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AimTo assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery.Materials and methodsA decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results.ResultsIn this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan.LimitationsThere are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided.ConclusionThis analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

Escherichia coli has been attributed to playing a major role in a cascade of events that affect the prevalence and severity of uterine disease in cattle. The objectives of this project were to (i) define the association between the prevalence of specific antimicrobial resistance and virulence factor genes in E. coli with the clinical status related to uterine infection, (ii) identify the genetic relationship between E. coli isolates from cows with diarrhea, with mastitis, and with and without metritis, and (iii) determine the association between the phenotypic and genotypic antimicrobial resistance identified on the E. coli isolated from postpartum cattle. Bacterial isolates (n = 148) were obtained from a larger cross-sectional study. Cows were categorized into one of three clinical groups before enrollment: metritis, cows with purulent discharge, and control cows. For genomic comparison, public genomes (n = 130) from cows with diarrhea, mastitis, and metritis were included in a genome-wide association study, to evaluate differences between the drug classes or the virulence factor category among clinical groups. A distinct E. coli genotype associated with metritis could not be identified. Instead, a high genetic diversity among the isolates from uterine sources was present. A virulence factor previously associated with metritis (fimH) using PCR was not associated with metritis. There was moderate accuracy for whole-genome sequencing to predict phenotypic resistance, which varied depending on the antimicrobial tested. Findings from this study contradict the traditional pathotype classification and the unique intrauterine E. coli genotype associated with metritis in dairy cows.IMPORTANCEMetritis is a common infectious disease in dairy cattle and the second most common reason for treating a cow with antimicrobials. The pathophysiology of the disease is complex and is not completely understood. Specific endometrial pathogenic Escherichia coli have been reported to be adapted to the endometrium and sometimes lead to uterine disease. Unfortunately, the specific genomic details of the endometrial-adapted isolates have not been investigated using enough genomes to represent the genomic diversity of this organism to identify specific virulence genes that are consistently associated with disease development and severity. Results from this study provide key microbial ecological advances by elucidating and challenging accepted concepts for the role of Intrauterine E. coli in metritis in dairy cattle, especially contradicting the existence of a unique intrauterine E. coli genotype associated with metritis in dairy cows, which was not found in our study.

ObjectiveTo evaluate differences based on intrauterine device (IUD) frame geometry in force, and stress, and strain at the stem/arms junction during simulated IUD removal.Study designWe manufactured injection-molded frame models for three Nova-T IUDs (Mirena [model M]; Liletta [model L]; Kyleena [model K]) and a Tatum-T IUD (Paragard [model P]) at two-times scaling. We created a custom fixture to simulate the uterus and used a screw-driven machine to pull models at various displacement rates through the 10 cm fixture cavity to measure force and strain and calculate stress at the IUD stem/arms junction. We tested models at 30 mm/min and higher displacement rates for exploratory analyses. We used Mann-Whitney U test for statistical testing.ResultsWe completed testing at 30 mm/min using five of each Nova-T model and nine model P samples. Resistance against the cavity walls created significantly more force on model P (11.83, interquartile range [IQR] 11.61-12.31) than any Nova-T model samples (p

Embryo-maternal crosstalk is essential to establish pregnancy, with the equine embryo moving throughout the uterus on days 9-15 (ovulation = day 0) as part of this interaction. We hypothesized that the presence of a mobile embryo induces local changes in the gene expression of the endometrium. On Day 12, the endometrial transcripts were compared among three groups: uterine horn with an embryo (P+, n = 7), without an embryo (P-, n = 7) in pregnant mares, and both uterine horns of nonbred mares (NB, n = 6). We identified 1,101 differentially expressed genes (DEGs) between P+ vs. NB and 1,229 DEGs between P- vs. NB. The genes upregulated in both P+ and P- relative to NB were involved in growth factor pathway and fatty acid activation, while downregulated genes were associated with oxytocin signaling pathway and estrogen receptor signaling. Comparing the transcriptome of P+ to that of P-, we found 59 DEGs, of which 30 genes had a higher expression in P+. These genes are associated with regulating vascular growth factors and the immune system, all known to be essential in early pregnancy. Overall, this study suggests that the mobile embryo influences the endometrial gene expression locally.

BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

MicroRNAs (miRNAs) are a type of specific molecules that control the activities of the uterus, such as the process of cellular maturing and evolution. A lot of substances like growth factors, cytokines, and transcription factors play a role in embryo-endometrial interaction. MiRNAs could regulate various these factors by attaching to the 3' UTR of their mRNAs. Moreover, current research show that miRNAs participate in formation of blood vessels in endometrium (miR-206, miR-17-5p, miR-16-5p...), decidualization (miR-154, miR-181, miR-9...), epithelial-mesenchymal transition (miR-30a-3p), immune response (miR-888, miR-376a, miR-300...) embryo attachment (miR-145, miR-27a,451...) and pinopod formation (mir-223-3p, mir-449a, mir-200c). In this study, the focus is on the role of miRNAs in managing the uterus' receptivity to an embryo and its ability to facilitate attachment. More specifically, we are exploring the mechanisms by which miRNAs regulate the presence of specific molecules involved in this crucial physiological process. [ABSTRACT FROM AUTHOR]

Background Objective Design and setting Results/outcomes Conclusion While uterus transplantation offers a promising treatment option for women with uterine factor infertility (UFI), the potential for graft failure and lack of organ availability could have subsequent psychological repercussions for women. Exploring baseline psychological well‐being for women with UFI who could become uterine transplant recipients is essential to identify specific psychological challenges to be considered prior to transplantation. UFI can be congenital uterine absence, namely Mayer‐Rokitansky‐Küster‐Hauser syndrome (MRKH), or acquired uterine absence (hysterectomy).To analyse baseline psychological well‐being among women with UFI.A survey including demographic data and two internationally validated psychological questionnaires, Depression, Anxiety and Stress Scale (DASS‐21),13 and Fertility Quality of Life (FertiQoL), was disseminated to women with UFI. Data from these instruments was compared between groups and then to data that uses these tools in the general infertility population.The study included 39 women (mean age 29.54 years). Higher scores for moderate symptoms of depression, anxiety, and stress were reported for the entire UFI cohort. More women with congenital UFI showed ‘severe’ symptoms for depression/anxiety, compared to women with acquired UFI. Women with acquired UFI showed poorer FertiQoL scores compared to both women with congenital UFI and to the general infertility population scores in previously published data.Clinicians should consider accessing increased psychological support for women with UFI when discussing fertility options including uterine transplant, and they may need to tailor this support depending on whether the patient has congenital or acquired UFI. [ABSTRACT FROM AUTHOR]

