Fertility assessment and treatment in adolescent and young adult cancer survivors.

In the survivorship setting, adolescent and young adult (AYA) cancer survivors frequently demonstrate little knowledge of infertility risk, are unclear regarding their fertility status, and may under- or overestimate their treatment-related risk for infertility. In female AYA survivors, ovarian function usually parallels fertility, and can be assessed with serum hormone levels and ultrasonography. Posttreatment fertility preservation may be appropriate for survivors at risk for primary ovarian insufficiency. In male AYA survivors, fertility and gonadal function are not always equally affected, and can be assessed with a semen analysis and serum hormones, respectively. As reproductive health issues are commonly cited as an important concern by survivors of AYA cancer, multidisciplinary care teams including oncology, endocrinology, psychology, and reproductive medicine are advocated, with the aim of optimal provision of fertility advice and care for AYA cancer survivors.

School-age outcomes among IVF-conceived children: A population-wide cohort study.

BACKGROUND: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. METHODS AND FINDINGS: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. CONCLUSIONS: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.

An algorithm to personalise the diagnosis of recurrent implantation failure based on theoretical cumulative implantation rate.

Recurrent implantation failure (RIF) is an imprecisely defined disorder lacking a robust scientific basis. The incomplete understanding of RIF provides significant diagnostic and therapeutic challenges, and a better understanding of the underlying issues is necessary to improve outcomes. We propose a novel concept termed 'Theoretical Cumulative Implantation Rate', the calculation of which is based on objective data, to define whether a patient should be diagnosed with RIF. An updated definition to assist with patient counselling and planning research studies, which is more precise and standardised, is well overdue.

Utilizing the Experience of Consumers in Consultation to Develop the Australasian Oncofertility Consortium Charter.

PURPOSE: In Australia and New Zealand, there has not been a national systematic development of oncofertility services for cancer patients of reproductive age although many cancer and fertility centers have independently developed services. A number of barriers exist to the development of these services, including a lack of clear referral pathways, a lack of communication between clinicians and patients about fertility preservation, differences in the knowledge base of clinicians about the risk of cancer treatment causing infertility and fertility preservation options, a lack of national health insurance funding covering all aspects of fertility preservation, and storage costs and cultural, religious, and ethical barriers. The development of strategies to overcome these barriers is a high priority for oncofertility care to ensure that equitable access to the best standard of care is available for all patients. METHOD: The FUTuRE Fertility Research Group led a collaborative consultation process with the Australasian Oncofertility Consumer group and oncofertility specialists to explore consumers' experiences of oncofertility care. Consumers participated in qualitative focus group meetings to define and develop a model of consumer driven or informed "gold standard oncofertility care" with the aim of putting together a Charter that specifically described this. CONCLUSIONS: The finalized Australasian Oncofertility Consortium Charter documents eight key elements of gold standard oncofertility care that will be used to monitor the implementation of oncofertility services nationally, to ensure that these key elements are incorporated into standard practice over time.

A Study Protocol for the Australasian Oncofertility Registry: Monitoring Referral Patterns and the Uptake, Quality, and Complications of Fertility Preservation Strategies in Australia and New Zealand.

Improvements in cancer diagnosis and treatment in patients of a reproductive age have led to significant improvements in survival rates; however, a patient's fertility can be affected by both cancer and its treatment. As survival rates improve, there is an expectation by clinicians and patients that patient's reproductive potential should be considered and protected as much as possible. However, there is a lack of data about current fertility preservation (FP) uptake as well as accurate data on the acute or permanent reproductive risks of cancer treatment, complications of FP in cancer patients, and the use and success of assisted reproductive technology by cancer survivors. FP remains a major gap in acute cancer management with lifelong implications for cancer survivors. The FUTuRE Fertility research team has established the first binational multisite Australasian Oncofertility Registry, which is collecting a complete oncofertility data set from cancer and fertility centers in Australia and New Zealand. Outcomes from the research study will monitor referral, uptake, and complications of FP, document patient's reproductive potential after treatment, and collect data on the use of assisted reproductive technology following cancer treatment. The data will be linked to other routine health and administrative data sets to allow for other research projects to be carried out. The changes in oncofertility care will be benchmarked against the Australasian Oncofertility Charter. The data will be used to develop evidence-based guidelines and resources, including development of accurate risk projections for patients' risk of infertility, allowing clinicians to make recommendations for FP or assisted reproductive technology. Australian New Zealand Clinical Trials Number-12615000221550.

