Episode 98: A Frank Discussion About Male Infertility

In this week’s episode, Dr Bahijja talks about male infertility with Dr Sarah Martins Da Silva, Clinical Lecturer in Reproductive Medicine at the University of Dundee.

Dr Martins Da Silva’s career journey

Dr Martins Da Silva is both a gynaecologist specialising in fertility and a researcher. Her research revolves around male fertility, specifically how sperm work and why some men may have fertility issues, with the aim of discovering new fertility treatments for men, as well as male contraceptives.

“I always wanted to be a doctor” – Dr Martins Da Silva

Dr Martins Da Silva explains that, for as long as she can remember, she had always wanted to pursue medicine. She felt intrigued by science, and it was also her strength at school, so she ended up going to the University of Edinburgh to study medicine. During her time as a medical student, she was involved in delivering babies and in fertility clinics, and through these experiences she found that she wanted to pursue gynaecology.

In the later stages of her clinical training, she moved to Dundee, which is a hotspot for research in sperm and male infertility. However, through the couples she spoke to about their fertility issues, she found that there was a huge lack of knowledge surrounding how sperm actually work. For this reason, there aren’t really any fertility treatments for men, and she highlights that although IVF can be used, it is treating a woman for a man’s health problem.

“The reality is that we don’t understand sperm” – Dr Martins Da Silva

What does infertility actually mean?

The clinical diagnosis of infertility describes a situation where a couple have been trying to have a baby for 12 months or longer and have not succeeded in getting pregnant naturally with regular intercourse.

Very few couples are sterile, however if a man has no sperm at all, or a woman has no eggs, then it is almost impossible to get pregnant without any intervention. Roughly 1 in 7 heterosexual couples trying to achieve pregnancy have difficulty conceiving, and although the focus seems to be predominantly on women, it is likely that half of the problem is to do with the male partner. Male fertility problems can include low sperm count or poor sperm swimming.

“1 in 15 men have a fertility problem, and 1 in 100 will have no sperm” – Dr Martins Da Silva

When investigating male fertility, what is generally tested is the percentage of sperm that are swimming well. However, these are just ‘population cut-offs’ and do not suggest whether a man is fertile or infertile, rather, whether the probability of getting pregnant is greater or lesser. If a sperm count is less than 16 million per mil or less than 30% of the sperm are swimming well enough, it is very likely that a fertility problem will arise. However, there are couples who have poorer sperm counts, yet still get pregnant, so although it is less likely, it is not impossible. On the other hand, a man may have a statistically ideal sperm count, yet also have a fertility problem that is not detected through testing sperm count.

Are there any conditions that affect male fertility?

In order to create sperm, hormones need to be produced in the pituitary gland – these hormones signal to the testicles to produce testosterone to build sperm. Having low testosterone levels can therefore result in inadequate sperm production. Men may notice low testosterone levels if they have little facial hair growth or difficulty producing and maintaining erections.

Low testosterone levels can be treated, but unlike conditions which affect women, such as endometriosis or polycystic ovary syndrome, there isn’t much else to suggest that a man could have a fertility problem – apart from possibly cystic fibrosis.

The importance of male reproductive health

Every year the BBC hold a programme, identifying 100 women from different walks of life, called ‘BBC 100 Women’. Dr Martins Da Silva was one of the 100 women in 2019, where she spoke about the pressing issue of male infertility and its impact on humanity.

“In the last 4 decades, men’s sperm count has halved” – Dr Martins Da Silva

Based on a meta-analysis conducted in Israel, men’s sperm counts are dropping rapidly by a huge amount. However, no one knows why this is happening, so nothing can yet be done to stop this trend. There are also increasing rates of testicular cancer and abnormalities in male genitalia.

Within the scientific community, it is thought that these things are linked, and that the increasing amount of pollution may have a role to play, leading to concerns surrounding general health and quality of life, not just conception. Men who are seen with fertility problems tend to have poorer, longer-term health outcomes such as cardiovascular disease or cancer.

What is sperm and semen?

Much of the sperm is made up of proteins and fructose – a sugar which is an energy source for the sperm. The actual sperm cells make up a small proportion of the seminal fluid (semen) that is ejaculated, the rest of the semen is made up of fluid proteins and enzymes. Sperm cells don’t contain much content internally, however they do have mitochondria which provide the energy that sperm need to travel, based off signals and cues they receive from the egg itself. On the front of the sperm is an element called the “acrosome” which is an enzyme used to penetrate into the egg.

Sperm have clusters of membrane pools along their tails called “catsper channels”. These channels are responsible for all of the calcium coming in and out of the sperm. When calcium enters the sperm, it changes the way that sperm move, helping them swim better. It is thought that the misalignment or misreading of calcium signals may impair the swimming ability of sperm – about 10% of sperm will have issues responding to calcium, possibly due to faulty channels, however it is not something that can yet be diagnosed.

Like women, men’s fertility also declines from late-20s onwards. As men get older, sperm count declines and sperm don’t swim as well. Additionally, sperm of older men have higher DNA damage.

Current treatments for male infertility

As of now, the only treatment for infertility affecting men is a type of IVF called ICSI (intracytoplasmic sperm injection) which involves directly injecting a sperm cell into an egg. The woman first undergoes IVF to stimulate the ovaries to grow a group of eggs which are collected. Each mature egg is then injected with one sperm cell to fertilise it – any embryos which are produced are then cultured for a number of days before picking the best one to put back.

With low sperm count or poor sperm swimming, the sperm don’t have the ability to get through the outer coat of the egg, the zona pellucida, so ICSI helps the sperm penetrate into the egg to enable fertilisation. The success rates of IVF and ICSI are very similar overall – roughly 25-30%, however the success rate declines with age.

The future of male infertility

Dr Martins Da Silva explains that infertility in general comes under gynaecology, and clinics need to be more inclusive of both men and women, as it is often seen as a women’s issue despite men having an important role to play in pregnancy success.

Oxidative stress is an umbrella term for the metabolic stress that cells are exposed to, and every cell makes reactive oxygen species through metabolism. Usually, these molecules are helpful to sperm, however too many of these highly active molecules can cause damage. Oxidative stress damages the cell membrane, affecting the sperm’s ability to swim, impair their DNA and also kill the sperm.

Antioxidants dampen down and absorb these reactive oxygen species – this includes Vitamin C, Vitamin E, selenium, zinc, carotenoids and more. However, from the studies that have been conducted, there isn’t much evidence to support the use of supplements in treating male fertility issues.

Dr Martins Da Silva’s research has been looking at tackling oxidative stress from another direction – inhibiting the enzymes which cause oxidative stress to occur. Her team added a repurposed AstraZeneca molecule to stressed sperm in a lab and found that it helps them swim better. They are currently performing clinical trials to test how effective this intervention is, through looking at differences in the seminal plasma or improvement in DNA damage.

It’s important for male infertility to be spoken about, both between men and within wider society so that the problem gets the recognition that it deserves – one that causes much pain to couples trying to conceive, affects the health of men, and is also worsening drastically.

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