Ny forskning om jente- og kvinnehelse

The benefit of interventions to improve neonatal outcomes of preterm birth (PTB) must be balanced with the associated fetal and maternal risks. Artificial intelligence (AI) could be used to assess uterine contractions and consequently help to predict PTB. This paper aims to assess the predictive accuracy and applicability of AI models currently using uterine contractions in PTB prediction. A systematic Embase, Medline, Pubmed and Web of Science review was conducted using PRISMA guidelines. Eligible studies assessed EHG or time-series data using AI methods, including deep learning/machine learning/neural networks to predict PTB. Data on AI model performance measures, validity, and applicability were collected. Results are reported as a narrative review due to study heterogeneity. Bias was assessed using the PROBAST framework. The studies used various Electrohysterography (EHG) contractility features and/or classifiers for AI analysis and varying performance measures to assess predictive accuracy for PTB. A wide range of EHG features were assessed included temporal, spectral, entropy and topological features. A total of 53 records were identified for inclusion. Of these, 18 examined EHG features, 22 assessed AI classifiers, and 3 tested both. Excellent classification performance (ACC and/or AUC ≥0.9) were reported by 38.8% (7/18) of studies examining EHG features and 86.3% (19/22) of studies assessing AI classifiers. Non-linear features outperformed linear features, and deep-learning models such as neural networks were the highest-performing classifiers. Bias assessment showed 86.7% (46/53) had an unclear or high risk of bias. Key concerns include unbalanced data, small sample size and lack of validity outside of sampled datasets. Non-linear features and DL models offer superior results. However, we did not find evidence of external validation, thus the applicability of models in uterine contraction assessment for the prediction of PTB remains limited. Future research requires an emphasis on clinical data integration within high-quality studies, as well as more more studies focusing on early PTB detection.

Uterine fibroids are benign tumors with high incidence and recurrence rates that still pose significant treatment challenges. Traditionally, it has been believed that estrogen and progesterone primarily drive the development and progression of uterine fibroids. Recent studies have revealed that hormonal imbalance can affect reactive oxygen species production and trigger a significant oxidative stress (OS) state. The OS status in uterine fibroids can further amplify the pathological effects caused by hormonal imbalance. This suggests that estrogen, progesterone, and OS may interact to form an estrogen-progesterone-oxidative stress (E-P-OS) network, collectively promoting the progression of uterine fibroids. This network model provides a theoretical basis for the high recurrence rates following hormone monotherapy or surgery. Therefore, we reviewed the molecular mechanisms underlying hormone-OS interactions within the E-P-OS network and elucidated its pathological effects in promoting uterine fibroid progression. The integrated perspective lays the theoretical foundation for developing novel therapies that simultaneously block hormone signaling and counteract oxidative damage. Additionally, we summarized current clinical strategies for hormone therapy and antioxidant treatment, identified potential combination therapy approaches, and explored key challenges in their clinical translation. This aims to provide new directions and evidence for advancing the precision treatment of uterine fibroids.

Uterine luminal fluid influences embryonic development and the subsequent phenotype of offspring, yet its detailed metabolomic composition remains poorly characterized. Here, minimally invasive transcervical techniques were employed to collect neat uterine fluid from postpartum dairy cows and cyclic beef cows to allow for metabolomic profiling via targeted mass spectrometry. Objectives were to 1) compare the metabolomic profile of uterine fluid with plasma in dairy cows and 2) assess the impact of dietary rumen-protected methionine and stage of estrous cycle (day 0 vs 7) on plasma and uterine fluid metabolomic profile in beef cows. Results revealed that the concentrations of many metabolites, including amino acids, signaling molecules (e.g. dopamine, gamma-aminobutyric acid) and lipids (e.g. ceramides, diacylglycerols), were higher in uterine fluid than in plasma. An oral bolus of rumen-protected methionine increased uterine concentration of methionine on day 0 of the estrous cycle. The uterine metabolome remained relatively stable between days 0 and 7 although there was temporal variability for a select number of metabolites (cysteine, methionine, methionine sulfoxide, asymmetric dimethylarginine, ceramides, and glycerophospholipids). Correlations between plasma and uterine fluid concentrations were strong or moderate for many amino acids. Collectively, these findings highlight that the uterine lumen is a specialized, selectively regulated biochemical compartment.

