“You pay the price for having cancer over and over again.” Mai Nguyen’s words are loaded with sorrow as she speaks about her 17-year-old daughter, Taylor Tran, who is dealing with fertility concerns more than a decade after she survived late-stage cancer.

Taylor Tran (left) and her mother Mai Nguyen. Taylor underwent cancer treatment when she was 2 years old, causing her to go into early menopause when she was just 16.

It’s easy to understand the indignation Mai feels: Her daughter was diagnosed with stage 3 single-cell sarcoma of the kidney when she was 2 years old and was treated with intense chemotherapy and radiation. Now, the treatments that saved her life have put her into early menopause.

“It’s been traumatic,” Mai says. “We tried so hard to allow Taylor to have a normal childhood and this feels like one more thing cancer has taken from her.”

Stories like Taylor’s inspired Seattle Children’s urologist Dr. Margarett Shnorhavorian to tackle a challenging area of research that was largely uncharted when she started more than a decade ago. Since then, she’s helped change perspectives and protocols for fertility preservation in childhood cancer survivors.

And she’s only getting started.

The end of a rainbow

Dr. Shnorhavorian’s passion stems from encounters she’s had with the families of childhood cancer patients since she started her practice 12 years ago. She often spoke with families who’d just received a devastating diagnosis about the importance of fertility preservation.

“Some providers believed families wouldn’t want to think about fertility when they were trying to deal with the chaos of cancer,” Dr. Shnorhavorian says. “But when I brought it up, I saw the tone in the room lift. Families were grateful we were talking about their life after cancer, because it meant we believed they would have one. It was like glimpsing the end of a rainbow.”

At the time, there was little information providers could offer about how a patient’s fertility might be affected by various cancer treatments. Families couldn’t find the answers they desperately wanted.

Dr. Shnorhavorian hoped to change that.

“I like a challenge”

While Dr. Shnorhavorian’s passion was undeniable, many in her field said recruiting enough participants to study the effects of cancer treatment on fertility would be difficult.

First, childhood cancer is relatively rare, so there were fewer eligible patients to draw from. Also, many providers were uncomfortable discussing fertility issues with patients and their families who were, understandably, focused on survival.

If adolescent and young adult participants did enroll, it would be difficult to keep track of them because they change addresses frequently. Dr. Shnorhavorian also had to make study participants comfortable contributing specimens such as sperm samples.

“The adolescent and young adult population is unique, so we developed research methods tailored to their needs,” she says.

Dr. Shnorhavorian created a data collection system allowing patients to participate wherever they were located. They could have blood drawn in their dorm room or collect their sperm sample at home and send it in the mail rather than going to a clinic.

“That was a game-changer in our field,” she says. “I knew my research questions would be hard to answer, but I like a challenge. The naysayers actually fueled me because they helped me troubleshoot.”

A pioneer in her field

Dr. Shnorhavorian’s innovative methods proved to be effective, earning her a National Institutes of Health Career Development grant followed by a $3 million research grant.

“I have been incredibly impressed with Dr. Shnorhavorian from day one,” says Dr. Bonnie Ramsey, director of Seattle Children’s Research Institute’s Center for Clinical and Translational Research (CCTR) and one of Dr. Shnorhavorian’s mentors. “She took on an important topic others weren’t brave or passionate enough to tackle. It’s very difficult to study a question that may take 10 to 20 years to answer, but she has set up a program that will have a profound, long-term impact.”

Now, Dr. Shnorhavorian is leading a multisite study to investigate the effects of chemotherapy on boys and men who have survived osteosarcoma, a common type of bone cancer. Patients are being recruited for the study from 178 Children’s Oncology Group (COG) institutions in the United States, Canada and Australia.

Dr. Shnorhavorian and her team hope to identify biomarkers of fertility risks and genetic susceptibility to fertility impairments and to better understand sperm development and how cancer therapies modify sperm DNA.

By studying these predicting factors, Dr. Shnorhavorian hopes to shed light on why some cancer survivors become infertile after treatment, with the hope of eventually finding preventive interventions.

A culture shift

Dr. Shnorhavorian’s study is ongoing, but the impact of her work is already evident in the field. Since starting her research, she has advocated for offering fertility preservation options to cancer patients and worked with COG to help develop protocols for sperm cryopreservation.

“I have seen a culture shift where providers are now expected to discuss fertility with newly diagnosed cancer patients who hadn’t always been informed of this long-term effect,” she says.

Looking ahead

When Taylor learned she was going into early menopause, she decided to freeze her eggs. “My cancer treatment gave me a second chance at life, but that doesn’t mean I shouldn’t get to have the same experiences others have.”

Dr. Shnorhavorian hopes her research will continue to grow so providers can one day offer oncology patients new opportunities to preserve their fertility before treatment or treat their cancer without harming their reproductive health.

 

“It is our obligation to give our patients hope,” she says. “We have a long way to go to offer fertility preservation to every child, but from my standpoint, it’s no longer a question of ‘Should we do this?’ but rather ‘How do we do it?’”

Mai finds the idea exciting.

“I want to see other kids, like Taylor, have the opportunity to raise their own genetic children,” Mai says. “It would be amazing if researchers can find a way to cure them without taking away that experience.”

— Rose Ibarra
Published Jan. 14, 2020