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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.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Purpose: Gonadal damage is a common consequence of treatment for pediatric malignancies. Nononcologic conditions may also utilize treatments with potential impact on fertility. Models for oncology fertility preservation programs have emerged and demonstrate that a multidisciplinary team approach can have a positive impact on referral patterns, appropriate risk counseling, and access to fertility preservation options. Expansion of programmatic breadth is needed, providing improved care to nonmalignant conditions where the disease itself may impact reproductive health or treatment modalities., Methods: With support from the Department of Pediatrics Chair's Initiative, a multidisciplinary, hospital-wide Fertility Preservation Service was created at the Children's Hospital of Philadelphia. A centralized team provides fertility consults across the institution, allowing for risk-based counseling and facilitation of fertility preservation options (both standard care and experimental)., Results: Team structure, consult process, and available fertility options for prepubertal and pubertal males and females are described. Preinitiative and postinitiative referral patterns were analyzed. Postinitiative referrals from divisions outside oncology more than doubled (34% vs. 15% at baseline)., Conclusions: A comprehensive model for fertility counseling provides accessible, high-value fertility preservation care to pediatric and young adult patients with a wide variety of diagnoses. A centralized point of contact ensures timely referrals and risk-based counseling and streamlines access to fertility preservation procedures., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach., Materials and Methods: We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values., Results: A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6 months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation., Conclusions: The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Future fertility is an important concern for many cancer survivors. Cancer therapies have been shown to adversely impact reproductive function. However, it is difficult to predict the extent to which reproductive dysfunction will occur. The purpose of this study was to compare measures of ovarian reserve (MOR) and pregnancy rates in young female cancer survivors and similar-aged controls., Procedures: A prospective cohort study was conducted in a university-hospital setting. Participants were followed annually for a mean 25 months to assess reproductive history, the incidence of pregnancy, and MOR (serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, anti-mullerian hormone (AMH), antral follicle counts and mean ovarian volume)., Results: Eighty-four female survivors (average age 26, and 14 years post-treatment) and 98 similar-aged controls that were sexually active with men were included. At baseline, 27/84 survivors and 42/98 controls reported a prior pregnancy. Adjusted models showed that anti-mullerian hormone (AMH) and antral follicle count (AFC) were impaired in survivors with a prior pregnancy compared to controls with a prior pregnancy (P < 0.01, P = 0.03). During follow-up in 56 survivors and 74 controls, 19 pregnancies occurred in survivors and 18 in controls. Comparison of MOR between survivors who became pregnant and controls who became pregnant revealed that AMH and AFC were impaired in survivors (P < 0.05). Compared to survivors who did not become pregnant, survivors who did were older (P < 0.01) and more likely to be cohabitating (P < 0.01), but had similar MOR and exposure to alkylators (P = 0.34)., Conclusions: Survivors achieved pregnancy at a rate similar to controls despite impaired MOR., (© 2013 Wiley Periodicals, Inc.)

Unlabelled: Over the past several decades, pediatric oncologists have seen the growth in the number of patients surviving their cancer. This is in large part due to the use of multimodal therapy including chemotherapy, surgery, and radiotherapy. As the number of survivors of pediatric cancer continues to grow, however, we need to begin to focus on improving the quality of the lives that are being saved. Unfortunately, many regimens used today to cure pediatric cancer patients are gonadotoxic. Therefore, many of our survivors must contend with infertility. It is critical that pediatric oncologists consider the likelihood of gonadotoxicity prior to beginning therapy in this patient population in order to counsel patients and their families properly in order to potentially offer fertility preservation options., Conclusion: Infertility is a critical quality of life issue for pediatric cancer survivors and their families. Fertility preservation techniques need to continue to be studied and developed in order to lessen the likelihood that future cancer survivors will be infertile. This review outlines the risk for infertility, provides an assessment of the survivors reproductive functioning, and summarizes the currently available methods of preserving fertility in pediatric cancer survivors.

More than 80% of those diagnosed with Hodgkins disease (HD) will survive long-term. For the past decade, a modified hybrid consisting of cyclophosphamide (2.4-3.6g/m(2)), vincristine, procarbazine, and prednisone (COPP) together with adriamycin, bleomycin, and vinblastine (ABV) has been used to treat patients with HD. Little data exists on how this modified hybrid impacts male fertility. Eleven male patients treated with COPP-ABV hybrid were studied. Nine out of 11 subjects were categorized as infertile by semen analysis; 7 of 9 were azoospermic. There was no association between fertility status and prepubertal status at diagnosis or gonadotropin status. Despite lower doses of cyclophosphamide, treatment with the current COPP/ABV hybrid leads to infertility in the majority of young men. It is likely that procarbazine, an effective yet potent gonadotoxic agent, is responsible for this outcome.

