Time to therapy and safety of testicular tissue cryopreservation in children undergoing gonadotoxic treatment or hematopoietic stem cell transplant.

BACKGROUND: With the use of multimodal treatments and hematopoietic stem cell transplant, the majority of children diagnosed with malignancies and hematologic diseases are now surviving into adulthood. Due to the gonadotoxic effects and potential for future infertility associated with many of these treatments, fertility counseling with sperm cryopreservation prior to starting therapy is the standard of care for post-pubertal males. Unfortunately, the options are limited for pre-pubertal patients or those unable to provide a specimen. Testicular tissue cryopreservation (TTC) is an investigational method to surgically obtain germ cells from testicular tissue and potentially restore future spermatogenesis. While TTC has been shown to be safe, little is reported on the time to treatment following the procedure to ensure adequate wound healing and avoid delays in definitive therapy. OBJECTIVES: The primary outcome was the time to initiation of treatment following TTC. Secondary outcomes were complication rates, delays in treatment due to TTC, and presence of germ cells. METHODS: We conducted a single-institution retrospective cohort study of patients undergoing TTC between 2017 and 2023. Patients at significant risk for treatment related infertility based on established criteria were eligible for TTC. Patients were excluded if they received their oncology or hematology care elsewhere. All patients were enrolled in an IRB approved research protocol with 75% of the tissue submitted for cryopreservation and 25% for research purposes. Time to therapy was defined as the first receipt of gonadotoxic treatment following TTC. RESULTS: A total of 122 patients (53 = malignant, 69 = non-malignant) underwent TTC with a median age of 5.9 years (IQR 2.3-9.35). Germ cells were identified in 115 (94%) specimens. A total of 109 (89%) patients underwent concomitant procedures. The median time to initiation of therapy was 5 (IQR 1.0-7.0) and 7 days (IQR 6.0-13.0) for malignant and non-malignant disease, respectively. The 30-day surgical complication rate was 2.5% and was similar between malignant vs non-malignant diagnoses (p = 0.58). All surgical complications were managed non-operatively. No patients had a delay in definitive treatment due to concern for wound healing or complications. DISCUSSION: Our surgical complication rates are similar to previous studies and are not affected by the time to treatment following TTC. Limitations of the study are its retrospective design, single institution, and short-term follow up. CONCLUSION: TTC can be performed safely, efficiently, and in conjunction with other necessary procedures without resulting in delays of definitive treatment. TTC affords the opportunity for fertility preservation in children who have no other options.

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.

Reduced-Intensity Conditioning Mitigates Risk for Primary Ovarian Insufficiency but Does Not Decrease Risk for Infertility in Pediatric and Young Adult Survivors of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many pediatric malignant and nonmalignant conditions. Gonadal insufficiency or infertility is present in almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. Reduced-intensity conditioning (RIC) regimens are being increasingly used in medically fragile patients or in patients with nonmalignant diagnoses to limit the toxicities associated with HSCT; however, the short-term and long-term gonadal toxicity of RIC regimens in pediatric and young adult survivors remains unknown. In this study, we compared the prevalence of gonadal insufficiency and infertility among pubertal and postpubertal pediatric and young adult survivors of HSCT who received a RIC regimen versus those who received a MAC regimen. Twenty-three females (RIC, n = 8; MAC, n = 15) and 35 males (RIC, n = 19; MAC, n = 16) were included in this single-center, retrospective cross-sectional study. Eligible patients were those with available laboratory results who were ≥1 year post-HSCT, age <40 years, and pubertal or postpubertal as assessed by an endocrinologist. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels were measured in females, and FSH, LH, total testosterone, and inhibin B (InhB) levels were measured in males. Twenty-one males (RIC, n = 11; MAC, n = 10) underwent semen analysis through a separate consent. Parametric and nonparametric analyses were undertaken to compare the RIC and MAC groups. Female patients who received RIC were less likely than those who received MAC to develop primary ovarian insufficiency, as demonstrated by elevated FSH (P = .02) and low estradiol (P = .01) or elevated LH (P = .09). Most females in the RIC (75%) and MAC (93%) groups had low AMH levels, indicating low or absent ovarian reserve, with no significant difference between the groups (P = .53). In males, there were no significant differences between the 2 groups in the prevalence of abnormal FSH, LH, testosterone, or InhB levels. Ten of 11 RIC males (91%) and 10 of 10 MAC males (100%) had azoospermia or oligospermia, at a median time to semen analysis from HSCT of 3.7 years (range, 1.3 to 12.2 years). RIC may pose less risk than MAC for primary ovarian insufficiency among female survivors of HSCT; however, both female and male recipients of either RIC or MAC regimens are at high risk for infertility. In the largest reported series of semen analyses of pediatric and young adult male recipients of RIC, azoospermia or oligospermia was found in nearly all (91%) RIC survivors. All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve fertility in patients undergoing either RIC or MAC.

