The case for male infertility - Prof Sheryl Homa

Response to Wes Streeting’s announced plans to launch a men’s health strategy

The Case for Male Infertility

Professor Sheryl Homa – July 2025

 

Background

Infertility affects approximately 2.5 to 12% men1,with approximately one in six couples experiencing infertility worldwide 2.For many couples, the inability to have a child is devastating, and indeed can be life changing. While women are routinely investigated for infertility, the men are marginalised with relatively few specialists in the field able to investigate and treat them appropriately3, even though a male factor is the underlying cause in up to 50% of couple infertility4. Importantly, there is considerable evidence that male infertility may also be an early marker of the overall status of a man’s health. In an extraordinary study that was published this year of 78,284 Danish men followed for up to 50years, there was a clear association between reduced semen parameters and an increase in all-causemortality5. In another study carried out in the USA of 134,796 infertile men and 242,282 controls who were followed for a mean of 3.6 and 3.1years respectively, infertile men had a higher risk of death, but the risk was higher for men with low sperm counts and particularly for those with no sperm in the ejaculate (azoospermia)6. It has been known for some time that poor semen quality is associated with co-morbidities, including cardiovascular disease, hypertension, hyperlipidaemia and diabetes, as well as more commonly known associations with prostate and testicular cancer7-9.

The importance of diagnosing and treating male infertility is therefore paramount, not only to improve fertility but also to identify underlying systemic illness. There is a disproportionate incidence of cardiovascular disease, hypertension and diabetes in men compared to women10 and of course there are certain illnesses that only affect men, such as testicular and prostate cancer. A diagnosis of male infertility may help identify these underlying conditions enabling men to be referred as soon as possible for treatment.

Investigation and diagnosis

General investigation

Diagnostic testing and treatment for male infertility is disproportionate compared to that for women. According to guidelines published by the European Association of Urology (EAU), the American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) investigation of male infertility requires taking a full medical, reproductive and family history, assessment of lifestyle and behaviour risk factors, a physical examination and a semen analysis11,12. A male reproductive hormone profile and genetic screening must be performed incases of low sperm count. A genitourinary tract infection screen can identify factors that can impact fertility, and a testicular ultrasound scan can confirm abnormalities in the testes such as varicocele. Similar tests are routinely offered for infertile women on the NHS, yet the only routine test offered to their male partners is a semen analysis. To make matters worse, semen analysis is not carried out according to best practice guidelines in many laboratories across the UK, and most do not have UKAS accreditation13. This may lead to inaccurate results with an inappropriate diagnosis and management for the patient.  

Oxidative stress

It is also essential to consider the 30% of cases of unexplained infertility, where there is no known cause for the problem. There is considerable evidence that oxidative stress (an imbalance in the proportion of oxidants to antioxidants in the male reproductive tract) is a leading cause of male infertility14. Indeed, men with infertility, and particularly those with unexplained infertility, have high levels of oxidative stress. While there is an entire industry selling male fertility supplements to counteract this, the evidence to support the benefits of these supplements is weak, mainly because they will only be beneficial if the patient has oxidative stress15. On the other hand, there is a simple cost-effective test that could be offered to mento detect oxidative stress that would enable supplement use to be directedappropriately14.

Sperm DNA fragmentation

Oxidative stress can lead to sperm DNA damage (DNA fragmentation) which is associated with poor embryo development, lower pregnancy rate and a higher rate of miscarriage16-20. Men with unexplained infertility also have higher rates of DNA fragmentation17.There are tests available for this as well16-18, and it is essential that this should form part of the investigation of men with unexplained infertility, failed fertility treatment or recurrent pregnancy losses (two or more). While this is the recommendation from the European11 andAmerican12 guidelines for male infertility investigation, this is not recommended by the National Institute for Health and Care Excellence (NICE)21.

Both oxidative stress and sperm DNA damage may result from poor lifestyle, or clinical causes, such as infection of the genitourinary tract, systemic illness or varicocele22, all of which should be addressed. A repeat test can be offered 12 weeks post treatment and lifestyle changes, to determine whether there has been an improvement. Many men are sent for costly IVF treatment following a semen analysis without any further investigation. Yet implementation of a test on the NHS for oxidative stress and DNA fragmentation prior to referral for IVF, may permit appropriate management of the infertility so that chances of a natural conception are increased and IVF treatment either becomes unnecessary or outcomes with assisted conception will be improved12,16-18.

