Dear Professor Winston,
Thank you for this chance to contact you, We have recently had 2 failed cycles of IVF(ICSI) The first round pretty much went to plan, though I did stimulate for a longer period of time. I produced 16 eggs of which 10 fertilised with ICSI. We had 2 eggs replaced on day 3 but apparently the egg quality was quite low. This resulted in a negative result. In order to move forward our clinic recommended an increase in meds (150 was increased to 187.5) I also had an endo scratch and IMSI was preformed on my husband’s sperm. This cycle was more successful in that I produced 19 eggs, 11 fertilised and of those we were able to have 2 day 5 embryos replaced and 1 was able to be frozen. This also resulted in a failed cycle. According to our clinic this was a text book cycle with everything going exactly how they would hope and expect. Also this time quality was excellent. Just no implantation again. We were told it is just simply bad luck and to just try again. Surely though there is something else to do or tests to be done? I would like to have a natural frozen cycle next with our one embryo but can’t help but think why would this one implant if 4 others have not. I have no known issues. I’m 30 yet have never fallen pregnant. My husband has a very low sperm count >1 mill. Could you offer any advice or direction, do we have any hope with a frozen cycle? Thank you so much for you time Professor, M.
Dear M,
Thank you for your email – but I do wish people would not use rather obscure acronyms! I take it that by ‘IMSI’ you mean ‘Intracytoplasmic morphologically selected sperm injection’? If so, for the benefit of those who read this website, this is a technology where ICSI is done as normal but a specially equipped high-power microscope is used which can give an individual view of each sperm up to around 1500x magnification. This enables the embryologist to select sperm with a seemingly normal looking nucleus. In the past various papers have suggested that by selecting the ‘best’ sperm in this way, pregnancy rates might be better. However no serious randomised trials (as far as I am aware) have been done. However, recently, in a paper published last year, Dr de Vos from Brussels and his colleagues in Belgium have undertaken a very clear study, the largest I think which has been published, where there was also a degree of randomisation. In many of the cases they studied, the sperm counts were possibly not as poor as in your husband’s case. I trust Dr de Vos because he is an acknowledged expert from an excellent Belgian unit.
Theirs was a detailed study as they examined 200 sperm under the microscope in each case, before undertaking injection. In a few patients, 20 in all they examined fewer than 200 sperm because the semen quality was so poor – consequently a choice was made from a minimum of 50 sperm. After choosing the sperm, ICSI was done on at least two eggs or more and they recorded fertilisation rates, embryonic development and pregnancy rates. Some of the patients (29 out of a total of 340) had previously had some kind of pregnancy so this is why I say presumably some of the sperm samples may have been of better quality than those of your husband. In all they undertook 350 cycles in the 340 patients they treated. The patients were selected i.e. the women were rather younger than average (none older than 37).
In each case, half of a patient’s eggs were chosen after examination by IMSI. In each case the best embryos were chosen for transfer either on day three or later as blastocysts. The overall pregnancy rate in the IMSI group was 34% and in the straight ICSI group 37%. Implantation rate after IMSI was 30% and after ICSI 32%. Live birth rate was 29.6% after IMSI and 30.2% after ICSI. They therefore concluded that their study did not show that IMSI was more effective than ICSI alone.
In your case, I would be a bit concerned about the number of eggs you have produced. You say that you got 16 in the first cycle and 19 in the second cycle and suggest therefore that the second cycle was better. I am not at all sure that this is ‘textbook’ as you suggest, in spite of what you have been told. This is a very large number of eggs for even a relatively young woman and it could be that this degree of stimulation may have produced eggs which were not matured precisely. For example, in experiments we did many years ago, when large numbers of eggs were produced there was a higher percentage that were chromosomally abnormal even though they fertilised and grew normally. I agree that your one remaining frozen embryo may also be somewhat ‘suspect’ but it would be difficult to conclude that it should not be transferred. Even if your eggs were chromosomally not ideal this would not increase your risk of an abnormal baby. With regard to the endometrial scratch – as I have said elsewhere on this website, the jury is still out on this issue.
In general, then, I would have thought that ICSI was indicated but perhaps with more gentle stimulation. IMSI is labour intensive and, I think, still experimental and I do not think it really can be shown to improve the results. I take it the clinic did not charge you for an experimental technique?
Warmest wishes
Robert Winston