Hysteroscopic tubal occlusion serves as an effective minimally invasive treatment, aiming to improve the efficacy of assisted reproductive technologies by preventing hydrosalpinx fluid from entering the uterine cavity. This study aims to investigate the specific alterations in the intrauterine microenvironment associated with this surgery and its positive impact on the success rate of in vitro fertilization and embryo transfer (IVF-ET). This retrospective study included 158 patients with hydrosalpinx who underwent hysteroscopic tubal occlusion between January 2019 and December 2021. Pre- and postoperative evaluations included endometrial total protein levels, cytokines (TNF-α, bFGF, IL-10), immune markers (CD138, CD38, CD68), hormone receptors (ER, PR), uterine microbial composition, postoperative recovery, and IVF-ET pregnancy outcomes. Postoperative total protein levels in endometrial tissues significantly increased ( p < 0.05). Protein levels of CD138, CD38, CD68, ER, and PR were all significantly reduced postoperatively ( p < 0.05). The abundance of Lactobacillus increased significantly from 81.56% to 91.71% (χ 2 =4.153, p = 0.042), while other microbial species showed no significant differences. Pain scores decreased significantly from 3.24 ± 0.68 to 1.36 ± 0.31, and the mean time to return to daily activities was 1.08 ± 0.26 days. IVF-ET outcomes showed a clinical pregnancy rate of 39.87%, ongoing pregnancy rate of 32.91%, live birth rate of 29.75%, and a miscarriage rate of 6.96%, with no ectopic pregnancies reported. Hysteroscopic tubal occlusion effectively alters the uterine microenviron-ment by modulating immune, hormonal, and microbial profiles, while improving patient recovery and supporting favorable pregnancy outcomes in IVF-ET.

To evaluate the feasibility and safety of performing myomectomy during cesarean delivery using a novel bleeding-reducing suture technique. This retrospective cohort study included pregnant women with intramural uterine fibroids. A total of 120 patients were divided into two groups: Group A consisted of women who underwent myomectomy during cesarean section between January 2020 and June 2024, and Group B included women who underwent cesarean section alone without myomectomy. The following data were obtained from hospital records and compared between the groups: maternal age, gravidity, parity, myoma size, gestational age at time, preoperative and postoperative hemoglobin (Hb) levels, need for blood transfusion, hospital stay, and duration of surgery. The primary outcome of the study was the change in Hb levels before and after the operation. The demographic and laboratory characteristics of 120 pregnant women with intramural leiomyomas who underwent either cesarean myomectomy or cesarean section alone were analyzed. Of these, 60 underwent cesarean section alone, while 60 underwent cesarean section with myomectomy. No statistically significant difference was found between the two groups in terms of preoperative Hb, postoperative 24-hour Hb, or Hb decrease ( p = .240, p = .270, and p = .420, respectively). Similarly, there was no significant difference in operation duration ( p = .160). A weak but statistically significant negative correlation was observed between myoma size and gestational age at delivery ( r = -0.21, p = .0009). No statistically significant correlations were found between myoma size and either operation time or hospital stay. Cesarean myomectomy appears to be a feasible and safe option when performed using the bleeding-reducing uterine isthmic circumferential suture technique. However, further multicenter studies with larger sample sizes are required to confirm these findings before recommending cesarean myomectomy as a routine approach.

Uterine carcinosarcoma, also known as malignant mixed Müllerian tumor, is currently regarded as a metaplastic carcinoma. The sarcomatous component usually consists of homologous or heterologous high-grade mesenchymal elements, whereas low-grade endometrial stromal sarcoma (LG-ESS) has not been recognized as a conventional component of uterine carcinosarcoma. This is a case report of an exceptionally rare biphasic uterine malignancy composed of an adenosquamous carcinoma and an LG-ESS-like stromal component with an extensive morphological transition. A 55-year-old nulliparous woman presented with an endometrial mass involving the myometrium and the endocervix. Endometrial biopsy revealed atypical hyperplasia, and cervical punch biopsy showed adenosquamous carcinoma. Subtotal hysterectomy revealed a high-grade endometrioid carcinoma with extensive malignant squamous differentiation (descriptively termed adenosquamous carcinoma in this report). The epithelial component gradually transitioned into diffuse stromal proliferation, which was morphologically consistent with LG-ESS. The stromal component exhibited infiltrative myometrial growth, extensive lymphovascular invasion, diffuse CD10 and vimentin expression, and loss of epithelial markers, whereas the epithelial component showed CK7, PAX8, CEA, and focal estrogen receptor expression. Squamous cell carcinoma, LG-ESS-like stromal component, and transitional area showed block-type p16 positivity and wild-type p53 staining pattern. Postoperatively, the patient received concurrent chemoradiotherapy but experienced rapid disease progression with pelvic recurrence and metastatic lymph node enlargement. Targeted next-generation sequencing revealed microsatellite stability and wild-type BRAF . Unlike previously reported synchronous or collision tumors composed of endometrial carcinoma and LG-ESS, this tumor demonstrated a continuous morphological and immunophenotypic spectrum linking the epithelial and stromal components. Although molecular confirmation of clonality was unavailable, the findings favored a single biphasic neoplasm with divergent differentiation rather than two independent tumors. This case expands the currently recognized morphological spectrum of uterine carcinosarcoma and highlights the potential role of epithelial-mesenchymal transition in generating an LG-ESS-like stromal component.

