Fertility testing: the forgotten man

A heterosexual relationship is generally comprised of equally contributing male and female partners. So why when a heterosexual couple present with infertility, is the focus mainly on the female with the male largely ignored and cast aside, particularly when having treatment via the NHS where options for male fertility testing are limited.

Placing more attention on the male contribution to infertility could reduce costs to the NHS, both by potentially discovering a treatable reason for male infertility that avoids the need for IVF and reducing the time to conception meaning less risk of any potential decline in female fertility. The more severe impact of treatment failures on a patient's mental health could also be avoided in some cases. Access to IVF treatment on the NHS is further complicated by the existence of the 'postcode lottery', where in England Clinical Commissioning Group (CCGs) decide which fertility investigations and treatments are offered to constituents in their area. When having fertility treatment via the NHS, one of the few funded investigations available to the male, is a standard semen analysis. This test provides a quantitative analysis of the sperm, assessing the concentration, motility and morphology of sperm against World Health Organisation (WHO) reference values for 'normal' samples, but fails to take into account possibly even more relevant qualitative factors, such as sperm DNA integrity.

Conventional semen analysis does provide some useful information and can be used to diagnose male factor infertility in cases of no sperm (azoospermia), low sperm count (oligozoospermia) or reduced motility (asthenozoospermia). This may reveal the need for the use of intracytoplasmic sperm injection as part of an IVF cycle, where a single sperm is selected and injected into the egg, or surgical retrieval of sperm from the testes in cases where no sperm is observed in the ejaculate.

Interestingly, surgical sperm retrieval (SSR) is commissioned by NHS England, although the patient must have funding in place for cryopreservation of any viable sperm retrieved, or IVF treatment, in order to access SSR via the NHS. However as both cryopreservation and IVF funding availability is determined at a local levels by CCGs access to this will vary according to the location of the patient. It is unclear from policy wording whether a patient can chose to self-fund cryopreservation or IVF, or if they must secure NHS funding. The clinical importance of sperm morphology assessment as part of a conventional semen analysis remains controversial and is prone to operator subjectivity (see BioNews 1109).

Evidence published in the journal Human Reproduction suggests sperm counts (particularly in Western countries) have been in decline over the past 40 years and as such, the focus on male fertility has become more prevalent. Approximately 40 percent of all infertility cases are attributable to a male factor issue. It is also known, that although the male may present with an apparently 'normal' result from a conventional semen analysis, their fertility may still be impaired due to sperm DNA damage. Despite an increasing body of evidence suggesting that sperm DNA damage can result in recurrent implantation failure and miscarriage, this test is still not routinely offered through the NHS as part of a male fertility assessment due to a perceived lack of robust studies (randomised controlled trials) proving its usefulness.

There is no national policy or guidance on the use of sperm DNA fragmentation testing and it is not referred to in National Institute for Health and Care Excellence (NICE) guidelines. This can mean that heterosexual couples where all conventional tests return as 'normal' may incorrectly be diagnosed with unexplained infertility. Paternal age has also been shown to correlate with higher levels of sperm DNA damage and so older males may be at particular risk of subfertility due to damaged sperm.

Sperm DNA fragmentation testing does not have a 'traffic light' classification assigned by the Human Fertilisation and Embryology Authority (HFEA), given it is a non-invasive, diagnostic procedure. They state on their website that the results of a sperm DNA damage test are unlikely to influence the management of fertility treatment, though it could be argued that in cases where results do affect treatment pathways, there is a significant benefit. The subject has not been discussed by the HFEA since 2018, though in the most recent edition of the WHO laboratory manual for the examination and processing of human semen (released in 2021), sperm DNA fragmentation testing is listed as an extended test.

A recent article in the Sun highlighted the story of Toby Trice and Katie Housley, who underwent two unsuccessful rounds of NHS funded IVF treatment. Further investigations revealed Trice had a varicocele (enlarged veins in the scrotum), which can lead to elevated levels of sperm DNA fragmentation, a paper in Fertility and Sterility described. Trice was able to have the varicocele repaired, after which the couple were able to conceive naturally.

As well as the emotional trauma of two failed treatment cycles, Housley commented that 'We could have saved the NHS a lot of money spent on IVF if more focus had been put on Toby, and he could have had this simple procedure much earlier.' So although offering further male testing including sperm DNA fragmentation analysis and physical or ultrasonographic examination of the testes on the NHS in the short term may cost the taxpayer, ensuring publicly funded IVF cycles are not 'wasted' by failing to diagnose a potential cause of infertility would make fiscal sense in the long term.

In 2019, Dr Sarah Martin Da Silva was named one of the BBC's most inspiring and influential women of the year for her work on sperm function. The ultimate goal of her research is to develop medications for male infertility, potentially removing the need for the female to undergo invasive treatment in some cases.

The patient pathway for assessment of male fertility should involve a routine semen analysis, sperm DNA fragmentation analysis as well as ultrasonography and physical examination of the testes, to ensure that abnormalities such as varicoceles are not potentially contributing to male factor infertility.