Modeling of live-birth rates and cost-effectiveness of oocyte cryopreservation for cancer patients prior to high- and low-risk gonadotoxic chemotherapy.

STUDY QUESTION: What is the live-birth rate (LBR) and cost-effectiveness of fertility preservation with oocyte cryopreservation (FP-OC) compared to expectant management in cancer patients age 25-40 based on estimated gonadotoxicity of treatments 5 years after cancer diagnosis? SUMMARY ANSWER: Oocyte cryopreservation prior to cancer treatment is more costly, yet more effective (producing more live births), than not undergoing oocyte cryopreservation but it is most beneficial for patients undergoing high-risk chemotherapy (HRC). WHAT IS KNOWN ALREADY: The decision to undergo FP prior to treatment is multifactorial and can be costly and delay treatment. Not all treatments carry the same gonadotoxicity and patients may choose to undergo FP-OC based on the probability of premature ovarian insufficiency, predicted outcomes and cost. A comprehensive model that incorporates age at diagnosis and toxicity of treatment to help guide patients in the decision to undergo FP-OC does not yet exist. STUDY DESIGN, SIZE DURATION: This study used a Decision Analysis Model to estimate effectiveness and cost of FP for cancer patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Age-based estimates of LBR and cost per live birth were calculated for ages 25-40 years based on gonadotoxicity of treatment. A decision analysis model was constructed using Treeage Pro 2015 with case base probabilities derived from national registries, practice guidelines and medical records from a national network of infertility practices (IntegraMed). MAIN RESULTS AND THE ROLE OF CHANCE: Compared to no FP-OC, FP-OC improved LBRs for women of all ages undergoing either low-risk chemotherapy (LRC) or HRC; however, it was most cost effective for women undergoing LRC at older ages or HRC at younger ages. Although FP-OC results in higher LBRs, it was always more costly. Using donor oocyte IVF can be a successful alternative to autologous FP-OC. LIMITATIONS REASONS FOR CAUTION: Decision tree results reflect probabilities of certain events and are compiled from multiple reputable sources but are not directly derived from a recruited cohort of patients. Outcomes are based on United States estimates and should be interpreted in the broader context of individual patient diagnoses, treatment care plans and country of origin. WIDER IMPLICATIONS OF THE FINDINGS: The development of this analytic model will help guide practitioners in their counseling of women from age 25 to 40 years, who are considering FP-OC at the time of cancer diagnosis. It provides a realistic pathway from diagnosis to LB and accounts for the majority of costs and outcome possibilities. STUDY FUNDING/COMPETING INTEREST(s): This study was partially funded by a grant from National Institute of Health (NIH)/National Institute of Child Health and Human Development (NICHD) (R01 HD67683) to A.Z.S. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of skin regeneration after burns in vivo and rescue of cells after thermal stress in vitro following treatment with a keratin biomaterial.

Thermal burns typically display an injury pattern dictated by the transfer of the thermal energy into the skin and underlying tissues and creation of three zones of injury represented by a necrotic zone of disrupted cells and tissue, an intermediate zone of injured and dying cells, and a distant zone of stressed cells that will recover with proper treatment. The wound healing capabilities of a keratin biomaterial hydrogel were studied in two pilot studies, one using a chemical burn model in mice and the other a thermal burn model in swine. In both studies, keratin was shown to prevent enlargement of the initial wound area and promote faster wound closure. Interestingly, treating thermally stressed dermal fibroblast in culture demonstrated that soluble keratin was able to maintain cell viability and promote proliferation. Separation of so-called alpha and gamma fractions of the keratin biomaterial had differential effects, with the gamma fraction producing more pronounced cell survival and recovery. These results suggest that the gamma fraction, composed essentially of degraded alpha keratin proteins, may facilitate cell rescue after thermal injury. Treatment of burns with gamma keratin may therefore represent a potential therapy for wounds with an intermediate zone of damaged tissue that has the potential to contribute to spontaneous healing.