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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.

Bacterial endometritis is among the most common causes of subfertility in mares. It has a major economic impact on the equine breeding industry. The sensitivity of detecting uterine microbes using culture-based methods, irrespective of the sample collection method, double-guarded endometrial swab, endometrial biopsy, or uterine low-volume lavage (LVL), is low. Therefore, equine bacterial endometritis often goes undiagnosed. Sixteen individual mares were enrolled, and an endometrial sample was obtained using each method from all mares. After trimming, quality control and decontamination, 3824 amplicon sequence variants were detected in the dataset. We found using 16S rRNA sequencing that the equine uterus harbors a distinct resident microbiome during estrus. All three sampling methods used yielded similar results in composition as well as relative abundance at phyla (Proteobacteria, Firmicutes, and Bacteroidota) and genus (Klebsiella, Mycoplasma, and Aeromonas) levels. A significant difference was found in alpha diversity (Chao1) between LVL and endometrial biopsy, suggesting that LVL is superior at detecting the low-abundant (rare) taxa. These new data could pave the way for innovative treatment methods for endometrial disease and subfertility in mares. This, in turn, could lead to more judicious antimicrobial use in the equine breeding industry.

Uterine artery (UA) hydrogen sulfide (H2S) production is augmented in pregnancy and, on stimulation by systemic/local vasodilators, contributes to pregnancy-dependent uterine vasodilation; however, how H2S exploits this role is largely unknown. S-sulfhydration converts free thiols to persulfides at reactive cysteine(s) on targeted proteins to affect the entire proteome posttranslationally, representing the main route for H2S to elicit its function. Here, we used Tag-Switch to quantify changes in sulfhydrated (SSH-) proteins (ie, sulfhydrome) in H2S-treated nonpregnant and pregnant human UA. We further used the low-pH quantitative thiol reactivity profiling platform by which paired sulfhydromes were subjected to liquid chromatography tandem mass spectrometry-based peptide sequencing to generate site (cysteine)-specific pregnancy-dependent H2S-responsive human UA sulfhydrome. Total levels of sulfhydrated proteins were significantly greater in pregnant vs nonpregnant human UA and further stimulated by treatment with sodium hydrosulfide. We identified a total of 360 and 1671 SSH-peptides from 480 and 1186 SSH-proteins in untreated and sodium hydrosulfide-treated human UA, respectively. Bioinformatics analyses identified pregnancy-dependent H2S-responsive human UA SSH peptides/proteins, which were categorized to various molecular functions, pathways, and biological processes, especially vascular smooth muscle contraction/relaxation. Pregnancy-dependent changes in these proteins were rectified by immunoblotting of the Tag-Switch labeled SSH proteins. Low-pH quantitative thiol reactivity profiling failed to identify low abundance SSH proteins such as KATP channels in human UA; however, immunoblotting of Tag-Switch-labeled SSH proteins identified pregnancy-dependent upregulation of SSH-KATP channels without altering their total proteins. Thus, comprehensive analyses of human UA sulfhydromes influenced by endogenous and exogenous H2S inform novel roles of protein sulfhydration in uterine hemodynamics regulation.

Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 μg/mouse/day (low); 0.6 μg/mouse/day (medium)) or supraphysiological (6 μg/mouse/day (high)) doses of E2 (17β-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (- 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (- 34% and - 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mERα signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.

Daifeng Hu,1,* Mengyue Miao,1,* Hui Zhou,1 Xia Gu,1,2 Xuedan Wang,3 Alexander Tobias Teichmann,1 Qin Wang,1 Youzhe Yang1,2 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China; 3Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Wang; Youzhe Yang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email wangq@swmu.edu.cn; yangyouzhe@swmu.edu.cnAbstract: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given.Keywords: perivascular epithelioid cell tumors, uterus, malignant, rare case, cervix