Background: Endometrial polyps are common benign lesions characterized by localized overgrowths of endometrial tissue within the uterine cavity. The etiology and pathogenesis of these polyps remain unclear. Human papillomavirus (HPV) infection, known for its association with various genital tract conditions, has been investigated concerning endometrial polyps, although research in this area is limited. Methods: A case-control study involving 62 premenopausal women was conducted, with endometrial polyp cases and control groups matched for age and BMI. Biopsy samples were collected for HPV testing using polymerase chain reaction (PCR). Clinical and demographic data were collected and analyzed for associations between HPV presence and endometrial polyps. Results: Results showed a higher prevalence of HPV (all types) in cases (4, 12.9%) compared to controls (1, 3.2%), with low-risk HPV being the most prevalent genotype detected and HPV 16 tested positive in one case diagnosed with polyp. While no significant association was found between HPV infection and the presence of endometrial polyps, the study suggests a potential role for HPV in their development. Interestingly, HPV presence in endometrial polyps was unrelated to histopathological features, patients' age, or BMI. Conclusion: This study provides insights into the potential involvement of HPV infection in the development of endometrial polyps. Despite no significant association found, the prevalence of HPV in these polyps suggests a possible contributory role. Further research with larger sample sizes and more robust methodologies is warranted to clarify this association and its clinical implications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions This study investigates the impact of intracavitary pressure levels on pain, visualization quality, and procedure duration in office hysteroscopy, comparing standard pressures (60–100 mmHg) with high pressures (110–150 mmHg).We conducted a retrospective cohort study involving non‐menopausal women undergoing diagnostic hysteroscopy at a tertiary clinic. Patients were categorized into two groups based on intracavitary pressure: the standard pressure group (60–100 mmHg; n = 72) and the high‐pressure group (110–150 mmHg; n = 37). Outcomes measured included pain scores, procedure duration, and fluid volume used. Logistic regression was employed to identify risk factors for severe pain.The high‐pressure group demonstrated significantly shorter procedure durations compared to the standard pressure group (96.56 ± 34.36 vs. 163.00 ± 61.78 s, p < 0.001). Pain scores were lower in the high‐pressure group (VAS 3.00 [0.00–7.00] vs. 3.50 [0.00–9.00], p = 0.041). Additionally, high‐pressure procedures used less fluid compared to standard pressure procedures, which helps to reduce the risk of fluid‐related complications. Logistic regression analysis identified higher fluid volumes (odds ratio [OR] = 1.005, 95% confidence interval [CI] = 1.001–1.010) and the need for pressure increases (OR = 3.914, 95% CI = 1.157–13.238) as significant risk factors for severe pain.Higher intracavitary pressure levels (above 100 mmHg) in office hysteroscopy are associated with reduced pain, shorter procedure durations, and decreased fluid use, enhancing visualization and procedural efficiency while maintaining patient comfort. [ABSTRACT FROM AUTHOR]

Streptococcus (S.) equi subspecies (subsp.) zooepidemicus is an important facultative pathogen in horses and can cause severe infections in other species including humans. Facing the post-antibiotic era, novel antimicrobials are needed for fighting bacterial infections. Bacteriophages (phages) are the natural predators of bacteria and discussed as a promising antimicrobial treatment option. The objective of this study was to isolate and characterize S. equi subsp. zooepidemicus- specific phages for the first time and to evaluate their efficacy in vitro and ex vivo. In total, 13 phages with lytic activity were isolated and host ranges were determined. Two phages with broad host ranges and high efficiency of plating (vB_SeqZP_LmqsRe26-2 (lytic activity: 30/37 bacterial isolates) and vB_SeqZP_LmqsRe26-3 (lytic activity: 29/37 bacterial isolates)) and one phage with relatively low efficiency of plating (vB_SeqZP_LmqsRe26-1) were selected for further characterization, including electron microscopy and whole genome sequencing. In in vitro planktonic killing assays at two tested multiplicities of infection (MOI 1 and MOI 10), significant bacterial growth reduction was observed when the phages vB_SeqZP_LmqsRe26-2 and vB_SeqZP_LmqsRe26-3 were added. These phages were subsequently co-incubated with clinical S. equi subsp. zooepidemicus isolates in an equine endometrial explant model but did not achieve bacterial growth reduction at MOI 1 and MOI 10. However, helium ion microscopy revealed presence of particles adherent to the bacteria on the explant after incubation (25 h), suggesting possible phage-bacteria interactions. In conclusion, phages against S. equi subsp. zooepidemicus were successfully isolated and characterized. Promising results were observed in in vitro but no significant reduction was detected in ex vivo experiments, requiring additional investigations. However, after further adaptations (e.g., optimization of MOIs and phage administration or use of phage-antibiotic combination), phages could be a potential antimicrobial tool for future therapeutic use in S. equi subsp. zooepidemicus infections, although the available results do not currently support the therapeutic usage. [ABSTRACT FROM AUTHOR]

Women suffering from absolute uterine factor infertility (AUFI), due to either lack of a uterus or one unable to sustain neonatal viability, presented as one of the last frontiers in conquering infertility. Following systematic animal research for over a decade, uterus transplantation was tested as a treatment for AUFI in 2012, which culminated in the first human live birth in 2014. The development of uterus transplantation from mouse to human has followed both the Moore criteria for introduction of a surgical innovation and the IDEAL concept for evaluation of a novel major surgical procedure. In this article we review the important preclinical animal and human studies that paved the way for the successful introduction of human uterus transplantation a decade ago. We discuss this in the context of the Moore criteria and describe the different procedures of preparation, surgeries, postoperative monitoring, and use of assisted reproduction in human uterus transplantation. We review the worldwide activities and associated results in the context of the IDEAL concept for evaluation of surgical innovation and appraise the ethical considerations relevant to uterus transplantation. We conclude that rigorous application of the Moore criteria and strict alignment with the IDEAL concept have resulted in the establishment of uterus transplantation as a novel, safe, and effective infertility therapy that is now being used worldwide for the treatment of women suffering from AUFI. [ABSTRACT FROM AUTHOR]

Introduction: The contribution of tubal factors to infertility is up to 30%. One of the tests used to evaluate tubal factor infertility is Doppler saline Sonosalpingography (SSG). The basic principle of SSG is to distend the uterine cavity with isotonic saline, which helps identify the uterine contour, intrauterine pathology, endometrial thickness and the presence of fluid in the Pouch of Douglas (POD). Adding Doppler increases its efficiency and accuracy. Aim: To ascertain the role of Doppler saline SSG in tubal infertility. Materials and Methods: This cross-sectional study was done for 18 months in the Obstetrics and Gynaecology Department of Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India involving 200 women with either primary or secondary infertility. These women were recruited in the midfollicular phase after obtaining written informed consent. Patients underwent Doppler SSG to assess tubal patency and the findings were compared with Diagnostic Hysterolaparoscopy (DHL). Diagnostic tests were used to calculate sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Inter-rater kappa agreement was used to find out the strength of the association between Doppler Saline SSG and diagnostic laparoscopy. A p-value of less than 0.05 was considered significant. The data was entered into an MS Excel spreadsheet and analysis was done using the licensed version of Statistical Package for Social Sciences (SPSS) version 21.0. Results: The mean age and mean duration of infertility were reported to be 29 years and five years, respectively. The sensitivity of Doppler SSG for tubal patency was reported as 85.4%, the specificity as 95.8%, PPV as 95.3%, NPV as 86.8% and the accuracy for tubal patency was 90.6%. Doppler SSG and laparoscopic chromopertubation findings had substantial association (k value -0.62). Conclusion: Doppler SSG is a reliable method for the assessment of tubal factors and can be used as a screening modality with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is present on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated forms. Since the exact pathomechanism of endometriosis has not yet been elucidated (although it has been associated with the development of endometrial and ovarian cancer), we asked whether extracellular Hsp70 and circulating endometriotic cells (CECs) reflect the presence and development of endometriosis. Therefore, circulating levels of free and lipid microvesicle-associated Hsp70 were measured using the Hsp70-exo ELISA, and the presence of circulating CECs in the peripheral blood of patients with endometriosis was determined using membrane Hsp70 (mHsp70) and EpCAM monoclonal antibody (mAb)-based bead isolation approaches. Isolated CECs were further characterized by immunofluorescence using reagents directed against cytokeratin (epithelial marker), CD45 (leukocyte marker), CD105/CD44 (mesenchymal stemness markers) and by comparative RNA analysis. Similar to the situation in patients with cancer, the levels of circulating Hsp70 were elevated in the blood of patients with histologically proven endometriosis compared to a healthy control cohort, with significantly elevated Hsp70 levels in endometriosis patients with lesions outside the uterine cavity. Moreover, CECs could be isolated using the cmHsp70.1 mAb-based, and to a lesser extent EpCAM mAb-based, bead approach in all patients with endometriosis, with the highest counts obtained using the mHsp70-targeting procedure in patients with extra-uterine involvement. The longevity in cell culture and the expression of the cytokeratins CD105 and CD44, together with differentially expressed genes related to epithelial-to-mesenchymal transition (EMT), revealed similarities between mHsp70-expressing CECs and circulating tumor cells (CTCs) and suggest a mesenchymal stem cell origin. These findings support the involvement of mHsp70-positive stem cell-like cells in the development of endometriotic lesions. In summary, elevated levels of Hsp70 and CECs in the circulation could serve as liquid biopsy markers for endometriosis with extra-uterine involvement and help to elucidate the underlying pathomechanism of the disease. [ABSTRACT FROM AUTHOR]

