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Just Before Blastocyst: The Morlula

 

 

award winning fertility doctor new york city

 

So what happens after day 3? Two days later we would like it to be a blastocyst. The day before it becomes a blastocyst, it should be a morula. A morula forms when the 8 cell embryo divides further, and at the same time the cells become very close to each other. Here it’s difficult to see the borders of the cells, so the morula looks like one big blob. It ‘s solid in the middle. It’s still inside the shell. There are about 12-30 cells in a morula.
Here are some pictures:

Here is a nice looking morula.

 

Here are a few others . The top right looks nice, the others look OK, the bottom right looks the worst.

 
 
 

 
 
 
Most morulas (some write the pleural morulae, but most write it morulas) look about the same, so we don’t give them a number or a grade. We may say “nice” for a good one, but that’s about it.
Is it ok to transfer a morula? If your doctor wants to transfer your embryos on day 4, you will probably have morulas, but it will be hard for you to get a handle on quality. Most programs transfer day 3 or day 5. Day 4 transfer is ok, but most of us would say if you are waiting till day 4, just wait till day 5 so that the embryos have more time to grow, and quality can be better assessed.
 
What if on day 5 you are told the best embryos are morulas, not blastocysts? Not so good. I have had patients get back 2 morulas and become pregnant with twins. However the chances of pregnancy are much higher if you have blastocysts.
 
 
If there are morulas on day 5, isn’t it better to wait another day until they are blastocysts? No, because even if they become blasts on day 6 they are still a day behind. Rarely, we transfer on day 6. This may happen if , for example, there are 4 morulas and we want to give them, one more day to see which ones, if any, develop a little more.
 
Can we do anything to make the embryos grow faster? The same answer as last time. We try to change things up a bit next cycle, but there is no special drug protocol for slow embryos. Its just a matter of trying again and hoping for a better outcome.
 
Thanks again,
 
Dr. Licciardi
 
References:
  • Prados F, Debrock S, Lemmen J, Agerholm I. The cleavage stage embryo. Human Reproduction, Vol.27, No.S1 pp. i50–i71, 2012.
  • Blake DA, Farquhar CM, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database Syst Rev. 2007 Oct 17 ;(4):CD002118.
  • Puissant F, Van Rysselberge M, Barlow P, Deweze J, Leroy F. Embryo scoring as a prognostic tool in IVF treatment. Hum Reprod 1987; 2(8):705-8.
  • Racowsky C. Combelles CM. Nureddin A. Pan Y. Finn A. Miles L. Gale S. O’Leary T. Jackson KV. Day 3 and day 5 morphological predictors of embryo viability. Reprod Biomed Online 2003; 6(3):323-31.

More About Embryos

divThe 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.
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.

The embryos shown at the beginning have no fragmentation.

Here is a 2 cell embryo with a little fragmentation
a href=”http://images.google.com/imgres?imgurl=http://www.advancedfertility.com/pics/2cellivfembryo.jpgamp;imgrefurl=http://www.advancedfertility.com/2-cell2.htmamp;usg=__ywcry_hhVF1QdC0zeAo1n2AxFCk=amp;h=307amp;w=301amp;sz=7amp;hl=enamp;start=1amp;sig2=vgF9rfghX9XQKIQNW2y3rQamp;um=1amp;tbnid=PhfEIvYxT_9C-M:amp;tbnh=117amp;tbnw=115amp;ei=AgVqSbL6KNW_tgf3hpGrBwamp;prev=/images?q=slight+fragmentationamp;um=1amp;hl=enamp;rls=com.microsoft:*:IE-SearchBoxamp;rlz=1I7ADBSamp;sa=G”/a
Here is a 6 cell embryo with little more.

Here is an embryo with a large amount of fragmentation. It looks similar to the embryo above, but there are fewer larger normal cells.
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.
Sometime 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
/div

References:

  • Papale L, Fiorentino A, Montag M, Tomasi G. The zygote. Human Reproduction, Vol.27, No.S1 pp. i22–i49, 2012.
  • Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011; 26:1270–1283.
  • Prados F, Debrock S, Lemmen J, Agerholm I. The cleavage stage embryo. Human Reproduction, Vol.27, No.S1 pp. i50–i71, 2012.
  • Blake DA, Farquhar CM, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database Syst Rev. 2007 Oct 17 ;(4):CD002118.
  • Puissant F, Van Rysselberge M, Barlow P, Deweze J, Leroy F. Embryo scoring as a prognostic tool in IVF treatment. Hum Reprod 1987; 2(8):705-8.
  • Racowsky C. Combelles CM. Nureddin A. Pan Y. Finn A. Miles L. Gale S. O’Leary T. Jackson KV. Day 3 and day 5 morphological predictors of embryo viability. Reprod Biomed Online 2003; 6(3):323-31.