Introduction: Endometriosis is a recurring chronic inflammatory condition that affects females of reproductive age. Endometriosis-associated Pelvic Pain (EAPP) adversely impacts physical, mental, and social well-being. Currently, there is no ideal treatment option. Dienogest, a selective progestin, shows a pronounced effect on endometriosis. Aim: To compare the efficacy and safety of Dienogest at doses of 2 mg and 4 mg/day orally in the treatment of endometriosis. Materials and Methods: An observer-blind, parallel-group, randomised clinical trial was conducted in the Department of Obstetrics and Gynaecology at IPGME&R, SSKM Hospital, Kolkata, West Bengal, India, from April 2016 to December 2017. A total of 190 women aged 20-45 years suffering from endometriosis were recruited and divided into two treatment groups, A and B, receiving daily doses of 2 mg and 4 mg, respectively, for 24 weeks. Relief of EAPP was assessed using the Visual Analogue Scale (VAS) score, and improvement in Quality of Life (QoL) was measured. Treatment-related adverse events were also recorded. Numerical variables were compared using Student’s t-test or the Mann-Whitney U Test, and categorical variables were compared using the Chi-square test or Fisher’s-exact test. Results: The absolute reduction in pelvic pain VAS score was 39.71±8.60 at 24 weeks from the initial score of 70.88 (Mean VAS score before treatment with Dienogest) in Group A, compared to 34.80±6.45 from 69.34 (Mean VAS score before treatment with Dienogest) in Group B (p=0.0001). The difference in mean VAS at 24 weeks between the two groups was statistically significant (p=0.0002). At 24 weeks, 18 (24.66%) patients in Group A experienced an irregular bleeding pattern compared to 27 (40.30%) in Group B, with spotting being the most common issue. Adverse effects such as weight gain, acne, alopecia, depression, and decreased libido were observed in both groups, but they were more pronounced in the 4 mg group. Conclusion: The efficacy and safety results from this dose-ranging study of Dienogest indicate that 2 mg/day is the effective dose for treating endometriosis and offers better tolerability compared to the 4 mg dose.

The new 2023 update of the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer incorporates the advances made in the understanding of the pathology and molecular classifications into the staging system. While the new staging system aids in precision medicine and may lead to better documentation of prognostic risk categories of endometrial cancer, it is complex and calls for an integrated approach and better communication between multiple disciplines involved in the management of endometrial cancer. In this review article, we address how the referral patterns to imaging services might change considering the updated staging system for endometrial cancer. We also discuss the practical aspects and nuances involved in the radiology service delivery and reporting practices as we adopt the new FIGO staging system for managing endometrial cancer patients.

Abstract The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20–30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency ‘slow wave’ which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

Background: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top‐ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles. Methods: Using a repeat cross‐sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai. Results: A significantly lower prevalence of doctor‐diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM2.5), coarse particles (PM2.5–10) and inhalable particles (PM10) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log‐binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM2.5, PM2.5–10 and PM10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24–1.56), 1.51 (95% CI:1.15–1.98) and 1.53 (95% CI:1.27–1.85) for DDA, respectively. The distributed lag non‐linear model showed the sensitive exposure window (SEW) was 5.5–11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding. Conclusions: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma. [ABSTRACT FROM AUTHOR]

Objective: To propose a new classification system (Urman‐Vitale Classification System) for intrauterine adhesions (IUAs) and to evaluate anatomical and fertility outcomes after hysteroscopic adhesiolysis accordingly. Methods: A retrospective analysis of consecutive patients treated over 11 years by a single operator in a tertiary care hospital. Women with sonographic suspicion of IUAs were scheduled for hysterosalpingography (HSG) and hysteroscopy for confirmation and treatment. IUAs were divided into five classes according to symptoms, ultrasound, HSG findings, and postsurgical hysteroscopic appearance. Hysteroscopic adhesiolysis was performed using a bipolar cutting electrode in an office setting. Evaluated outcomes were restoration of the uterine cavity, clinical pregnancy, pregnancy loss, and live birth rates. Results: A total of 227 patients (479 procedures) were included. Mean number of hysteroscopies increased in frequency with class of adhesions from Class 1 to Class 5 (1.0 ± 0.2 vs 2.3 ± 0.5; P = 0.001). Full restoration of the cavity was achieved in 100% of patients with Class 1 compared with 18.5% for Class 5 (43/43 vs 5/27; P = 0.001). Clinical pregnancy (Class 1 vs Class 4: P = 0.034; 1 vs 5: P = 0.006; 2 vs 5: P = 0.024) and live birth (Class 1 vs Class 4: P = 0.001; 1 vs 5: P = 0.006; 2 vs 4: P = 0.007; 2 vs 5: P = 0.0208) rates decreased with increasing severity of IUAs. Pregnancy loss rate was related to IUA severity (Class 1 vs Class 4: P = 0.012; 1 vs 5: P = 0.003: 2 vs 4: P = 0.014; 2 vs 5: P = 0.021). Conclusion: A classification based on symptoms, imaging findings, and postsurgical macroscopic appearance of the uterine cavity could be useful in predicting prognosis and fertility in women with IUAs. Synopsis: A new classification for intrauterine adhesions based on symptoms, imaging, and hysteroscopic appearance of the uterine cavity could simplify postsurgical prognosis and fertility. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) present in oviductal (OF) and uterine fluid (UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes (LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabolism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within EVs in maternal reproductive fluids, such as microRNAs (miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional mechanisms. Results: This study evaluated miRNA cargo in OF-EVs from the early luteal phase and UF-EVs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LMGs and signaling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups. From the 20 differentially expressed miRNAs, 19 up-regulated in UF-EVs (bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one (bta-miR-148b) in OF-EVs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, MAPK, and lipid metabolism and degradation. Differences in miRNAs found in OF-EVs from the early luteal phase and UF-EVs from mid-luteal phase may reflect different environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and implantation. Conclusions: Our study suggests that miRNAs within OF- and UF-EVs could modulate bovine embryo development and quality, providing insights into the intricate maternal-embryonic communication that might be involved in modulating lipid metabolism, immune response, and implantation during early pregnancy. [ABSTRACT FROM AUTHOR]

