Seeding Success With New Male Infertility Test

Episona's Seed Kit. Photo Credit: Alan Horsager.

Seeding Success With New Male Infertility Test

Researchers from the Huntsman Cancer Institute, USC, and the U work together to create a new infertility test based on epigenetics

Co-inventor Douglas Carrell, professor of surgery

Couples struggling to conceive are often surprised to hear that half of infertility issues are on the male side. Sometimes the cause is straightforward, a blocked duct, chromosomal anomaly, or lifestyle factor. However, up to half the time, the cause is a frustrating unknown.[9]

Those one in four couples being treated for infertility have what appears to be healthy sperm based on traditional analysis, yet the sperm lacks the ability to fertilize and assist the egg through early development. For a long time, scientists and physicians had not been able to predict or explain why, leaving patients in the dark as they made expensive, emotional, and often invasive choices about their treatment without really knowing their odds of success. However, recent discoveries by U scientists point to epigenetics: modifications to the sperm’s DNA sometimes caused by external factors and lifestyle choices such as the food we eat, physical activity, and aging that control which genes are turned on and off during and after fertilization.[10],[11]

A microarray, a tool utilized by Episona

To Alan Horsager, president and CEO of U-spinout Episona, a molecular information company, the news of epigenetics’ role in infertility called out for the development of a diagnostic test. He had been discussing how epigenetics affects neurodevelopment with Andrew Smith, associate professor of biological sciences at the University of Southern California. In this conversation, Smith mentioned some important infertility research by U scientists Bradley Cairns, professor of oncological sciences at the Huntsman Cancer Institute and Douglas Carrell, professor of surgery. “I thought, ‘I’m going to call them up and ask whether there is an opportunity to develop a diagnostic test for male infertility based on epigenetic profiles,’” says Horsager. The combination of Horsager as scientist and entrepreneur, Smith’s ability to navigate computational biology and analytics, Cairns’ background in epigenetics and stem cells, and Carrell’s clinical knowledge quickly lead to the development of technology based on their combined expertise.

Fertility treatment counseling

“Doctors cannot accurately diagnose male infertility—basic semen analysis does not provide enough information. When the sperm connects with the egg, the sperm basically melds into the egg. If that connection isn’t happening properly, then you’re not fertilizing properly and that’s not going to show up on any analysis. Now we are starting to use epigenetics to recognize when genes affecting fertility have been altered,” explains Horsager. The Carrell laboratory had been using microarrays and other techniques to pinpoint aberrant epigenetics in sperm of infertility patients. The collaborators looked to adapt the same techniques for use with individual patients, creating a test that would determine fertility at a molecular level.

The first product based on their collaboration is “Seed,” a diagnostic test offered by Episona that both predicts fertility and identifies epigenetic abnormalities in fertility genes. Following up a successful pilot study last year, Episona is currently working with nine well-known fertility clinics to validate the technology. Patients will collect a sperm sample at home and send it to a lab that uses microarrays to analyze 480,000 regions of the epigenome, a map of compounds that attach to DNA and modify its expression. That information will be processed into an individualized report so the patient can review the results and treatment options with his physician.

Co-inventor Bradley Cairns, professor of oncological sciences

The key to developing Seed, says Cairns, was the open nature of the collaboration between Smith, Cairns, Carrell, and Horsager. “You have a set of people who each come from different training backgrounds, so we all looked at this problem from a different perspective. At the end of the day we all wanted to figure out, ‘How do you make a healthy baby?’”

“I’m the intermediary between the science and the clinic so I’m kind of building a bridge between what we see and what’s really needed in the clinic,” explains Carrell, whose work besides research includes directing the in-vitro fertilization (IVF) and Andrology Laboratories at the U. “We haven’t really understood what’s causing reduced fertility at the molecular and cellular levels. Genetics has answered some of our questions, but didn’t go as far as we’d hoped. With epigenetics hopefully we’ll go further and will understand what really is causing infertility and what we can potentially do to treat it.”

Collaborator Andrew Smith, associate professor of biological sciences at the University of Southern California

Carrell predicts Seed will become a routine test at fertility clinics for couples that do not become pregnant after their first round of IVF. “It’s heartbreaking for a physician to say, ‘I have no idea whether the problem is the sperm or the eggs and cannot tell you the chances of failure for future attempts.’ We have to give patients a better idea. Even if the results come back abnormal and the couple still wants to go through IVF, there are some clinical things that we can change to improve their odds.”

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[9] ““How Common Is Male Infertility, and What Are Its Causes?” Eunice Kennedy Shriver National Institute of Child Health and Human Development, last modified Nov. 11, 2012, accessed July 10, 2016, https://www.nichd.nih.gov/health/topics/menshealth/conditioninfo/Pages/infertility.aspx.

[10] Kenneth I. Aston, Philip J. Uren, Timothy G. Jenkins, Alan Horsager, Bradley R. Cairns, Andrew D. Smith, Douglas T. Carrell, “Aberrant Sperm DNA Methylation Predicts Male Fertility Status and Embryo Quality,” Fertility and Sterility 104, no. 6 (December 2015): 1388-1397.e5.

[11] “The Young Sperm, Poised for Greatness,” Huntsman Cancer Institute at the University of Utah, May 18, 2014, accessed July 10, 2016, http://healthcare.utah.edu/publicaffairs/news/2014/05/05-18-14-Young-Sperm-Totipotency.php.