The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center.

BACKGROUND: Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center. METHODS: Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database. RESULTS: The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model. CONCLUSIONS: The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.

Diminished ovarian reserve in adolescent cancer survivors treated with heavy metal chemotherapy.

The extent to which heavy metal chemotherapy results in treatment-related ovarian damage is controversial. Anti-Mullerian hormone (AMH) levels measured more than 1 year after cancer therapy completion were abstracted from the medical records of 39 female survivors of childhood cancer aged 11 years and older, whose only gonadotoxic exposure was heavy metal chemotherapy. One-fifth of survivors who received cisplatin had AMH levels indicative of diminished ovarian reserve at last measurement. There was an observed clustering of low AMH in patients diagnosed in the peripubertal age range (i.e., 10-12 years). These findings may support a small, but present, risk of gonadal damage after heavy metal chemotherapy.

Oncofertility patient navigation: The frontlines of fertility and reproductive health care in cancer.

Oncofertility is an emerging field that incorporates diverse disciplines working together to care for oncology patients from birth to adulthood who are facing surgery, radiation therapy, or chemotherapy that may impact their fertility potential and reproductive function. Providing this care to newly diagnosed oncology patients in an expedited manner can be challenging. There is currently a paucity of published data about how this care is provided, training and education of individuals providing this care, and patient-reported outcomes related specifically to oncofertility care. The role of the oncofertility patient navigator is to bridge the institutional and disciplinary boundaries so oncology patients of all ages can receive timely information regarding fertility risk and preservation options at diagnosis and throughout survivorship care. The purpose of this paper is to define the role of the oncofertility patient navigator within diverse models of care and health care systems, and provide a framework for ongoing efforts to improve reproductive care for those affected by cancer in their years of child-bearing potential.

Fertility-related worry among emerging adult cancer survivors.

PURPOSE: Cancer survivors with a history of gonadotoxic treatment are at risk for future infertility and reproductive concerns, including worry about infertility. The purpose of this study was to describe factors associated with fertility-related worry among emerging adult survivors of childhood cancer. METHODS: This chart review included patients aged 18.00-25.99 years and > 1 year from cancer treatment completion with a history of gonadotoxic treatment. Survivors were offered structured fertility-focused discussions at age ≥ 18 years, which assessed worry about future infertility. Data from this discussion (i.e., reported fertility-related worry (yes/no), sociodemographic, and clinical characteristics were abstracted from the medical record. Multivariable logistic regression with backwards elimination was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with fertility-related worry. RESULTS: Survivors (N = 249) were a mean age of 19.1 ± 1.2 years at initial fertility discussion; 55.8% were male, 58.2% non-Hispanic White, and 27.3% were at high risk for future treatment-related infertility. Fertility-related worry was reported by 66.3% of survivors. Factors related to worry on multivariable analysis included female sex (OR: 2.64, 95%CI: 1.44-4.96, p = .002), solid tumor diagnosis (OR: 2.31, 95%CI: 1.15-4.71, p = .019), moderate and high risk of infertility (OR: 2.94, 95%CI: 1.23-7.64, p = .02; OR: 3.25, 95%CI: 1.55-7.17, p = .002), and ≥ 2 fertility discussions during survivorship care OR: 2.71, 95%CI: 1.46-5.20, p = .002). CONCLUSIONS: Two-thirds of emerging adult cancer survivors expressed worry about future infertility, which has been linked to a variety of adverse quality of life outcomes. Survivors who are worried about infertility may benefit from psychological interventions.

Interest in fertility status assessment among young adult survivors of childhood cancer.

BACKGROUND: Cancer survivors who received gonadotoxic treatment are at-risk for future infertility and may desire a fertility status assessment (FSA), defined as semen analysis for males and consultation with a reproductive specialist for females. The purpose of this study was to describe the proportion of, and factors associated with, interest in FSA among young adult survivors of childhood cancer. METHODS: This retrospective single-institution review included patients with prior gonadotoxic treatment, aged 18-25 years and >1 year from cancer treatment completion, who received a fertility-focused discussion during survivorship. Documentation of interest in and completion of FSA, worry about infertility, sociodemographic, and clinical characteristics were abstracted from medical records. Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with interest in FSA. RESULTS: Survivors (N = 259) were on average 19.2 ± 1.2 years at their fertility discussion; 55.6% were male and 57.9% non-Hispanic white. Interest in FSA was reported by 50.7% of males and 46.1% of females. Factors related to interest in FSA for males and females respectively, included worry about infertility (OR 2.40, 95%CI 1.11-5.27, p = 0.026 and OR 4.37, 95%CI 1.71-12.43, p = 0.003) and ≥2 fertility discussions (OR 3.78, 95%CI 1.70-8.75, p = 0.001 and 2.45, 95%CI 1.08-5.67, p = 0.033). Among males, fertility preservation consult/procedure at diagnosis (OR 3.02, 95%CI 1.09-9.04, p = 0.039) and high-risk for infertility (OR 2.47, 95%CI 1.07-5.87, p = 0.036) were also associated with interest in FSA. CONCLUSIONS: Cancer survivors are interested in FSA, particularly those who have had repeated fertility-focused discussions during survivorship care and who report worry about infertility.

Female Reproductive Health Outcomes after Hematopoietic Cell Transplantation for Sickle Cell Disease: Is Reduced Intensity Better Than Myeloablative Conditioning?

Curative therapy for sickle cell disease (SCD) through hematopoietic cell transplantation (HCT) is associated with a high level of risk for treatment-related gonadal dysfunction and future infertility. Both the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens used for SCD HCT are considered to carry a high risk for ovarian damage. Cyclophosphamide equivalent doses (CEDs) are thought to correlate with the degree of gonadal damage in pediatric oncology patients. We aimed to evaluate ovarian outcomes previously reported from our center, characterize the conditioning regimens as MAC or RIC, and calculate the CED for each regimen. The ovarian outcomes diminished ovarian reserve (DOR), as determined by an anti-Müllerian hormone (AMH) below the normal limits for age and assay or <5%, and premature ovarian insufficiency (POI), defined as a follicle-stimulating hormone (FSH) level >40 mIU/ML, are presented by conditioning regimen from 3 clinical studies from our center (2 published and 1 presented as an abstract in 2022). The studies were not mutually exclusive of patients. CEDs were calculated for each regimen. The CED ranged from 3388 to 9705 mg/m2 for MAC regimens and from 5600 to 18,750 mg/m2 for RIC regimens. DOR was observed in all regimens; however, in one study 2 patients had normal AMH levels after a fludarabine/melphalan regimen, and 1 patient had a normal AMH level after a fludarabine/melphalan/thiotepa regimen. Rates of POI were more variable and ranged from 40% to 100% after MAC regimens and from 0 to 100% after RIC regimens. Female patients with SCD who undergo HCT have very high rates of DOR after both MAC HCT and RIC HCT. Two of the 3 RIC regimens evaluated had higher CEDs than were seen in any of the MAC regimens evaluated. Rates of POI were more variable but may increase with time from transplantation. All SCD patients need to be counseled about the risk of infertility and provided information about fertility preservation.