Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Gonadal Tissue Cryopreservation for Children with Differences of Sex Development.

INTRODUCTION: Infertility is common for individuals with differences of sex development (DSD) and is a significant concern to these individuals. Fertility potential in many DSD conditions is poorly understood. Gonadal tissue cryopreservation (GTC) for fertility preservation (FP) is offered to children with cancer undergoing gonadotoxic therapy. Our team sought to expand the field of FP by offering and evaluating the success of GTC for individuals with DSD. MATERIALS AND METHODS: GTC was offered to patients with DSD undergoing prophylactic gonadectomy, after extensive multidisciplinary counseling. For those who elected to attempt GTC, data were retrospectively abstracted, including: DSD diagnosis, age at gonadectomy, indication for gonadectomy, pathology results, and final decision about long-term gonadal tissue storage. RESULTS: Ten patients were enrolled to attempt GTC, with a mean age of 11.5 years (range 1-18). Five of the 10 patients had germ cells (GCs) present. Diagnoses (age at gonadectomy) for patients with GCs included ovotesticular DSD (13 months), mixed gonadal dysgenesis (17 months), partial gonadal dysgenesis (3 years), partial androgen insensitivity syndrome (11 years), and mixed gonadal dysgenesis (12 years). Four of the 5 subjects with GCs elected for GTC. One opted against GTC, citing immature gametes that did not match gender identity. CONCLUSION: GTC at the time of gonadectomy for patients with DSD is feasible. In many patients, GCs are present. While questions remain about the timing of gonadectomy, quality of GCs, and future success for use of the tissue based on technological advancement, GTC represents a novel approach to experimental FP for individuals with DSD.

Testicular wedge biopsy for fertility preservation in children at significant risk for azoospermia after gonadotoxic therapy.

BACKGROUND/PURPOSE: Testicular tissue cryopreservation (TTC) provides an experimental option for fertility preservation for male children at significant risk for azoospermia owing to high-risk gonadotoxic treatments. METHODS: A single institution, retrospective review of TTC cases from 2015 to 2017. Children at significant risk for azoospermia were eligible for study inclusion. A unilateral wedge biopsy of the testis was performed for TTC. RESULTS: TTC was performed in 23 patients. Average age was 10 years old (5 months to 18 years). Diagnoses included solid tumor (74%, n = 17), hematologic malignancy (17%, n = 4), and benign hematologic disease (13%, n = 3). Six patients had TTC at the time of disease relapse. Nine patients were referred for TTC prior to stem cell transplantation. The majority (70%, n = 16) of patients had an additional procedure at the time of TTC. One patient developed postoperative scrotal cellulitis that was treated with antibiotics. The majority of patients (96%, n = 22) had normal testicular tissue with the presence of germ cells on histopathological analysis. Median time to start of medical therapy was seven days with no unanticipated treatment delays. CONCLUSIONS: Testicular wedge biopsy for TTC can be performed safely, coordinated with other necessary procedures, and does not delay the start of treatment. TTC remains an experimental option for fertility preservation for children, as no spermatogenic recovery or pregnancies from cryopreserved testicular tissues have been reported to date. LEVEL OF EVIDENCE: IV.

Laparoscopic unilateral oophorectomy for ovarian tissue cryopreservation in children.

BACKGROUND/PURPOSE: Many survivors of childhood cancer will experience premature gonadal insufficiency or infertility as a consequence of their medical treatments. Ovarian tissue cryopreservation (OTC) remains an experimental means of fertility preservation with few reports focused on the surgical technique and postoperative outcomes for OTC in children. METHODS: This is a single institution, retrospective review of OTC cases from January 2011 to December 2017. Children were eligible for OTC if they had a greater than 80% risk of premature ovarian insufficiency or infertility owing to their anticipated gonadotoxic medical treatment. RESULTS: OTC was performed in 64 patients. Median age was 12 years old (range: 5 months-23 years). Nearly half (48%) of the patients were premenarchal. Laparoscopic unilateral oophorectomy was performed in 84% of patients. There were no surgical complications. In 76% of patients, OTC was performed in conjunction with an ancillary procedure. The majority (96%) of patients were discharged within 24 hours. Median time from operation to medical therapy was six days, with no unanticipated treatments delays attributable to OTC. CONCLUSIONS: Laparoscopic unilateral oophorectomy for OTC can be performed safely, in combination with other ancillary procedures, as an outpatient procedure without delaying medical therapy for children facing a fertility-threatening diagnosis or treatment. LEVEL OF EVIDENCE: IV.

Gonadal Tissue Cryopreservation for a Girl With Partial Androgen Insensitivity Syndrome.

Individuals with differences/disorders of sex development (DSD) have increased rates of infertility. For children and youth undergoing prophylactic gonadectomy for malignancy risk, our institution offers gonadal tissue cryopreservation, an experimental technique to preserve fertility cryopotential. An 11-year-old girl with partial androgen insensitivity syndrome presented for evaluation for fertility preservation in the setting of a planned bilateral gonadectomy at an outside institution. At presentation, the patient had begun puberty with an elevated serum androgen level and was experiencing undesired virilization. She expressed a strong female gender identity, an understanding of the various treatment options, and a preference for gonadectomy to prevent further virilization. After thorough counseling with the patient and family in our institution's multidisciplinary DSD clinic, she underwent bilateral gonadectomy with gonadal tissue cryopreservation. Her gonadal pathologic examination demonstrated well-developed peripubertal testes, with present, albeit decreased, numbers of spermatogonial germ cells, decreased Leydig cells, and nonspecific degenerative changes. The patient and her family chose to maintain the cryopreserved tissue for the patient's potential future use. To the best of our knowledge, the present case is the first reported case of gonadal tissue cryopreservation in a patient with partial androgen insensitivity syndrome. Storage of gonadal tissue is a feasible method of germ cell preservation in patients with DSD undergoing gonadectomy, although further research advances are required to facilitate development of this tissue into mature gametes capable of biological fertility.

Fertility Preservation for Transgender Adolescents.

PURPOSE: To describe fertility preservation (FP) utilization by transgender adolescents within a pediatric gender clinic between July 2013 and July 2016. METHODS: A retrospective chart review was conducted to abstract demographic and clinical information among adolescents initiating gender-affirming hormones, including patient age at initial FP consultation, birth-assigned sex, race/ethnicity, and outcome of FP consultation. RESULTS: In our sample of 105 transgender adolescents, a total of 13 (seven transgender men and six transgender women) between the age of 14.2 and 20.6 years were seen in formal consultation for FP before initiating hormones. Of these adolescents, four completed sperm cryopreservation and one completed oocyte cryopreservation. CONCLUSIONS: Rates of FP utilization among transgender youth were low, which is consistent with a recently published report of FP utilization among transgender youth at another pediatric institution. Identified barriers to FP in our sample included cost, invasiveness of procedures, and desire not to delay medical transition.

Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications.

PURPOSE: As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life. METHODS: The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus. RESULTS: This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed. CONCLUSION: Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.