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical and ultrasonographic features of uterine perivascular epithelioid cell tumor (PEComa) using standardized terminology. Methods: This was a retrospective analysis of patients with uterine PEComa diagnosed and confirmed by pathology and immunohistochemistry at West China Second University Hospital, Sichuan University, Sichuan, China, between January 2010 and September 2023. The Morphological Uterus Sonographic Assessment (MUSA) consensus and the International Endometrial Tumor Analysis (IETA) consensus were utilized for the standardized description of the sonographic characteristics of uterine PEComa. We summarized the clinical and ultrasound features of uterine PEComa in cases from our center and those found in a review of the literature conducted using PubMed from 1 January 2013 to 30 September 2023 (inclusive). Results: Five patients, aged 33–57 (median, 52) years, with a total of six uterine PEComa lesions were included in our cohort. All cases had complete ultrasonographic and pathological images. None of the patients had a history of tuberous sclerosis complex. Two patients had malignant PEComa (one patient had two lesions) and three had benign PEComa, originating from the cervix, myometrium or uterine cavity. Patients presented with symptoms including increased vaginal discharge, vaginal bleeding and pelvic or abdominal pain. The three patients with benign PEComa underwent total hysterectomy and bilateral adnexectomy, tumor excision and conservative management, respectively, while both malignant cases underwent total hysterectomy and bilateral adnexectomy followed by chemotherapy. Regular follow‐up (from 6 to 24 months) revealed recurrence in one case. Two lesions were misdiagnosed as uterine fibroids, two as cervical cancer, one as metastatic cervical cancer (with myometrial invasion) and one was indeterminate. Ultrasound examination showed that most lesions displayed regular round or ovoid shape (66.7%), uniform echoes (66.7%) and hypoechogenicity (66.7%), with one (16.7%) malignant PEComa showing cystic areas and one (16.7%) benign PEComa showing punctate calcifications. All lesions lacked shadowing and the majority showed moderate to abundant vascularity (color score of 3–4, 83.3%). The color score was 2–4 in the periphery in 100% of cases and internally in 83.3% of cases. The three benign PEComas showed similar characteristics in vascular distribution, with scattered internal vessels and peripheral vessels exhibiting a circular pattern. The literature search identified 11 articles describing the ultrasonographic appearance of 18 cases of uterine PEComa, with similar characteristics to those in our cohort. Conclusions: The sonographic features of uterine PEComa include a uniform or non‐uniform hypoechogenic mass, typically round or ovoid with regular margins, occasionally containing cystic areas or calcifications, lacking shadowing and often showing moderate to abundant vascularity. Although the preoperative ultrasound diagnosis of uterine PEComa remains challenging, particularly given the non‐specific nature of the sonographic characteristics described here, dispersed intratumoral vessels and a peripheral circular vascular distribution may serve as diagnostic clues for uterine PEComa, but more cases are needed for confirmation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

• Mayer–Rokitanski–Kuster–Hauser syndrome is a congenital aplasia of uterus and vagina. • It causes absolute infertility, determining psychological disorders. • Psychological evaluation is needed to plan a management strategy and support patients and partners. Mayer–Rokitanski–Kuster–Hauser (MRKH) syndrome consists of a congenital aplasia of the uterus and the upper part of the vagina. It is the most frequent congenital cause of absolute uterine factor infertility, determining psychological disorders due to infertility and reduced quality of sexual activity. Being the necessity of baseline and prolonged assessments, clinicians need evaluation parameters for the monitoring of patients to plan a suitable management strategy and for efficient support before and after interventions, such as neovagina and uterus transplantation. Research of the literature was performed in PubMed and SCOPUS by searching for the terms "Mayer-Rokitanski-Kuster-Hauser" AND "psychological disorders"; from the 60 articles obtained, only 35 articles regarding neovagina creation and uterus transplantation were considered for the present manuscript. Based on the literature, management of MRKH syndrome by neovagina creation, either surgically or not, can restore a satisfactory sexual life and to reduce stress, signs of mental disorder and depression and improve sexual activity and quality of life. A psychological assessment of candidates to UT and of their partners is necessary. Recipients had low levels of anxiety compared to the normal population at baseline but a transiently lowered physical quality of life 1 year after surgery; elevated anxiety scores are associated with childlessness in the long-term evaluation. Further research is necessary to develop suitable evaluation protocols and adequate supportive services, to improve the outcomes of patients who undergo neovagina creation and uterus transplantation. [ABSTRACT FROM AUTHOR]

• Hysteroscopy is the gold-standard approach for treating most intrauterine lesions. • Hysteroscopic visualization may not suffice for optimal management in complex cases. • Intraoperative ultrasound in hysteroscopy reduces uterine perforation risk. • Ultrasound-guided hysteroscopy increases the rate of complete resection of lesions. Hysteroscopy stands as the gold-standard approach for managing intrauterine pathology. However, in complex clinical cases, hysteroscopic evaluation alone may prove insufficient for the safest and successful patient management. Intraoperative ultrasound (IOUS) has emerged as a valuable adjunct to hysteroscopic surgery, offering real-time visualization of endometrial cavity, uterine walls and instruments within the uterine cavity, enabling precise delineation of anatomical structures, and helping to assess the extent of pathology during intricate interventions. This review aims to comprehensively assess the applications, efficacy and utility of IOUS in hysteroscopic surgery. Available evidence indicates that in hysteroscopic myomectomy, IOUS significantly reduces the risk of uterine perforation, particularly in submucosal FIGO 2 myomas, and enhances the likelihood of a single-step procedure. During hysteroscopic metroplasty, ultrasound guidance decreases the chance of incomplete uterine septum resection. In the hysteroscopic management of severe Asherman syndrome, IOUS reduces the risk of uterine perforation or false passage. For cesarean scar pregnancy (CSP), ultrasound is crucial in defining the most appropriate surgical approach and is effective in guiding the hysteroscopic treatment of endogenic CSP. The use of IOUS in hysteroscopy proves valuable in complex cases where the risk of uterine perforation or incomplete procedure is increased. [ABSTRACT FROM AUTHOR]

Introduction: We present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri. Case: The patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free. Discussion: Primary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors. Conclusion: Decision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient. [ABSTRACT FROM AUTHOR]

Undifferentiated uterine sarcoma is an extremely rare cytologically challenging finding in pleural effusions undistinguished from the more common causes of malignant effusions. Cellblock is a valuable diagnostic tool when combined with certain diagnostic clues, relevant immunoprofile and knowledge of the patient's history. [ABSTRACT FROM AUTHOR]

Telocytes (TCs) are characterized by a small oval-shaped cell body with long prolongations that are called telopods (Tps). PDGFR-β and c-kit markers may assist for the immunohistochemical identification of TCs; however, by these means they cannot be identified with absolute specificity. Transmission electron microscopy (TEM) is considered as a gold standard method for TCs observation. Studies on TCs in the female reproductive system are limited, and there is a lack of awareness regarding TCs in rat ovaries. We aimed to demonstrate the existence and morphology of TCs in rat ovaries, alongside previously studied TCs in rat uteri. Thus, ovaries and uteri from young adult Sprague–Dawley female rats (n = 8) with regular estrous cycles were collected. Then, left ovaries and uteri were proccessed for TEM analysis, while the right ones were used for immunohistochemistry. As a result, TCs were seen throughout the rat's ovarian stroma with their characteristic cell bodies, Tps, podomes (Pds) and podomers (Pdms). Tps were situated within the thecal layer of the follicles, surrounding the corpus luteum and blood vessels. Ovarian TCs were recognized to have relationship with other TCs/stromal cells. Subsequently, TCs were seen in stroma of endometrium with surrounding blood vessels and uterine glands, myometrium and perimetrium in rat uteri. There was also no statistical significance between the number of c-kit+ and PDGFR-β+ telocyte-like cells in both rat ovarian (p = 0.137) and endometrial stroma (p = 0.450). Further investigation of the roles and functions of TCs in the female reproductive system is needed. [ABSTRACT FROM AUTHOR]

