Fragmentation and egg quality
1 Replies
mary5 - April 20

Hi Dr Smith,

I have had 3 cycles, am 32 and fsh is around 5, our only diagnosis is immune problems diagnosed before the 3rd cycle.
Cycle 1: Menopur/cetrotide, 9 eggs, 8 fert with IVF, day 2 transfer of 2x4cell grade 1 (best), remainder grade 3-4 only got to 6-7 cells on day 3 and very fragmented

Cycle 2: Menopur/cetrotide, 6 eggs, 4 fert with IVF but 2 had 3pn so transferred remaining 2 on day 2, they were 2x4cells but grade 3 with fragmentation. this cycle egg retrieval was done day 11, wondered if this was too early?

Cycle 3:New RE and clinic, long lupron, follistim 300 for 13 days, 19 eggs, 17 were mature, did a split ivf/icsi, 5 were injected for icsi and all 5 fert, remaining 12 were ivf'd and 8 fertilised so 13 embryos in total. By day 3 about 5 were at 7-8 cell stage, the rest were all still dividing but more slowly. The ivf embryos were all very fragmented but icsi embryos were better grade. transferred 2 7 cells on day 3, minimal fragmentation, both grade 1-2, remaining 11 were grown to day 5/6 and 3 'formed cavity but had indistinct trophectoderm and inner cell mass' so were not suitable for freezing. this cycle i also had treatment for elevated nk cells

given the above history my questions are:
1. Does this history of fragmentation suggest poor egg quality? we usually get only a few good grade embryos each cycle. If i had poor egg quality would we get poorer fertilisation rates and a reduced response to the stimulation drugs?
2. Why was there are marked difference between fragmentation in the ivf and icsi embryos? This leads us to lean towards trying icsi on all the eggs in a future cycle, what is your opinion on this?
3. what can be done to improve embryo fragmentation? i have read it may be drug-related so is it caused by eggs that are overmature or not mature enough?
4. can you explain what is meant when a day 5 embryo forms a cavity but the trophectoderm is indistinct? Is this actually at the blastocyst stage or not?
5. Am i correct in assuming that fragmentation is a marker of embryo quality as this is partially the basis for embryo grading? Is it common to see a range of quality over several cycles or is the quality always likely to be similar despite changes in protocols or stim drugs?

thank you in advance for answering my many questions, I have learned alot from the information on here,


Dr Smith - April 21

A1. Significant fragmentation (>20% of the embryo volume) observed prior to Day 3 of development is attributed to poor egg quality. It turns out that fertilization [i]per se[/i] is not a definitive indicator of egg quality. Poor quality eggs can show signs of timely fertilization only to subsequently deteriorate during embryo development. During your first two cycles, you had a lower-than-expected (based on your age) response. The third cycle was within the expected range of about 15 eggs. Poor egg quality does not cause a diminshed response, however the converse may be true. A "weak", short or prolonged stimulation can result in poor quality eggs.

A2. You bring up an interesting point that is currently debated among embryologists. In order to achieve fertilization in vitro, the egg must be exposed to between 25,000 and 50,000 sperm in a very low volume of culture medium for a period of 17-19 hours. The metabolic activity of such a high number of sperm in the vicinity of the egg may be having a detrimental effect (i.e. subsequent fragmentation) to the egg/early embryo. Consequently, embryologist have studied shortened incubation times of 3-5 hours instead of 17-19 and found, comparable fertilization rates, reduced fragmentation and better development in the resulting embryos thus adding support to this idea. Alternatively, ICSI bypasses the sperm-egg co-incubation and may explain the reduced fragmentation in your case. However, its a trade off, because the egg may do a better job of choosing the "right" sperm compared to the embryologist performing ICSI, so the overall developmental competence may be reduced by performing ICSI. The jury is still out on all these issues.

A3. Apart from altering the stimulation protocol/medications, there's not much that can be done in the lab to reduce fragmentation (although ICSI may help - see above). Its not the specific medications [i]per se[/i] that cause the fragmentation, it how the medications are used by the RE. Some RE's are better/more agressive at stimulation than others.

A4. In the early stages of blastocyst development, fluid is pumped into a central cavity of the embryo (the process is referred to as cavitation). As more and more fluid is pumped into the cavity, the cavity expands and the two cell types (stem cells and trophectoderm) become easy to visualize and grade. Embryos that initiate cavitation, but fail to expand to a full sized blastocyst (roughly 3x that of the original egg) by the morning of Day 6 are considered to be developmentaly compromised and, therefore, not worthy of cryopreservation. Your embryos were technically blastocysts (define a the presence of a cavity, even a small one), but not very good ones.

A5. Excessive embryo fragmentation (>20% of the embryo volume) is considered a marker for embryos with compromised developmental potential. These embryos rarely make it past the 8-cell stage and it is likely they also are genetically abnormal. Embryos exhibiting <20% fragmentation may continue to develop normally to the blastocyst stage. Fragmentation due to an inherent defect in the egg cytoplasm is consistent from one cycle to the next. Fragmentation due to a poor or mismanaged stimulation can improve as the protocol or management of the stimulation is changed on subsequent cycles.



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