Modeling Variation in the Reproductive Lifespan of Female Adolescent and Young Adult Cancer Survivors Using AMH.

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.

Reproductive intentions in childless female adolescent and young adult cancer survivors.

OBJECTIVE: To examine the association between prior cancer treatments, medical comorbidities, and voluntary childlessness in reproductive-age women who are survivors of cancers diagnosed as adolescents and young adults (AYA survivors). DESIGN: Cross-sectional analysis. SETTING: Participants were recruited from California and Texas cancer registries, fertility preservation programs, and cancer advocacy groups. PATIENT(S): Women (n = 413) ages 18-40 who were diagnosed with cancer between ages 15 and 35, completed primary cancer treatments, had at least one ovary, and were nulliparous. INTERVENTION(S): Cancer treatment gonadotoxicity and medical comorbidities. MAIN OUTCOME MEASURE(S): Voluntary childlessness. RESULT(S): The mean age of survivors was 31.8 years (SD, 4.9) with a mean of 6.5 years (SD, 4.4) since cancer diagnosis. Breast (26%), thyroid (19%), and Hodgkin lymphoma (18%) were the most common cancers. Twenty-two percent of the cohort was voluntarily childless. Medical comorbidities, cancer diagnosis, prior surgery, prior chemotherapy, and prior gonadotoxic treatments were not significantly associated with voluntary childlessness. In adjusted analysis, survivors of older reproductive age (adjusted odds ratio = 2.97 [1.71-5.18]) and nonheterosexual participants (adjusted odds ratio = 4.71 [2.15-10.32]) were more likely to report voluntary childlessness. CONCLUSION(S): A moderate proportion of AYA cancer survivors are voluntarily childless, but reproductive intentions were not related to cancer type or cancer treatments. AYA survivors of older age and nonheterosexual identification were more likely to be voluntarily childless. These data support assessing reproductive intentions and tailoring reproductive care such as fertility and contraception counseling that is appropriate for a survivor's intentions.

Efficacy of a web-based women's health survivorship care plan for young breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivorship care plans (SCP) have limited content addressing women's health issues. This trial tested if young breast cancer survivors who receive a web-based, women's health SCP were more likely to improve on at least one of the four targeted issues (hot flashes, fertility-related concerns, contraception, and vaginal symptoms) compared to attention controls. METHODS: A randomized controlled trial recruited female survivors ages 18-45 at diagnosis, 18-50 at enrollment, completed primary cancer treatment, and had a significant women's health issue: moderate or higher fertility-related concerns; ≥ 4 hot flashes/day with ≥ 1 of moderate severity; ≥ 1 moderate vaginal atrophy symptoms; or not contracepting/using less effective methods. Survivors underwent stratified, block randomization with equal allocation to intervention and control groups. The intervention group accessed the online SCP; controls accessed curated resource lists. In intention-to-treat analysis, the primary outcome of improvement in at least one issue by 24 weeks was compared by group. RESULTS: 182 participants (86 intervention, 96 control), mean age 40.0 ± 5.9 and 4.4 ± 3.2 years since diagnosis, were randomized. 61 intervention group participants (70.9%) improved, compared to 55 controls (57.3%) (OR 1.82, 95% CI 0.99-3.4, p = 0.057). The following issue-specific improvements were observed in the intervention versus control arms: fertility-related concerns (27.9% vs. 14.6%, OR 2.3, 95% CI 1.1-4.8); hot flashes (58.5% vs. 55.8%, OR 1.1, 95% CI 0.57-2.2); vaginal symptoms (42.5% vs. 40.7%, OR 1.1, 95% CI 0.6-2.0); contraception (50% vs. 42.6%, OR 1.4, 95% CI 0.74-2.5). CONCLUSIONS: In young breast cancer survivors, a novel, web-based SCP did not result in more change in the primary outcome of improvement in at least one of the four targeted women's health issues, than the attention control condition. The intervention was associated with improved infertility concerns, supporting efficacy of disseminating accessible, evidence-based women's health information to this population.

