Researchers at the University of British Columbia (UBC) are making groundbreaking progress in the fight against male infertility. Led by Dr. Ryan Flannigan, a team of experts is exploring new possibilities using 3D bioprinting and advanced technologies to offer hope for men suffering from severe infertility.
Nivan Sharma’s dream of fatherhood has been complicated by his past battle with cancer. At just 16, Nivan was diagnosed with osteosarcoma, a form of bone cancer, which led to months of chemotherapy and a high risk of infertility. Although cancer-free today, Nivan’s diagnosis included a warning about the potential long-term effects of his treatments, which could impact his ability to father children.
“I found out I had infertility after undergoing treatment and was devastated by the news,” says Nivan. Despite storing sperm before his cancer treatment, he later received a call from the lab confirming that no sperm could be found.
Unfortunately, Nivan’s experience is not unique. Research suggests that up to two-thirds of male pediatric cancer survivors face infertility later in life. One of the most severe forms of male infertility is known as non-obstructive azoospermia (NOA), where the body produces very few or no sperm. This condition affects approximately one in 100 men, including many individuals assigned male at birth across different gender identities.
NOA is difficult to diagnose and often arises for reasons that remain unclear. It is a condition that profoundly impacts couples struggling with fertility, with male factors contributing to around half of all infertility cases worldwide. Currently, about 15% of infertile men experience NOA.
The Challenge of NOA
The standard treatment for NOA involves a surgical procedure to extract testicular tissue in search of any viable sperm. However, this process can be invasive, time-consuming, and often unsuccessful. Dr. Flannigan explains, “We find sperm only about 50% of the time, but even when we do, it doesn’t guarantee that IVF will succeed.
In hopes of improving this process, Dr. Flannigan partnered with Dr. Hongshen Ma, a professor at UBC’s Department of Mechanical Engineering, to develop an AI-powered tool to accelerate the search for viable sperm. The tool uses machine learning to sift through millions of cells, improving the chances of finding sperm that could be used in IVF.
“We believe AI could significantly enhance the IVF process, making it faster and more effective,” says Dr. Flannigan. However, this method still falls short for many patients, especially for those with NOA who do not have any sperm available.
Moving Toward Lab-Grown Sperm
To address this gap, Dr. Flannigan’s team is exploring an innovative approach: lab-grown sperm. Using 3D bioprinting, they are working to recreate human testicular tissue that could eventually produce sperm. This tissue is created using human-induced pluripotent stem cells (iPSCs), which have the ability to turn into any type of cell in the body.
The team’s bioprinting efforts aim to replicate the natural environment of the human testicle. Using a special gel and engineered “bio-ink,” they’ve managed to create tiny structures that resemble the tubes in the testes where sperm are produced. These structures have shown early signs of development similar to puberty — the period when sperm production begins in healthy males.
“If we can understand what makes these cells mature and produce sperm, we may be able to generate sperm for patients with NOA,” says Dr. Flannigan. The challenge, however, is complex. Sperm production involves many intricate processes, and scientists are still uncovering the precise chemical signals and cellular interactions involved.
The Role of Microfluidics in Understanding Infertility
As part of their multi-disciplinary approach, Dr. Flannigan’s team is collaborating with Dr. Govind Kaigala, a biomedical engineering expert at UBC. Together, they are developing microfluidic chips that can provide deeper insights into sperm production at the molecular level. By using these chips, the team hopes to identify what goes wrong when sperm production is impaired.
“We can use these chips to study the complex processes of sperm production, which could help us pinpoint the specific molecules needed to fix infertility,” says Dr. Kaigala. These devices, originally designed for cancer research, may offer a new way to examine male infertility from a molecular perspective.
Looking Ahead
While the journey to creating lab-grown sperm is still in its early stages, Dr. Flannigan and his team are hopeful. The potential to restore fertility to men suffering from NOA or those who are too young to store sperm before cancer treatment could be life-changing.
Nivan Sharma, whose infertility struggles were shaped by his cancer treatments, is encouraged by this research. “If this research leads to a breakthrough, it will change the lives of so many people, especially childhood cancer survivors who don’t have the option to store sperm,” says Nivan.
As AI, 3D bioprinting, and microfluidics converge, Dr. Flannigan is optimistic that these innovative approaches will one day offer a solution to one of the most challenging problems in reproductive medicine. With clinical trials expected to begin in the next few years, the future of fertility treatments looks more promising than ever.
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