Study objective: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. Design: A prospective, randomized, controlled trial study. Setting: A tertiary university hospital. Patients: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5–8) and severe (AFS score of 9–12) intrauterine adhesions were recruited. Interventions: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). Measurements and main results: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. Conclusion: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. Trial registration: This research was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/enIndex.aspx); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 (http://www.chictr.org.cn/showprojen.aspx?proj=17979). Date of trial registration: July 11, 2017. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy of modified uterine stent in the treatment of mild-to-moderate intrauterine adhesions and explore the relative indicators affecting prognosis prediction. Methods: A total of 115 patients with mild-to-moderate intrauterine adhesions received a modified uterine stent placement after hysteroscopy adhesiolysis. The second-look hysteroscopy operated after 3 months surgery, and the third-look hysteroscopy operated after 6 months surgery if necessary. The stent was removed when the cavity shape was repaired, then the reproductive outcomes were followed up one year. Results: Menstrual blood volume, endometrial thickness and volume had increased significantly after 3 months surgery. The rates of cavity repaired were 86.96% (100/115) after 3 months surgery and 100% (115/115) after 6 months surgery cumulatively. Endometrial thickness after 3-months surgery was positively associated with uterine cavity shape repaired (P<0.01). The receive operating characteristic (ROC) curve showed the rate of uterine cavity shape repaired predicted by the model was 0.92, based on the endometrial thickness after 3-months surgery. The rate of pregnancy was 86.09% (99/115) in one year, while the rate of miscarriage accounted for 26.26% (26/99). The median time interval between stent removal and subsequent conception was 3 months. It showed adhesion recurrence was the risk factor for subsequent pregnancy (P<0.01). Conclusions: A modified uterine stent placement under hysteroscopy was an effective approach for mild-to-moderate intrauterine adhesions, which is easy to operate and worthy for clinical promotion. Endometrial thickness measured by ultrasonography probably has predictive value in adhesion recurrence and subsequent pregnancy. Trial Registration: ChiCTR2100051524. Date of registration (retrospectively registered): 26/09/2021. [ABSTRACT FROM AUTHOR]

The current understanding of inflammatory myofibroblastic tumours (IMTs) of the gynaecological tract has recently been enhanced by their increased recognition. This increase is largely due to greater accessibility to RNA‐based molecular assays used to identify their defining ALK rearrangements. This review summarises the clinical characteristics, morphological spectrum, immunohistochemical profile and molecular underpinnings of uterine IMT. Additionally, this review discusses practical diagnostic considerations including overlap between uterine IMT and smooth muscle tumours as well as pregnancy‐associated uterine IMT. Finally, we highlight recent literature demonstrating the potential for aggressive behaviour in uterine IMT, including a novel risk stratification model for identifying high‐risk IMT. [ABSTRACT FROM AUTHOR]