The American Institute of Ultrasound in Medicine (AIUM) has developed the Practice Parameter for the Performance of Ultrasound of the Female Pelvis, which provides recommendations for high-quality ultrasound examinations in this specialty area. The document outlines indications for pelvic sonography, qualifications and responsibilities of personnel, preparation for the examination, and detailed specifications for evaluating the uterus, adnexae (ovaries and fallopian tubes), and cul-de-sac. It emphasizes the importance of accurate documentation, equipment specifications, quality assurance, safety, infection control, and adherence to the ALARA principle. The parameter was developed in collaboration with various organizations and committees, reflecting a multidisciplinary approach to advancing the safe and effective use of ultrasound in medicine. [Extracted from the article]

Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial–mesenchymal transition (EMT) of endometrial epithelial cells and endothelial–mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-β1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-β1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-β1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-β1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-β1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA. [ABSTRACT FROM AUTHOR]

Embryo survival and pre‐implantation development depend on uterine luminal fluid, which is believed to play a role in early embryonic death and infertility in cows. Extracellular vesicles (EVs) in the uterine luminal fluid contain microRNAs (miRNAs), crucial mediators of intercellular communication. miRNAs regulate conceptus–maternal interactions and participate in embryonic development by suppressing gene expression. Therefore, we hypothesized that miRNAs in the intrauterine EVs of low‐fertility cows would hinder embryonic survival and development. EVs were collected from the bovine uterine luminal fluid of both normal‐ and low‐fertility cows 7 days post‐estrus. Small RNA‐sequencing analysis of miRNAs isolated from these EVs identified eight miRNAs that were highly expressed in normal‐fertility cows (normal‐fertility miRNAs) and eight with elevated expression in low‐fertility cows (low‐fertility miRNAs). These two sets of miRNAs were transfected into hatched blastocysts via lipofection. RNA‐seq following lipofection with low‐fertility miRNAs identified 424 differentially expressed genes (DEGs) relative to the control; in contrast, following lipofection with normal‐fertility miRNAs, seven DEGs were identified. Pathway analysis of the DEGs identified following lipofection with low‐fertility miRNAs revealed substantial enrichment of mitogen‐activated protein kinase (MAPK) signaling. Expression of activator protein 1 (AP1) and interferon‐tau (IFNT) mRNA was significantly lower in the low‐fertility miRNA transfection group than in the control. IFNT is essential for maternal pregnancy recognition. Therefore, miRNAs in intrauterine EVs from low‐fertility cows at 7 days post‐estrus may inhibit embryo development and suppress IFNT expression by altering MAPK signaling. [ABSTRACT FROM AUTHOR]

Background: Nesfatin-1 is a neuropeptide that regulates the hypothalamic-pituitary-gonadal axis and may play a role in uterus function. It is co-expressed with other peptides, such as phoenixin, which can influence sex hormone secretion. Our previous research has confirmed that phoenixin-14 is involved in the development of cystic endometrial hyperplasia (CEH) and pyometra in dogs. Therefore, based on the similarities and interactions between these neuropeptides, we hypothesized that nesfatin-1 might also regulate the reproductive system in dogs. This study aimed to determine the expression of nesfatin-1 and its interaction with phoenixin-14 in dogs with CEH or pyometra compared to healthy females, and concerning animals' body condition score (BCS 4–5/9 vs. BCS > 5/9). Results: The analysis of nesfatin-1 in the uterus of bitches consisted of qPCR, western blot and immunofluorescence assays, and ELISAs. The results showed significantly higher nesfatin-1 encoding gene, nucleobindin-2 mRNA (Nucb2) and nesfatin-1 protein expression in overweight females and those suffering from CEH or pyometra compared to healthy animals. The immunoreactivity of nesfatin-1 was elevated in the uteri of bitches with higher BCS > 5/9. Moreover, nesfatin-1 blood concentrations increased in all examined overweight bitches. In the case of phoenixin signals, we found opposite results, regardless of the female body condition score. Conclusion: The etiology of CEH and pyometra are not fully known, although we have expanded the level of knowledge with respect to the possible interaction of nesfatin-1 and phoenixin in female dogs' uteri. They interact oppositely. With increasing female body weight, the expression of nesfatin-1 in the uterus and its peripheral blood concentration increased. However, for female dogs affected by CEH and pyometra, a decreased level of phoenixin-14, irrespective of their body condition score is characteristic. This knowledge could be crucial in the development of biomarkers for these conditions, which may lead to earlier recognition. [ABSTRACT FROM AUTHOR]

Adenomatoid tumors are rare benign neoplasms arising from mesothelial cells, commonly found in the female genital system, particularly the uterus and fallopian tubes. The giant cystic variant of adenomatoid tumor is exceptionally rare and can cause massive growth mimicking malignant gynecological conditions. Histology and immunohistochemistry play a crucial role in confirming the diagnosis, with markers such as calretinin, D2‐40, CK7, BAP1, ER, and WT1 proving useful. A 51‐year‐old female with a history of breast cancer presented with pelvic pressure and vague pain. Imaging revealed an enlarged uterus with multiple heterogeneously enhancing masses and a predominantly cystic mass arising from the fundus, all believed to be leiomyomas. Surgical exploration and subsequent pathologic examination identified the cystic tumor as cystic adenomatoid tumor coexisting with leiomyomas, adenomyosis, and abdominal endometriosis. Diagnosing cystic adenomatoid tumor presents challenges, especially in patients with complex gynecologic histories. Cystic adenomatoid tumors typically have a favorable prognosis following surgical intervention. This case demonstrates one of the few reports of a giant cystic adenomatoid tumor (11.5 cm) and highlights diagnostic mimics. As these tumors are typically small and often seen only microscopically, the large size can confuse the pathologist who may be unaware of this feature leading to a misdiagnosis. [ABSTRACT FROM AUTHOR]

Study Objective Measurements and Main Results Conclusions This study aimed to observe and quantitatively analyze the morphology and distribution of uterine nerve fibers using fluorescence micro‐optical sectioning tomography (fMOST). The goal was to provide an accurate morphological reference for pathological evaluations of uterine nerves.Using fMOST technique, we observed and analyzed the distribution of nerve fibers within the uterus. Our findings revealed a radial dispersion of nerve fibers radiating from myometrium to endometrium. The cervix uteri region exhibited a high density of nerve fibers, displaying terminations in a flower spray pattern. In contrast, nerve fibers in corpus uteri were comparatively sparse. However, we identified a unique “vine‐like” pattern of a single nerve fiber extending from myometrium to endometrial layer in areas with concentrated nerves.The fMOST technique is able to effectively elucidate the morphology and distribution of uterine nerve fibers. This method enables three‐dimensional visualization of nerves in myometrium and offers a novel approach to observe the pathological changes in uterine nerves. [ABSTRACT FROM AUTHOR]

Mullerian adenosarcoma is rare, usually found in the uterine corpus and rarely in the cervix. Adenosarcoma that grows diffusely in the uterine cavity and the cervical canal is even rarer without symptoms. Herein, we report a rare case of multiple primary malignant neoplasms of Mullerian adenosarcoma accidentally detected and coexisting with cervical carcinoma in situ. Fortunately, the tumor was in the early stage and the Mullerian adenosarcoma was treated together with the cervical carcinoma in situ by hysterectomy + bilateral adnexectomy. Histopathology and immunohistochemistry results confirmed this diagnosis, further confirmed by a pathology consultation at the University Hospital. The patient recovered well from the surgical treatment and was discharged with regular follow-up. The patient did not undergo pelvis--abdomen CT and diagnostic curettage preoperatively, and no malignancy was detected by cryopathology intraoperatively, which may be related to the rarity of the disease and the relative lack of awareness and experience of our clinicians and pathologists for this tumor. We hope that this rare case can provide some lessons for gynecologists and pathologists. [ABSTRACT FROM AUTHOR]