Recurrent Pregnancy Loss

Recurrent miscarriage is associated with a plethora of factors ,and there are miscarriage clinics around the UK that couples can be referred to investigate this. While the women are usually investigated thoroughly, the only test recommended for the male partner is a full blood chromosome analysis. As mentioned above, there is considerable evidence to show the association between sperm DNA fragmentation and recurrent pregnancy loss23 and all men whose partners are experiencing this, should be tested11,12.

Improving access to treatment

There is an enormous lack of facilities providing investigation for male infertility on the NHS. Semen analysis is not offered universally, so it is essential that every health authority offers a UKAS accredited Andrology laboratory service to carry out semen analysis and other required diagnostic tests.

Surgical sperm retrieval

One in a hundred men suffer from complete absence of sperm in the ejaculate (azoospermia) which rises to 10 to 15% of all men experiencinginfertility24. In general, the only option for these men to father a child is to perform testicular sperm retrieval (TESE) which is offered on the NHS however there are eligibility criteria such as demonstrating a high risk of permanent infertility, including men undergoing treatment for cancer or men with a genetic condition that affects fertility. In addition, patients must have confirmed funding for the next stages of the treatment process, including freezing of the sperm (cryopreservation) and/or IVF treatment25. As funding for IVF is a postcode lottery, not all infertile men will be able to secure funding for IVF treatment on the NHS and will therefore be unable to qualify for TESE procedures on the NHS. Since access to surgical procedures for gynaecological problems affecting fertility such as myomectomies (fibroid removal), treatment for endometriosis etc. are easily provided for women on the NHS, it is only fair that equivalent access to testicular sperm retrievals is provided for the men.

Varicocele

Equally, since varicocele is the largest known cause for male infertility, affecting 35–44% men with primary infertility and up to 80% in men with secondary infertility26, men should be able to access treatment for varicocele repair as well. There is good evidence that sperm quality can be improved27 with a reduction in DNA damage and oxidative stress27,28 and more importantly, pregnancy rates whether naturally or with IVF, can also be significantly improved29. Even in cases of azoospermia associated with varicocele, evidence shows sperm returning to the ejaculate in up to 27% men following varicocele repair and a spontaneous pregnancy rate of 5.4%30. However, there are eligibility criteria for varicocele repair. While the NHS will refer men with pain or discomfort for varicocele repair, both NICE21,31 and the Royal College of Surgeons32do not recommend surgery for varicocele solely to improve fertility. This is in stark contrast to the guidance from the rest of the world. The European Association of Urology (EAU), states that there is strong evidence to 'treat infertile men with a clinical varicocele, abnormal semen parameters and otherwise unexplained infertility in a couple where the female partner has good ovarian reserve, to improve fertility rates11. Guidelines from the American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) state that varicocele repair should be considered in men who are trying to conceive, have a palpable varicocele(s), infertility, and abnormal semen parameters12.

Fertility Preservation

Another area where there is a paucity of access is for fertility preservation. Sperm storage can be offered on the NHS, but it is not widely available and there are eligibility criteria. Availability depends on the funding policies of the local Integrated Care Board (ICB) or Clinical Commissioning Group (CCG). While fertility clinics both in the private and public sector will agree to cryopreserve sperm for men undergoing treatment with them, people requiring long-term storage due to the risk of irreversible harm to their fertility such as cancer patients undergoing radio or chemotherapy, those requiring surgery that may affect their fertility, or those about to embark on gender reassignment, are usually turned away. This is very concerning as these individuals are facing the inevitable long-term consequences of never having their own biological child.

Management of complex genetic infertility

Genetic causes contribute between 15 and 30% to maleinfertility33. Klinefelter syndrome is the most common cause of azoospermia occurring in approximately 11% of cases. However, there are very few centres that have the appropriate multidisciplinary teams (MDTs) that are required to manage these patients. The national Klinefelter syndrome clinic was established at Guys Hospital for this purpose but there is an urgent need for more of these clinics nationally (https://theklinefeltersyndromeclinic.com/)

Prevention 

Prevention of infertility should involve addressing lifestyle and diet, carrying out a semen analysis and offering appropriate treatment11,12. It has been proposed by the international community that semen analysis should be offered to young men to determine those who are infertile and thus likely to develop co-morbidities in the future34. Furthermore, PSA is a test that can easily be offered routinely to all men to detect prostate cancer early on. By identifying those most at risk early on, and addressing the infertility early, the burden of the high cost of treatment for systemic disease (the total cost of cardiovascular disease alone in the UK in 2021/22 estimated at £29.021 billion35) as well as fertility treatment (cost of fertility treatment in the UK estimated at £68 million per annum as of 201836) in the future may thus be avoided.

