to continue developing. At this point, the embryos (called zygotes) still consist of 1 cell. Some clinics will continue to culture embryos that do not show signs of fertilization, but these embryos typically do not continue to develop.
Most clinics will not look at your embryos on day 2. This allows the embryos to grow without any disruptions. On day 2, the embryos should divide from 1 –> 2-4 cells early in the day and –> 6 cells at the end of the day. Cell division occurs when the cells in the embryo replicate their DNA and break apart into 2 identical cells.
Some clinics will observe your embryos on day 3, and some clinics choose to perform assisted hatching on your embryos on this day, as well. Assisted hatching occurs when the embryologist creates a hole in the shell (zona pellucida) of the embryo. On day 3, the embryo should divide from ~6 cells –> 12+ cells. Around this time, the cells will begin to clump together to form an early morula (Latin for mulberry since it looks like a cluster of mulberries).
Most clinics do not look at your embryos on day 4, though some may perform assisted hatching on day 4 (each clinic has their own protocol). On day 4, the early morula should condense into a tighter ball, which is called a morula. The morula will then form a small cavity (blastocoel) inside of it. When this occurs, the embryo becomes known as an early blastocyst.
Days 5, 6, (and 7 in some clinics)
Almost every IVF clinic will observe your embryos on day 5. At this point, the embryo (now called a blastocyst) should have a large blastocoel and a large number of cells. As the embryo grows, the shell surrounding the embryo begins to thin out (unless it has already been hatched). Eventually, the embryo will create a hole in the shell and will hatch out of its shell. Embryos that are at a certain stage of development and are good quality can be transferred, biopsied, and/or frozen. If your embryos are still growing, the embryologist will keep them in the incubator overnight and will observe them the next morning. Some clinics also culture growing embryos to day 7, but not many will culture embryos past this day.
Keep in mind that embryos that are biopsied will be automatically hatched in order to retrieve cells from the embryo.
A good quality embryo on days 5-7 will be at the expanded, hatching, or fully hatched stage (the embryo needs to be hatching or hatched in order to implant into the uterine lining). The embryo will also have a lot of cells that are even in appearance. Embryos are graded based on the quality of their inner cell mass (the part of the embryo that becomes the baby) and their trophectoderm (the part of the embryo that becomes the placenta). Each clinic has their own system for grading embryos, so be sure to ask how their system works.