The Mayo Clinic Pediatric Fertility Preservation Program

Oct. 22, 2019

Childhood cancer management requires multidisciplinary care to mitigate long-term health consequences while maximizing chances of a complete cure. The Mayo Clinic Pediatric Fertility Preservation Program, a part of the Mayo Clinic Children's Center, is one of two programs in the upper Midwest offering both ovarian and testicular tissue cryopreservation to children under Institutional Review Board-approved research protocols.

Asma J. Chattha, M.B.B.S., with Pediatric Gynecology at Mayo Clinic in Rochester, Minnesota, a co-founder of the Pediatric Fertility Preservation Program, notes: "As childhood cancer survival rates have improved, reaching upwards of 80% for the first time in decades, concern pertaining to long-term survivorship is growing. Research shows that fertility preservation counseling, particularly in pre-pubertal children, is not occurring frequently enough, despite being a key quality-of-life indicator for survivors."

While post-pubertal males can undergo sperm cryopreservation and post-menarchal females, if time allows, can proceed with egg (oocyte) cryopreservation, options for pre-pubertal children are not clinically available.

The Mayo Clinic Pediatric Fertility Preservation Program was established in 2016 as a multidisciplinary effort: It brings together the expertise of Pediatric Fertility Preservation Program to discuss next steps," explains Carola A S. Arndt, M.D., with Pediatric Hematology/Oncology at Mayo Clinic in Rochester, Minnesota.

Siobhan T. Pittock, M.B., B.Ch., with Pediatric Endocrinology at Mayo Clinic in Rochester, Minnesota, expands, "Depending on the age, gender and pubertal status of the child, fertility preservation protocols are discussed."

"One of the unique aspects of the Pediatric Fertility Preservation Program is its inclusion of indications other than oncologic conditions that could impair fertility, such as Turner or Klinefelter syndrome; nephrologic and rheumatologic conditions requiring gonadotoxic therapy; and transgender youth," expands Candace F. Granberg, M.D., with Urology at Mayo Clinic in Rochester, Minnesota. Dr. Granberg is a co-founder of the Pediatric Fertility Preservation Program.

Both ovarian and testicular tissue cryopreservation protocols remain experimental. However, over 130 live births have been reported from ovarian tissue reimplantation following conclusion of treatment.

"It is estimated that hormone function returns as a result of ovarian tissue reimplantation in over 90% of cases. It is difficult to determine the actual percentage of success of fertility potential returning after ovarian tissue reimplantation, but estimates run between 30% and 52%," clarifies Zaraq Khan, M.B.B.S., with Reproductive Endocrinology & Infertility at Mayo Clinic in Rochester, Minnesota. Dr. Khan is also a co-founder of the Pediatric Fertility Preservation Program.

Testicular tissue cryopreservation has not yielded live births in humans, but success has been achieved in rodents and primates with recent production of functional sperm and birth of healthy offspring after autologous grafting of cryopreserved pre-pubertal testes in rhesus macaques.

"In vitro maturation of immature oocytes is currently being explored under research protocols at Mayo Clinic, hopefully expanding fertility preservation options from ovarian tissue in the future," announces Yulian Zhao, M.D., Ph.D., with Reproductive Endocrinology & Infertility and director of the Fertility Testing Laboratory at Mayo Clinic in Rochester, Minnesota.

The process of ovarian and testicular tissue cryopreservation

"After discussion and completion of the informed consent process, preservation of ovarian tissue for future fertility or hormone replacement is performed via a laparoscopic unilateral oophorectomy," explains D. Dean Potter Jr., M.D., chair of Pediatric Surgery at Mayo Clinic in Rochester, Minnesota.

"This is coordinated with clinically indicated medical procedures such as central line placement or biopsy in order to reduce anesthesia-related risks and costs," adds Vidhu B. Joshi with Urology Research at Mayo Clinic in Rochester, Minnesota.

"Following removal of the ovary, a pathologist examines the tissue to exclude presence of malignant cells. The tissue is prepared into strips from the ovarian cortex by the fertility lab team," elaborates David L. Walker with Reproductive Endocrinology & Infertility at Mayo Clinic in Rochester, Minnesota.

"Testicular tissue cryopreservation entails a biopsy or wedge resection of one testicle, with care taken to avoid asymmetry," says Patricio C. Gargollo, M.D., with Urology at Mayo Clinic in Rochester, Minnesota.

For both ovarian and testicular tissue cryopreservation, the majority of the tissue (80%) is saved for future use by the patient, and the remainder de-identified for research purposes. Storage costs are $250 a year. Infectious agent screening for hepatitis B and C viruses as well as human immunodeficiency virus required by the Food and Drug Administration is completed prior to the procedure.

Monitoring occurs one week after surgery and then annually thereafter to assess for emergence of adverse events as well as patient and family satisfaction. As part of clinically indicated surveillance, children are monitored for hormonal deficiency through anthropomorphic measurements, growth velocity curves and Tanner staging.

Early results from the Pediatric Fertility Preservation Program

Overall, childhood cancers represent more than 90% of the fertility-threatening conditions in this group, while other indications such as aplastic anemia and transgender identity are less frequent. The most common indications in males are hematologic malignancies (56%) such as lymphomas and leukemias, whereas rhabdomyosarcomas or other sarcomas (45%) are most common in females. The median age of male and female participants is 9 years (range 0.92 to 14 years) and 11 years (0.83 to 17 years), respectively.

Ovarian and testicular tissue cryopreservation procedures have been well tolerated without adverse events. High levels of satisfaction were reported during follow-up surveys; 90% of patients and families feel confident recommending the program to another parent. The future availability of this option for their child was rated as the most positive aspect of the decision to proceed with cryopreservation.

The Pediatric Fertility Preservation Program offers both ovarian and testicular tissue cryopreservation options for individuals undergoing cancer therapy or facing other fertility-threatening conditions or treatments, to preserve reproductive potential in a timely manner regardless of pubertal status.