Trainee-Led Quality Improvement Project to Improve Fertility Preservation Counseling for Patients With Cancer.

PURPOSE: Oncofertility counseling regarding the reproductive risks associated with cancer therapy is essential for quality cancer care. We aimed to increase the rate of oncofertility counseling for patients of reproductive age (18-40 years) with cancer who were initiating systemic therapy at the Johns Hopkins Cancer Center from a baseline rate of 37% (25 of 68, June 2019-January 2020) to 70% by February 2021. METHODS: We formed an interprofessional, multidisciplinary team as part of the ASCO Quality Training Program. We obtained data from the electronic medical record and verified data with patients by phone. We surveyed patients, oncologists, and fertility specialists to identify barriers. After considering a prioritization matrix, we implemented Plan-Do-Study-Act (PDSA) cycles. RESULTS: We identified the following improvement opportunities: (1) oncologist self-reported lack of knowledge about counseling and local fertility preservation options and (2) lack of a standardized referral mechanism to fertility services. During the first PDSA cycle (February 2020-August 2020, disrupted by COVID-19), we introduced the initiative to increase oncofertility counseling at faculty meetings. From September 2020 to November 2020, we implemented a second PDSA cycle: (1) educating and presenting the initiative at Oncology Grand Rounds, (2) distributing informative pamphlets to oncologists and patients, and (3) implementing an electronic medical record order set. In the third PDSA cycle (December 2020-February 2021), we redesigned the order set to add information (eg, contact information for fertility coordinator) to the patient after-visit summary. Postimplementation (September 2020-February 2021), counseling rates increased from 37% to 81% (38 of 47). CONCLUSION: We demonstrate how a trainee-led, patient-centered initiative improved oncofertility care. Ongoing work focuses on ensuring sustainability and assessing the quality of counseling.

Mutation and methylation profiles of ectopic and eutopic endometrial tissues.

Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal-appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co-evolve in ectopic locations remains unclear. Here, we analyzed exome-wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium-stroma progenitor cells. While a patient-specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal-appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometrium-related disorders. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Cost-effectiveness of preimplantation genetic testing for aneuploidy for fresh donor oocyte cycles.

OBJECTIVE: To determine whether in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) is cost effective to achieve a live birth compared with IVF alone in fresh donor oocyte cycles. DESIGN: Theoretical cost-effectiveness study. SETTING: Not applicable. PATIENTS: None. INTERVENTIONS: Comparison between the cost of IVF with PGT-A vs. IVF alone to achieve a live birth. The model analyzed a hypothetical single fresh oocyte donor IVF cycle with PGT-A vs. IVF alone and followed the progression of a single embryo through the different decision nodes. Cost estimates assigned to each clinical event were based on data obtained from the literature and institutional costs. MAIN OUTCOME MEASURES: Cost per live birth. RESULTS: In the base-case analysis, IVF with PGT-A was not cost effective in fresh donor oocyte cycles when compared with IVF alone to achieve a live birth. The cycles using PGT-A cost an additional $6,018.66. The incremental cost-effectiveness ratio was found to be $119,606.59 per additional live birth achieved with IVF with PGT-A. Monte Carlo simulations demonstrated that IVF with PGT-A was not cost effective in nearly all iterations. CONCLUSIONS: PGT-A in fresh donor oocyte IVF cycles is not cost effective compared with IVF alone over a wide range of probabilities and costs.

Pathology and Pathogenesis of Adenomyosis.

Adenomyosis represents a unique pathophysiological condition in which normal-appearing endometrial mucosa resides within myometrium and is thus protected from menstrual shedding. The resulting ectopic presence of endometrial tissue composed of glands and stroma is thought to affect normal contractile function and peristalsis of uterine smooth muscle, causing menometrorrhagia, infertility, and adverse obstetric outcomes. Since the first description of adenomyosis more than 150 years ago, pathologists have studied this lesion by examining tissue specimens, and have proposed multiple explanations to account for its pathogenesis. However, as compared with endometriosis, progress of adenomyosis research has been, at best, incremental mainly due to the lack of standardized protocols in sampling tissue and a lack of consensus diagnostic criteria in pathology practice. Despite these limitations, recent advances in revealing the detailed anatomy and biology of eutopic endometrium offer an unprecedented opportunity to study this common but relatively understudied disorder. Here, we briefly summarize the pathological aspects of adenomyosis from an historical background, and discuss conventional morphology and recent tissue-based molecular studies with a special emphasis on elucidating its tissue of origin from a pathologist's perspective. We also discuss unmet needs in pathology studies that would be important for advancing adenomyosis research.