This study was conducted to re-evaluate the utility of subendometrial enhancement (SEE) in assessing the interface between the endometrium and myometrium. In total, 110 women who underwent pelvic magnetic resonance imaging (MRI) for non-endometrial gynecologic diseases were enrolled in this prospective study. Two radiologists independently assessed the presence or absence of subendometrial enhancement (SEE) on dynamic contrast-enhanced (CE) MRI. A subgroup analysis was performed to evaluate the impact of menstrual status on the detection of SEE. Identified areas of SEE were rated using a 4-point Likert scale to determine their reliability in assessing the interface between the endometrium and myometrium. SEE was identified in 44.5% (49/110) of cases by radiologist 1 and in 39.1% (43/110) by radiologist 2. A subgroup analysis indicated no significant differences in the detection of SEE based on menstrual status. The identified areas of SEE were deemed reliable for assessing the interface between the endometrium and myometrium in 24.5% (12/49) of the cases evaluated by radiologist 1 and in 32.6% (14/43) of those evaluated by radiologist 2. Among the 110 women studied, reliable areas of SEE for assessing the interface between the endometrium and myometrium were observed in 10.9% (n = 12) by radiologist 1 and 12.7% (n = 14) by radiologist 2. The evaluation of SEE using dynamic CE MRI may be limited in its ability to assess the interface between the endometrium and myometrium. [ABSTRACT FROM AUTHOR]

Background: During early pregnancy, glucose is essential for the uterine epithelium and the developing embryo. In cows, progesterone increases the secretion of glucose into the uterine lumen. The uterine epithelium can convert glucose to fructose, but other fates of glucose in the uterine epithelium have been sparsely investigated. Therefore, our objective was to investigate how progesterone influences glucose metabolism in immortalized bovine uterine epithelial (BUTE) cells. Methods: BUTE cells were grown to 80% confluence and treated with vehicle (DMSO) or 10 µM progesterone for 24 h. Cells were collected and analyzed. Immunohistochemistry was performed on endometrial samples collected from the bovine endometrium on days 1 and 11 of the reproductive cycle. Results: Progesterone treatment increased glucose consumption of BUTE cells. RNAseq identified 3,072 genes regulated by progesterone. KEGG analysis indicated that progesterone altered genes associated with metabolic pathways and glutathione metabolism. Manually examining genes unique to specific glucose metabolic pathways identified an increase in the rate-limiting enzyme in the pentose phosphate pathway—glucose-6-phosphate dehydrogenase. Functionally, a major product of the pentose phosphate pathway is NADPH, and progesterone treatment increased NADPH levels in BUTE cells. In cows, immunohistochemistry confirmed that glucose-6-phosphate dehydrogenase levels were higher in the uterine epithelium in the luteal phase when progesterone concentrations are high. Conclusions: Progesterone increased glucose-6-phosphate dehydrogenase expression and metabolism via the pentose phosphate pathway in the bovine uterine epithelium. This metabolism could provide substrates for cell proliferation, molecules to be secreted into the uterine lumen, or maintain reduction/oxidation balance in the uterine epithelium. [ABSTRACT FROM AUTHOR]

Found in as many as 80% of women, uterine leiomyomas are a frequent cause of abnormal uterine bleeding, pelvic pain, and infertility. Despite their significant clinical impact, the mechanisms responsible for driving leiomyoma growth remain poorly understood. After obtaining IRB permission, expression of ecto‐5′‐nucleotidase (NT5E, CD73) was assessed in matched specimens of myometrium and leiomyoma by real‐time qPCR, Western blot, and immunohistochemistry (IHC). Adenosine concentrations were measured by enzyme‐linked assay. Primary cultures were used to assess the impact of adenosine and/or adenosine receptor agonists on proliferation, apoptosis, and patterns of intracellular signaling in vitro. When compared to matched specimens of healthy myometrium, uterine leiomyomas were characterized by reduced CD73 expression. Largely limited to thin‐walled vascular structures and the pseudocapsule of leiomyomas despite diffuse myometrial distribution. Restricted intra‐tumoral CD73 expression was accompanied by decreased levels of intra‐tumoral adenosine. In vitro, incubation of primary leiomyoma cultures with adenosine or its hydrolysis‐resistant analog 2‐chloro‐adenosine (2‐CL‐AD) inhibited proliferation, induced apoptosis, and reduced proportion of myocytes in S‐ and G2‐M phases of the cell cycle. Decreased proliferation was accompanied by reduced expression of phospho‐Akt, phospho‐Cdk2‐Tyr15, and phospho‐Histone H3. Enforced expression of the A2B adenosine receptor (ADORA2B) and ADORA2B‐selective agonists similarly suppressed proliferation and inhibited Akt phosphorylation. Collectively, these observations broadly implicate CD73 and reduced extracellular concentrations of adenosine as key regulators of leiomyoma growth and potentially identify novel strategies for clinically managing these common tumors. [ABSTRACT FROM AUTHOR]

Several seminal plasma components, besides NGF, are implicated as ovulation-inducing factors in mammals. This study investigated the IL1B and its receptor IL1R1 in the testis (T), male accessory glands, prostate (P) and seminal vesicles (SV), and uterus (U) of adult rabbits using immunohistochemistry (IHC) and quantitative reverse transcription PCR (RT-qPCR). We also assessed the presence of IL1B in seminal plasma through Western blotting (WB) and examined the interaction between IL1B and NGF in vitro by measuring their production with enzyme-linked immunosorbent assay (ELISA) in the presence of NGF and IL1B alone or with their respective receptor antagonists. IHC revealed IL1B system expression in all reproductive organs studied, with IL1B and IL1R1 localized to the germinative epithelium of the T and the epithelial cells of the accessory glands and U. IL1B gene transcript levels were significantly higher (p < 0.01) in the P and SV compared to the T, while IL1R1 levels were significantly higher (p < 0.001) in the P compared to the other tissues, while IL1R1 levels were three times higher (p < 0.001) in the P. WB confirmed the presence of IL1B in seminal plasma with a 30–35 kDa band. The in vitro study demonstrated that IL1B increased (p < 0.05) basal NGF production in the U, whereas NGF had no effect on IL1B production. These findings provide evidence of the expression of the IL1B/IL1R1 system in both male and female rabbit reproductive tracts and suggest that IL1B in seminal plasma may influence uterine endocrine activity. The results propose a potential role for IL1B in ovulation, in conjunction with NGF, supporting that ovulation may involve inflammatory-like processes. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Uterine transplantation was developed for the treatment of absolute uterine factor infertility. As it is a new modality of transplantation, there is still room for technical improvement. A factor that impacts graft survival in organ transplantation is the warm ischemia time. In uterine transplantation specifically, at least two vascular anastomoses are performed on each side of the uterus, and the graft revascularization takes place when the vascular clamps of the arteries and veins are released on both sides simultaneously. For this reason, the warm ischemia time in uterine transplant is expected to be considerably long. The purpose of this study was to compare the sequential technique of uterine graft revascularization, which aims to reduce the warm ischemia time of the procedure, with the simultaneous revascularization technique.For the procedure, the uterine auto‐transplantation technique was performed using 10 non‐pregnant adult ewes weighing about 45 kg, divided into two groups: simultaneous revascularization group (5 animals) and sequential revascularization group (5 animals). To evaluate the groups, we analyzed the procedure and warm ischemia times, graft macroscopy, hemodynamic, laboratory, and histological parameters of the uterus.The sequential revascularization technique group had similar surgical procedure times, and the warm ischemia time was significantly shorter with medians of 32 min in the sequential group versus 72 min in the simultaneous group (p < 0.008). The graft macroscopy and hemodynamic, laboratory, and histological parameters evaluated were similar between the groups.The sequential revascularization technique proved to reduce the warm ischemia time in the sheep uterine auto‐transplantation model without compromising graft viability. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Methods: Next-generation sequencing dataset GSE243039 was obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein–protein interaction (PPI) network was constructed and modules were analyzed using the Human Integrated Protein–Protein Interaction rEference database and Cytoscape software, and hub genes were identified. Subsequently, a network between miRNAs and hub genes, and network between TFs and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve analysis was used to validate the hub genes. Results: A total of 958 DEGs, including 479 upregulated genes and 479 downregulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 and actc1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including tcf3 (transcription factor 3) and clock (clock circadian regulator), were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. Conclusions: This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment and monitoring of endometriosis. [ABSTRACT FROM AUTHOR]

