Impact of abnormal uterine bleeding care in premenopausal patients prior to endometrial malignancy diagnosis.

Background: Literature evaluating the management of abnormal uterine bleeding in premenopausal patients prior to endometrial malignancy diagnosis is lacking. Objective: To evaluate predictors and consequences of inadequate evaluation and management of abnormal uterine bleeding and time to endometrial sampling in premenopausal patients prior to endometrial malignancy diagnosis.Study Design.This was a retrospective cohort study of premenopausal individuals with endometrioid endometrial cancer or atypical hyperplasia at a single institution from 2015 to 2020.. Complete noninvasive management encompassed pelvic exam, ultrasound, and progestin treatment before or in conjunction with the endometrial sampling of diagnosis. Multivariable logistic and ordinal odds models were used to evaluate predictors and outcomes. Results: 152 subjects were included, 80.3 % with cancer and 19.7 % with atypical hyperplasia. The majority of patients had anovulatory bleeding, obesityand recent health care. Only 20.4 % had complete nonvinvasive management, and only 12.5 % had complete noninvasive management or endometrial sampling within 2 months of presentation with abnormal bleeding. Class III obesity reduced the likelihood of complete assessment and increased time to sampling, while age 45 and up and parity reduced time to sampling. Most patients had partial workup but no progestin treatment and long intervals before endometrial sampling after presentation to a provider with abnormal bleeding. Incomplete workup correlated to worse cancer grade and stage. Conclusion: Despite high clinical risk and health care contact, most patients had insufficient gynecologic management preceding a diagnosis of endometrial malignancy. Inadequate care correlated to worse oncologic outcomes and demonstrates missed opportunities for early detection and prevention of endometrial cancer.

ß-catenin, Pax2, and Pten Panel Identifies Precancers Among Histologically Subdiagnostic Endometrial Lesions.

Despite refinements in histologic criteria for the diagnosis of endometrioid precancers, many challenging cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of ß-catenin, Pax2, and Pten was identified as a useful diagnostic adjunct. However, previous studies focused either on cancers or diagnostically unambiguous precancers, leaving questions about the applicability and utility of the panel in endometria with architectural features near or below the threshold of accepted histologic criteria for endometrioid precancers. Here, in a retrospective study of 90 patients, we evaluated the performance of the 3-marker panel. Notably, the panel detected a subset of disordered proliferative endometria (8/44, 18%), nonatypical hyperplasias (19/40, 48%), and cases with ambiguous features (3/6, 50%) with aberrancy for ≥1 markers. Marker-aberrant cases were more likely to progress to endometrioid precancer or cancer ( P =0.0002). Patterns of marker aberrancy in the index and progressor cases from individual patients provided evidence for origin in a common precursor, and next-generation sequencing of the progressor cases rationalized marker aberrancy for ß-catenin and Pten. The results unequivocally demonstrate that some lesions that do not approach current histologic thresholds are bona fide neoplastic precursors with clinically-relevant driver events that can be detected by the 3-marker panel. The findings provide further validation for the diagnostic utility of the panel in clinical practice and its application in difficult or ambiguous cases.

Longitudinal trends in fertility in women of advanced maternal age in the United States and Sweden from 1935-2018 and comparison to maternal mortality ratios.

Advanced maternal age (AMA, >35 years at delivery) confers maternal and foetal risks, particularly with age >45 years and nulliparity, but longitudinal comparative data on age- and parity-specific AMA fertility is lacking. We used the Human Fertility Database (HFD), a publicly available, international database, to analyse fertility in US and Swedish women aged 35-54 from 1935 to 2018. Age-specific fertility rates (ASFR), total birth counts, and proportion of AMA births were evaluated across maternal age, parity, and time, and compared to maternal mortality rates during the same time. In the US, total AMA births nadired in the 1970s, and have risen since. Until 1980, most AMA births were to women completing parity 5 or higher; since then, most have been to low parity women. While ASFR in 35 to 39 year olds was highest in 2015, ASFR in women 40-44 and 45-49 were highest in 1935, though they have been rising recently, especially in low-parity women. While the same AMA fertility trends were seen in the US and Sweden from 1970-2018, maternal mortality rates have risen in the US despite remaining low in Sweden. Although AMA is known to contribute to maternal mortality, this discrepancy merits further consideration.

Emergency department visits and emergency-to-inpatient admissions for abnormal uterine bleeding in the USA nationwide.

BACKGROUND: Abnormal uterine bleeding (AUB) is a common but understudied gynaecological problem, and data are lacking on emergency department (ED) visits and associated ED-to-inpatient admissions for AUB. This project aims to further understanding of the burden of AUB on patients and the healthcare system by establishing the number and characteristics of women with AUB in the ED and evaluating predictors of AUB-related inpatient hospitalisation in the USA. METHODS: This is a cross-sectional study of women presenting to the ED with non-malignant AUB in the 2016 US Nationwide Emergency Department Sample (NEDS). Clinical, demographic and hospital system factors were evaluated. χ2 and Mann-Whitney tests were used to compare the proportion of visits with each characteristic, resulting in inpatient admission versus discharge from the ED. Multivariable logistic regression models were used to analyse predictors of AUB in the ED and of AUB-related hospitalisations. RESULTS: There were 1.03 million AUB-related visits in the 2016 NEDS, of which 11.2% resulted in inpatient admission. Clinical as well as demographic and hospital system factors influenced ED disposition. Women with AUB tended to be of reproductive age, be underinsured, live in lower income and urban areas, and present to urban and public hospitals. However, older age, higher income, better insurance, presentation to private hospitals and rural residence predicted inpatient admission. CONCLUSIONS: Our study highlights the ED as an essential place of care for women with AUB while also demonstrating the importance of access to outpatient gynaecology services as some AUB-related ED visits may be preventable with outpatient care. The significant demographic and hospital system differences, as well as expected clinical differences, between women with AUB admitted to inpatient and women discharged from the ED imply structural biases impacting AUB-related ED care and add to the deepening understanding of health disparities.

