BACKGROUND: Despite being a highly debated issue, subtotal or supracervical hysterectomy (SCH) is still considered a safe and effective treatment for women with benign gynecological lesions. Benign and malignant cervical diseases have been reported after SCH, with fibroids being the most frequently diagnosed lesions in the excised cervical stump. Recurrence of cervical disease after SCH usually presents with vaginal bleeding, pelvic mass, or abdominal pain; moreover, it may necessitate reoperation and resection of the cervical stump or trachelectomy. Trachelectomy is known to be a difficult surgical procedure that may be associated with significant intra- and post-operative morbidity.
METHODS: We presented here a case of a 41-year-old nulliparous woman with a pelvic mass related to the cervical stump presented 2 years after subtotal hysterectomy, performed due to interactable abnormal uterine bleeding, which was attributed to a multiple fibroid uterus. Six years ago, she complained of pelvic pain, excessive vaginal discharge, and spotting. A transvaginal sonography and magnetic resonance imaging with contrast were performed, which revealed a 10.2 × 7.6 × 6.5 cm heterogeneous pelvic mass with irregular borders and marked vascularity on color Doppler. Surgical exploration and resection of the mass with cervical stump excision were performed. Histopathology confirmed the diagnosis of cervical stump multiple benign leiomyomata with no atypical features.
CONCLUSIONS: Recurrence or De novo development of leiomyomata and other cervical lesions might occur after supracervical or subtotal hysterectomy; thus, thorough pre-operative counseling for women requesting a SCH regarding the pros and cons of the procedure compared with total hysterectomy should be optimized. Meticulous follow-up, including the continuation of routine cervical cytological smears, is mandatory for patients with a retained cervix.

BACKGROUND: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL.
METHODS: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p\'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders.
RESULTS: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (β comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (β for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p\'-DDE were inversely associated with UL (β = -0.06, 95 % CrI: -0.21, 0.10 and β = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs.
CONCLUSIONS: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions.

Uterine fibroids are common benign tumors originating from the uterus\'s smooth muscle layer, often leading to symptoms such as pelvic pain, and reproductive issues. Early detection is crucial to prevent complications such as infertility or the need for invasive treatments like hysterectomy. One of the main challenges in diagnosing uterine fibroids is the lack of specific symptoms, which can mimic other gynecological conditions. This often leads to under-diagnosis or misdiagnosis, delaying appropriate management. In this research, an attention based fine-tuned EfficientNetB0 model is proposed for the classification of uterine fibroids from ultrasound images. Attention mechanisms, permit the model to focus on particular parts of an image and move forward the model\'s execution by empowering it to specifically go to imperative highlights whereas overlooking irrelevant ones. The proposed approach has used a total of 1990 images divided into two classes: Non-uterine fibroid and uterine fibroid. The data augmentation methods have been connected to improve generalization and strength by exposing it to a wider range of varieties within the training data. The proposed model has obtained the value of accuracy as 0.99. Future research should focus on improving the accuracy and efficiency of diagnostic techniques, as well as evaluating their effectiveness in diverse populations with higher sensitivity and specificity for the detection of uterine fibroids, as well as biomarkers to aid in diagnosis.

OBJECTIVE: To determine if engineered HMGA2 overexpressing uterine primary myometrial cells recapitulate the transcriptional and epigenomic features of HMGA2-subtype leiomyomas.
METHODS: Isolated primary, \"normal\" myometrial cells from 3 patients were engineered to overexpress HMGA2 to determine how HMGA2 establishes transcriptomic and epigenomic features of HMGA2-overexpressing leiomyoma.
METHODS: Academic research laboratory PATIENTS: Primary myometrial cells were isolated from normal myometrium obtained from three patients undergoing hysterectomy.
METHODS: Not applicable MAIN OUTCOME MEASURES: Determined genome-wide transcriptomic and epigenomic features of engineered HMGA2-overexpressing uterine primary myometrial cells.
RESULTS: Engineered HMGA2-V5-overexpressing primary myometrial cells approximated the HMGA2 expression level observed in HMGA2-overexpression subtype leiomyoma. HMGA2-V5 expression resulted in differential expression of 1612 genes (FDR < 0.05) which were found to be enriched in pathways associated with leiomyoma formation, including extracellular matrix organization. Comparative gene expression analysis between HMGA2-V5 engineered primary cells and HMGA2-overexpression subtype leiomyoma revealed significant overlap of differentially expressed genes. Mechanistically, HMGA2-V5 overexpression resulted in 41,323 regions with differential H3K27ac deposition (FDR < 0.05) and 205,605 regions of altered chromatin accessibility (FDR < 0.05). Transcription factor binding site analysis implicated the AP-1 family of transcription factors.
UNASSIGNED: • What clinical problem is addressed by these studies? About 10-15% of the uterine leiomyoma cases exhibit increased expression of HMGA2; our study addresses the primary role of HMGA2 overexpression in the pathogenesis of leiomyoma. • What are the key findings? Ectopic expression of HMGA2 in primary myometrial cells transforms transcriptional and epigenomic machinery in these cells which to some extent resemble features of leiomyoma. • How do these findings apply to human fertility or the reproductive process? Our study provides a comprehensive analysis into the changes occurring in epigenome of myometrial cells when HMGA2 is overexpressed. Because epigenome can be targeted with drugs, therefore understanding alterations in epigenome provides new avenues for treating leiomyoma which affects reproductive age women.