Introduction: Endometriosis is a recurring chronic inflammatory condition that affects females of reproductive age. Endometriosis-associated Pelvic Pain (EAPP) adversely impacts physical, mental, and social well-being. Currently, there is no ideal treatment option. Dienogest, a selective progestin, shows a pronounced effect on endometriosis. Aim: To compare the efficacy and safety of Dienogest at doses of 2 mg and 4 mg/day orally in the treatment of endometriosis. Materials and Methods: An observer-blind, parallel-group, randomised clinical trial was conducted in the Department of Obstetrics and Gynaecology at IPGME&R, SSKM Hospital, Kolkata, West Bengal, India, from April 2016 to December 2017. A total of 190 women aged 20-45 years suffering from endometriosis were recruited and divided into two treatment groups, A and B, receiving daily doses of 2 mg and 4 mg, respectively, for 24 weeks. Relief of EAPP was assessed using the Visual Analogue Scale (VAS) score, and improvement in Quality of Life (QoL) was measured. Treatment-related adverse events were also recorded. Numerical variables were compared using Student's t-test or the Mann-Whitney U Test, and categorical variables were compared using the Chi-square test or Fisher'sexact test. Results: The absolute reduction in pelvic pain VAS score was 39.71±8.60 at 24 weeks from the initial score of 70.88 (Mean VAS score before treatment with Dienogest) in Group A, compared to 34.80±6.45 from 69.34 (Mean VAS score before treatment with Dienogest) in Group B (p=0.0001). The difference in mean VAS at 24 weeks between the two groups was statistically significant (p=0.0002). At 24 weeks, 18 (24.66%) patients in Group A experienced an irregular bleeding pattern compared to 27 (40.30%) in Group B, with spotting being the most common issue. Adverse effects such as weight gain, acne, alopecia, depression, and decreased libido were observed in both groups, but they were more pronounced in the 4 mg group. Conclusion: The efficacy and safety results from this doseranging study of Dienogest indicate that 2 mg/day is the effective dose for treating endometriosis and offers better tolerability compared to the 4 mg dose. [ABSTRACT FROM AUTHOR]

Simple Summary: This article discusses the potential of deep learning (DL) models in aiding the diagnosis of endometrial pathologies through hysteroscopic images. While hysteroscopy with endometrial biopsy is currently the gold standard for diagnosis, it heavily relies on the expertise of gynecologists. The study aims to develop a DL model for automated detection and classification of endometrial pathologies. Conducted as a monocentric observational retrospective cohort study, it reviewed records and videos of hysteroscopies from patients with confirmed intrauterine lesions. The DL model was trained using these images, with or without incorporating clinical factors. Results indicate that while the DL model showed promising results, its diagnostic performance remained relatively low, even with the inclusion of clinical data. The best performance was achieved when clinical factors were included, with precision, recall, specificity, and F1 scores ranging from 80 to 90% for classification and 85 to 93% for identification tasks. Despite slight improvements in clinical data, further refinement of DL models is warranted for more accurate diagnosis of endometrial pathologies. Background: Although hysteroscopy with endometrial biopsy is the gold standard in the diagnosis of endometrial pathology, the gynecologist experience is crucial for a correct diagnosis. Deep learning (DL), as an artificial intelligence method, might help to overcome this limitation. Unfortunately, only preliminary findings are available, with the absence of studies evaluating the performance of DL models in identifying intrauterine lesions and the possible aid related to the inclusion of clinical factors in the model. Aim: To develop a DL model as an automated tool for detecting and classifying endometrial pathologies from hysteroscopic images. Methods: A monocentric observational retrospective cohort study was performed by reviewing clinical records, electronic databases, and stored videos of hysteroscopies from consecutive patients with pathologically confirmed intrauterine lesions at our Center from January 2021 to May 2021. Retrieved hysteroscopic images were used to build a DL model for the classification and identification of intracavitary uterine lesions with or without the aid of clinical factors. Study outcomes were DL model diagnostic metrics in the classification and identification of intracavitary uterine lesions with and without the aid of clinical factors. Results: We reviewed 1500 images from 266 patients: 186 patients had benign focal lesions, 25 benign diffuse lesions, and 55 preneoplastic/neoplastic lesions. For both the classification and identification tasks, the best performance was achieved with the aid of clinical factors, with an overall precision of 80.11%, recall of 80.11%, specificity of 90.06%, F1 score of 80.11%, and accuracy of 86.74 for the classification task, and overall detection of 85.82%, precision of 93.12%, recall of 91.63%, and an F1 score of 92.37% for the identification task. Conclusion: Our DL model achieved a low diagnostic performance in the detection and classification of intracavitary uterine lesions from hysteroscopic images. Although the best diagnostic performance was obtained with the aid of clinical data, such an improvement was slight. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine overpopulation is a major problem in many countries. It has been described in some female mammalian species that postnatal androgenization causes reproductive abnormalities. The objective of this study was to describe the reproductive effect of postnatal androgens in female dogs for contraceptive purposes. Ten newborn female puppies were administered testosterone (TE; n = 5) or placebo (PL; n = 5) subcutaneously. The puppies were followed up until puberty when ovulation was tested and then spayed. The genital tracts were grossly and microscopically examined. At puberty, all the females had normal estrous behavior and ovulated without age and body weight differences. All TE puppies presented mild clitoris enlargement. Ovaries did not reveal differences between groups. Conversely, the uterine glands as well as the height of the uterine epithelium were higher in TE. It was concluded that a postnatal dose of testosterone did not affect ovulatory capacity, nor did it cause gonadal alterations, although it caused an increased area of endometrial glands and a higher uterine epithelium. It has been described in some female mammalian species that postnatal androgenization causes reproductive structural and functional abnormalities. The objective of this study was to describe the clinical, ovulatory and genital effects of postnatal androgens in female dogs. Ten newborn female crossbred puppies were randomly assigned to: testosterone enanthate 18 mg/100 g sc (TE; n = 5) or placebo sc (PL; n = 5). The puppies were physically followed up until puberty when ovulation was tested by serum progesterone. Then, ovariohysterectomies were performed, and genital tracts were grossly and histomorphometrically examined. At puberty, all the females had normal estrous behavior and ovulated without age and body weight differences. All TE puppies presented mild clitoris enlargement. Gross and microscopical ovarian examination did not reveal differences. Conversely, the endometrial area occupied by uterine glands as well as the height of the glandular and luminal epithelium were higher in the TE than in the PL group (<0.01). The height of the endometrium and myometrial thickness did not differ between groups. It was concluded that a supraphysiological postnatal dose of testosterone did not affect ovulatory capacity, nor did it provoke gonadal histological alterations, although it caused an increased area of endometrial glands and a higher uterine epithelium. [ABSTRACT FROM AUTHOR]