Accessory cavitated uterine malformation or mass (ACUM) is a rare and under-recognized cause of dysmenorrhea and chronic pelvic pain (CPP). Various diagnostic criteria have been proposed; patients may present with atypical features. This study aimed to describe the clinical presentation, diagnostic challenges, and management outcomes of ACUM. Retrospective analysis of prospectively collected data was done at a tertiary care institution over 6 years. All women diagnosed with ACUM were included. Clinical presentation, imaging, preoperative diagnosis, intraoperative picture, and management outcomes were analyzed. Eighteen women were enrolled. The median age at presentation was 26.5 years (18-46), with 17 in the reproductive age group and one postmenopausal. The median duration of symptoms was 4 years (2 months to 11 years). Dysmenorrhea with prominent pain on one side, localized to the side of the lesion, was the predominant symptom, occurring in 17/18 (94.4%). Of these, 10/18 (55.6%) experienced both CPP and dysmenorrhea, 7/18 (38.9%) had only dysmenorrhea. Only CPP was reported in 1/18 (5.6%), woman with postmenopausal ACUM. On initial 2D-USG, one case was correctly diagnosed, while 5/18(27.8%) were misdiagnosed as rudimentary horn, 7/18(38.9%) as degenerated fibroid, 4/18(22.2%) as endometrioma, and 1/18(5.6%) as dermoid cyst. Diagnosis was confirmed on further imaging with 3D-USG or MRI in 11/18 (61.1%) cases. Seventeen women underwent surgical management, with 16/17 had excision, and one postmenopausal woman was treated by laparoscopic aspiration. ACUM is an important differential of intractable dysmenorrhea or CPP, especially if pain is localized to either side, even in postmenopausal females.

Disseminated intravascular coagulation (DIC) secondary to consumptive coagulopathy from a degenerative uterine leiomyoma (UL) is an exceptionally rare complication during pregnancy. A 35-year-old woman (gravida 2, para 0) presented at 25 weeks of gestation with lower abdominal pain. Ultrasonography confirmed fetal well-being and a normal placenta and identified a 6.5 cm UL associated with marked tenderness on physical examination. Although acetaminophen provided temporary pain relief, subcutaneous bleeding developed, and laboratory evaluation revealed significant coagulopathy. Magnetic resonance imaging demonstrated progressive degeneration of the UL, localized to the subserosal component. Therefore, DIC was attributed to the degenerative UL. The coagulopathy resolved following transfusion therapy, and the patient was discharged 6 days after admission. At 38 weeks of gestation, an elective cesarean section with concurrent myomectomy was performed. Both mother and neonate were discharged in stable condition without complications. This case highlights that conservative management without the need for pregnancy termination, may be a feasible and effective approach for DIC associated with degenerative UL during pregnancy.

Successful pregnancy requires maternal cardiovascular adaptation, including expansion and remodeling of the uterine arteries, to accommodate a progressive rise in uteroplacental blood flow. Chronic maternal hypertension is associated with impaired uterine artery adaptation and adverse pregnancy outcomes, including fetal growth restriction, yet the mechanisms driving these vascular changes remain incompletely understood. Osteopontin, a matricellular protein implicated in vascular pathology in hypertension, is a potential mediator of impaired uterine artery adaptation during pregnancy. In this study, we compared uterine artery remodeling in pregnant normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive stroke-prone rats (SHRSP), a model of chronic hypertension. To investigate the contribution of osteopontin, we characterized an osteopontin-deficient SHRSP strain. Uterine artery hemodynamics were assessed by Doppler ultrasound, arterial structure was evaluated by histology, and molecular profiles were characterized by RNA sequencing. Fetal weight and length were measured at mid- and late gestation. We found that, compared with WKY, SHRSP fetuses were smaller and uterine arteries exhibited inward hypertrophic remodeling, including increased wall thickness, reduced lumen area, and an elevated resistance index. SHRSP uterine arteries also showed enrichment of pathways related to inflammation and vascular pathology. Among the most highly upregulated genes was Spp1 , which encodes osteopontin. Compared with control SHRSP, osteopontin-deficient SHRSP had larger uterine artery lumen areas, lower resistance indices, and reduced expression of select inflammation-associated genes. Fetal growth trajectories were also improved. These findings identify osteopontin as a contributor to uterine artery dysfunction in chronic hypertensive pregnancy and demonstrate that osteopontin deficiency improves vascular adaptation and fetal growth. NEW & NOTEWORTHY This study characterizes uterine artery dysfunction in a rat model of chronic maternal hypertension and identifies inflammation-related and matrix remodeling pathways associated with vascular pathology. We further demonstrate that osteopontin contributes to uterine artery dysfunction and introduce a novel osteopontin-deficient hypertensive rat model that exhibits improved uterine artery adaptation and fetal growth trajectory despite persistent maternal hypertension.

