Fragmentation
15 Replies
allison - September 9

This is my first IVF cycle. I responded very well to stimulation and produced 14 eggs, of which 6 fertilized. Today is day 3 post retrieval. The lab called and said all are at the 6-8 cell stage, but all are fragmented. They said they have seen embryos mature to blastocyst stage and "push out" the fragments. They are all graded at this point a "C". Could you please explain this to me and tell me exactly what the fragments are and what do you think our chances are? Thank you for your time.

Allison

 

Dr Smith - September 11

Fragmentation are little bits of cytoplasm that are excruded from the embryonic cells when they divide. A little bit (<20%) of fragmentation is O.K. A lot is not. It there is minor fragmentation, I too have seen the fragments pushed out of the way when the embryo expands at the blastocyst stage. Different labs have different grading systems, so I don't know what a "C" grade is in relation to the degree of fragmentation in your lab. Your chances will depend on the degree of fragmentation. Also, it is difficult to predict the possibilty of a successful cycle following a Day 3 transfer. Its still up in the air at that point.

 

allison - September 11

I did not have a day 3 transfer. Today is day 5. I am awaiting a call to see how they are for transfer this afternoon. Is it a good sign they let them grow to blast? Unfortunately they did not tell me what % they were fragmented, I did not know what to ask. Again, Thank you.

 

allison - September 11

Just spoke with embryologist. She said 3 of the embryos look really bad. Of the remaining 3, 1 is a morula stage and the other 2 only half of the embryo is at early blast stage. She recommended we continue with transfer and see what happens. I am not optimistic at all.

 

Dr Smith - September 11

Sounds O.K. The embryos that have reached the early blastocyst stage by the morning of Day 5 are right on schedule. The morula is a little bit behind, but probably O.K. too. I'm glad to hear they let them grow to the blastocyst stage. It is easier to interpret your chances of success. Now that two of the embryos have reached the blastocyst stage, the important thing to predict success is the number of stem cells (or the size of the inner cell mass) present in the blastocyst. The stem cells/inner cell mass is usually graded on an A-B-C scale with A being the best. If they transfer two reasonably good quality blastocysts (A or B grade inner cell mass), I'd say your chances are about 50/50. Considering your age, if they also transfer the morula, you may be flirting with twins. It appears that the small amount of fragmentation in these three embryos did not interfere with morula/blastocyst development. The fragments were pushed off to the side just like they said. The heavily fragmented embryos arrested development as expected.

Best of luck.

 

Eliza - September 24

Dear Dr Smith,
I had to post through this ladys post as I was having problems creating a new topic.
I hope you can advise me.
I am 38 yrs old and have PCOS with elevated LH levels.
My husbands sperm is normal.My FSH is 6.6
I had an anembryonic miscarriage last year and have had 3 cycles of ovulation induction with clomid and metformin with variable ovulatory response.
I had my first cycle of IVF recently.They used 4 amps of menopure and the flare protocol.
I got 20 follicles from which 15 eggs were collected.
14 fertililzed - 2 did not divide and 10 went onto to become grade 3/4 embryos.Only 2 grade 2 four cell embryos remained.These were replaced on day 2.
The cycle was unsuccessful.
My questions are as follows
- What caused my embryos to be of such poor quality?
- Why was the fertilization rate so good and the subsequent quality so poor?
- Should I be thinking about donor eggs at this stage?
I would really appreciate your expert opionon
Eliza

 

Dr Smith - September 26

Eggs from PCOS patients often result in embryos with slow growth and/or arrested development. It may be from the number of follicles that develop in the ovary during stimulation. There is an optimal number of 10-15 follicles that results in optimal egg quality. There is also the issue of stimulation length. It the stimulation was less than 9 days, the eggs may not have had sufficient time to mature in the follicles before the retrieval. Eggs with immmature cytoplasm also show slow and arrested deveopment. Another explanation is that the higher LH present during a PCOS stimulation may act to stimulate androgen production which may, in turn, have a negative effect of egg maturation. No one is really sure what goes wrong in PCOS patients, but the end result is often the same - poor quality embryos.

I would not suggest using donated eggs just yet. I would recommend another IVF cycle with a different stimulation protocol that will allow adequate cytoplasmic maturation of the eggs. Cytoplasmic maturation is distinctly different from the term "maturity" used to determine if an egg is mature enough to be fertilized. When they tell you that x eggs were "mature" and could be fertilized, they are not talking about cytoplasmic maturation. Fertilization is one thing, embryo development is another.

 

Eliza - September 26

Dear Dr Smith,
Thank you so very much for your advice. It is so nice to have the opionon of someone so knowledgable and insightful. I shall try again with my own eggs and hopefully they will adjust my protocol.
Thanks again
Eliza

 

allison - October 5

Dr. Smith

This was my original post and unfortunately am not pregnant. We transfered the morula and the best looking 1 of the other 2 embryos. None of them were very pretty on day 5, lots of fragmentation. I wish I could show you pictures so you could really give me advise.

My RE is suggesting a different protocol and ICSI. We did the micro-dose Lupron protocol due to RE thinking I would be a poor responder from endometriosis. I responded very well, so he wants to change. Could a different protocol result in better egg quality? Will ICSI reduce fragmentation? Any help will be greatly appreciated.

Thank you,
Allison

 

Dr Smith - October 6

Changing the stimulation protocol may help reduce fragmentation by allowing the eggs to mature properly prior to retrieval. Regardless of stimulation protocol, the optimal stimulation period is 9-12 days and on the day of hCG, the E2 should be approximately 200 pg/ml for each mature (>16mm) follicle. Inadequate egg maturation can result in slow embryonic growth and significant fragmentation.

ICSI may improve the fertilization rate (about 80% of the mature will fertilize by ICSI), but if there are inherent problems with the eggs, ICSI will not address slow growth or fragmentation.

 

allison - October 7

Thank you so much for you advise. Do you know which protocol you see the best results from?

 

Dr Smith - October 10

Ever person is different. I know that sounds like a BS answer, but its true. No, really. Ovarian stimulation is not an exact science and it can take a few tries to get it right. The objective of the stimulation is to use a protocol that will control the rate of follicular growth and estrogen secretion so that the stimulation takes about 10 days and the E2 is about 200 pg/ml for each mature follicle (>16mm). Some people have a better stimulation on one protocol while other people on another. Your RE will figure out what's best for you.

 

allison - October 10

My E2 was over 3000 with 14 follicles (13 turned out to be mature), but only 6 fertilized. So, this part sounds good, so maybe it is a fertilization problem?? Maybe ICSI will do some good? I know we won't know for sure until we try, but we are only doing 1 more cycle and then throwing in the towel. We never actually planned to do more than 1 cycle to begin with, but are reconsidering now. Again, thank you so much.

 

Dr Smith - October 11

Has the endometriosis been treated recently (i.e. laser ablation of the endo lesions)? Grade 4 endo can also affect egg quality and cause some problems with fertilization and implantation (sorry, I didn't notice that in your signature before). I'd talk with your RE about the possibility of a few months on Lupron to quiet down the endometriosis before the next IVF attempt. I agree that ICSI is the way to go next time, just in case the low fertilization rate was a result of a subtle sperm problem. ICSI won't make bad eggs good, but it will get you off to a better start.

 

allison - October 12

I have been on birth control for the last 2-3 years. I had to go off of it for 1 month before beginning IVF treatment. Is that good enough, or definately Lupron?

Thanks for everything!!

 

Dr Smith - October 13

Sorry, but your question is of a medical nature. I'm not a physician. Please post your question on Dr Jacob's Infertility 101 Message Board. He will be able to answer your question.

 

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