Attitudes towards potentially carrying the FMR1 premutation: before vs after testing of non-carrier females with diminished ovarian reserve.

Diminished ovarian reserve (DOR) and premature ovarian failure are associated with elevated FMR1 CGG repeat alleles. We assessed pretest attitudes about potentially carrying the FMR1 premutation (FXP) (>55 CGG repeats) among reproductive age women compared with attitudes after learning their non-carrier status. Ninety-two women with DOR, regular menses and no family history of Fragile X Syndrome underwent FMR1 testing and completed attitudinal questionnaires before (T1) and 3 months after learning the test results (T2). The analysis utilized signed rank tests and α = 0.05. Very few women thought they were likely to have a FXP (6.6%). More participants thought FMR1 premutations were "serious" at T2 (62.9%) than at T1 (46.1%, p < 0.0003). When asked at T1 to "describe your feelings when you consider that you are potentially a carrier" of a FXP, 10% had negative feelings, 50% felt ambivalent, and 40% had positive feelings. At T2, feelings about not being a carrier were significantly more favorable (p < 0.0001): negative (0%), ambivalent (6.5%), positive (93%). Corroborating prior reports, few women had a negative view of FXP, perhaps anticipating that carrying the FXP explains their infertility. Perception of the seriousness of FXP increased after learning they did not carry the FXP, which would be predicted by health belief models.

Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice.

BACKGROUND: Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf2(-/-)) causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis. PRINCIPAL FINDINGS: To investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf2(-/-) mice with apoliporotein E-deficient (ApoE(-/-)) mice. ApoE(-/-) and ApoE(-/-)Nrf2(-/-) mice were fed an atherogenic diet for 20 weeks, and plaque area was assessed in the aortas. Surprisingly, ApoE(-/-)Nrf2(-/-) mice exhibited significantly smaller plaque area than ApoE(-/-) controls (11.5% vs 29.5%). This decrease in plaque area observed in ApoE(-/-)Nrf2(-/-) mice was associated with a significant decrease in uptake of modified low density lipoproteins (AcLDL) by isolated macrophages from ApoE(-/-)Nrf2(-/-) mice. Furthermore, atherosclerotic plaques and isolated macrophages from ApoE(-/-)Nrf2(-/-) mice exhibited decreased expression of the scavenger receptor CD36. CONCLUSIONS: Nrf2 is pro-atherogenic in mice, despite its antioxidative function. The net pro-atherogenic effect of Nrf2 may be mediated via positive regulation of CD36. Our data demonstrates that the potential effects of Nrf2-targeted therapies on cardiovascular disease need to be investigated.

Rede social de apoio à mulher no período puerperal / Support for women at puerperium / La rede social de apoyo a la mujer en el periodo puerperal

Objetivou-se identificar e analisar redes de apoio recebidas pelas puérperas. Pesquisa qualitativa, em que entrevistou-se dez puérperas cadastradas no Centro de Treinamento em Atenção Primária. Em relação ao apoio recebido, houve maior participação familiar, mas destacaram-se apoio do enfermeiro e de amigos. A participação familiar foi citada como fundamental, identificada pelo apoio financeiro, ajuda doméstica e adaptação do papel materno. Concluímos ser necessário o apoio social à puérpera, pelo momento de fragilidade para mulher e familiares. Sugerimos que o cuidado de enfermagem não englobe apenas a esfera física, mas uma dimensão maior, favorecendo uma adaptação eficaz.

This study analyzes the support women get at purperium. It is a qualitative study. Ten women from a primary care health training center were interviewed. Most of the support they received came from their families, but they highlighted the help received from nurses and friends. Family help was quoted as fundamental through financial support, help at home and adaptation of the role of mother. Social support for these women is considered essential because of their fragility and that of their families at this phase. We suggest nursing care should cover not only the physical side, but a wider dimension which will help them to adapt more effectively.

Este estudio analiza las redes de apoyo recibidas por mujeres durante el puerperio. Se trata de una investigación cualitativa con diez mujeres registradas en el Centro de Capacitación en Atención Primaria. En cuanto al apoyo recibido se constató más participación familiar pero se destacó, sobre todo, el apoyo del enfermero y de los amigos. La participación familiar se mencionó como básica y fundamental, identificada por el apoyo financiero, ayuda doméstica y adaptación al rol materno. Llegamos a la conclusión de que el apoyo social a las mujeres durante el puerperio es algo necesario ya que se trata de un momento de fragilidad tanto para la mujer como para la familia. Esperamos que el cuidado de enfermería no se restrinja sólo a la esfera física sino que abarque una dimensión más grande y que favorezca una adaptación eficaz.