To develop and internally validate a pretreatment quantitative magnetic resonance imaging-based predictive model for uterine fibroid volume reduction following gonadotropin-releasing hormone antagonist therapy. In this single-center retrospective study, 106 women with uterine fibroids treated with relugolix underwent pre- and intratreatment magnetic resonance imaging. The dominant fibroid was assessed for T2-weighted imaging fibroid-to-iliopsoas signal intensity ratio, apparent diffusion coefficient, flow voids, and fibroid location. The primary outcome was a ≥ 30% reduction in dominant fibroid volume between pre and intratreatment magnetic resonance imaging. Eight baseline variables were entered into a Least Absolute Shrinkage and Selection Operator-penalized logistic regression model with bootstrap internal validation. Sixty patients (56.6%) achieved a ≥ 30% volume reduction. In the univariate analyses, a higher T2-weighted imaging signal intensity ratio and location were significantly associated with response. A purely data-driven Least Absolute Shrinkage and Selection Operator model retained two predictors: dichotomized T2-weighted imaging signal intensity ratio and location. A T2-weighted imaging ratio ≥ 2.0 was the strongest positive predictor, whereas subserosal and cervical locations showed negative associations and submucosal location showed a slight positive association relative to intramural fibroids. The model showed moderate discrimination (apparent area under the receiver operating characteristic curve, 0.746; optimism-corrected area, 0.671) with acceptable calibration. Quantitative pretreatment T2-weighted imaging (ratio ≥ 2.0) is strongly associated with fibroid volume reduction under gonadotropin-releasing hormone antagonist therapy. An internally validated Least Absolute Shrinkage and Selection Operator-based model incorporating T2-weighted imaging signal intensity and location may aid individualized treatment selection and preoperative planning.

Identification and treatment of pregnancies at risk for preterm birth is a central challenge in obstetric research. Many of the known causes of preterm birth originate from mechanical failure in reproductive tissues. To better understand the biomechanical environment of the gravid uterus and its potential contribution to preterm birth, this computational study presents a parametric method for modeling maternal reproductive anatomy during the early second trimester. A finite element modeling approach was built using existing sonographic measurements from early second-trimester maternal anatomy and material properties from published mechanical tests. We applied the same physiologically relevant intrauterine pressure to all models and quantified the resulting tissue stretch. The sensitivity of the stretch in the proximal cervix was explored by varying material properties and sonographic maternal anatomy dimensions. Cervical material properties, particularly the fiber stiffness modulus and ground substance Young's modulus, were found to have the greatest effect on proximal cervix stretch compared to other material properties and sonographic dimensions. Among the sonographic dimension measurements, those defining the region surrounding the proximal cervix had the greatest effect on proximal cervix stretch, including the curvature of the posterior uterine wall and the thickness of the lower uterine segment. The computational modeling approach presented here enables future patient-specific studies of gravid reproductive tissues to elucidate differences between individuals who do and do not deliver preterm. Additionally, this study is foundational for building digital twins to support future virtual clinical studies on diagnostic and therapeutic device design to prevent preterm birth.

To measure the association between treatment options and clinical outcomes in adolescent patients with acute uterine bleeding. A cohort study was conducted using data collected through chart review of all patients under 19 years old treated for acute uterine bleeding from 2012 to 2022 in our tertiary-care hospital center. The association between the treatment options (high-dose estrogens versus progestins) and 2 primary outcomes (change in hemoglobin level from baseline to discharge and time to bleeding cessation) was measured using linear regressions with adjustment for potential confounding variables. As secondary outcomes, change in hemoglobin from baseline to 1 and 4 months, side effects, and adverse events were analyzed. We included 150 patients in our study, 116 exposed to high-dose estrogens and 34 to high-dose progestins. The median time to bleeding cessation was 36 hours overall (Q25,75: 17.5, 85.5) without a statistically significant difference between treatment groups. The change in hemoglobin at discharge and at 4 months, after adjustment, showed a tendency towards a greater increase in hemoglobin levels in the progestin group, without statistical significance. The progestin group experienced fewer side effects compared with the estrogen group (adjusted OR 0.31; 95% CI 0.10-0.89 for a composite nausea outcome). Treatment failure occurred in 23.1% of cases, without a significant difference across groups, and no thromboembolic event were reported. This study suggests no statistically significant difference in the effectiveness between the 2 treatment protocols, but a better side effect profile for high-dose progestins.

Uterine glands synthesize and secrete compounds essential for embryonic and fetal development. They are critical for pregnancy, and their optimal function enhances prenatal survival and thus increases sow lifetime productivity. The gut microbe-uterus axis plays an important role in uterine development and function. Probiotics, especially Limosilactobacillus reuteri (L. reuteri), have been fed to improve female reproductive function, however, the beneficial effects remain unknow. The current study isolated one native L. reuteri (LRY15) from sow intestines that increased the number of uterine glands, and there elevated the protein expression of an important gene FOXA2. Moreover, LRY15 increased the expression of uterine genes related to angiogenesis, placental development, cell junction proteins, antioxidant enzymes, hormone metabolism, and transcriptional factors. Simultaneously, the protein levels of these factors (including blood vessel markers CD31 and VEGF, and cell junction proteins ZO-1 and occludin) were higher in LRY15 uteri compared to controls. The beneficial blood metabolites such as the tocopherol metabolite, antioxidant metabolites including retinol and the polyunsaturated fatty acids, and the levels of some cholic acids metabolites were elevated in LRY15 gilt blood (P < 0.05). Moreover, LRY15 improved cell-cell junction formation to enhance intestinal function. This is the first report to show that the native probiotic LRY15 can enhance uterine development and function; it is therefore a promising tool for increasing mammalian reproductive capacity in the future.

