Abstract Context Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown. Objective To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age. Design In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis. Results 763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P < 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction < 0.001). Conclusions In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.

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Background Younger breast cancer survivors consistently report a greater impact of their cancer experience on quality of life compared with older survivors, including higher rates of body image disturbances, sexual dysfunction, and fatigue. One potential strategy to improve quality of life is through physical activity, but this has been understudied in younger breast cancer survivors, who often decrease their activity during and after cancer treatment. Objective The aim of this study is to explore the feasibility and acceptability of a technology-based, remotely delivered, peer-led physical activity intervention for younger breast cancer survivors. We will also assess the preliminary impact of the intervention on changes in physical activity and multiple aspects of quality of life. Methods This study is a community-academic partnership between University of California, San Diego and Haus of Volta, a nonprofit organization that promotes positive self-image in younger breast cancer survivors. This ongoing pilot study aims to recruit 30 younger breast cancer survivors across the United States (<55 years old, >6 months post primary cancer treatment, self-report <60 min of moderate-to-vigorous-intensity physical activity [MVPA]) into a 3-month peer-delivered, fully remote exercise program. Participants will complete 6 biweekly video chat sessions with a trained peer mentor, a fellow younger breast cancer survivor. Participants will receive a Fitbit Charge 3; weekly feedback on Fitbit data from their peer mentor; and access to a private, in-app Fitbit Community to provide and receive support from other participants and all peer mentors. At baseline, 3 months, and 6 months, participants will complete quality of life questionnaires, and MVPA will be measured using the ActiGraph accelerometer. Feasibility and acceptability will be explored through a mixed methods approach (ie, quantitative questionnaires and qualitative interviews). Intervention delivery and adaptations by peer mentors will be tracked through peer mentor self-evaluations and reflections, review of video-recorded mentoring sessions, and monthly templated reflections by the research team. Results Recruitment began in September 2019. As of February 2020, the physical activity intervention is ongoing. Final measures are expected to occur in summer 2020. Conclusions This study explores the potential for physical activity to improve sexual function, body image, and fatigue, key quality of life issues in younger breast cancer survivors. Using peer mentors extends our reach into the young survivor community. The detailed process evaluation of intervention delivery and adaptations by mentors could inform a future hybrid-effectiveness implementation trial. Finally, remote delivery with commercially available technology could promote broader dissemination. Trial Registration ClinicalTrials.gov NCT04064892; https://clinicaltrials.gov/ct2/show/NCT04064892 International Registered Report Identifier (IRRID) DERR1-10.2196/18420

Context While stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors). Objective To evaluate applying STRAW+10 criteria in AYA survivors using bleeding patterns with and without endocrine biomarkers, and assess how cancer treatment gonadotoxicity is related to reproductive aging stage. Design The sample (n=338) included AYA survivors from the Window Study cohort. Menstrual bleeding data and dried blood spots for AMH and FSH measurements (Ansh DBS ELISAs) were utilized for reproductive aging stage assessment. Cancer treatment data were abstracted from medical records. Results Among participants, mean age 34.0±4.5 and at a mean of 6.9±4.6 years since cancer treatment, the most common cancers were lymphomas(31%), breast(23%), and thyroid(17%). Twenty-nine percent was unclassifiable by STRAW+10 criteria, occuring more frequently in the first 2 years from treatment . Most unclassifiable survivors exhibited bleeding patterns consistent with the menopausal transition, but had reproductive phase AMH and/or FSH levels. For classifiable survivors (48% peak reproductive, 30% late reproductive, 12% early transition, 3% late transition, 7% post-menopause), endocrine biomarkers distinguished among peak, early and late stages within the reproductive and transition phases. Gonadotoxic treatments were associated with more advanced stages. Conclusions We demonstrate a novel association between gonadotoxic treatments and advanced stages of reproductive aging. Without endocrine biomarkers, bleeding pattern alone can misclassify AYA survivors into either more or less advanced stages. Moreover, a large proportion of AYA survivors exhibited combinations of endocrine biomarkers and bleeding patterns that do not fit STRAW+10 criteria, suggesting the need for modified staging for this population.

Objective: To examine the association between prior cancer treatments, medical comorbidities, and voluntary childlessness in reproductive-aged women who are survivors of cancers diagnosed as adolescents and young adults (AYA survivors).

Objective To describe a clinical approach to and outcomes of in vitro fertilization in reproductive-aged cancer survivors on targeted cancer therapies. Design Case report Setting Academic fertility preservation program Patients The first case is of a female patient with metastatic lung cancer on long-term crizotinib, an ALK inhibitor. The second case is of a female patient with metastatic colon cancer on long-term denosumab, a RANKL antibody. Both patients presented desiring fertility. Interventions In vitro fertilization Main outcome measures Live birth and embryo banking Results The potential impact of targeted therapy on oocytes and pregnancy was investigated via literature review and pharmaceutical company inquiries. Following oncologic, fertility and psychological counseling, both survivors underwent ovarian stimulation, in vitro fertilization and preimplantation genetic screening. One couple achieved live births of dizygotic twins via gestational surrogacy. The second couple froze one euploid blastocyst for future fertility. Both survivors are stable from their cancer standpoints. Conclusion Successful fertility treatments are possible in the context of exposure to crizotinib, and denosumab.

Twin pregnancies in uterine didelphys and uterus bicornuate bicollis represent dicavitary twin pregnancies that can be managed using similar principles.Consideration must be given to delivery planning including mode of delivery and uterine incision.

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