SUMMARY Objective Fertility preservation (FP) is a widespread practice in paediatric oncology when gonadotoxic medications such as cyclophosphamide (CPO) are used. FP practice outside of oncology has not been studied, although nephrologists regularly use CPO. This is the first study to explore FP practice by paediatric nephrologists when CPO is used. Design Survey study. Descriptive statistics and chi-squared analyses were employed to analyse the data. Participants US paediatric nephrologists were sent a survey via email. The survey queried participants about FP practice behaviours, FP attitudes and barriers to practice. Main Outcome Measures Of 579 nephrologists invited, 32% responded to the survey. Results CPO was dosed in mg/kg by 23% of physicians, g/m2 by 40% and both by 37%. About 80% agreed that pubertal females should be offered a fertility referral, while 58% report that they actually refer. Factors negatively associated with referral include lack of training, lack of referral network and adherence to gonadotoxic dose limits. Results were similar for male patients. Conclusion The survey showed that FP practice in the United States is widespread among nephrologists. Lack of referral networks is a notable barrier for nephrologists. Perceived adherence to dose limits may be problematic given the variable dosing regimens utilised. This is due to the risk of unintended overdose in large adolescents dosed in mg/kg whose cumulative dose exceeds gonadotoxic limits in g/m2. This paper has implications for nephrology care providers and other specialists who utilise CPO, generalists who care for these patients and oncologists with extant FP referral networks. [ABSTRACT FROM AUTHOR]

Craniospinal irradiation (CSI) is associated with infertility risk for adolescent/young adult women. We explore two methods of reducing ovarian exposure: oophoropexy (surgical removal of the ovaries from the path of the X-ray beam) and proton therapy (to allow the beam to stop without exposing the ovaries/uterus). In the case discussed, oophoropexy followed by X-ray CSI reduced ovarian dose to that at which 50% of oocytes are expected to survive, and the patient appears to have viable oocytes; this technique did not reduce uterine dose. Proton therapy would have eliminated the ovarian and uterine dose and the need for oophoropexy. [ABSTRACT FROM AUTHOR]

Background: As advancements in cancer therapies have led to dramatic improvements in long term survival, there has been increasing interest in methods to expand fertility preservation options for cancer patients. Methods: An experimental protocol for ovarian tissue cryopreservation was developed at the University of Pennsylvania for patients requiring gonadotoxic therapies. The protocol for adults was implemented at the Hospital of the University of Pennsylvania and for children at the Children's Hospital of Philadelphia in collaboration with the Oncofertility Consortium and the National Physicians Cooperative (NPC). Results: A total of twenty-one patients (age range: 8-36 years) have cryopreserved ovarian tissue as part of this study. While patients had a variety of diagnoses and treatment exposures, 10/21 (48 %) patients suffered from hematologic disorders and 43 % were anticipating stem cell transplantation. No patients have requested that the tissue be used for clinical purposes. Conclusions: Ovarian tissue cryopreservation protocols can be implemented at pediatric and adult institutions through multi-disciplinary collaboration. While more research is needed to determine the safety and efficacy of ovarian tissue cryopreservation, this procedure provides hope for preserving the ability to have biological offspring to patients facing gonadotoxic therapies for a variety of medical conditions. [ABSTRACT FROM AUTHOR]

Abstract: Recent advances in treatment for pediatric cancers has increased overall survival rates. As more and more survive pediatric cancer, we continue to see the emergence of late effects of treatment within pediatric and the growing adult survivor population. The evaluation of late effects was initiated approximately two decades ago, and has become an extremely important facet of pediatric oncology. This review delves into several of the most serious organ-specific late effects of pediatric cancer treatment, outline what we know and what we do not currently understand about preventing or reducing them. Clinical and bench researach are necessary to develope interventions that will avoid or mitigate late effects and improve the health of pediatric cancer survivors. [Copyright &y& Elsevier]

Objective: To identify factors associated with ovarian reserve impairment during and immediately after chemotherapy. Design: Prospective cohort study. Setting: Four university hospitals. Patient(s): Forty-six adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy. Intervention(s): None. Main Outcome Measure(s): Measurements of ovarian reserve via levels of serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, and antimüllerian hormone (AMH) as well as antral follicle counts and mean ovarian volume at 3-month intervals. Result(s): Changes in ovarian reserve were quantified for both the acute impact of treatment using linear regression and the longitudinal recovery after therapy using mixed-effects models adjusted for baseline ovarian reserve, use of alkylating agent, and hormone use. The women had at least one pretreatment and two posttreatment study visits (mean follow-up interval: 12 months). All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy. Alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment, and pretreatment AMH levels were associated with the rate of recovery of AMH after treatment. In adjusted models, participants with a pretreatment AMH level >2 ng/mL recovered at a rate of 11.9% per month after chemotherapy, whereas participants with pretreatment AMH levels ≤2 ng/mL recovered at a rate of 2.6% per month after therapy. Conclusion(s): Baseline ovarian reserve and alkylating agent exposure effect the magnitude of acute changes in ovarian reserve from chemotherapy. The rate of recovery of AMH is impacted by pretreatment levels. This should be considered during pretreatment fertility preservation counseling. [ABSTRACT FROM AUTHOR]

Objective: To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age. Design: Cross-sectional analysis of data from a prospective cohort study. Setting: University medical center. Patient(s): Seventy-one cancer survivors aged 15–39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40–52 years). Intervention(s): None. Main Outcome Measure(s): Early follicular-phase hormones (FSH, E2, inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression. Result(s): In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40–42-year-old controls. Conclusion(s): Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. ClinicalTrials.gov identifier: NCT01143844. [ABSTRACT FROM AUTHOR]