To compare the image quality of diffusion-weighted imaging (DWI) between deep learning reconstruction (DLR)-applied Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) and MUltiplexed Sensitivity Encoding (MUSE) sequences in MRI of uterine malignancies. This retrospective study included 66 MRI examinations of 48 patients. The cohort consisted of cases with uterine malignancies (cervical cancer (n = 50), endometrial cancer (n = 15) and endometrial stromal sarcoma (n = 1)) at different clinical settings (initial staging, post-treatment, or recurrence). DWI was performed using both DLR-applied PROPELLER and MUSE sequences using b-values of 0 and 800 s/mm 2 . Two independent reviewers evaluated overall image quality, artifacts, sharpness, and lesion conspicuity using a 5-point Likert scale. Apparent diffusion coefficient (ADC), apparent signal-to-noise ratio (aSNR), and apparent contrast-to-noise ratio (aCNR) were quantitatively measured in both sequences. In the qualitative assessment, DLR-applied PROPELLER-DWI showed significantly fewer artifacts and better lesion conspicuity than MUSE-DWI. No significant difference was found in overall image quality or sharpness. Inter-reader agreement was slight to moderate, except for strong agreement on DLR-applied PROPELLER-DWI lesion conspicuity (κ = 0.696, good). Quantitatively, the mean ADC values were significantly higher with DLR-applied PROPELLER-DWI compared to MUSE-DWI for both readers (p < 0.001). Furthermore, both aSNR and aCNR were significantly higher with DLR-applied PROPELLER-DWI compared to MUSE-DWI. DLR-applied PROPELLER-DWI demonstrated fewer artifacts and better lesion conspicuity than MUSE-DWI, with higher measured aSNR and aCNR. However, DLR-applied PROPELLER-DWI yielded significantly higher mean ADC values.

Uterine cancers include endometrial cancer (EC), cervical cancer (CC), and uterine sarcomas, with leiomyosarcoma being the most common subtype. Each tumour type has distinct biological behaviour, imaging features, and treatment approaches. Radiologists must be familiar with normal uterine anatomy and its variations, as well as key imaging characteristics and common patterns of tumour spread to ensure accurate staging and optimal treatment selection. MRI is the imaging modality of choice for evaluating uterine malignancies due to its excellent soft tissue contrast and multiplanar capabilities. Accurate assessment requires dedicated multiparametric protocols, as recommended by the European Society of Urogenital Radiology (ESUR), including high-resolution T2-weighted imaging, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) sequences when appropriate. 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) complements MRI in patients with CC by providing the highest accuracy for detecting lymph-node and distant metastases. CT is mainly used for systemic evaluation. This article presents a practical guide for radiologists, describing the main clinical indications, patient preparation, and tailored MRI protocols. It also highlights key imaging findings that should be evaluated and reported. KEY POINTS: MRI is the preferred imaging modality for evaluating uterine malignancies due to its superior soft tissue contrast and multiplanar capabilities. Common clinical indications include MRI staging of endometrial and cervical cancers, assessment of eligibility for fertility preservation, and characterisation of indeterminate myometrial lesions. Adherence to established imaging guidelines is strongly recommended to ensure high-quality images as well as complete and clinically relevant radiology reports.

Leiomyomas remain highly prevalent by midlife, with persistent racial disparities in age at onset and tumor burden. Although they are traditionally expected to regress after menopause, longitudinal data demonstrate variable behavior, with many leiomyomas persisting, some regressing modestly, and a subset continuing to grow. This structured, nonsystematic review of the contemporary literature was conducted using PubMed and Embase, supplemented by guideline and reference review, with the objective of guiding the evaluation and management of uterine leiomyomas across the menopausal transition. In perimenopausal and postmenopausal patients, abnormal uterine bleeding and pelvic pain require systematic evaluation to exclude endometrial pathology and alternative causes. Transvaginal ultrasonography with structured assessment provides the foundation for evaluation, and magnetic resonance imaging serves as an adjunct when findings are indeterminate or clinical concern is elevated. No single imaging feature reliably distinguishes benign leiomyoma from leiomyosarcoma, and the prevalence of unsuspected leiomyosarcoma at surgery remains low, increasing with age. Management should be individualized and symptom driven, incorporating patient age, comorbidities, hormonal exposures, imaging findings, and preferences, with expectant management appropriate for asymptomatic patients and intervention reserved for refractory symptoms or diagnostic uncertainty.

Metastasis to the female genital tract from extragenital primaries is uncommon, with breast and gastrointestinal malignancies representing the predominant sources. Uterine involvement accounts for fewer than 10% of genital tract metastases and most frequently occurs in the setting of disseminated disease with concomitant ovarian involvement. Invasive lobular carcinoma (ILC), despite comprising only 5%-20% of breast malignancies, accounts for over 80% of breast cancer metastases to the female genital tract, a predilection attributed to loss of E-cadherin expression-facilitating tumor cell detachment and hematogenous dissemination-and its diffuse infiltrative growth pattern. Metastasis to uterine leiomyomas is exceptionally rare, with approximately 30 cases reported to date. The underlying pathophysiologic mechanism is postulated to involve the hormonally enriched microenvironment of leiomyomas, wherein tissue concentrations of estrogen and progesterone receptors significantly exceed those of the surrounding myometrium, thereby conferring preferential tropism for circulating hormone receptor-positive breast carcinoma cells. Supporting this, 92.3% of reported cases were estrogen receptor positive. Concurrent lymphatic and hematogenous dissemination pathways are implicated based on patterns of organ involvement, with isolated uterine metastasis in the absence of ovarian disease favoring hematogenous spread. We report a case of metastatic invasive ductal/lobular carcinoma (ER+/PR+/HER2-) infiltrating a uterine leiomyoma, identified incidentally on histopathologic examination six years after primary treatment, in an asymptomatic African American woman undergoing hysterectomy for pelvic organ prolapse-representing, to our knowledge, the first such case reported in an African American patient. Immunohistochemical profiling confirmed breast origin and receptor concordance with the primary tumor.

