Male subfertility: diagnosis and management options

A diagnosis of infertility can be devastating for those trying to conceive. But fertility experts warn that all too often, a referral is made to an IVF clinic without first testing male subfertility, which could potentially lie at the heart of the problem.

“Many men will go to fertility units with their partners for IVF [in vitro fertilisation], but the man is never examined,” says Jonathan Ramsay, a consultant urologist, and specialist in male fertility treatment and surgery, based in London.

Men with fertility issues are often diagnosed very late, says Mr Tet Yap, a consultant specialising in urology and male fertility at the Lister Fertility Clinic, part of HCA Healthcare UK. And he explains that there’s a common belief that if the man does have an issue with his sperm, “as long as there’s some sperm you can do IVF”. “But actually what you’re missing is: why is there a problem with the sperm? You could be missing diagnosing a disease. And also that sperm could be ineffective,” he says.

Even if it is established that the man has subfertility issues, the severe impact this can have on both him and his partner is often not acknowledged, and support can be lacking.

“This is not just about bad luck or lifestyle – it’s a very serious diagnosis. There is a severe psychological aspect to this condition, which can have physical consequences, like depression and loss of sleep. And some men become suicidal,” says Mr Ramsay.

Male subfertility: on the increase

The need for vital support for male subfertility is all too common. The definition of infertility is based on the inability of a couple to achieve spontaneous pregnancy within a year of trying to conceive. An estimated 15% of couples may fall into this definition, and in about 50% of cases, male factor infertility is implicated. ¹

Recent research shows that there is a historical increase in male subfertility, with a year on year reduction in sperm parameters across men globally, which is likely to be linked to changing environmental and lifestyle conditions. ²

Male subfertility: causes and risks

There are “a multitude of factors that may be involved with male factor infertility”, says Ms Eleni Anastasiadis, a consultant urological surgeon and andrologist at Croydon University Hospital, and an honorary consultant at St George’s University Hospitals NHS Trust. She explains these include non-treatable conditions, such as a genetic or congenital disorder, undescended testicle(s), and previous treatments for cancer, such as chemotherapy.

Issues involved with male factor infertility also include treatable reversible conditions, such as hormone problems, infections, increased scrotal temperature, and varicoceles. Genetic factors include men diagnosed with Klinefelter Syndrome and cystic fibrosis (congenital bilateral absence of vas deferens).¹

Ms Anastasiadis says men at risk may include those with previously undescended testicle(s) at birth – whether it has been corrected or not – previous surgery to the testicle(s), previous cancer, and cancer treatments (including, but not limited men with previous testicular cancer), previous infections of the testicles (such as mumps), and high scrotal temperatures. Also at risk are men with varicoceles, sperm auto-antibodies, systemic diseases such as sarcoma, those with a previous vasectomy, or injury, and those who are taking medications for chronic conditions such as hypertension.

The increasing age of the man has emerged as a risk factor for male subfertility, says  Ms Anastasiadis.³ “This is an important consideration, as increasingly couples choose to delay childbearing for various reasons,” she says.

Another important area that many men might overlook is the impact of lifestyle factors on sperm quality, says Ms Anastasiadis. Oxidative stress is considered important to male infertility, which may lead to sperm DNA damage and poorer DNA integrity. This is often associated with poor lifestyle, for example smoking, diet, and environmental exposures, she says. ^1,4

Unfortunately, in about 30-40% of male infertility cases, no factors are found to explain the abnormal sperm parameters  – termed ‘idiopathic male infertility’, says Ms Anastasiadis.  And it may be that the female partner is also subfertile, resulting in a subfertile couple, she says.

In most cases there are no specific symptoms of male subfertility, says Mr Bassel Wattar, a consultant obstetrician and gynaecologist at Epsom and St Helier University Hospitals NHS Trust, and a sub-specialist in reproductive medicine and surgery. He says those with hormonal or genetic disorders may have a small volume of their testis or other abnormalities in the sperm transport system that could be detected with clinical examination.

An abnormal mass in the groin or the scrotum could also signal an abnormality in the male reproductive system such infection, varicocele – enlargement of the veins around the testis – or a tumour, he says.

Mr Wattar says a key test to assess the severity of the problem is to conduct a semen analysis, which would tell how well the male reproductive system is working. “Normal sperm production is a general sign of good health in men,” he says.

GPs should be “mindful of patients with a history of undescended testes, of testicular pain, of testicular abnormality, and also if the man has had surgery to his testicles or even a hernia operation, because surgery can cause fibrosis and inflammation and obstruction”, says Mr Ramsay.

Impact of male subfertility

The impact of these issues can be “massive for that individual man and the couple”, says Ms Anastasiadis. “Of course, the impact will largely depend on the severity of the male infertility and the underlying cause,” she says.

“In men with azoospermia (no sperm seen in ejaculate), the news of having no sperm can be devastating and may result in mental health issues and significant relationship difficulties. In addition, the diagnosis of an underlying genetic disorder might have equally complex and life changing impact,” she says.

The impact of infertility on the couple may also create a lot of anxiety and stress, and in some cases, men may have difficulties in achieving erections, says Ms Anastasiadis.

The man’s experience at a fertility unit may inadvertently “actually reinforce his unhappiness and misery”, says Mr Ramsay. For example, if a man has few sperm, the fertility clinic may say there is nothing that can be done. Then, when a cycle of IVF doesn’t work, the man is “absolutely convinced that it’s his fault”,  even though other, equally important reasons could be involved,  he says.

