Male infertility: how lab-produced sperm could transform fertility treatment in the future

Imagine a future where a diagnosis of untreatable male infertility is no longer the end of the road – because science has found a way to produce human sperm from lab-engineered testicular tissue.

This might sound like science fiction, but I’m leading a team of researchers at the University of Limerick (UL) to work on making the production of human sperm from lab-engineered testicular tissue a reality. If successful, this could redefine fertility treatment and bring hope to the millions of people around the world affected by male infertility.

Why now? Because male reproductive health is in decline – and the numbers are too stark to ignore.

Over the past seven decades, sperm counts have decreased dramatically while conditions like testicular cancer, hormone imbalances and genital malformations – which can all have an effect on sperm counts – are on the rise.

The precise causes of declining male reproductive health are still being debated. While genetics may play a role, no single genetic factor has been shown to affect male fertility at a population level. Instead, much of the focus has turned to the environment, particularly endocrine-disrupting chemicals.

These chemicals, which can interfere with hormone function, are found in common items such as plastics, pesticides, cosmetics and even painkillers. There is growing evidence that exposure to these substances in the womb can increase the risk of testicular cancer, reduce sperm quality, and lead to male infertility later in life.

For some men, fertility issues are treatable – lifestyle changes, hormone therapy, or surgery to correct blockages in the reproductive tract can help. But for a large proportion, there is no identifiable cause.

This type of unexplained infertility, known as idiopathic infertility, currently leaves patients with only one option: surgical sperm retrieval (SSR).

SSR involves surgically opening the testicles to search for viable sperm for use in assisted reproductive technologies like IVF. However, success is far from guaranteed. In some cases, the chance of finding even a single usable sperm cell is as low as 40%.

In addition to its physical and emotional toll, SSR places the burden of fertility treatment on the female partner’s reproductive system, meaning women’s bodies are often the target of fertility medications and procedures. It does little to address the underlying health risks associated with male infertility, including higher rates of illness and early mortality.

And if SSR fails, the only option left is to use donor sperm – a difficult and emotional decision for many people.

Root of the problem

To address male infertility, scientists need to get to the root of the problem and develop solutions that restore natural fertility.

So, given the ethical and biological limits on experimenting directly with humans, researchers have turned to preclinical models to study the human testes. These include ex vivo tissue (human or animal tissue studied outside the body), in vitro cell cultures (human testicular cells grown on lab plates), and animal models (typically rodents or primates).

However, human sperm production is vastly different – and much less efficient – than in other mammals, making animal models unreliable. To move forward, researchers need preclinical models that closely mimic human testes and their ability to produce sperm.

This remains one of the biggest scientific hurdles in the field. While researchers have successfully produced sperm in the lab from mouse testicular tissue, the same has never been achieved in humans.

Our research is attempting to overcome this challenge by combining biology with mechanical engineering and materials science. We started by analysing human testicular tissue samples from a range of donors, building a detailed understanding of how the tissue functions.

This data was fed into the design of model systems that replicate human testicular tissue – not just biologically, but mechanically and structurally. The ultimate goal is to create a model that can not only mimic testicular function but produce viable human sperm.

Lab-produced sperm could revolutionise fertility care. It might one day offer a solution to men who have undergone failed SSR procedures, childhood cancer survivors whose fertility was damaged by chemotherapy or radiation, and male patients with severe, unexplained infertility who currently have no treatment options.

This isn’t just a scientific experiment. It’s about restoring hope to those for whom existing medical approaches have run out of answers.

Eoghan Cunnane receives funding from the European Research Council, Research Ireland, and the UL Foundation.