Obesity is associated with disrupted estrous cyclicity, impaired follicular development, and altered uterine responses. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, produces time-dependent effects on the reproductive axis; however, its actions under severe obesity remain poorly defined. This study evaluated the effects of LA on metabolic parameters, estrous cyclicity, ovarian morphology, and uterine morphometry in obese Zucker rats. Thirty-six adult female rats were used: normal-weight Long-Evans (LE) and obese Zucker (OZ) rats were assigned to untreated control, vehicle, or LA-treated groups (n = 6/group). LA was administered subcutaneously at 2.5 μg/rat/day for 21 consecutive days. Estrous cyclicity was evaluated before and during treatment, and metabolic, ovarian, and uterine outcomes were assessed after treatment. Obese Zucker rats exhibited greater adiposity, metabolic alterations, prolonged and disrupted estrous cycles, impaired follicular development, increased follicular atresia, fewer corpora lutea, and altered uterine morphometry. LA produced condition-dependent reproductive responses. In obese rats, LA shortened the prolonged estrous cycle and shifted estrous-stage distribution toward the pattern observed in normal-weight animals. LA also increased healthy, developing, antral, and preovulatory follicles, markedly increased corpora lutea, and reduced follicular atresia and cystic structures. In contrast, LA produced predominantly suppressive follicular and estrous-cycle changes in normal-weight rats. LA markedly reduced total cholesterol in obese rats without modifying serum glucose, whereas no condition-specific treatment effect on triglycerides was detected. At the uterine level, LA reduced uterine diameter in obese rats but did not modify endometrial thickness. These findings indicate that LA produces markedly different reproductive responses according to the metabolic and reproductive context, improving several follicular and luteal histomorphometric indices in obese Zucker rats without a parallel restoration of uterine morphometry.

Inactivating mutations in TP53 and ATRX are key alterations defining the genomic landscape of uterine leiomyosarcoma (uLMS), creating chronic replication stress and increasing dependency on Ataxia telangiectasia and Rad3-related kinase (ATR) signaling for survival. ATR-CHK1 signaling limits the efficacy of standard-of-care gemcitabine by facilitating the stabilization of stalled replication forks and preventing lethal DNA strand breaks in checkpoint-deficient cells. Here, we show that ATR inhibitors (elimusertib, ceralasertib, berzosertib) preferentially synergize with gemcitabine over docetaxel or doxorubicin, across a panel of TP53-mutant/ATRX-wildtype uLMS models. When simultaneously administered, gemcitabine/elimusertib demonstrated enhanced synergy and efficacy compared to standard-of-care gemcitabine/docetaxel. This combination benefit was absent in a TP53-wildtype uterine sarcoma control line, highlighting TP53 mutation status as a critical predictive biomarker. Combined gemcitabine/ATRi treatment demonstrated reciprocal potency enhancement at low-nanomolar concentrations and significantly increased apoptotic populations compared to monotherapy. Gemcitabine monotherapy induced CHK1 (S345) phosphorylation and a corresponding S-phase arrest. Elimusertib abrogated this checkpoint, transforming protective S-phase arrest into a cytotoxic response characterized by a marked increase in the sub-G1 population. This transition was driven by the inhibition of gemcitabine-induced CHK1 phosphorylation, resulting in marked accumulation of unrepaired DNA damage (γH2AX) and the induction of apoptosis as evidenced by cleaved caspase-3 expression. These findings demonstrate that elimusertib strongly potentiates gemcitabine-induced damage to kill TP53-mutant uLMS in vitro, outperforming standard gemcitabine/docetaxel when concurrently administered. This combination strategy broadens the clinical utility of ATR inhibitors to uLMS harboring the prevalent TP53-mutant/ATRX-wildtype genotype and supports the clinical evaluation of gemcitabine/ATRi combinations as a novel therapy for uLMS.