Factors Associated With Fertility Preservation in a Pediatric, Adolescent and Young Adult Population.

OBJECTIVE: To determine the patient characteristics associated with pursuing fertility preservation (FP) before gonadotoxic therapy in a pediatric, adolescent and young adult patient population. METHODS: This is a retrospective cohort study of patient data at Cincinnati Children's Hospital Medical Center. Demographics, clinical diagnoses, and treatment characteristics were compared between participants that selected FP versus those that declined. Variables were analyzed separately for males and females by logistic regression. RESULTS: Patients with a hematologic cancer were less likely to be eligible for preservation: 53.9% of ineligible males, P <0.001, and 51.8% of ineligible females, P <0.0001. Among patients who were candidates for FP, those receiving high-risk therapy were more likely to elect for FP (65.3% males, P <0.0001, and 87.5% of females, P <0.0001). Pubertal males were more likely to undergo preservation than prepubertal males (70.5% vs. 29.5%, P <0.0001; however, this trend was not demonstrated among female patients. In both males and females, race, ethnicity, religion, primary language, and insurance status were not shown to be statistically significant factors in predicting utilization of FP. CONCLUSION: Risk of infertility, type of cancer, and developmental status influenced decisions on pursuing FP in pediatric, adolescent and young adult patients facing iatrogenic infertility.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Active and Protected: Developing a "Safer Sex" Handout for Adolescents and Young Adults with Cancer.

There is a critical need to engage adolescents and young adults (AYAs) with cancer in conversations regarding "safer" sexual activity during treatment. Many providers, however, report lacking the knowledge and/or tools to engage in these discussions. This article describes the experience of one pediatric institution in assessing and addressing provider barriers to safer sexual activity discussions among AYAs with cancer. Feedback from patients and providers resulted in an educational handout detailing recommendations regarding safer sex practices for AYAs with cancer. Handout adoption, acceptability, appropriateness, and feasibility are described alongside barriers to assist other institutions seeking to develop similar interventions.

2019 Pediatric Initiative Network: Progress, Proceedings, and Plans.

Impairment of fertility and sexual/reproductive health are common after oncologic therapy, and are known to have negative impacts on romantic relationships and psychosocial well-being among childhood cancer survivors. The Pediatric Initiative Network (PIN) is an international, multidisciplinary group of providers within the Oncofertility Consortium dedicated to preserving and protecting the fertility of children and adolescents at risk for infertility due to medical conditions or treatments. The PIN and its Best Practices and Research committees meet virtually throughout the year, with one annual in-person meeting. The purpose of this "proceedings" is to highlight key discussion points from the annual PIN meeting which took place on November 11, 2019, to 1) provide a context for pediatric groups across the country on what oncofertility programs are currently doing and why, and 2) inform stakeholders of past, present and future initiatives that may be of value to them and the patient populations they serve.

Development of a Pediatric Fertility Preservation Program: A Report From the Pediatric Initiative Network of the Oncofertility Consortium.

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist. This report was developed from the institutional experiences of members of the Pediatric Initiative Network of the Oncofertility Consortium, with the intent of providing guidance for health care providers aiming to establish programs at institutions lacking pediatric fertility preservation services. The mechanics of building a fertility preservation program are discussed, including essential team members, target populations, fertility preservation options (both established and experimental), survivorship issues, research opportunities, and ethical considerations. Common barriers to program development and utilization, including low referral rates and financial concerns, are also discussed, and recommendations made for overcoming such barriers.