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For your information both of these cycles were with ICSI

Inadequate cytoplasmic maturation could be the problem. While maturing in the follicle, the egg cytoplasm must produce and store all the components it will need to respond to the sperm once it has entered the cytoplasm (a complex process called egg activation). If one or more of the componenets is absent or in short supply, the egg will not activate in the presence of the sperm. We see this in borderline mature eggs - mature enough to ICSI, not mature enough to activate. These eggs usually, but not always, are retrieved from small follicles. If there was significant folliclular discordance (more small follicles than big ones) on both cycles, this could explain it.

The other explanation is that there is an inherent problem with the majority of the eggs. It would impossible to figure out which component is missing or in short supply in most, but not all, of the eggs that prevents activation. It it were a genetic trait, one would expect all the eggs to be affected.

so if we are having inadequate cytoplasmic maturation....what is the solution to this? Different stimulation protocol? I am not sure at this time if we had more small follicles than big ones.

Not necessarily a different stimulation protocol. Perhaps the same protocol, but managed to obtain better follicular synchrony and the appropriate cycle length (9-12 days of medication).

Another thing came to mind. If the morphology is extremely poor (i.e. 0% normal forms on two more semen analyses), that may be contributing to the problem. The sperm must be compentent of initiating the activation of the egg upon entering. The sperm contibutes very little to the activation process, but its presence does get the ball rolling. We usually see adequate fertilization, even when ICSI is performed with morohologically abnormal sperm. Subesquent embryo development is compromised in these cases, but we do achieve a reasonable fertilization rate (60-70%). That's why I suspected an egg maturation problem as the most likely explanation.

I suggest that you discuss your stimulation, follicular development, etc., with your RE.

Thank you for your response. For both cycles on was on follistim 225 units for 9 days triggered on day 10. E2 levels were very similar in both cycles during stimms and at 3288 on trigger day.
So, it sounds like I should stay on the same medication. But just stimm another couple days? Is it okay to stimm another couple days when e2 levels are at this level? How do you or can you better synchronize follicular growth?
Another question...we also had just average quality embryos 1-8 cell, 7, 2-6 cell, a couple 5 cell but all grade 3 except 1. Is the embryo quality most likely related to the egg maturation? I am hoping that if we get better fertiliztion we will also get better quality embryos?
After two failed cycles...both with same result, I am getting some second opinions before the next cycle....I appreciate your advice too...

correction- I was on stimm meds for 10 days for both cycles. Triggered on day 11.

I am wondering how you know not to overstim or understim? I am sure it is a fine line between the two.
I think I had the same amount of follicles for both cycles. About 26 follicles total if that info helps. I will find out the sizes and let you know.
Here is my E2 levels if that helps:
pre-stimm E2=9
stimm day 5= 155
stimm day 7=759
stimm day 9=1804
stimm day 10=2785
trigger day= 3288
E2 levels were very similar both cycles. 19 eggs retrieved first cycle (15 mature) 5 fertilized. second cycle 11 retrieved, 11 mature, 3 fertilized.
Haven't met with my RE yet regarding this cycle. Will let you know what he thinks and the second opinions say. I appreciate your input!!!

also FYI: my DH's sperm numbers are about 10-20 million/ml 10-30% motile and 1-5% morph. From what you say and what I have researched....we should be getting better fertilization rates even with his sperm issues. So it really makes sense that it is an egg maturity issue.

Synchonous follicular growth is a bit of a holy grail. However, down regulation of the pituitary with Lupron prio to stimulation can help. I imagine they did this in both cycles anyway. You stimulated for the appropriate length of time to achieve egg maturation and your E2 level was high, but appropriate for the number of follicles you developed. I would not say that you were over or under stimulated. The only other thing I could suggest is "coasting". Coasting means that you do not take any medication for the last 1-2 days of the stimulation. This allows your E2 to drop a bit, the follicles are given another couple of days to mature and coasting reduces your risk of hyperstimulation. They could begin coasting on day 8 or 9 of your stimulation. The poor fertilization still looks like an egg maturation issue to me. Have been diagnosed with PCOS? Eggs from PCOS patients do not fertilize well, even by ICSI. In PCOS patients there appears to be an inherent problem with the eggs.

I did take BCP 3 weeks, lupron 10units one week and then 5 units during follistim stimms for both cycles. I will mention coasting to my doctor and see what the second opinions say. I will let you know...I appreciate your help.
I have no symptoms of PCOS and have not been diagnosed with it. My hormone levels are normal, normal BMI, very regular menstrual cycles, etc.
DO you think I was on the appropriate stimm medication? What about the LH stimm meds? such as repronex with follistim? Wondering if that has an effect on egg maturity? Thanks again for your help..

hello-
I had one of my second opinion consults today. He seemed to think it could be an egg maturity issue as well. He said he would add in a little LH and that could make the difference. He recommended immune testing (antibodies, natural killer cells) which could effect egg quality, embryo quality and implantation. What do you think about LH? THis dr said with the long lupron the LH goes to zero...that is why he adds it in. I didn't get a chance to ask him about coasting, etc. This was just a free phone consult. I figure I can ask him if I decide to be a patient with him.
Would love to hear your thoughts about LH. Why do some clinics just use FSH only?

The consensus opinion is that LH is required when Lupron is used, so I agree with the second opinion. See how it goes with LH add back. You may not need coasting. Why do some clinics continue to use only FSH? Old habits die hard.

Thanks so much for your opinions/responses!! I meet with my RE next week. I am curious to see what he has to say.....