Objective: Uterine inflammatory myofibroblastic tumor (UIMT) is a rare tumor of the female reproductive tract with uncertain malignant potential. Previous case series reports have limited our understanding of its diagnosis and treatment. Therefore, we conducted a retrospective analysis of patient files at West China Second University Hospital, Sichuan University to contribute valuable clinical insights to future treatment strategies for this disease. Method: We comprehensively reviewed patient files of individuals diagnosed with UIMT from January 1st, 2013 to May 1st, 2023. Results: We included twenty-seven cases of uterine inflammatory myofibroblastic tumor in our study. Of these, 51.85% (14 cases) were diagnosed with abnormal uterine bleeding, 2 cases had dysmenorrhea, and 12 were unexpectedly diagnosed with suspected uterine fibroids. Ten cases performed total hysterectomy, and 17 cases underwent lesion resection. The positive rate of anaplastic lymphoma kinase (ALK) immunohistochemistry reached 96.3%. After a median of 8 months follow-up time, all patients were disease-free and had survived. Conclusion: Uterine inflammatory myofibroblastic tumor is easily misdiagnosed, making its diagnosis challenging. Histological features, immunohistochemical results, and molecular confirmation using fluorescence in situ hybridization (FISH) or Next-generation sequencing should be used to confirm the diagnosis. Positive ALK immunohistochemistry, ALK rearrangement, ALK fusion are helpful in diagnosis and ALK inhibitor therapy. Total hysterectomy is often performed for women who do not require fertility, while lesion resection and close follow-up may be considered for those who require fertility preservation. [ABSTRACT FROM AUTHOR]

Acrylonitrile (ACN) is an organic synthetic monomer that is widely used in food packaging and manufacturing. Our current study aimed to investigate toxic pathological effects and biochemical alterations in ACN-treated female mice. Seventy female mice were assigned into 3 groups and received oral distilled water, ACN (10.17 mg/kg b.w, 1/10 of LD50) twice a week and ACN (10.17 mg/kg b. w) three times a week, respectively. After 45, 90 and 120 days of treatment, blood samples and tissue specimens from the uteri were obtained for measurement of catalase (CAT) and malondialdehyde (MDA), and histopathological examination, respectively. It was found that ACN significantly reduced CAT levels in group 2 and 3 after 120 days of treatment compared to group 1. Moreover, CAT levels in group 3 were significantly decreased compared to that in group 2 after both times intervals, 45 and 90 days. ACN raised MDA concentration in group 3 after 120 days of treatment compared to groups 1 and 2. Histopathologically, ACN was seen to damage the uterus as it markedly caused congestion, hemorrhages, thrombosis, severe necrosis, and local and diffuse granulomatous inflammation. In conclusion, exposure of female mice to ACN induces pronounced hazardous toxic and pathological effects in the form of imbalance in the oxidantantioxidant harmony and marked histopathological changes. The study recommends avoiding overeating products containing ACN to keep proper health of the female genital system. [ABSTRACT FROM AUTHOR]

Background: Ectopic Pregnancy is defined as pregnancy that occurs outside normal uterine cavity in an aberrant site. In developing countries like India, late presentations with tubal rupture and haemodynamic instability, causes maternal morbidity and mortality. Aims and Objectives: To determine the incidence, risk factors, clinical features, associated with ectopic pregnancy in a tertiary care hospital and interventions for early diagnosis and conservative management. Materials and Methods: In this Time bound, Observational descriptive study with Longitudinal design conducted at Dept of G&O, R. G. Kar Medical College and Hospital, between March 2021 to August 2022. 138 participants, suspected to have ectopic pregnancy were enrolled for the study and detailed history taking and physical examination was done. Basic investigations including CBC, ABO &RH typing, UPT and USG were done. Post-op HPE reports were collected and final diagnosis was made. Results: 63.8% of the study population belonged to 21 to 30 years of age. 63.7% patients presented with >5 wks. - 8 wks. of amenorrhoea.18.1% of the study population were sterilized. The most common risk factor and clinical symptom was h/o Previous C-section (31.8%) and abdominal pain present in 131(94.9%),44 (31.9%) participants had all the three classical symptoms with 100 % specificity. Forniceal fullness/tenderness was the most specific examination finding. The most common USG finding was Adnexal mass with empty Uterine cavity with Free fluid (49.2%). Most of the patients were managed with Partial Salpingectomy (30.4%). The final diagnosis of ectopic was made in 129 patients, which was confirmed by HPE reports in 124 patients. 5 patients underwent medical treatment. Conclusion: Early diagnosis before rupture and referral are the key factor in reducing the maternal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the ultrasonic characteristics of endometrial polyps in breast cancer patients after anti-estrogen endocrine therapy. Methods: A total of 91 patients with endometrial polyps who had breast cancer surgery at Yantai Muping District Hospital of Traditional Chinese Medicine, Yantai, China between February 2021 and August 2023 were randomly assigned to study (n = 42) and control groups (n = 49) based on postsurgery anti-estrogen endocrine therapy. The study group received tamoxifen (20 mg orally once daily for 6 months). Control group did not receive any post-surgery anti-estrogen endocrine therapy. Ultrasound characteristics of the study and control groups were assessed and compared. Results: The study group exhibited significantly increased endometrial thickness compared to control group (p < 0.05). However, both maximum and mean polyp diameters were significantly larger in the study group (p < 0.05). Linear endometrial echoes predominated in treated patients, contrasting with predominantly uniform echoes in the control group. Visualization issues of the uterine cavity line were significantly more common in the study group, while control group experienced more deviation and unclear visualization. Also, the study group mostly presented with strip-shaped polyps, differing from the round or oval shapes prevalent in control group. Furthermore, there were significant variations in internal echo characteristics and blood flow parameters between the two groups (p < 0.05). Conclusion: Endometrial polyps caused by postoperative anti-estrogen endocrine therapy in patients with breast cancer have unique ultrasonic characteristics, good ultrasonic diagnostic effect and a high detection rate as long as it is detected early and treated on time. Further analyses are needed with a larger sample size to investigate the underlying mechanism involved in developing endometrial polyps. [ABSTRACT FROM AUTHOR]

