After 3 failed ICSI cycles, should we continue?

Dear Professor Winston,
Thank you so much for your wonderful book, The Essential Fertility Guide. It was the first fertility book I’d read that really gave a sense of empathy with our situation, and inspired me to seek more clarification for our own fertility treatment.
I don’t want to sound greedy, but in addition to the invaluable information from your book, I was wondering if you may have any further advice that I can try, as we are eager to explore every chance (as I’m sure are many others).
Our background at present is of 3 failed ICSI cycles (1 x NHS, 2 x privately funded, all at the same clinic), none of which produced any additional embryo’s suitable for freezing. Apologies for the lengthy email, but I’m hoping to supply you with as much information as possible.
We had our first ICSI cycle in Feb 2014. Initial tests highlighted severe oligospermia with my husband, with levels of <1% normal morphology, 0% motility & less than ten single sperm. He has a previous history of an undescended testicle, to which he had surgery at approximately age 4. Our blood tests showed that my AMH & FSH were “a little low” for my age, but otherwise normal. Although, now having the wisdom from your book, I now notice that I never had a HSG test. Our first cycle used the long protocol, used Buserelin for down reg, & Gonal F 300 iu (reduced later to 225 iu due to me over-responding). I produced 10 eggs, of which 3 fertilised, and we had one embryo replaced.
The second cycle was in July 2014. Same long protocol, but with the “endo scratch” treatment added. Same Buserelin, but this time with Menopur 300 iu instead of the Gonal F. I produced 5 mature eggs, and again 3 fertilised. This time we had 2x embryo’s put back. This cycle did produce a positive pregnancy, but devastatingly it was ectopic when we had a 6 week scan. I then had a laproscopy & salpingectomy on the right side.
The final cycle was March 2015, with the same long protocol, the “endoscratch” procedure, & the same Buserelin. My husband’s sperm had improved to approximately 2 million. This time our consultant advised a combination of stimulants (6 days of Gonal F 375 iu, followed by 6 days of Menopur 375 iu) as it was hoped that this would optimise the quality & quantity of my eggs. During this cycle my husband had a UTI (with blood in the semen & low semen volume) just prior to the egg collection/sperm sample. We sought advice from our consultant who advised a six week course of antibiotics (Suprafloxin), and referred us to a urologist as they suspected prostatitis. I again produced 5 mature eggs, and 3 fertilised. We again had 2x embryo’s replaced. The urologist completed an ultrasound flow rate scan, prostate exam, and additional blood tests which all came back normal. An MRI was completed which suggested a congenital abnormality with the seminal vesicles, but no further treatment was indicated.
After each cycle we have met with our consultant who has (in fairness) been very compassionate throughout and has discussed with us their reasoning behind the cycles so far. We are pleased to note that my husband’s sperm does seem to have improved over the last 12 months, but we’re not sure if this will continue to improve. At our last clinic review, our consultant suggested to repeating my FSH & AMH levels, and repeating a sperm sample before we make any further decisions.
I am very keen to hear your thoughts on if there is anything else at all that we can try to help to improve our chances, and if you feel there is any merit in us continuing to try with ICSI. We are both aged 33, don’t smoke, rarely drink, exercise well, and are not overweight. For supplements, we take Pregnacare conception (his & hers), and I also take DHEA. My husband also takes omega 3 supplements. I am a little sceptical of these supplements, but I guess they can’t hurt and it gives us a tiny sense of being able to contribute to our treatment (although I’d be interested to hear your thoughts if these are evidence based or not).
We are quite realistic, and feel as though there is not much hope to continue with the ICSI as we have a few issues from both our sides. I am also concerned with the risk of further ectopics and wondered if you feel that a HSG would still be useful at this stage?
We are desperate for a child of our own, and I feel that the ICSI dangles a carrot of hope, but I admit that I am finding it more difficult to cope with the grief that each cycle so far has brought us. I think the decision of when to cease treatment is very difficult, and any impartial advice that you can offer would greatly help with our decision. We are keen to try anything that may improve our chances.
I’m sure you get many letters like this, and I can’t express how grateful we are for your time and expertise.
Many heartfelt thanks.
N & S

Dear N & S,

It sounds to me as if you have been properly treated. Sadly, I think that with the sperm evaluation you describe a spontaneous natural pregnancy is always unlikely, and this view is increased by the fact that you had the ecotopic pregnancy – an event which I am sure was devastating. Unfortunately, the work I did with Gloria Vasquez and others in the 1970s clearly showed that nearly all ectopics are associated with pathological changes in the fallopian tube. Moreover our further research strongly suggested that this kind of damage was nearly always bilateral – i.e. affecting both tubes. So even if your remaining tube looked normal at laparoscopy it is highly probably that the cells in the lining of the tube are not functioning normal, making another pregnancy less likely and the chance of an ectopic pregnancy higher. Now I know it seems odd that using IVF, the embryo is put into the uterus, thus bypassing the tube, so how is it that you then end up with implantation in the tube. The evidence is now fairly clear that embryos placed in the uterus in the early stage of development are shunted into one or other tube (possibly by muscular contractions). It seems that the whole of the genital tract is programmed. It turns out that there’s solid evidence that in normal conditions after natural fertilisation, the fertilised egg spends about 116 hours in one or other tube, slowly making its way into the uterus, arriving there at around five days after conception. Various experiments in animals have shown that if you physically remove an embryo from where it is travelling in one part of the tube and place it in another area, that embryo immediately returns to where it was sited at the time of its removal. It then proceeds in the normal way, with normal timing into the uterus. And if you are unlucky to have damage to the inside of the tube, that is often where the embryo may stick before it arrives in the womb if it doesn’t successfully complete this journey.

Consequently, if you have a fertilised egg placed in the uterus two or three days after IVF it is likely that it does not generally stay there – one of the reasons why I believe the use of EmbryoGlue is pointless. I know that this glue is used widely but there really is very little evidence that it improves pregnancy rates. Incidentally, just another example of how the market has managed to effect evidence-based medical management in IVF. Which rather brings me to your other question: You say you take supplements, Pregnacare (his & hers), and also DHEA whilst your husband also takes omega 3. I am sorry to say that none of these medications have stood up to good randomised controlled trials and their use is dubious. I don’t think they do the slightest harm, but that is arguably a poor reason for using them. With regard to DHEA, there really is very little evidence, if any, that it genuinely makes a difference for example.

The interesting issue is the ‘scratch’ – I have written on this website before about it and there are conflicting bits of information. I suspect that the inflammatory response it sets up may aid embryo implantation, but this is not totally certain. The Israel medical scientist, Nava Dekel, feels that it really does help and she has looked at the scientific background of its effect. So in summary, that probably may be an advantage – how the scratch might affect the transport of the embryo in the genital tract, I really don’t know. I don’t think there is any evidence that it increases or decreases the risk of an ectopic pregnancy.

So there you have it. Not very helpful I am afraid. My feeling is that it is worth persisting with ICSI but only you and your husband can weigh up what that means to you emotionally. It is true that the chances are significantly higher in people who have conceived, even with an ectopic, than those that haven’t – small comfort I know.

My warmest wishes to you,
Robert Winston