NK Killer cells

Dear Lord Winston,

I’m writing to ask for your advice since I know you have spoken out about clinics failing to investigate the underlying causes of infertility before advising patients to embark on costly and emotionally gruelling cycles of IVF. Im a 40 year old fit and healthy woman and we have been trying to conceive for 5 years. My husband is 38, fit, healthy and has no fertility issues. We recently underwent our fourth round of IVF which sadly failed. We are being treated at an NHS clinic but are now self funded, having used up our one free NHS-funded cycle – the IVF postcode funding lottery is another gripe! Until earlier this year my infertility was unexplained. In March after an endometrial biopsy I was found to have a high level of uterine NK cells which responded well to steroid treatment. We have always produced good quality embryos – not in huge numbers – but they have never properly implanted. Needless to say the whole process has taken its toll – more emotionally than physically. I want to know whether you think it is worth us trying again or perhaps trying to move on and come to terms with the fact we may not be able to have children? My history is as follows: May 2009 – started trying to conceive Nov 2010 – mild endometriosis diagnosed and treated with laparoscopy Dec 2011- further surgery for mild endometriosis due to pain Jan 2012 – ectopic pregnancy following 6 months treatment with clomid (pregnant until discovery of condition at 8 weeks) left fallopian tube removed Nov 2012 first IVF (NHS funded) – chemical pregnancy March 2013 – frozen embryo transfer – negative Nov 2013 – second fresh IVF (privately funded) – negative March 2014 – diagnosis of high NK cells July 2014 – third fresh IVF (privately funded) with Prednisolone for high NK cells – negative. Ive had basic tests for implantation failure which have all come back as normal. I had a Hysteroscopy this year which was normal. I understand my FSH levels are good for my age. My consultant regularly reminds me that my age is probably the main factor preventing me from getting pregnant but I havent always been 40 and we are still producing good quality embryos, which makes it hard to give up. I feel angry and frustrated that we have undergone three cycles of IVF that were never going to work due to my NK cell diagnosis. I was only diagnosed with the condition after I researched it online and asked if I could be tested. We are considering another cycle at a private clinic as I believe these clinics are more likely to tailor treatment to the patients needs and offer new techniques such as intralipids etc. But I am wondering whether realistically I am too old now? Id be grateful for any advice. Kind regards. P

Dear P

I understand why you feel frustrated and upset, but I am not sure you should feel angry. I am very unimpressed that a high NK cell count is at all meaningful and most professional immunologists would agree with me. The people who push this ‘diagnosis’ and who offer treatment, including prednisolone, are using what is merely likely to be a piece of ‘magic’. I have scoured the research literature and I can find no good randomised controlled trials which clearly show that NK cells, elevated or not, treated or not, make any measurable difference to the real outcome in fertility treatment and IVF. In any case, if you really had an immune cause for your infertility, a viable ectopic seems an unlikely event.

I think you have a diagnosis as to what is causing your infertility, already. The fact is you have had an ectopic pregnancy and the research that Gloria Vasquez and I did nearly forty years ago shows quite unequivocally that ectopic pregnancy is nearly always caused by tubal damage. The damage is often at the microscopic level and we published extensive data showing that individual ciliated cells which waft the embryo down the tube are compromised. Moreover, this damage is nearly always bilateral – that is to say both fallopian tubes are nearly always affected. And it is very unlikely indeed you have two totally separate causes for your infertility.

So really, if you are not getting pregnant and the tubes are not affected by adhesions or blocked (in which case microsurgery offers some prospect of a natural pregnancy) IVF is a proper method of treatment. I think your consultant is right; as we age IVF becomes less successful. Bear in mind the average overall chance of pregnancy at any age with IVF is around 25%, so it is perfectly possible to go through more than four cycles without success – the record in my experience was a woman who finally had a successful pregnancy after fourteen cycles of fresh IVF (no freezing) in my clinic. A reliable colleague is Israel (where IVF is largely freely available under their healthcare system) tells me he had one successful birth after 16 cycles in an Arab woman of 43.

I note you have been told you have ‘good’ embryos. This is rubbish, of course. Embryologists really should refrain from saying this to patients. They mean well as they want to reassure you, but the appearance of an embryo down a microscope is a very imperfect and inaccurate way of assessing embryo quality, as I have stated on this website many times previously. The microscope we use in an in vitro fertilisation clinic is nowhere nearly powerful enough to see the detailed structure of an embryo, and certainly cannot identify genetic changes that may occur as we age.

So I realise I haven’t come up with an easy answer and only you and your husband can decide how much anxiety and hurt you can manage with endless treatments. But I must say that to fail four cycles is well within the statistical limits of probability. Clearly as you continue, if you do, the chance of success gradually diminishes but I think it would be wrong to blame your doctors who seem to me to be quite rational in the way they are trying to support and help you.

My best wishes
Robert Winston