Association of platinum-based chemotherapy with live birth and infertility in female survivors of adolescent and young adult cancer.

OBJECTIVE: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. DESIGN: Retrospective cohort study. SETTING: US administrative database. PATIENTS: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. INTERVENTION: Platinum-based chemotherapy. MAIN OUTCOME MEASURES: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). RESULTS: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively. CONCLUSIONS: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions.

Development, Usability Testing, and Implementation Assessment of Cancer Related Infertility Score Predictor, an Online Cancer Related Infertility Risk Counseling Tool.

Purpose: Oncofertility counseling of female cancer patients lacks efficient access to tailored and valid infertility risk estimates to support shared decision-making on fertility preservation treatments. The objective was to develop, conduct user-centered design, and plan clinic-based implementation of the Cancer Related Infertility Score Predictor (CRISP), a web-based tool to support infertility risk counseling. Methods: Using a mixed methods design, literature review was undertaken to abstract data on infertility, primary ovarian insufficiency, and amenorrhea risks of common cancer treatments. The CRISP website was programmed to take user input about patient ages and cancer treatments and generate a risk summary. Using user experience methodology and semistructured interviews, usability testing and implementation assessment were conducted with 12 providers recruited from 5 medical centers in Southern California. Results: The web-based CRISP tool encompasses infertility risk data for 60 treatment regimens among 10 cancer types. Usability testing demonstrated that the tool is intuitive and informed minor modifications, including adding crowd-sourced submission of additional cancer treatments. Participants rated the tool as credible, advantageous over current provider methods to ascertain infertility risks, and useful for tailoring treatment planning and counseling patients. A key barrier was lack of information on some cancer treatments. Fit within clinical workflow was feasible, particularly with electronic health record integration. Conclusions: The novel, web-based CRISP tool is a feasible, acceptable, and appropriate tool to address provider knowledge gap about cancer related infertility risks and use for patient counseling. CRISP has significant potential to support tailored oncofertility counseling in the heterogeneous young cancer patient population.

Maternal comorbidity and adverse perinatal outcomes in survivors of adolescent and young adult cancer: A cohort study.

OBJECTIVE: To evaluate risks of preterm birth (PTB) and severe maternal morbidity (SMM) in female survivors of adolescent and young adult cancer and assess maternal comorbidity as a potential mechanism. To determine whether associations differ by use of assisted reproductive technology (ART). DESIGN: Retrospective cohort. SETTING: Commercially insured females in the USA. SAMPLE: Females with live births from 2000-2019 within a de-identified US administrative health claims data set. METHODS: Log-binomial regression models estimated relative risks of PTB and SMM by cancer status and tested for effect modification. Causal mediation analysis evaluated the proportions explained by maternal comorbidity. MAIN OUTCOME MEASURES: PTB and SMM. RESULTS: Among 46 064 cancer survivors, 2440 singleton births, 214 multiple births and 2590 linked newborns occurred after cancer diagnosis. In singleton births, the incidence of PTB was 14.8% in cancer survivors versus 12.4% in females without cancer (aRR 1.19, 95% CI 1.06-1.34); the incidence of SMM was 3.9% in cancer survivors versus 2.4% in females without cancer (aRR 1.44, 95% CI 1.13-1.83). Cancer survivors had more maternal comorbidities before and during pregnancy; 26% of the association between cancer and PTB and 30% of the association between cancer and SMM was mediated by maternal comorbidities. Tests for effect modification of cancer status on perinatal outcomes by ART were non-significant. CONCLUSIONS: Preterm birth and SMM risks were modestly increased after cancer. Significant proportions of elevated risks may result from increased comorbidities. ART did not significantly modify the association between adolescent and young adult cancer and adverse perinatal outcomes. The prevention and treatment of comorbidities provides an opportunity to improve perinatal outcomes among cancer survivors.

Long-term antimüllerian hormone patterns differ by cancer treatment exposures in young breast cancer survivors.

