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More About Embryos

Posted Apr 28 2009 1:41pm
The questions: at the time of this writing there were 84 questions to answer. I will read through them and get to most, but probably not all. I am sure this is most difficult for those who write about the here and now, i.e. questions about a cycle in progress. Many of you have commented that the topics are more helpful than the questions, so I want to continue with the embryo blogs, and then go to more questions. I do like answering the questions.

The egg is one cell, the fertilized egg is one cell, and then the egg divides, becoming 2 cells. The 2 cells are smaller than the one big one, and with each division, the cells become smaller. After 2 they become 4. Actually many times they become 3. Both the 2 cells may not divide at the same time. That’s why an embryo can be a 3, 4, 5, 6, 7, 8 or other cell number. It does not need to be an even number.

So here are pictures of 2 cell, cell 4 cell and 8 cell embryos.

The overall size of the embryo does not change. The zonna pellucida stays the same size, so the cells need to fit inside. Just like a developing chick can’t be bigger than the egg, till the end.
These are pictures of perfect looking embryos. Most embryos do not look like these, and that’s ok. These are the typical embryos you see on web sites.
Most of the questions about embryo development we cannot answer. Why do some embryos look prettier than others? Why are some embryos slower than others? Why are some embryos fragmented? We are not close to understanding these questions. We prefer if an embryo looks “better”, meaning the cells are dividing at the right rate and there is minimal fragmentation.
How quickly should an embryo grow? 1 day after the retrieval, they are still one cell, but the next day division should take place. A 4 cell may be the best, but a 2 or 3 may be ok. And of course, they have to keep growing, so that the next day, day 3, they should be 5-8 cells. A 4 cell on day 3 is really slow. Certainly, as with many other slow embryos, a baby is possible with a 4 cell on day 3, but it’s better to have an embryo that is more advanced. The closer you get to 8 the better, 6 is the minimum “good” number”.
Most clinics have their own classification system for grading embryos. Some labs call their best embryos A’s. Some 1’s, some 5’s. There is a reason for this. IVF is a relatively new science and many of the lab directors who started 10-20 years ago had little human IVF experience. There just were not a large group of scientists who previously worked in IVF labs. They had backgrounds in brain science, animal science and all sorts of other areas. Some of them turned into great lab directors (hats off to our lab director, Dr. Krey), but there was not grading system that the whole country followed. Each program just made up its own system for grading day 3 embryos. We could all get on the same page, but now it’s too hard to go back.
It would be really difficult for each program to go back through 20 years of charts and change the numbers assigned to each embryo. Plus if we all change now to a new system, it’s hard have some embryos graded one way and some another, especially for research purposes. So things will stay as they are. It just makes it a little difficult when you talk to your friends to compare embryos. To jump ahead a little, there is a system most of us follow for day 5 embryos.

What is fragmentation? Fragments are little pieces of the cell that break off as the embryo divides. A little bit of fragmentation is normal. As the degree of fragmentation increase, the odds of implantation go down.
Let’s look at some day 3 embryos to see varying amounts of fragmentation.
This close up shows the normal larger cells, and some smaller round “fragments”.

Here is a group of embryos from the same woman. The embryo far right is the best. It has very few fragments. The top embryo looks good too. The bottom middle looks ok, but is a bit more fragmented.

This embryo has a high degree of fragmentation (compare to the nice embryos at the begining).

In this picture, the far right embryo is full of fragments.

We frequently assign a fragmentation score by estimating the percentage of the embryo volume that is replaced by fragments. 0% is actually rare, some fragments are expected. 0% is ok, but it does not happen much. We consider up to about 10% to still be very good. 10-20% is still OK, not quite as good. More than 20% is more abnormal, we consider the embryo to be of poorer quality. Pregnancy can occur with a fragmented embryo, but the odds are lower.
Sometimes fragments are removed from an embryo in the lab, by making a small hole in the shell and sucking out the fragments on day 3. This is done at the time of hatching since the hole is the same. The embryo can look much better, but we do not know if it means the embryo is really in better shape.

Can we reduce a woman’s chance of producing fragmented embryos? We try, but we never know if our efforts helped, or things improved as a result of chance. We add lupron, remove lupron, add LH, remove LH, lower doses, increase doses, give few days or more days of stimulation, etc etc.

So what’s worse, a slow embryo or a fragmented embryo? Of course it depends on how slow or how fragmented, but basically, it’s a tie
An important issue here is that if you have done 1-2 cycles of IVF, and you make eggs and embryos and have fragmented embryos, donor eggs may still not be necessary. Get a second opinion at the best program possible. Maybe DE is the best thing for you, but maybe another try under different conditions will do the trick.

Thanks for reading, and please read disclaimer 5/17/06.
Dr. Licciardi
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