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

Differences in gonadal tissue cryopreservation practices for differences of sex development across regions in the United States

ObjectiveSome individuals with differences of sex development (DSD) conditions undergo medically indicated prophylactic gonadectomy. Gonads of individuals with DSD can contain germ cells and precursors and patients interested in future fertility preservation and hormonal restoration can participate in DSD-specific research protocols to cryopreserve this tissue. However, it is unclear how many providers or institutions offer gonadal tissue cryopreservation (GTC) and how widespread GTC for DSD is across the United States (US). The Pediatric Initiative Network (PIN) and Non-Oncologic Conditions committees of the Oncofertility Consortium sought to assess the current state of GTC for patients with DSD.MethodsAn electronic survey was sent to providers caring for patients with DSD via special interest groups of professional societies and research networks.ResultsThe survey was administered between November 15, 2021 and March 14, 2022. A total of 155 providers responded to the survey, of which 132 respondents care for patients with DSD, and 78 work at facilities that offer medically indicated gonadectomy to patients with DSD diagnoses. They represented 55 US institutions including 47 pediatric hospitals, and 5 international sites (Canada, Denmark, Germany, Qatar). Of individual providers, 41% offer cryopreservation after prophylactic gonadectomy for patients with DSD (32/78). At an institutional level, GTC after medically indicated gonadectomy is available at 54.4% (24/46) of institutions. GTC is offered for a variety of DSD diagnoses, most commonly 45,X/46,XY DSD (i.e., Turner Syndrome with Y-chromosome material and mixed gonadal dysgenesis), ovotesticular DSD, complete androgen insensitivity syndrome (CAIS), and complete gonadal dysgenesis. Responses demonstrate regional trends in GTC practices with 83.3% of institutions in the Midwest, 66.7% in the Northeast, 54.6% in the West, and 35.3% in the South providing GTC. All represented institutions (100%) send gonadal tissue for pathological evaluation, and 22.7% preserve tissue for research purposes.ConclusionsGTC after gonadectomy is offered at half of the US institutions represented in our survey, though a minority are currently preserving tissue for research purposes. GTC is offered for several DSD conditions. Future research will focus on examining presence and quality of germ cells to support clinical decision making related to fertility preservation for patients with DSD

Fertility preservation for male patients with childhood, adolescent, and young adult cancer:recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Item does not contain fulltextMale patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life

Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations

BACKGROUND: To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer's disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer's disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid- peptides (A). We have here studied the effects of small amounts of A25-35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with A25-35. A25-35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25-35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements. CONCLUSIONS/SIGNIFICANCE: Nanomolar A25-35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25-35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system

Installing oncofertility programs for common cancers in optimum resource settings (Repro-Can-OPEN Study Part II): a committee opinion

The main objective of Repro-Can-OPEN Study Part 2 is to learn more about oncofertility practices in optimum resource settings to provide a roadmap to establish oncofertility best practice models. As an extrapolation for oncofertility best practice models in optimum resource settings, we surveyed 25 leading and well-resourced oncofertility centers and institutions from the USA, Europe, Australia, and Japan. The survey included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed three major characteristics of oncofertility practice in optimum resource settings: (1) strong utilization of sperm freezing, egg freezing, embryo freezing, ovarian tissue freezing, gonadal shielding, and fractionation of chemo- and radiotherapy; (2) promising utilization of GnRH analogs, oophoropexy, testicular tissue freezing, and oocyte in vitro maturation (IVM); and (3) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, in vitro spermatogenesis, and stem cell reproductive technology as they are still in preclinical or early clinical research settings. Proper technical and ethical concerns should be considered when offering advanced and experimental oncofertility options to patients. Our Repro-Can-OPEN Study Part 2 proposed installing specific oncofertility programs for common cancers in optimum resource settings as an extrapolation for best practice models. This will provide efficient oncofertility edification and modeling to oncofertility teams and related healthcare providers around the globe and help them offer the best care possible to their patients

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

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. 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. 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. 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

Reproductive health in transgender and gender diverse individuals: A narrative review to guide clinical care and international guidelines

Background: Hormonal treatments and surgical interventions practiced with the aim to affirm gender identity in transgender and gender diverse patients may impact their future reproductive ability, family building, and family planning options. Whereas it is recommended by international guidelines to discuss the potential risks of infertility and to present fertility preservation (FP) options to transgender individuals and their families prior to initiating any of these treatments, many barriers still remain. Further, transgender and gender diverse individuals often experience barriers to accessing contraception, abortion, pre-conception care, and comprehensive perinatal care. Aims: In this review we summarize the current literature on reproductive healthcare issues reported in transgender people including fertility issues, fertility preservation (FP), contraception, pregnancy and lactation and perinatal health. Methods: A narrative literature search of major databases (Pubmed, Medline, PsycInfo, Google Scholar, Web of Science) was conducted. Given the paucity and heterogeneity of studies, summative review tactics were not available. The literature was critically reviewed by international experts in the field with focus on the impact of gender-affirming medical interventions on future fertility, current FP options and reproductive health issues in transgender people. Results: The current literature supports that transgender and gender diverse individuals may wish to have genetically related children in the future, rendering the issue of FP relevant to this patient group. The cryopreservation of mature gametes is an efficacious option for FP for post-pubertal adolescents and adults. It is recommended to discuss these options at time of planning for gender-affirming hormonal therapy (GAHT) or engaging with other gender-affirming procedures that can limit future fertility. Discontinuation of GAHT may allow individuals to undergo FP later, but data are limited and there is the concern of symptoms and consequences of stopping GAHT. For pre-pubertal and early pubertal children, FP options are limited to the cryopreservation of gonadal tissue. At present the tissue can become functional only after re-transplantation, which might be undesirable by transgender individuals in the future. Preconception counseling, prenatal surveillance, perinatal support, contraceptive, and pregnancy termination related healthcare need to be meaningfully adapted for this patient population, and many knowledge gaps remain. Discussion: Specialized FP reproductive healthcare for transgender and gender diverse individuals is in early evolution. Research should be conducted to examine effects of medical interventions on fertility, timing of FP, gamete preservation and outcome of the fertility treatments. Strategies to inform and educate transgender and gender diverse patients can lead to optimization of reproductive care and counseling and decision making of FP for this population