Uterine fibroids (UFs) substantially affect the health of women of reproductive age. Minimally invasive and noninvasive therapies have become the main alternatives to traditional surgery; however, evidence on their comparative efficacy remains fragmented. This network meta-analysis compared high-intensity focused ultrasound (HIFU), radiofrequency ablation (RFA), microwave ablation (MWA), and uterine artery embolization (UAE) with myomectomy (Myo) for symptomatic UFs. Eight databases were searched (Jan 2016-Dec 2025) for randomized controlled trials (RCTs). ROB 2.0 and Stata 15.1 were used to analyze fibroid volume, recurrence counts, luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E 2 ], and adverse events using surface under the cumulative ranking curve (SUCRA) values, weighted mean differences (WMDs), and 95% confidence intervals (95% CIs). Thirty-one RCTs (2622 patients) were included. HIFU ranked highest for fibroid volume reduction (SUCRA = 96.7%; vs UAE: WMD = 10.31, 95% CIs: 3.52-17.10; vs RFA: WMD = 3.66, 95% CIs: 1.71-5.61) and recurrence prevention (SUCRA = 70.1%). Fluctuations in ovarian function indicators across therapies were clinically acceptable. HIFU ranked first for stabilizing LH (SUCRA = 58.4%) and FSH (SUCRA = 68.4%), whereas UAE ranked first for E 2 stability (SUCRA = 77.0%). For safety, MWA (SUCRA = 78.8%) and HIFU (SUCRA = 69.7%) had the lowest incidence of adverse events. HIFU showed overall efficacy advantages, MWA showed a safety advantage, and UAE may suit specific patient populations. This study provides evidence-based support for individualized treatment decisions for UFs. However, these findings require cautious interpretation due to limited evidence. PROSPERO (CRD420251273503).

To evaluate the relationship between race and social determinants of health and receipt of hysterectomy versus uterine-preserving fibroid treatment. A retrospective cohort study using deidentified claims and longitudinal health data from OptumLabs ® Data Warehouse. Patients aged 15-55 years with newly diagnosed fibroids between 2010 and 2023 were included. Menopausal individuals and those with gynecological cancer were excluded. The primary outcome was hysterectomy by any route versus uterine-preserving fibroid surgery within 180 days of fibroid diagnosis. We used logistic regression to assess associations between socioeconomic factors and receipt of hysterectomy after adjusting for pertinent covariates. A total of 73,479 individuals were included; 50,645 received hysterectomy, 22,834 received a uterine-preserving treatment. Race, income, education level, and rurality were independently associated with the probability of hysterectomy. Odds of hysterectomy were lower for all people of color compared with White individuals (Asian odds ratio [OR] 0.61 [95% confidence interval (CI): 0.56-0.66], Black OR: 0.70 [95% CI: 0.67-0.73], and Hispanic OR: 0.90 [95% CI: 0.86-0.95]). Individuals with household income <$40,000, less than high school education, and rural address were more likely to undergo hysterectomy compared with those with income >$124,999 (OR: 1.15, 95% CI: 1.09-1.21), bachelor's degree or higher (OR: 2.55, 95% CI: 1.78-3.65), and metropolitan address (OR: 1.70, 95% CI: 1.44-2.01). All associations were significant at p < 0.05. People with fewer socioeconomic advantages, such as lower household income, lower educational attainment, and rural address were more likely to receive hysterectomy rather than uterine-preserving fibroid treatment. After controlling for age, surgery year, and socioeconomic factors, people of color were less likely to receive hysterectomy rather than uterine-preserving fibroid treatment.

Placenta accreta spectrum (PAS) poses high maternal morbidity from adverse pregnancy outcomes (APOs), yet uterine artery Doppler has limited predictive value, and the additive role of three‑dimensional power Doppler (3D‑PD) remains unclear. A retrospective study was carried out on 180 patients with PAS, who were divided into an APO group ( n = 76) and a non-APO ( n = 104) group. Placental 3D-PD parameters, including the vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI), as well as uterine artery flow parameters, including the pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D), were collected and compared between the two groups. Multivariate logistic regression was used to identify independent predictors. Internal validation was performed with 1,000 bootstrap resamples, and calibration was evaluated using the Hosmer-Lemeshow test. The predictive value of each parameter and of a combined model was assessed using receiver operating characteristic curves. The overall incidence of APOs in patients with PAS was 42.22% (76/180). The APO group had higher VI, FI and VFI values but lower PI, RI and S/D values than the non-APO group (all p < 0.05). After adjusting for gestational age at delivery, all six parameters remained independent predictors ( p < 0.05). Each single parameter showed only poor predictive value, with AUCs ranging from 0.604 to 0.656. The combined model based on all six parameters demonstrated better predictive ability (AUC = 0.793; 95% confidence interval: 0.726-0.859), with a sensitivity of 83.65% and a specificity of 61.84%. APOs in patients with PAS are associated with increased placental vascularisation and reduced uterine artery resistance. The combined model outperforms any single parameter and may aid in early risk stratification. Placenta accreta is a condition where the placenta grows too deeply into the womb. This can cause severe bleeding during birth and other problems for mothers. Predicting which women will have complications helps doctors plan better care and be prepared. In this study, researchers reviewed records of 180 pregnant women with placenta accreta. They used ultrasound to measure blood flow in the placenta and uterine arteries. The goal was to see if these measures could predict serious issues like heavy bleeding or early delivery. Amongst the 180 women, 76 (42%) had complications. Those with complications had higher placental blood flow and lower artery resistance. But no single measure was accurate enough. Combining six measures into one model improved prediction. This model correctly identified 84% of high‑risk women, catching most cases. It also correctly ruled out 62% of low‑risk women, so it was moderately helpful. Even with this limitation, the model can guide doctors to decide who needs closer monitoring and earlier action. This could reduce severe bleeding and other risks, leading to safer labours for mothers with this condition.