Uterine fibroids and endometriosis may be associated with an increased risk of ovarian cancer. Less is known about the role of hysterectomy in these associations. We estimated the independent and joint associations of hysterectomy, fibroids, and endometriosis with ovarian cancer incidence in the prospective Sister Study cohort (2003-2009). We used time-varying Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). By the end of follow-up, 34% of 40,928 eligible participants had fibroids, 13% had endometriosis, and 7% had both. A total of 274 women developed ovarian cancer during follow-up (median=12.3 years). In mutually adjusted models, fibroids (HR=1.65, 95% CI: 1.28, 2.12) and possibly endometriosis (HR=1.16, 95% CI: 0.82, 1.63), were positively associated with ovarian cancer. Hysterectomies (20% of participants) were also positively associated with ovarian cancer (HR=1.29, 95% CI: 0.95, 1.74). There was some evidence that hysterectomies may mitigate ovarian cancer risk among women with fibroids (HR=0.83, 95% CI: 0.56, 1.24), but not among women with endometriosis (HR=1.20, 95% CI: 0.65, 2.22). Identifying these joint associations adds to our understanding of ovarian cancer etiology and may help inform decisions about how women with fibroids, endometriosis, and hysterectomies are treated and surveilled for ovarian cancer.

Background/Objectives: Our objective was to evaluate changes in the management of symptomatic fibroids after establishing a multidisciplinary fibroid center with minimally invasive gynecologic surgery (MIGS) and interventional radiology (IR). Methods: A retrospective cohort study was conducted at the fibroid center created in September 2020. Patients were offered same-day consults with both MIGS and IR providers. Data were collected for patients with initial consultations from January to June 2019 (pre-fibroid center) and from January to June 2021 (post-fibroid center). Results: Among 615 patients meeting inclusion criteria, 273 had consultations pre-center and 342 post-center. More patients seen post-center had previously attempted medical management (30.1% vs. 20.2%), with a significant proportion having no prior medical or surgical treatment (53.2% vs. 61.5%). Post-center, there were more MIGS consultations (65.5% vs. 53.1%) and a decrease in general gynecology (GYN) consultations (19.0% vs. 25.6%). More patients sought additional opinions post-center (83.6% vs. 67.0%), particularly with MIGS (58.8% vs. 37.0%). General GYNs referred to MIGS (79.3% vs. 73.1%) and IR specialists (16.0% vs. 13.0%) more often in 2021. In 2021, use of MRI increased (66.5% vs. 52.4%), and more patients underwent uterine artery embolization (UAE) within 1 year of consultation compared to the pre-center period (13.8% vs. 6.9%). Conclusions: Patients with symptomatic fibroids often seek the expertise of specialists to explore treatment options. A multidisciplinary fibroid center that integrates efforts of MIGS and IR enables thorough counseling and a rise in the utilization of minimally invasive procedures, including UAE.

BACKGROUND: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient\'s quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP.
METHODS: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2.
RESULTS: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺.
CONCLUSIONS: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFβ, and Wnt/β-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/β-catenin inhibition, and TGFβ cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

Uterine fibroids represent the most prevalent genital tract tumours among women, with a disproportionately higher impact on ethnic minority groups, notably black women. These hormonally dependent monoclonal tumours, characterized by excessive extracellular matrix and influenced by genetic, epigenetic, and lifestyle factors, significantly affect women\'s quality of life and pose substantial economic burdens on healthcare systems. Recent advances in early detection and minimally invasive treatment options have shifted management paradigms towards personalized care, yet challenges in early diagnosis, education and access to treatment persist. This review synthesizes current knowledge on uterine fibroids, highlighting the impact of fibroids on women\'s health, risk factors, principles of screening, diagnostic tools, and treatment modalities. It emphasizes the importance of early screening and individualized management strategies in improving patient outcomes and reducing healthcare costs. The article also discusses the socio-economic and health disparities affecting the disease burden, underscoring the need for improved patient education, clinician training, and public health strategies to enhance fibroid management. This review proposes a pathway to not only ameliorate the quality of life for women with fibroids, but also to advance global women\'s health equity.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products.
OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity.
METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL.
RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth.
UNASSIGNED: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.