Mr Wattar says that  addition to the “significant impact” of the couple’s ability to start a family, male subfertility often has a negative impact on men’s self-esteem and mental health. Many men “struggle to open up and discuss their emotions when dealing with such problems, as they are often associated with significant stigma”, he says.

“Seeking help from a specialist – an andrologist or fertility specialist – is key to sign post the right avenues to access specialised help that could address the various impact of this condition on men’s general health and wellbeing,” he says.

Treatments for male subfertility

“People with fertility issues should be seen as a couple, “ says Mr Yap. “And the initial assessments should be for the couple, and not just a female or male assessment,” he says.

Performing a semen analysis is easy to arrange in the community, and would offer a rapid first test to check on male fertility, says Mr Wattar. “Often a repeat sample is needed in case any subtle abnormalities are noted, so there is no need to worry the patient if subtle abnormalities are detected after the first sample.” He says it’s important to offer support to help men deal with the implications of having semen abnormalities beyond just helping them to start a family, such as offering lifestyle advice, mental health support, and peer support in the community.

The main course of treatment for subfertility is to reverse any detected abnormality where possible, says Mr Wattar. For example, if reduced male hormone – testosterone – production is detected, it can be supplemented pharmacologically to restore normal sperm production. Also, if advanced varicocele are found, seeking embolization could help to restore normal semen, depending on their severity, he says.

He explains that in many cases, it is hard to restore normal sperm, and so advanced assisted conception technology is the main mode of treatment, especially in vitro fertilisation with the help of intra-cytoplasmic sperm injection (ICSI).

ICSI “helps to bypass most sperm weaknesses by selecting the best looking quality sperm under the microscope, and directly injecting it to the partner’s egg to achieve fertilisation”, says Mr Wattar. “This treatment is now a mainstream option to many couples seeking to start a family, and offers high success rate to bypass any sperm weakness,”  he says.

It is also important to be aware that causes of male subfertility can have a “long term health impact beyond just starting a family, and therefore, seeking a holistic and individualised treatment with a specialist is of key importance”, he says.

Offering advice and support

When offering advice and support, “the most important thing for the GPs and nurses is to appreciate how difficult the fertility journey might be for these couples”, says Ms Anastasiadis.

“Often there are long delays in diagnosis, and the NHS will not always be able to provide funding for assisted reproductive treatments. Couples are often left waiting many months and even years for diagnosis and treatment.”

She says that for this reason, “the best thing GPs can do is consider an early referral to a urologist and a fertility clinic, even if there is a ‘male factor’ or abnormal sperm, as often the female will need to be assessed, and the male factor is not always reversible necessitating treatment in a fertility centre”.

Practitioners call also offer health and lifestyle advice and support. Improving diet, and fertility multivitamins are often advocated as these factors may improve sperm quality, studies have found.⁴

Mr Yap advises avoiding hot baths and saunas, quitting smoking, and reducing alcohol and caffeine intake. And he recommends men regularly examine their testicles  in order to find any changes.

Practitioners can also signpost people to sources of advice and information about infertility, including charities and support groups.

While male subfertility is a common health problem, it is one that is very treatable, says Mr Wattar. But this condition “often comes with significant stigma”, so, “seeking early diagnosis and help is key to avoid any of its adverse consequences”, he says.

Ultimately, “ it is no longer right to treat male infertility as bad luck,” says Mr Ramsay. “You must treat it as you treat any other condition, and try to make a diagnosis, which will depend on taking a history, physical examination, and investigations.

“You treat male infertility like any other condition. You don’t treat it by putting the woman through a difficult treatment programme, and just ignore what could be the matter with the man – which is what happens.”

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Further information/signposting to support

Fertility Network UK provides free and impartial support, advice, information and understanding for anyone affected by fertility issues: https://fertilitynetworkuk.org/

HIM fertility: https://fertilitynetworkuk.org/himfertility/

British Fertility Society: https://www.britishfertilitysociety.org.uk/

The Urology Foundation: www.theurologyfoundation.org

The Fertility Foundation: a UK fertility charity which provides IVF Grants and support for anyone affected by infertility https://fertilityfoundation.org/

Human Fertilisation & Embryology Authority (HFEA): a source of information when seeking assisted conception treatments like IVF https://www.hfea.gov.uk/

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References

1. Sexual and Reproductive Health in EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6. Available at: https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/male-infertility.
2. Levine H et al. Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries. Human reproduction update. 2023 Mar 1;29(2):157-76.) Available at: https://www.ncbi.nlm.nih.gov/books/NBK562258/#:~:text=%5B2%5D%20Male%20infertility%20is%20defined,40%25%20of%20all%20infertility%20cases
3. Brandt JS et al. Advanced paternal age, infertility, and reproductive risks: A review of the literature. Prenatal Diagnosis. 2019 Jan;39(2):81-87. doi: 10.1002/pd.5402. Epub 2019 Jan 10. PMID: 30520056. Available at: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.5402
4. Bisht S et al. Oxidative stress and male infertility. Nature Reviews Urology. 2017 Aug;14(8):470-485. doi: 10.1038/nrurol.2017.69. Epub 2017 May 16. PMID: 28508879. Available at: https://www.nature.com/articles/nrurol.2017.69