Endometrial findings among transgender and gender nonbinary people using testosterone at the time of gender-affirming hysterectomy.

OBJECTIVE: To describe clinical characteristics and associated endometrial findings of transgender and gender nonbinary people using gender-affirming testosterone. DESIGN: Retrospective case series. SETTING: Academic medical center and public safety net hospital. PATIENT(S): Eighty-one patients using gender-affirming testosterone therapy undergoing hysterectomy for the indication of gender affirmation from 2000 to 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preoperative clinical characteristics and endometrium surgical pathology diagnoses. RESULT(S): Median age was 31 years (interquartile range [IQR] 27-40), and median body mass index 27 kg/m2 (IQR 24-30). Six patients (7%) were parous and 60 (74%) had amenorrhea. Thirty-three patients (40%) had proliferative and 40 (50%) atrophic endometrium. Endometrial polyps were found in nine patients (11%) of the sample. Endometrial findings were similar in the subgroup of 60 patients with preoperative amenorrhea. There were no cases of endometrial hyperplasia or malignancy. In bivariate analysis, those with proliferative endometrium were found to be, on average, 5.6 years younger than those with atrophic endometrium. There were no clinical factors associated with having proliferative versus atrophic endometrium in multivariable models. CONCLUSION(S): People using gender-affirming testosterone may have either proliferative or atrophic endometrium, including people who present with amenorrhea. Further study is needed to develop evidence-based guidelines for appropriate screening for endometrial hyperplasia or cancer in this population.

Specimen Fragmentation and Loop Electrosurgical Excision Procedure and Cold Knife Cone Biopsy Outcomes.

OBJECTIVE: Surgical technique for loop electrosurgical excision procedure (LEEP) and cold knife cone (CKC) emphasizes a uniform specimen, but sequelae of specimen fragmentation are not established. We evaluated outcomes between fragmented and unfragmented excisional biopsy specimens. MATERIALS AND METHODS: Loop electrosurgical excision procedure and CKCs from January 2010 to October 2013 were reviewed. Intraepithelial lesion grade, fragmentation, margin, and Endocervical curettage status were analyzed. Adenocarcinoma in situ and cancer were excluded. Repeat procedures during the study period were included in follow-up. Loop electrosurgical excision procedures with top hat with no separate fragments were analyzed independently versus those with fragmented LEEP and/or top hat. Indeterminate margin was defined as inconclusive or unevaluable margin, or intraepithelial lesion in unidentifiable margin or fragment. Outcomes involved residual or recurrent disease and repeat procedures for intraepithelial lesion. χ was used for statistical analysis. RESULTS: Fragmented specimens were more likely to have any positive margin (p = .01), multiple positive margins (p < .001), and indeterminate margin (p < .001) than unfragmented specimens. There was no significant difference in rates of positive, insufficient, or high-grade Endocervical curettage (p = .74, 0.54, 0.92). Patients with fragmented specimens were more likely to have high-grade lesion recurrence in the following 3 years (p = .04) versus patients with index unfragmented specimens, though not compared with those with unfragmented LEEP + top-hat cases. Overall rates of repeat LEEP/CKC or hysterectomy for dysplasia were not different (p = .56). CONCLUSIONS: Fragmentation of LEEP and CKC specimens is associated with higher rates of positive margins, recurrent high-grade intraepithelial lesions, and indeterminate margins. These may cause diagnostic uncertainty, require closer follow-up, and increase cost with more visits and studies.

Nonadditive indirect effects of group genetic diversity on larval viability in Drosophila melanogaster imply key role of maternal decision-making.

Genetic variation can have important consequences for populations: high population genetic diversity is typically associated with ecological success. Some mechanisms that account for these benefits assume that local social groups with high genetic diversity are more successful than low-diversity groups. At the same time, active decision-making by individuals can influence group genetic diversity. Here, we examine how maternal decisions that determine group genetic diversity influence the viability of Drosophila melanogaster larvae. Our groups contained wild-type larvae, whose genetic diversity we manipulated, and genetically marked 'tester' larvae, whose genotype and frequency were identical in all trials. We measured wild-type and tester viability for each group. Surprisingly, the viability of wild-type larvae was neither augmented nor reduced when group genetic diversity was altered. However, the viability of the tester genotype was substantially depressed in large, high-diversity groups. Further, not all high-diversity groups produced this effect: certain combinations of wild-type genotypes were deleterious to tester viability, while other groups of the same diversity-but containing different wild-type genotypes-were not deleterious. These deleterious combinations of wild-type genotypes could not be predicted by observing the performance of the same tester and wild-type genotypes in low-diversity groups. Taken together, these results suggest that nonadditive interactions among genotypes, rather than genetic diversity per se, account for between-group differences in viability in D. melanogaster and that predicting the consequences of genetic diversity at the population level may not be straightforward.