In recent years, significant progress has been made in understanding the biological and molecular pathways that regulate the effects of ischemia–reperfusion (I/R) injuries. However, despite these developments, various pharmacological agents are still being tested to either protect against or mitigate the damage caused by the IR's harmful consequences. JWH133 is a CB2R-selective agonist and belongs to the class of Δ8-tetrahydrocannabinol. The present study aimed to determine the in vivo effect of JWH-133 on uterine IR injury via the TLR4/NF-κB, pathway. Female Wistar albino rats (n = 40) were randomly divided into five groups. Three different doses of JWH-133 (0.2, 1, and 5 mg/kg) were administered to the rats. RNA was isolated from uterine tissue samples, and gene expression was measured by RT-PCR using specific primers. The interaction energies and binding affinities of JWH-133 with IL-1β, IL-6, NF-κB, TLR-4, and TNF-α were calculated through molecular docking analysis. The expression analysis revealed that JWH-133 administration significantly reduced the expression levels of IL-1β, IL-6, NF-κB, TLR-4, and TNF-α (p < 0.05). Notably, in the 1 mg/kg JWH-133 group, all of the gene expression levels decreased significantly (p < 0.05). The molecular docking results showed that JWH-133 formed hydrogen bonds with GLU64 of IL-1β, SER226 of IL-6, and SER62 of TNF-α. This study highlights the molecular binding affinity of JWH-133 and its potential effects on inflammation in IR injury. These results pave the way for future research on its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age leading to infertility. Besides reproductive and hormonal disturbances, PCOS is often characterized by vitamin D3 (VD) deficiency. This study aimed to determine the effect of VD on uterine histoarchitecture, the biochemical composition of gland secretions, and the insulin signal transduction pathway using a PCOS rat model. The experiment was conducted on four animal groups (n=8/group): control (C), VD supplemented (VD; 500 IU/day), letrozole-treated (PCOS; 1 mg/kg body weight), and VD-treated PCOS (PCOS+VD) group. Herein, VD supplementation did not improve histomorphometric parameters in the PCOS uterus, whereas clearly influenced sugar composition in uterine gland secretions, restoring their content to that observed in the C group. Furthermore, we found that VD can reduce peripheral and local uterine insulin resistance developed in the PCOS rats via activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and subsequent glucose metabolism in the uterus. To sum up, the present results suggest a possible beneficial role of VD supplementation for the maintenance of uterus functions in PCOS rats. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic inflammatory disease that affects about 10% of women, and it is characterized by the presence of endometrial tissue outside the uterine cavity. Associated symptoms are dyspareunia, chronic pelvic pain, and infertility. The diagnosis of endometriosis can be challenging due to various clinical and imaging presentations. Laparoscopy is the gold standard for the diagnosis, but it is an invasive procedure. The literature has increasingly promoted a switch to less invasive imaging techniques, such as ultrasound and magnetic resonance imaging (MRI). The latter, also in relation to the latest technological advances, allows a comprehensive and accurate assessment of the pelvis and it can also identify sites of endometriosis that escape laparoscopic evaluation. Furthermore, MRI has been found to be more accurate than other imaging techniques in relation to its improved sensitivity and specificity in identifying disease sites, also due to the role of new emerging sequences. This article aims to review the current role of advanced MRI applications in the assessment of endometriosis. [ABSTRACT FROM AUTHOR]

Objective: Uterine-sparing surgery for pelvic organ prolapse (POP) repair has shown good results, but the potential negative implications of leaving the uterus in place are yet to be fully defined. We aimed to assess the risk of unanticipated abnormal gynecological pathology at the time of reconstructive pelvic surgery. Methods: A retrospective consecutive case series including women who underwent vaginal hysterectomy for POP repair at a tertiary medical center in 2006–2020. All patients were offered a free Pap smear test at the age of 65 years as part of a national screening program. Transvaginal ultrasound was routinely performed preoperatively. Standard 3 pedicle hysterectomy was performed with/without bilateral salpingo-oophorectomy (BSO). Results: The study comprised 462 women of mean age 63 ± 9.3 years without previous known malignant or premalignant pathology. Benign pathology was observed in 286 patients (61.9%). Endometrial malignancy was found in three patients (0.7%) and significant premalignant pathology in 15 patients (3.2%), including cervical intraepithelial neoplasia stage 2–3 in seven patients (1.5%) and complex hyperplasia with atypia in eight patients (1.7%). All these pathologies were found in postmenopausal women. None had preoperative clinical symptoms or endometrial thickness of ≥5 mm on preoperative ultrasound. In the 35 patients after BSO, adnexal findings were normal (77.2%) or benign (22.8%). Conclusions: Premenopausal women with uterovaginal prolapse and normal preoperative evaluation have a minimal risk of significant abnormal uterine pathology. In postmenopausal women, the risk of unanticipated malignant uterine pathology is 0.7% and 3.2% for significant premalignancy. [ABSTRACT FROM AUTHOR]

Aims: Our research aims to shed light on the connection between histopathological differences that affect the prognosis of endometrial cancer and Doppler indices measured in the uterine arteries. Methods: Seventy‐four women with a confirmed diagnosis of endometrial cancer participated in this prospective study. The flow characteristics of the bilateral uterine arteries were evaluated and recorded using color Doppler sonography. After hysterectomy, a correlation analysis was performed between these factors and histological findings. Results: Patients who complained of menometrorrhagia had significantly higher uterine artery peak systolic flow (p = 0.020) than those who had postmenopausal vaginal bleeding. Endometrioid adenocarcinoma was the most common type (71.4%). Doppler pulsatility index and resistance index in the uterine arteries didn't show statistically significant differences between histologic subtypes, tumor grade, myometrial invasion, lymphovascular invasion, lymph node involvement, malignant peritoneal cytology, genetic mutation, or extrauterine involvement. Those without cervical involvement had higher uterine artery Doppler peak systolic flow/end diastolic flow (p = 0.024). Conclusions: Endometrial cancer made uterine artery, myometrium and endometrium less resistant to blood flow. However, these blood flow indices have not been standardized enough to be utilized as diagnostic tests just yet. Standardization based on more advanced studies would make it possible to use ultrasonography for non‐invasive diagnosis and would accelerate and facilitate clinical management. [ABSTRACT FROM AUTHOR]

Human reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation. [ABSTRACT FROM AUTHOR]

Introduction: Contrast‐enhanced computed tomography (CECT) is an emergent diagnostic imaging modality to identify the bleeding site and survey the abdominal cavity. The diagnostic utility of CECT for ectopic pregnancy (EP) has not been well‐investigated. The objective of this study was to evaluate the characteristics of CECT findings in patients with EP and extract specific findings that could contribute to the identification of implantation sites. Method: We conducted a retrospective study, reviewing suspected EP cases between April 2015 and March 2018 in our hospital. Clinical symptoms, blood test results, transvaginal sonography findings, and surgical and pathologic findings from the medical records were assessed. CECT images were evaluated by a certified radiologist and gynecologist retrospectively in consensus. The following were selected as positive findings for specific determination of the ectopic implantation site: the ectopic gestational sac, lateralization of the hemoperitoneum around the adnexa on either side, and extravascular leakage of the contrast agent outside the uterine cavity. Results: CECT was performed in 41 women with an EP. The ectopic implantation site was detectable on CECT in 90.2% (37/41), whereas it was noted in 70.0% (32/41) on transvaginal ultrasonography (TVS). Of nine patients with an EP with an undetectable implantation site on TVS, six were positive for the specific determination of the ectopic implantation site on CECT. Conclusion: CECT has the potential to predict ectopic implantation sites with high‐level sensitivity. As CECT is an urgent diagnostic imaging tool to be used in an emergent setting, it may be a good option for EP diagnosis when the availability of magnetic resonance imaging is limited. Synopsis: Contrast‐enhanced computed tomography has the potential to predict ectopic implantation sites and is a useful imaging tool in emergency situations. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the rate of disease progression and the factors associated with such progression in patients with an ultrasound diagnosis of adenomyosis. Methods: This was a single center, prospective, observational, cohort study performed at a tertiary referral center. Patients who obtained an ultrasound diagnosis of adenomyosis from May 2022 to August 2022 were recruited. Demographic, clinical and ultrasound data were recorded at the first visit (T0) and after 12 months (T1) for enrolled patients and compared between T0 and T1. The study population was divided in two groups according to progression (increase in uterine volume >20%) or stability/regression (decrease or increase in uterine volume ≤20%) of adenomyosis at T1. Primary study outcome was the rate of adenomyosis progression, while secondary study outcome was the association of adenomyosis progression with demographic and clinical factors. Post hoc subgroups analyses for primary and secondary study outcomes were performed based on hormonal therapy (untreated and treated). Results: A total of 221 patients were enrolled in the study, with no significant difference in terms of baseline data among the two study groups and no patients were lost to follow‐up. The overall rate of adenomyosis progression was 21.3% (47/221 patients). The rate was 30.77% in hormonally untreated women, and 18.34% in hormonally treated women. Progression was associated with the presence of focal adenomyosis of the outer myometrium (P = 0.037), moderate to severe dysmenorrhea (P = 0.001), chronic pelvic pain (P = 0.05), dyschezia (P = 0.05), and worsening of chronic pelvic pain (P = 0.04) at T1. Conclusion: Adenomyosis showed a rate of disease progression of 21.3% at the 12‐month follow‐up (30.77% in hormonally untreated women, and 18.34% in hormonally treated women). The presence and/or worsening of painful symptoms, such as severe dysmenorrhea, dyschezia and chronic pelvic pain, as well as the presence focal adenomyosis of the outer myometrium, might help identify patients at higher risk of disease progression and tailor their follow‐up. Synopsis: Adenomyosis ultrasonographic progression rate was found to be 21.3% and was associated with moderate/severe dysmenorrhea, chronic pelvic pain, dyschezia, and worsening chronic pelvic pain. [ABSTRACT FROM AUTHOR]