Ineffective uterine contractions contribute to labour dystocia and are a leading indication for primary caesarean delivery. Although oxytocin is the standard therapy for augmentation, prolonged exposure may result in receptor desensitisation and reduced effectiveness. Calcium is essential for myometrial contraction; however, systemic calcium homeostasis is tightly regulated, and it is unclear whether oral calcium supplementation can meaningfully influence uterine activity. This study aimed to evaluate the effect of oral calcium carbonate on uterine contractility. We conducted a single-centre randomised controlled pilot trial at a tertiary care teaching hospital (ClinicalTrials.gov: NCT07056062). Term patients with singleton foetus in cephalic presentation and an intrauterine pressure catheter in place were randomised 1:1 to receive a single 2,000 mg oral dose of calcium carbonate or no intervention. Uterine activity was measured using Montevideo units (MVUs) at baseline and at 30-minute intervals for two hours. Secondary outcomes included contraction frequency, peak contraction pressure, labour duration, mode of delivery, oxytocin dose, and postpartum haemorrhage. Oxytocin infusion rates were held constant during the observation period. Eighty-nine patients were analysed (45 control; 44 intervention) with similar baseline characteristics. No statistically significant difference in baseline MVUs was observed between groups ( p = 0.1825). Although absolute MVUs were higher in the intervention group at 30 minutes ( p = 0.0500), this difference was not sustained at subsequent time points and was absent in change-from-baseline analyses, suggesting no clinically meaningful treatment effect. No statistically significant differences were identified in secondary outcomes. Oral calcium carbonate did not result in a statistically significant improvement in uterine contractility or clinical outcomes. These findings likely reflect the limited physiologic effect of oral calcium on serum calcium levels. Oral calcium carbonate appears unlikely to be an effective intervention for labour augmentation; future research should focus on strategies with more controllable mechanisms. During labour, the uterus contracts to help the baby move through the birth canal. If contractions are too weak or poorly coordinated, labour may progress slowly, increasing the likelihood of caesarean delivery. Oxytocin is commonly used to strengthen contractions, but prolonged exposure may make the uterus less responsive over time. Calcium is an important mineral that helps muscle cells contract, including the muscles of the uterus. Because of this, we conducted a randomised clinical trial to determine whether providing calcium during labour could improve contractions. We found no meaningful differences in contraction strength or labour outcomes between patients who received calcium and those who did not. Although a difference in contraction strength was observed at one early time point, this was not sustained and did not translate into clinical benefit. These findings suggest that a single dose of oral calcium carbonate does not improve uterine contractions during labour.

Do different subtypes of congenital uterine anomaly (CUA) differentially affect outcomes after the first single euploid frozen blastocyst transfer following preimplantation genetic testing for aneuploidy (PGT-A)? This retrospective cohort included 163 women with CUA, including septate uterus (n = 73), arcuate uterus [as defined by the American Society for Reproductive Medicine (ASRM)] (n = 65), unicornuate uterus (n = 21) and uterus didelphys (n = 4), undergoing their first single euploid frozen blastocyst transfer after PGT-A at Peking University Third Hospital between 2019 and 2023. They were matched 1:3 by age and body mass index (BMI) with 489 women with a normal uterus. The primary endpoint was live birth rate; secondary outcomes included clinical pregnancy rate, pregnancy loss rate, and perinatal outcomes. Compared with controls, women with CUA had lower clinical pregnancy [29.4% (48/163) versus 49.1% (240/489); adjusted risk ratio (aRR) = 0.599, 95% CI 0.465-0.773; P < 0.001] and live birth rates [15.3% (25/163) versus 36.2% (177/489); aRR = 0.426, 95% CI 0.292-0.622; P < 0.001], but a higher first-trimester loss rate [35.4% (17/48) versus 12.1% (29/240); aRR = 3.103, 95% CI 1.938-4.968; P < 0.001]. Subtype-specific analyses showed that septate uterus was associated with lower clinical pregnancy [21.9% (16/73) versus 47.0% (103/219); P < 0.001] and live birth rates [8.2% (6/73) versus 35.6% (78/219); P < 0.001], and a higher first-trimester loss rate [62.5% (10/16) versus 14.6% (15/103); P < 0.001]. ASRM-defined arcuate uterus was associated with a lower clinical pregnancy rate [33.8% (22/65) versus 49.7% (97/195); P = 0.037], whereas the reduction in live birth rate was non-significant [21.5% (14/65) versus 33.8% (66/195)]. Despite PGT-A control of embryo ploidy, CUA, especially arcuate and septate subtypes, remained associated with adverse outcomes, supporting an independent uterine effect and the need for standardized imaging definitions and subtype-specific management.

This research letter expands the phenotypic spectrum of ACTG2-associated autosomal dominant visceral myopathy to include isolated uterine involvement based on a case of an individual harboring a known pathogenic ACTG2 variant with uterine atony as her only symptom.