Hi Sorry to trouble you again Dr Smith, but wondered what you make of this... Last Friday, I spoke to our embryologist about another SA to see if we were eligible for IUI with my husbands sperm. Anyway, I got talking to her about our recent failed cycle and our embryo's. On embryo transfer day, she very clearly told us that our remaining three embryo's had one pro-nucleated cell and couldn't be used fresh or frozen. (You explained to me what this meant.). On Friday however, with our notes in front of her, she told me that 2 out of the 3 remaining embryo's were multi-nucleated, which she said was caused by the egg thinking it's been fertilized when it hasn't. She pointed out also that this is quite common, especially when ladies are on the higher doses of stims, like I was. She said our other "left over" embryo was simply a grade 3 and therefore wasn't a good enough quality to freeze. I'm confused now, because this is a really different story to what she told us on transfer day When I questioned the change of story, she brushed over it, making out she never said 1 pro-nucleated cell at all What makes it even stranger is when we had our follow up appointment, re: failure, our consultant, who had our notes in front of him, said we had 3 grade 2's and 2 grade 3's, and that the reference to pro-nucleated, just meant that they had fertilized normally
A similar thing happened after our first IVF cycle. On e/t day we were told that out of 5 eggs injected, 4 fertilized, but the two "left over" ones were too fragmented to freeze. On our notes, which our IVF nurse showed, us, it said 1 grade 1, 2 grade 2's, and 1 grade 3. Yet when I spoke to the embryologist about this cycle, she said we only had 3 fertilized, and the other one died, shortly after. Which completly contradicts the notes that we saw
I'm just wondering if they're muddling us up with other patients, or if there's something fishy going on, and wondered what you make of it? Also if we are getting multi-nucleated embryo's, doe this mean there's a problem with some of my eggs? Many Thanks Dr Smith Nat
You are getting conflicting information which is just as confusing to me as it is to you. There is no easy way to reconcile the conflicting information. It sounds like two different cycles/patients to me (?). I think its time for a second opinion. Ask for a copy of all of your records and have another RE and embryologist from different practice evaluate them for you. Perhaps they will be able to reconcile the differences. I'm afraid I can't.
Embryos exhibiting multinucleation in one or more cells are genetically abnormal. This is usually traced back to "egg quality" issues (e.g. age). The embryologist made it sound like high doses of gonadotropins cause multinucleation. This is not true. However, women who require high doses of gonadotropins to stimulate follicular growth often have "egg problems" as well. So, the two issues are related, but it is not a cause and effect.
Thanks for that Dr Smith, I really appreciate your thoughts on the matter. We have already decided that we will go to another clinic for a third cycle, but if we are eligible for IUI we were going to use the same clinic, simply because it's nearer. Trouble is I have no faith in them at all
In your experience is getting some multinucleated embryo's in a cycle common? I'm only 32, have had an FSH range from 6.3-9.4, but I do wonder if the reason I have only an average number of eggs is because the down regulation regime I was on was far too long, at around 8wks. A lot of ladies I talk to online are only d/r for between 2 and 3 weeks on suprefact. Do you think it is possible I would respond better on such a regime? I'm worried now about the quality of my eggs, and wonder if ART will ever work for us Many thanks, Nat
Multinucleation of eggs or embryonic cells is fairly common. At 32, roughly half of your eggs are genetically abnormal. Sometimes the genetic abnormality shows up as multinucleation, sometimes as arrested development.
Prolonged down regulation (e.g. 8 weeks) can blunt the ovarian response to the stimulation medications. It is possible that you may do better with a shorter down regulation period (e.g. 2 weeks).
The IUI issue is a bit tricky. Has your husband been evaluated for antisperm antibodies (ASA)? ASA usually develop following a vasectomy and become problematic following a vasectomy reversal. The ASA cause the sperm to agglutinate and there are not enough indivdually swimming sperm left over to fertilize an egg. It is possible to process the semen very rapidly (e.g. your husband would ejaculate into a cup containing a specially prepared culture medium and the sperm would be immediately process by density gradient centrifugation), thereby minimizing their exposure to the ASA in the seminal fluid. This is an old (pre-ICSI) sperm processing technique, but it worked pretty well.
Thank you so much for that I feel much better knowing that it's normal at my age to have abnormal eggs and embryo's. I think though, like you pointed out to me before, that it's important for us to take our embryo's beyond 2 days, to see if they continue to develop in the lab.
When I spoke to the embryologist, she said IUI with my husbands sperm was "questionable" due to the aggultination of sperm, caused by the ASA's. (Everything else is not too bad, though not ideal, esp the morphology) count 40 mil per mil, motilty around 40% and morphology 11.9%) We don't know the percentage of ASA's because he hasn't had this test and our clinic don't do it, although the embryologist did say she could refer us. On Thursday, he's going to have another SA done, and they said they will leave the sample over night to assess the damage caused by the ASA's over time. Thankyou so much for telling me about the pre ICSI technique, I've not heard of this before, as this has never been mentioned by the clinic, but I will be asking now!
In th event of IUI not being possible, do you think it is possible for us do standard IVF rather than ICSI with the density gradient centrifugation technique? It's just that I can't help but wonder if better sperm will fertilize the eggs with standard IVF than with ICSI.
Many, many thanks for all your helpful advice It's really helped us to decide, how we are going about our next treatment cycle. We will definitely not be going back to our current clinic for IVF. I just don't have alot of faith or trust in them, and I think that is so important when going through the rollercoaster of IF. My husband said to me, that a lot of the stress of treatment has been caused by the clinic themselves, and when you add the failures into the mix, it's made for a very stressful time for us. I have found a clinic which comes highly recommended by a friend who has been to my current clinic and moved there. They do AH and blast and their success rates are around 15% higher than our current clinic. Wish we could go to your clinic though I'd feel as if I was in better hands having treatment in the US, but as my husband says, never say never! With Warmest regards, Nat
Depending on the severity of the ASA problem, it may be possible to perform a conventional IVF insemination. However, to avoid taking chance of failed fertilization, insemination by ICSI has become the standard of care for ASA patients. You are probably better off with ICSI.
I'm glad you found a better clinic. Sounds like you're on the right track. Have your records evaluated at the new clinic and see what they recommend. Good luck.
Thankyou! We're currently waiting on the results of my husband's latest SA, to see if IUI is possible or if it's going to have to be a third round of ICSI. I'm still waiting for my AF to start (been 6 wks now and still no sign) before we make an appointment with the new clinic, but we will be making sure they have a good look over our records when we have our initital consultation. Many thanks for all your helpful advice, I really appreciate it Nat
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Sorry to trouble you again Dr Smith, but wondered what you make of this...
When I questioned the change of story, she brushed over it, making out she never said 1 pro-nucleated cell at all 
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