Vaginal childbirth is the final phase of pregnancy when one or more fetuses pass through the birth canal from the uterus, and it is a biomechanical process. The uterine active contraction, causing the pushing force on the fetus, plays a vital role in regulating the fetus delivery process. In this project, the active contraction behaviors of muscle tissue were first modeled and investigated. After that, a finite element method (FEM) model to simulate the uterine cyclic active contraction and delivery of a fetus was developed in LS-DYNA. The active contraction was driven through contractile fibers modeled as one-dimensional truss elements, with the Hill material model governing their response. Fibers were assembled in the longitudinal, circumferential, and normal (transverse) directions to correspond to tissue microstructure, and they were divided into seven regions to represent the strong anisotropy of the fiber distribution and activity within the uterus. The passive portion of the uterine tissue was modeled with a Neo Hookean hyperelastic material model. Three active contraction cycles were modeled. The cyclic uterine active contraction behaviors were analyzed. Finally, the fetus delivery through the uterus was simulated. The model of the uterine active contraction presented in this paper modeled the contractile fibers in three-dimensions, considered the anisotropy of the fiber distribution, provided the uterine cyclic active contraction and propagation of the contraction waves, performed a large deformation, and caused the pushing effect on the fetus. This model will be combined with a model of pelvic structures so that a complete system simulating the second stage of the delivery process of a fetus can be established. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common chronic gynecological condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to chronic inflammation, pelvic nodules and masses, pelvic pain, and infertility. Acupuncture has been shown to improve pain associated with endometriosis by modulating abnormal levels of prostaglandins, β-endorphins, dynorphins, electrolytes, and substance P. This review aims to evaluate the clinical efficacy of acupuncture in treating endometriosis, specifically focusing on its efficacy in relieving pain associated with endometriosis. Methods: A comprehensive search was conducted in eight databases (PubMed, EMBASE, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), the China Biology Medicine (CBM), Wanfang, and Weipu database) to identify randomized controlled trials (RCTs) published from database inception to December 16, 2022, which investigated the use of acupuncture for endometriosis-related pain. Two researchers independently screened articles, extracted data, and assessed methodological quality using the Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using Stata statistical software. Results: A total of 1991 articles were identified, and ultimately, 14 studies involving 793 patients (387 in the acupuncture group and 359 in the control group) were included. The control interventions in the included studies included placebo, traditional Chinese medicine (TCM), and Western medicine treatments. Meta-analysis results showed that compared to the control group, acupuncture treatment for pain associated with endometriosis demonstrated significant reductions in pain severity [SMD = − 1.10, 95% CI (− 1.45, − 0.75), P < 0.001], improved response rate [RR = 1.25, 95% CI (1.09, 1.44), P = 0.02], and decreased serum CA-125 levels [SMD = − 0.62, 95% CI (− 1.15, − 0.08), P = 0.024]. Furthermore, subgroup analysis revealed that electroacupuncture and auricular acupuncture were superior to the control group in reducing pain severity, while auricular acupuncture and warm needling showed greater clinical efficacy compared to the control group. However, there were no significant differences between electroacupuncture or fire needling and the control group in terms of pain relief. The findings suggest that acupuncture is effective in improving pain associated with endometriosis. Conclusions: In conclusion, acupuncture is effective in alleviating dysmenorrhea and pelvic pain associated with endometriosis, reducing serum CA-125 levels, decreasing the size of nodules, improving patients' quality of life, and lowering the recurrence rate. However, it should be noted that the current evidence is limited by the design and quality flaws of the original studies, as well as a lack of research specifically focusing on subtypes of acupuncture. Therefore, caution should be exercised when interpreting the results. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a frequent disease in women of reproductive age in which the endometrium occurs outside the uterine cavity. Multimodal treatment approaches are necessary due to loss of quality of life and the chronic nature of the disease. Digital health applications (DiGa) are becoming increasingly important. This research project investigates how a healthcare app can influence the subjective experience of illness in patients with endometriosis. Methods: Empiric data were collected through semi-structured interviews. Data analysis was carried out using qualitative focussed interview analysis. Reliability was ensured by joint interdisciplinary and interprofessional evaluation of the interviews by experts and those affected. Results: Ten patients with endometriosis and the prescribed healthcare app Endo-App© were examined. Categories were defined from the superordinate categories "Factors influencing the experience of illness" and "Evaluation of the app". The app provided reliable information, promoted self-efficacy through exercises and strengthened the perception of the individuality of the illness. It helped to minimise nocebo effects from internet research and enabled a positive change of perspective. Patients criticised the time required for data input and had data protection concerns. The educational elements were often seen as redundant. Some patients only used the app briefly, or not at all. Conclusion: Once a DiGa has been prescribed, it may be useful to explain its use on an outpatient basis and validate regular use. Blind re-prescribing of DiGas should be avoided. Younger patients with a recent diagnosis or patients following rehabilitation may benefit more from prescribing. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UT) is a surgical procedure that seeks to correct absolute uterine infertility. As such, it is coupled with assisted reproductive technologies (ART). Currently performed as an investigational procedure in France, this technique could be subject to a legal framework in the future. Given its specificities, the French legislator will need to state their position on several matters. Regarding the donor, they will need to determine whether the benefits for the infertile woman justify exposure of a living person to the risks of the removal procedure. If necessary, they will have full freedom to set the criteria for selecting the living donor based on age, the existence or not of past pregnancies or the nature of the donor-recipient relationship. On the other side, the conditions for becoming a recipient should be consistent with the existing rules for ART. Other considerations could include age and past pregnancies again. Lastly, the legislator will also need to address the possible desire for UT without the endpoint of pregnancy. [ABSTRACT FROM AUTHOR]

This article traces the rise of the embryological interpretation of Gen 2:7 and how it came to provide arguments for dyophysite Christology. By the late 4th century, many Christian writers saw in the formation of Adam a depiction of the formation and ensoulment of a human embryo. Moreover, authors around the 5th century connected the embryological reading of Adam's formation with the life of Christ in the womb. But in the 6th and 7th centuries, this interpretation of Gen 2:7 became controversial. Debates about Christ raised the stakes of disagreement over the time of human ensoulment, and embryological readings of Adam's creation were caught up in these debates. In this context, East Syrian Babai the Great (551–628) deployed the embryological reading of Gen 2:7 against Christological rivals in defense of his theory of Christ's delayed ensoulment in the womb. In doing so, he offers a biological account of Christ's pre-ensouled life as a plant and zoophyte. But the connection between an embryological reading of Gen 2:7 and dyophysite Christology also prompted opponents to turn to exegetical strategies that excluded any analogy with delayed ensoulment. This article thus presents an example of how theological controversy and the history of science affected biblical exegesis. [ABSTRACT FROM AUTHOR]