8 October 2018

Professor Sheena Lewis

Emeritus professor, Queens University, Belfast By

Appeared in BioNews 970

There has been much media interest in male infertility care this year, but two major issues have stood out. The first is the inadequacy of care for the man, from incomplete diagnosis to non-information about his treatment choices. The second is the use of a vulnerable woman to undergo invasive fertility treatment in order to treat a third party – her male partner. This is unparalleled in other branches of medicine.

There are clear reasons why this situation has come about. There are also clear motivations for why we must act to change it, both at an individual and a societal level. To understand more, let's explore some contributing factors.

Mind the gap

The advent of intracytoplasmic sperm injection (ICSI), where a sperm cell is injected directly into the egg cell, was a quantum leap in short-term clinical success. But it has led to a lethargy in progressing our evidence-based diagnosis of male infertility. We must make it a research priority to plug these knowledge gaps.

In their recent focused issue of Translational Andrology and Urology, Dr James Hotaling of the University of Utah and Dr Ranjith Ramasamy of the University of Miami suggest that 'we need to identify what issues need to be solved to bring male infertility care to the same level of diagnosis and treatment as female infertility'.

Inadequate diagnosis

Conventional semen analysis is routinely used in male fertility diagnoses. But it is widely reported that there is little association between semen parameters and male infertility diagnosis. It also has little relationship with IVF outcomes and no relationship with ICSI outcomes.

Further, around 30 percent of couples are given a diagnosis of unexplained infertility. These couples are often referred for ICSI, rather than using some of the tests shown to identify defects such as sperm DNA damage that are present in the majority of these men. If there is no diagnosis, there can be no direct solution. This leads to expensive, invasive, prolonged and often unsuccessful cycles of treatment. Since ICSI now accounts for a significant proportion of fertility treatments across Europe, we particularly need a test to predict which patients will benefit from it.

Inequality of care

Fertility treatment is primarily focused on women. This is to be expected since the speciality is run by gynaecologists and obstetricians whose training is in female, not male, reproduction. However, this can lead to men feeling ignored and emasculated by the whole fertility journey. There are even examples of doctors telling the female partners the devasting result of azoospermia, rather than telling her male partner to whom the results relate.

The woman is also affected by inequality of care. In up to 30 percent of ICSI cycles, the woman has no detectable reproductive anomalies, yet she undergoes this invasive form of treatment to treat a dysfunction in her partner. She consents to this procedure willingly as usually she is told there is no other way to conceive the child they yearn for.

Inadequate treatment options

In all branches of medicine except reproductive technology, interventions are to treat the patient's symptoms. In our speciality, ICSI is used to bypass the problem of male symptoms. Since treatment is unsuccessful for so many couples, would it not seem prudent to suggest interventions to improve the quality of sperm before treatment?

There are simple ways to do this. Doctors must take a detailed clinical history of the patient, examine him and know which medications he is taking. He may be on drugs as seemingly innocuous as drug treatments for hair loss, which can lower his sperm count. His semen also needs more than the 'first step' semen analysis. Semen should be cultured to detect infections that can be treated with antibiotics. Specialised tests for oxidative stress and sperm DNA quality should be done to find out if he needs antioxidant supplementation. Using supplements as a panacea without a clinical indication can damage his health and his sperm.

Since men have a turnover in sperm every few months, lifestyle changes can bring about rapid improvements. Simple changes in diet, weight loss and reduction or cessation of smoking, anabolic steroid use and recreational drug use can improve sperm health. These low-cost and effective interventions are too often ignored.

Static success rates

IVF success rates have remained at their modest level of less than 30 percent live birth rate for many years now. Improvements have been among the couples who can be treated for an underlying condition. For example, we can now treat men with obstructive azoospermia with testicular sperm. Single women can use donor sperm and gay couples can use surrogacy. But the actual IVF success rate per couple has remained disappointingly low.

Given that the numbers of couples seeking fertility investigations are increasing by eight to nine percent a year across Europe, it is imperative that success rates are improved. How is this most likely to occur? I would suggest it will be through advancements in male investigations leading to more accurate male diagnosis, complemented by therapy pre-ART.

Impact on offspring

We have, as yet, little evidence of the health of people conceived by ICSI as they reach middle-age. However, we already know that young men conceived by ICSI inherit poor semen quality and possibly infertility from their fathers. A recent small study suggested that IVF children have a six times higher risk of hypertension than children conceived naturally (see BioNews 966).

Using aging and smoking as paradigms for poor sperm quality, there are reports – such as one I authored – that ART is linked to increases in childhood cancers and psychiatric disease in offspring. Does this not create a further moral imperative to improve sperm quality as much as possible before ART?

An indicator of male health

Poor semen quality, as assessed by semen analysis, has been highlighted as a significant predictor for cardiovascular risk, late-onset cancers and shortened life expectancy. This may lead to its use as an inexpensive, non-invasive biomarker of late-onset disease. If we had a better test for sperm quality, this could prove useful in this application too.

One mechanism for change

So, what can we do about these shortcomings in our speciality? Perhaps we can follow the Australian example of forming a national 'centre without walls' funded by government to raise awareness of male reproductive health disorders and their associations with chronic disease. Andrology Australia provides a range of activities to educate men and improve their reproductive health of males through community and professional education. Perhaps it's time that we in the UK followed suit.