Dear Professor Winston,

I am currently 39 years old. We have been trying to conceive our second child for over 3 years. Our first child was conceived naturally in 2008 without any medication/support after 14 months of trying. We had some initial hormonal blood tests, sperm count and I had a HyCosy but no issues were found. We started to try for our second child in 2011 but after no success in 12 months we went to a private IVF Clinic. As we had only been trying a relatively short amount of time they suggested 3 attempts of IUI before they would consider IVF. We had 2 natural cycles and 1 medicated but all were unsuccesful. We had our first IVF cycle in October 2012. 11 eggs were retrieved, 4 fertilised and 2 were transferred. I suffered mild/moderate OHSS. The cycle was unsuccesful. We tried again in July 2013. 11 eggs were retrieved again. This time we achieved 7 blastocyst emrbyos. 1 was transferred which resulted in a biochemical pregnancy ending at about 5/6weeks. We conceived naturally the next month but again this resulted in an early miscarriage at about 7 weeks, although I had not known I was pregnant as I had bled inbetween. We tried a FET of 2 blastocysts in Jan 2014 but this was negative. As a result of the 2 biochemical pregnancies and repeated failures to inplant we had further tests which revealed slightly elevated natural killer cell activity and borderline high cytokines and no leukocyte antibody. Up to this point our infertility was unexplained. We had another FET, 2 blastocysts, in July 2014 with added steroids, Clexane and intralipid infusion. Again this was negative. We have 2 blastocyst embryos left and wondered if you have any advise as my partner and I have agreed this is our last attempt. We would dearly like a sibling for our son but have little hope left. We appreciate your time and any help you could offer us. Yours sincerely J


Dear J,

I have no idea what the underlying problem can be, because of course, we haven’t met and I haven’t examined you. But as I have repeatedly asserted on this website, I am very unconvinced by stories of marginal killer cell activity, questionable cytokine measurements and so on. Nor have I seen, after fairly extensive review of the serious scientific literature, good evidence that the treatments which are sometimes given for these ‘conditions’ are either needed or really effective. So I seriously question therapy with steroids, clexane, intralipid and so on.

So I find myself asking whether your whole management has been a bit too narrowly focused. There is an adage in medicine which is worth remembering: “Common things occur commonly”. Now even if immune disorders are a reality or not, there is very little evidence they are common. And against the idea of your having an immune problem is the fact that you have been successfully pregnant. So I am thinking of what is the commonest cause of secondary infertility – that is, infertility after a pregnancy. Experience shows that mild subacute infection or inflammation after pregnancy is particularly common, especially if the pregnancy or delivery has been complicated in any way. Such inflammation can compromise the interior of the uterus occasionally, and much more commonly the anatomical relationship between the fallopian tubes and ovaries. Adhesions are common; totally blocked tubes much less so but probably still more common than immune disorders.

The next issue is your age. You are 39 and at that age, Wallace and Kelsey in Edinburgh in an excellent paper have calculated that the average woman only has about 10% of the original complement of eggs left in the ovaries. And we know from various other studies that a number of these eggs that are remaining are more likely to have defects which may prevent fertilisation, or allow it without further embryonic development or possibly proper implantation. Moreover, it is my belief that as women get older the drugs we give to encourage superovulation during IVF are more likely to produce eggs with defects. For example, various laboratories around the world including my own have shown that these drugs certainly seem to increase chromosomal abnormalities – so called aneuploidy. The other issue with age is the integrity of the uterus as women get older. As many as 25% of women by the age of 40 have fibroids and these perfectly benign tumours, too, can sometimes interfere with fertility.

So it follows that I wonder whether the basis for your infertility has been adequately investigated. My first comment is that HyCoSy, even in experienced hands with the best ultrasound, is greatly inferior to an old-fashioned, carefully done hysterosalpingogram (HSG). This is because X-rays, due to their wavelength and physical properties, give much higher resolution, than does ultrasound (the basis for HyCoSy). So they are more likely to reveal subtle changes in the tubes, defects in the uterus, such as scars or adhesions and fibroids – as well as other pathology. Secondly, as I repeatedly assert, laparoscopy is the gold standard in infertility investigation, especially secondary infertility. This is because it allows direct visual inspection of the whole of the pelvic organs and their surface in great detail. And the surface, properly studied, can reveal underlying damage.

Please don’t stop reading at this point. Because, of course, your immediate reaction will be “but my embryos are not implanting properly”. My contention is that this may be simply a general factor of your age and the fact that IVF is not, as I have explained, a very efficient treatment for women in their late thirties or early forties. So it makes a great deal of sense to fully understand what chances you have for spontaneous conception, which may be greatly improved if you have an underlying condition – adhesions around the tubes or a fibroid in the uterus for example – which might be very easily treated and at less cost. We have got so hooked onto IVF these days, that we forget that the value of serious attempts at making a diagnosis are really important. Once you start IVF, you are inevitably sucked into more and more high technology treatment of this kind which does not necessarily deal with the underlying problem you face.

I have gone on at too great a length. Of course, get the remaining blastocysts transferred if you feel robust – and it really sounds as if you do. And of course, it would be wonderful for your son to have a sibling. I’ve just spent a weekend with three of my grandchildren and it is wonderful to see the six-year-old boy taking such such care of his baby sister of 15 months. But don’t be persuaded that an only child is in some way disadvantaged – the love and care you give to any child is the really important issue.

As I say, I have no idea what the underlying problem is but I hope this over-long answer may help. I do wish you well in whatever decision you come to.

My warm wishes

Robert Winston

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