 

Health literacy, education and training 

Lack of information provided in schools regarding reproductive health

Men have limited knowledge about their fertility and the impact their health and lifestyle may have upon their ability to father a child37. Information about male infertility should be introduced into the curriculum in secondary schools to explain the risks to fertility of lifestyle choices such as binge drinking alcohol, recreational drug use, cigarette smoking38,diet, STIs39 and especially anabolic steroids40 which may have permanent harmful effects.

Lack of information provided to medical students and GPs

There are no specific Andrology modules in a standard UK undergraduate degree in medicine (MBBS) that teaches the study of the physiology and pathology of the male reproductive tract. In contrast, they include a substantial component of obstetrics and gynaecology. Consequently, while GPs can manage women with infertility, they have no formal training in Andrology and therefore do not possess the skills required to interpret a semen analysis, often resulting in an inappropriate diagnosis and mismanagement of the patient. The consequences of misinterpretation include:

a) no referral for a full investigation of male infertility or treatment for their reproductive health

b) indications for co-morbidities listed above maybe missed

c) referral for treatment that is not required e.g. unnecessary IVF treatment which is a costly burden to NHS

d) over investigation of the female partner

It is therefore essential that GPs are appropriately trained to discuss the implications of a semen analysis, to offer the appropriate tests based on the results of this test, and to triage the patient as necessary to a urologist who specialises in male infertility (Uro-Andrologist). Most men are currently being referred by GPs to a gynaecologist in a fertility clinic who will not perform further investigation and will only provide costly IVF treatment. Furthermore, they have no specialist training in male infertility. In no other field of medicine would a patient receive such an in appropriate referral to a clinician with training in another speciality.

Out of date NICE guidelines

The GPs rely on the NICE guidelines21 for their practice and a major issue preventing appropriate diagnosis and management of male infertility is that the NICE guidelines for this are superficial, in sufficient and out of date21. The most recent guidance was published in 2017and incorporates both male and female problems around fertility. Within this, the section for male infertility has not been updated since 2004. Virtually no investigation of the male or treatment for infertility is recommended and there is only one page referencing the management of male factor infertility. In contrast, a thorough up to date protocol for male infertility assessment and management has been published by the European Association of Urological Surgeon Guidelines, which has a 260 page document devoted to investigation and management of male sexual and reproductive health11.

Male infertility and mental health

Male infertility takes a considerable toll on men’s emotional and mental health, resulting in higher risk of anxiety, depression, and psychological distress, worse quality of some aspects of life, feelings of emasculation and lower self-esteem than fertile men 4,31,42. It can also have a devastating effect on couples’relationships43, with men often stating that they can provide their partners with everything they want, with the exception of the one thing they most desire. Many have suggested offering to end the relationship for their partner’s benefit. Men are rarely seen on their own when attending appointments for male infertility, in contrast to their female partners. Consequently, men’s true feelings are rarely heard especially as they are usually putting on a brave front for their partners. I have experience providing consultations for men on their own and the effect on their mental health is considerable. I therefore consider it essential that the NHS provide counselling and support for men with male factor infertility.

Summary of main points:

  • Male reproductive health should be taught in schools and Andrology must be included universally as part of the curriculum for undergraduate medical degrees alongside Gynaecology.
  • There should be formal training for GPs regarding male infertility investigation, diagnosis and management
  • Men with infertility and especially those with poor semen parameters, should be thoroughly investigated.
  • Every health authority should offer a UKAS accredited Andrology laboratory service to carry out semen analysis
  • Men diagnosed with infertility must have access to a Uro-andrologist, not a Gynaecologist, for management of their condition
  • Referral for costly IVF treatment should be made only as a last resort if male infertility cannot be treated
  • Sperm cryopreservation should be offered to all people on the NHS when there is a considerable risk of irreversible damage to their sperm
  • NICE guidelines must be updated for male infertility by a committee of several specialist Andrologists and Urologists
  • Counselling should be made available for men with infertility

It is hard to reconcile why this Victorian attitude of only investigating the women for infertility is perpetuated today. Funding issues are often cited as the reasons behind the failure to adequately provide access to fertility investigation treatment and particularly male infertility which is low on the agenda for distribution of NHS funds. It is time we recognised the full impact of male infertility especially as it can have serious consequences for male health over a lifetime. Addressing male infertility can reduce not only the high cost of IVF treatment to the NHS but also prevent certain systemic illnesses and their burden on the NHS. It is high time that investigation and management of male infertility is given the attention it deserves.

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