Perceived infertility and contraceptive use in the female, reproductive-age cancer survivor.

OBJECTIVE: To estimate the association between perceived fertility potential and contraception use and to characterize factors important in contraceptive decision making in reproductive-age, female cancer survivors. DESIGN: Cross-sectional study. SETTING: Participants were from two state cancer registries, physician referrals, and cancer survivor advocacy groups in the United States. PATIENT(S): A total of 483 female survivors aged 18-40 years. INTERVENTION(S): Online questionnaire. MAIN OUTCOME MEASURE(S): Contraception use. RESULT(S): Eighty-four percent of participants used contraception; 49.7% used highly effective, World Health Organization tiers I and II methods (surgical sterilization, intrauterine devices, contraceptive implant, combined hormonal contraceptives, medroxyprogesterone acetate, progestin-only pills, contraceptive diaphragm). Contraception non-use was more common among survivors who perceived themselves to be infertile, compared with survivors who perceived themselves to be as or more fertile than similarly aged peers (prevalence ratio 4.0, 95% confidence interval 2.5-7.4). In mediation analysis that adjusted for clinical infertility, 59% of the association between prior chemotherapy and contraception non-use was explained by perceived infertility. Contraception efficacy (n = 62, 25.8%) and ease of use (n = 50, 20.8%) were the most cited reasons for using tier I/II methods; compared with lack of hormones (n = 81, 49.7%) as the predominant reason for using less-effective, tier III/IV methods. CONCLUSION(S): Although female, reproductive-age cancer survivors had high uptake of contraception, those who perceived themselves to be infertile were less likely to use contraception. Throughout survivorship, clinicians should counsel survivors on fertility potential in the context of their prior cancer treatments and on factors, including contraceptive efficacy and hormone-free contraception, that inform reproductive decision making in this population.

Design of a randomized controlled trial on the efficacy of a reproductive health survivorship care plan in young breast cancer survivors.

BACKGROUND: Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE: Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS: SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. RESULTS: Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5-90.7%) and confidence (50.0-74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. CONCLUSION: Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management.

Use of emergency contraception among female young adult cancer survivors.

OBJECTIVE: To test whether emergency contraception use in reproductive-aged cancer survivors is higher than in the general U.S. population and evaluate factors associated with use among survivors. DESIGN: A retrospective cohort study compared emergency contraception use between cancer survivors in the Reproductive Window Study on ovarian function after cancer and in the general population in the 2006-2010 National Survey for Family Growth. In a cross-sectional analysis of survivors, multivariable models were used to test associations between participant characteristics and emergency contraception use. SETTING: Not applicable. PATIENT(S): A total of 616 female cancer survivors aged 18-40. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-reported emergency contraception use. RESULT(S): The mean age of survivors was 33.4 ± 4.7, at a mean 7.5 years since diagnosis. Breast cancer (22%), Hodgkin lymphoma (18%), and leukemia (8%) were the most common cancers. Since diagnosis, 156 (25.3%) used emergency contraception, 60% because of not otherwise using contraception. Age-adjusted prevalence of use was higher in survivors than in the general population (28.3% [95% confidence interval (CI) 24.7-31.9] vs. 12.0% [95% CI 11.1-12.9]). In multivariable analysis among survivors, nonwhite race (prevalence ratio [PR] 1.3, 95% CI 1.0-1.8), breast cancer (PR 0.6, 95% CI 0.4-1.0), partnered relationship (PR 0.6, 95% CI 0.5-0.9), and older age (age 36-40 vs. 31-35; PR 0.7, 95% CI 0.5-1.0) were associated with emergency contraception. CONCLUSION(S): Female young adult cancer survivors were significantly more likely to use emergency contraception compared with the general population. Populations including nonwhite survivors have a higher risk, suggesting differences in family planning care. Strategies to improve contraception and decrease the need for emergency contraception are needed.