A pilot study to assess the use of the gonadotrophin antagonist cetrorelix in preserving ovarian function during chemotherapy.

Cyclophosphamide treatment can cause premature ovarian failure. This pilot study evaluates the protective effect of the gonadotrophin releasing hormone (GnRH) antagonist, cetrorelix, on ovarian function, when used during cyclophosphamide chemotherapy in women aged 18-35. Primary outcomes measured were serum follicle stimulating hormone (FSH) and inhibin prior to and at 6 and 12 months after chemotherapy. Secondary outcomes were hormonal evidence of a suppressive effect and the side effect profile.

The first Australian experience of heterotopic grafting of cryopreserved ovarian tissue: evidence of establishment of normal ovarian function.

Cryostorage of reproductive potential, in the form of ovarian cortex, for young women about to undergo cytotoxic therapies has been offered clinically for some time. However, the prospects of re-establishing reproductive function using this tissue remain unclear. We now report reproducible follicular development, oocyte retrieval and embryo development following heterotopic grafting of cryopreserved ovarian cortex which had been stored for over 10 years.

Detection of Hodgkin lymphoma within ovarian tissue.

OBJECTIVE: To describe the detection of Hodgkin lymphoma within ovarian tissue taken at the time of harvest for cryopreservation. DESIGN: Case report. SETTING: University-affiliated women's hospital. PATIENT(S): A 19-year-old woman diagnosed with Hodgkin lymphoma. INTERVENTION(S): Laparoscopic removal of ovarian tissue for cryopreservation. MAIN OUTCOME MEASURE(S): Histologic and immunohistochemical evaluation of ovarian tissue harvested for fertility preservation. RESULT(S): Histologic and immunohistochemical identification of Hodgkin lymphoma within ovarian tissue harvested for cryopreservation. CONCLUSION(S): Ovarian cryopreservation and subsequent autografting is a procedure still in an experimental phase that has yielded promising findings. This option is frequently offered to young women with neoplasms such as Hodgkin lymphoma. Although the risk of Hodgkin lymphoma infiltration into the ovary may be low, the identification of lymphoma in this case emphasizes the importance of histologic examination of ovarian tissue before freezing and indicates that there is a possibility of reintroducing tumor.

Fertility preservation in adolescents and young adults with cancer.

Preservation of fertility is important to adolescent and young adult (AYA) survivors of cancer. Many survivors will maintain their reproductive potential after the successful completion of treatment for cancer. However total-body irradiation, radiation to the gonads, and chemotherapy regimens containing high-dose alkylators can place women at risk for acute ovarian failure or premature menopause and men at risk for temporary or permanent azoospermia. The most effective and established means of preserving fertility in this population is embryo cryopreservation in women and sperm cryopreservation in men before the initiation of cancer-directed therapy. Cryopreservation of mature oocytes is also becoming more commonplace as methods of thawing become more sophisticated. The use of in vitro fertilization and intracytoplasmic sperm injection has added to the viability of sperm and oocyte cryopreservation. Cryopreservation and transplantation of gonadal tissue in both males and females remains experimental but continues to be evaluated. Hormonal suppression has not been shown to be effective in males but may have promise in females, although larger scale trials are needed to evaluate this. Providing information about risk of infertility and possible interventions to maintain reproductive potential are critical for the AYA population at the time of diagnosis. Given the competing demands of providing complicated and detailed information about cancer treatment, the evolving information related to fertility preservation, and the ethical issues involved, it may be preferable, where possible, to have a specialized team, rather than the primary oncologist, address these issues with AYA patients.

Fertility preservation in female oncology patients.

Survival rates for patients treated for the majority of childhood and young adult cancers have improved dramatically in recent years. Despite the high probability of survival, and often good quality of life in female survivors, until recently the concept of fertility preservation has not been seen to be an important component of the overall management of these patients. Over the last few years, various protection and preservation strategies have been developed, which may address potential reproductive concerns. Gametes or embryos may be frozen prior to potentially gonadotoxic cancer therapy, and ovarian tissue may be frozen and stored, with several pregnancies described after subsequent grafting. There is also increasing interest in the possibility of ovarian protection using gonadotrophin-releasing hormone analogues during chemotherapy, despite the lack of randomised controlled trials. Additionally, there are reports of novel protective strategies, including therapeutic alteration or manipulation of the sphingomyelin pathways. This review summarises methods of fertility protection and preservation currently available, as well as the emergence of promising new strategies.