OBJECTIVE: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data. DESIGN: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups. SETTING: Commercially insured females in the United States. PATIENT(S): Females with and without breast cancer. EXPOSURE(S): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy. MAIN OUTCOME MEASURE(S): AMH levels. RESULT(S): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed. CONCLUSION(S): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan.

Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome.

CAPSULE: Hyperandrogenemia in an obese PCOS mouse model results in altered glucose/insulin metabolism and mitochondrial structure and function in the oocytes, in part explaining adverse outcomes and inheritance patterns seen in PCOS. OBJECTIVE: To study the oocyte quality by means of mitochondrial structure and function in a well-established classic PCOS mouse model. DESIGN: Animal study using an obese PCOS mouse model compared with control. SETTING: Animal research facility in a tertiary care university hospital setting. ANIMALS: C57/B6J mice. INTERVENTION: Three week old mice had subdermal implants of DHT controlled release pellet or placebo for 90 days. MAIN OUTCOME MEASURES: The mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were subsequently isolated and were used to investigate mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy. RESULTS: Results showed glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of the oocytes demonstrated impaired inner mitochondrial membrane function, increased ATP production and mtDNA copy number, altered RNA transcript abundance and aberrant ovarian histology. Electron microscopy of the oocytes showed severely impaired mitochondrial ultrastructure. CONCLUSION: The obese PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial function.

Molar pregnancy after in vitro fertilization with euploid single embryo transfer.

OBJECTIVE: To describe a case of molar pregnancy after in vitro fertilization (IVF) resulting from the transfer of a euploid embryo derived from a monopronuclear zygote. DESIGN: Case report and review of the literature. SETTING: Private practice IVF center. PATIENTS: A 42-year-old woman, gravida 3 para 0, with advanced maternal age and infertility who underwent IVF. INTERVENTIONS: Preimplantation genetic testing for aneuploidy using next-generation sequencing, single frozen euploid blastocyst transfer, and medical management of suspected missed abortion. MAIN OUTCOME MEASURES: Genetic examination of products of conception and correlation with embryonic preimplantation genetic testing for aneuploidy results. RESULTS: Transfer of the euploid embryo derived from an abnormally fertilized oocyte (monopronuclear zygote) resulted in a clinical pregnancy suspected to be a missed abortion. Products of conception collected after medical management of the suspected missed abortion were analyzed using next-generation sequencing with the report "46,XX complete molar pregnancy". CONCLUSIONS: To our knowledge, this is the first account of a complete molar pregnancy resulting from the transfer of a reported euploid embryo, highlighting the importance of understanding the limitations of genetic testing platforms in the setting of abnormally fertilized oocyte-derived embryos.

PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering.

By mimicking the native extracellular matrix, electrospun nanofibrous scaffolds (ENSs) can provide both chemical and physical cues to modulate cell adherence and differentiation and to promote tissue regeneration while retaining bioresorbable and biocompatible properties. In this study, ENSs were developed to deliver multiple biomolecules by loading them into the core-sheath structure and/or by conjugating them to the nanofiber surfaces. In this work, poly(L-lactide)-poly(ethylene glycol)-NH(2) and poly(L-lactide) were emulsion electrospun into nanofibers with a core-sheath structure. A model drug, tetracycline hydrochloride, was loaded within the nanofibers. Amino and carboxyl reactive groups were then activated on the fiber surfaces using saturated water vapor exposure and base hydrolysis, respectively. These reactive groups allowed the surface of the ENS to be functionalized with two other bioactive molecules, fluorescein isothiocyanate- and rhodamine-labeled bovine serum albumins, which were used as model proteins. The ENSs were shown to retain their antimicrobial capacity after two functionalization reactions, indicating that multifunctional nanofibers can potentially be developed into functional wound dressings or periodontal membranes or used in more complicated tissue systems where multiple growth factors and anti-infection precautions are critical for the successful implantation and regeneration of tissues.