The new NICE guidelines, varicocele and DNA fragmentation; two steps forward and one step backward
This blog draws on four sources: first, the new NICE guidelines on male fertility (guideline 257, just published two months ago); second, the newspaper article, a journalistic response to these guidelines, with comments from my friend Professor Suks Minhas and from me; thirdly, a recent publication, a meta-analysis about the measurable effects of treating varicoceles; and fourthly, the correlation between DNA fragmentation and the treatment of varicoceles, also an extensive meta-analysis.
First, let us look at the NICE guidelines. There are three very relevant new statements:
‘First, offer an examination of the scrotum and the testes.’
‘Second, consider radiological or surgical treatment for varicocele.’
‘Third, do not carry out testing of sperm DNA integrity (sperm DNA fragmentation).’
So first of all, whatever is ‘NICE’ and does it matter?
NICE means the ‘National Institute for Clinical Excellence’ and, like many initiatives of Tony Blair’s government, the use of the word ‘excellence’ is both typical and optimistic.
But if we are dealing with the National Health Service, with all the correct and laudable motives of socialised medicine, then the Institute must consider both ‘clinical effectiveness’ and ‘cost-effectiveness’. Once we are in the realms of cost-effectiveness, we have moved from innovation and aspiration to ‘measurement of what has gone before’. Inevitably, progress is slow and those who question the status quo risk being branded as charlatans or mavericks or – worse – only being interested in private practice.
Of course, to prove anything in fertility treatment is exceedingly difficult, as these two papers, or meta-analyses, very clearly identify. Let us look at the first paper, about the impact of varicocele treatment on pregnancy and live birth outcomes. The most extraordinary observation is that there have been more than 3500 research groups looking at this seemingly straightforward question, and when all of their publications were reviewed (to construct a meta-analysis), only two of those publications were of sufficient quality (yes, only two of 3500) to scrutinise more closely. The conclusion was that the treatment of varicocele did improve live birth rate, particularly by natural conception… Phew, at last I think we can agree. As NICE recommends this year, we indeed should be considering and treating varicoceles.
But here is the more important question. Why should we be treating varicoceles and when should we be treating them?
So let us look at the second publication, ‘Sperm DNA Fragmentation in Men with Varicocele; a systematic review and meta-analysis’.
Well, this paper does give some clarity. It tells us that treating varicoceles does improve the parameters of ordinary semen analyses, and that treatment also improves general measures of DNA fragmentation (total SDF). The powerful implication of these measured statements is that abnormal total SDF should be an indication for the need of varicocele treatment (somewhat at variance with one of the three new NICE statements).
But here is the new thing. Sperm DNA fragmentation is a broad concept which needs further definition. All the routinely available SDF tests measure one broad type of sperm DNA damage common in men with varicocele, but these tests do not measure a more important form of DNA damage – double-strand DNA fragmentation (DSDF). I suspect that this DSDF happens independently of varicocele and other lifestyle factors and represents a separate (although maybe parallel) cause of male infertility.
So what is the message beyond NICE 2026, and probably beyond the best current published research?
First, varicoceles do reduce male fertility and certainly should be considered for treatment.
Second, varicoceles are a cause of sperm DNA fragmentation but, and here is the even newer bit, we should measure the subset of DNA fragmentation, the double-strand breakage, to be sure that the infertility does not have a different intrinsic cause which treatment of varicocele alone will probably not fix.
I suspect that much of the apparent confusion and debate about both varicocele and DNA fragmentation measurements (exemplified by the inconsistency of two of the current NHS statements) is in fact explained by the small group of men who have a separate cause of subfertility – double-strand breakage.
Watch this space, because there will be, I think, much more interest in this subset of men with double-strand DNA breakage in their sperm.
Finally, if you compare the NICE guidelines with these two most recent and thorough publications, and then look at the journalist’s interpretation of the status quo, although I hesitate to say it, I think the journalist has done the most straightforward and comprehensive job!
So I wish you all well, especially those who are having their varicoceles treated, probably by embolisation, and I hope that in your particular case sperm quality will improve and your ambitions to start a family may be more easily realised.
