Slower growing embryos
3 Replies
Lana - September 26

Dear dr Smith

I am 37, on 4th IVF cycle, and would appreciate your views on the following: Our first IVF (day 3 transfer)ended in chemical pregnancy at 7 wks, no further BFP's despite the transfer of 2 'perfect' blasts on the 2nd IVF. The third IVF, as well as the current one, we also waited for day 5 transfer, but in both cases ended up with 'compacts' rather than blasts. Some fragmentation of embryos beneath zona seen in this last cycle as well. They transfered 3 of these yesterday. So now for the wait again...I'm afraid I don't feel very optimistic. Please let me know what your experience is (if any) with embryos developing at slower pace and not reaching blast stage at day 5.

I've logged in again to give you more detail after having read through some extensive discussions on this forum on the same issue. Our embryos develop well and on schedule until day 3 (we had 7 8-cells this time). Does this point to a sperm DNA abnormality or not necessarily. My husband's sperm shows above average quality (according to Kruger analysis) - would it in your view be worth having sperm DNA tested? The good blasts in our 2nd IVF puzzle me though - surely sperm DNA would not vary and the fact that we did have blasts the one time means that this is unlikely to be the cause?

I should also mention that I normally have long follicular phase - I do ovulate w/o meds, but only around day 22/23 sometimes. The only time when we had blasts was when they did retrieval on day 16 (rather than 12,13 etc) so could it be useful to try to align the medicated cycle more with the natural cycle? How would they do that? I was on Menogon and Gonal-F this time and it pretty much seemed like a bus without breaks, once the follicles are there they grow. Would there be a way of inducing a slower response on stims?

I would appreciate your views!


Dr Smith - September 26

O.K., there's a lot of questions here. Let me try to go through them one-by-one.

Embryos that reach the compacted morula stage on Day 5 can and do result in healthy pregnancies. It is not unusual to have embryos that reach the blastocyst stage on Day 5 and Day 6. What usually ends up happening is that we transfer 2 of the Day 5 blastocysts and freeze the ones that develop by Day 6. A little bit of fragmentation in the embryo is no big deal. I see it frequently and it does not interfere with blastocyst development. A lot of fragmentation is another story.

The impact of DNA fragmentation on embryo development can cause embryos to arrest at the compacted morula stage or form blastocysts with too few stem cells. These are good reasons to wait until Day 6 to make sure the Day 5 morulas are developmentally compentent. However, from the information you provided, I don't see any of the tell tale signs of sperm DNA fragmentation.

The slow down at the 8-cell + stage can also be caused by cytoplasmic maturation issues. Stimulations are not entirely like a bus without brakes (I like this turn of phase and I may, with your permission, use it at a later date). The can "coast" the cycle by decreasing or withdrawing medication for a couple of days prior to retrieval to deliberately give the follicles/eggs extra time. I agree that stretching out the cycles a few more days can give your eggs the extra time they need. Everybody's different and one size does not fit all. Oh, you can't hurry love. No, you'll just have to wait... I digress.

Another possibile explanation is immune problems that interfere with implantation (good embryos - but no implantation). Natural Killer cells can become elevated or activate inappropriately following an early miscarriage. For more information on NK cells, see It may be worthwhile to have immune testing performed if the curent cycle is a bust. However, keep your chin up. I ain't over 'till its over.

Best of luck.


Lana - September 27

Dear dr Smith

Many thanks for your comprehensive reply - I really do appreciate it. I've just spoken to the embryologist to try to find more specific information regarding the fragmentation seen in these morulae (also to hear that none of our other embi's made it to freezing, but anyway...he chose the best ones to transfer so I'm not yet giving up hope).

The fragmentation, according to him, were small fragments like little "bobbles" (for lack of a better word) distributed evenly on the inside of the zona, basically surrounding the central bunch of cells. It sounded a bit like something they don't really see. He said that it was probably less than 10% of the total though. Have you seen anything like this before?

Re. the immune issues: I've read about it and mentioned it to a few people (at my clinic and at a local university's Reproductive Biol dept) and have had no enthusiasm to explore this possibility - these RE's all reckon it is not scientifically proven and basically not worth investigating. Unfortunately my location (South Africa) means that I don't have access to the lab facilities on the URL.

For NK activation would the treatment be IVIg? (which I'm also not sure would be available here but maybe I'm mistaken).


Dr Smith - September 29

I've seem a small amount a fragmentation (i.e. 10%) often and it does not interfere with embryo development. As they described, when the cells of the embryo compact into a tight ball at the morula stage, the fragments are excluded from the compacted cells and are pushed off to the periphery immediately under the zona. When the blastocyst forms and hatches out of the zona, these fragments are left behind within the zona. No worries.

The jury is still out about immune issues and implantation, but more and more evidence is accumulating to support the concept that an abnormal immune response can prevent or retard implantation. In your case, the docs may be pooh-poohing the testing because it is not available in you region. NK activation is a highly specialized test performed in only a few labs in the US. In any case, NK problems can be treated empirically (without knowing if you have a problem or not) with IVIg or corticosteroids such as Solu-Cortef. Solu-Cortef is probably available in S.A., but goes under another brand name. It is cheap (compared to IVIg) and does not seem to have any side effects when used in a single dose at the time of embryo transfer. You might be able to talk your docs into that one.



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