June 27, 2016
The choice between life-saving chemotherapy and preserving one’s fertility can be an agonizing dilemma, but for 16-year-old Sydney Small, the decision was rather straightforward.
The Indiana teen knew she definitely wanted children one day. So when she was told that her non-Hodgkin’s lymphoma had evolved into a highly aggressive form despite cycle after cycle of chemotherapy and required a more potent drug regimen, Sydney refused. She feared that, along with the cancer, a more toxic chemo would wipe out her chances of conceiving one day.
That fear was well justified. The new chemotherapy — a four-drug cocktail used in refractory non-Hodgkin’s lymphoma — along with a stem cell transplant and previous chemotherapy rendered her high risk for infertility, says pediatric surgeon Erin Rowell, MD, who is at the forefront of salvaging the fertility of children undergoing treatment for cancer.
Sydney’s case posed a challenging clinical scenario, Rowell says. As a post-pubertal female, Sydney could undergo oocyte stimulation and harvesting, but that route was medically contraindicated in her case because she’d have to go off chemo for several weeks to receive hormone injections that stimulate follicle-production. Additionally, Rowell says, the procedure would require a transvaginal ultrasound and surgical oocyte retrieval.
Rowell, however, had something else in mind. Sydney was a prime candidate for another, more experimental approach — ovarian tissue cryopreservation, which Rowell and colleagues perform as part of an ongoing clinical trial at Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine.
As part of the study, Rowell would remove laparoscopically one of Sydney’s ovaries and cryopreserve it for future use.
Even though Sydney had already undergone six months of chemotherapy before her procedure, she was still a good candidate for ovarian cryopreservation, a point Rowell says, she cannot emphasize enough.
“We know that even girls who have undergone cancer treatment can still have follicles in their ovaries,” Rowell says.
Certain chemotherapy agents put patients at risk for infertility, but that risk varies by treatment type and from patient to patient, says Barbara Lockart, DPN, APN, an oncology nurse practitioner specializing in fertility preservation.
“Don’t just assume that because a female patient has had chemo or radiation all hope is lost,” says Marleta Reynolds, MD, the Lurie Children’s surgeon-in-chief who has seen her fair share of such cases. “Recurrent cancer generally requires more intense — and more toxic — chemotherapy, so salvaging reproductive tissue before such treatment becomes that much more critical.”
Case in point: Sydney Small.
In February, Sydney underwent an outpatient oophorectomy. When Rowell received the pathology report, she was excited, if not all that surprised. It read: Ovary with numerous follicles of varying degrees of maturation containing viable oocytes. No lymphoma seen.
“We’re so happy we could do that,” says Sydney’s mother, Judy Small. “We have to focus on Sydney’s immediate treatment, but we take comfort in knowing she can still have children when the time comes.”
Lurie Children’s surgeons are part of the national Oncofertility Consortium, headquartered at neighboring Northwestern University, a multidisciplinary research effort aimed at unraveling the basic mechanisms as well as developing fertility-salvaging strategies in clinic for patients with cancer, autoimmune diseases and disorders of sexual differentiation. Led by Teresa Woodruff, PhD, in addition to surgeons, the group also includes fertility experts, oncologists, urologists, endocrinologists, advanced practice nurses, medical ethicists and basic and translational scientists.
So far Lurie Children’s surgeons have performed more than 30 ovarian tissue cryopreservation (OTC) procedures, more than half of them in prepubescent girls. The pre-pubertal subgroup constitutes one of the nation’s largest case series to date, the team says. Northwestern is the lead repository site for ovarian tissue from pre and post-adolescent girls, while the University of Pittsburgh is the main banking site for testicular tissue.
In a recent first, Rowell obtained testicular tissue for cryopreservation on the youngest patient ever to have this procedure, a 5-month-old infant.
The question of how much testicular tissue should be removed for banking to ensure optimal spermatogenesis down the road remains an open-ended one, Rowell says. In this particular case, she removed about one-third of the testicle, under the premise that removing less would allow the organ to heal and grow better, increasing the likelihood of normal physiologic function. Cosmetic considerations also play a role.
“Ensuring symmetry is important for patients and parents and less emotionally taxing on the family,” Rowell says.
Pre-pubertal gonadal tissue preservation has been around for a mere few years in the United States — far longer in Europe and parts of the Middle East — and the first generation of U.S. patients who had these fertility-rescue procedures has not yet reached an age to start families.
“A successful pregnancy or fathering of a child by an adult cancer survivor who underwent fertility preservation before he or she reached puberty is the holy grail of our work,” Rowell says. “I hope we’re on the cusp of seeing this happen.”
To push science even farther, Rowell and colleagues have extended their efforts beyond the clinic. Rowell is collaborating with Northwestern scientist Monica Laronda, PhD, who is working to create an artificial ovary. Laronda has designed a 3-D printed bio-scaffold made of gelatin to be seeded with ovarian follicles and implanted in mice. The animals successfully conceived and gave birth following implantation of the follicle-seeded scaffold. Laronda and Rowell hope to repeat this success in a larger-animal model. The ultimate goal would be to create a biologically viable ovary for transplantation, to restore normal hormone function and fertility in human patients.
Lurie Children’s is a referral center offering fertility preservation counseling and fertility preservation services to patients receiving their oncology care elsewhere.