The numerous votive uteri found across the central Italian peninsula from the fourth to first centuries BCE are puzzlingly evocative of the human simplex uterus, which is visually distinct from the bicornuate uteri characteristic of most other mammals. However, human dissection is not attested for this time and place, while animal butchery was common. This article uses modern veterinary anatomical imagery to argue that animal uteri — specifically as they appear when pregnant — were indeed models underlying the votive depictions. Some of the variant forms of the votives are highly evocative of various features of the pregnant bicornuate uterus. Further, medical views on the human uterus throughout classical antiquity were informed by animal uteri. Taken together, the visual and textual evidence indicate that animal models were inextricably integrated into ancient conceptions of the human uterus across the classical world, including in the production of the Italic votives in question. [ABSTRACT FROM AUTHOR]

Objective: To evaluate Cesarean scar defects using saline contrast sonohysterography (SCSH) in women with a history of Cesarean scar pregnancy (CSP). Methods: A cohort of 38 non‐pregnant women with a history of CSP treated with combined local and systemic methotrexate was investigated prospectively by SCSH. For the purpose of analysis, they were classified, according to the modified Delphi consensus criteria for CSP in early gestation, into three subgroups based on the depth of the gestational sac herniation in the midsagittal plane. Subgroup A included eight (21.1%) cases, in which the largest part of the gestational sac protruded towards the uterine cavity; Subgroup B included 20 (52.6%) cases, in which the largest part of the gestational sac was embedded in the myometrium; and Subgroup C included 10 (26.3%) cases, in which the gestational sac was located partially outside the outer contour of the cervix or uterus. Results: SCSH revealed that all women in Subgroup C had a uterine niche. The median niche length (P = 0.006) and depth (P = 0.015) were significantly greater in Subgroup C than in Subgroups A or B. The median residual myometrial thickness (RMT) was significantly lower in Subgroup C than in Subgroups A or B (P = 0.006). Conclusions: Women with prior CSP who had a gestational sac protruding beyond the serosal line had a significantly greater niche length and depth, and lower RMT. This knowledge may guide individualized risk counseling. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To assess the ability of the International Endometrial Tumor Analysis (IETA)‐1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. Methods: This was a retrospective study, in which we validated the IETA‐1 model on the IETA‐3 study cohort (n = 1745). The IETA‐3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow‐up of non‐endometrial pathology, in the work‐up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow‐up of at least 1 year if endometrial sampling was not performed. The IETA‐1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non‐uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver‐operating‐characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). Results: The median age of the women in the IETA‐3 cohort was 51 (range, 20–85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA‐1 model had an AUC of 0.81 (95% CI, 0.73–0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA‐1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA‐1 model gave an AUC of 0.81 (95% CI, 0.71–0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20). Conclusion: The IETA‐1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Female sex has been associated with worse outcomes after groin hernia repair (GHR), including a higher rate of chronic pain and recurrence. Most of the studies in GHR are performed in males, and the recommendations for females extrapolate from these studies, even though females have anatomy intricacies. The round ligament of the uterus (RLU) is associated with pelvic stabilization and plays a role in sensory function. Transection of the RLU during GHR is controversial as it can allow easier mesh placement but can favor genitourinary complications and chronic pain. As no previous meta-analysis compared preserving versus transecting the RLU during minimally invasive (MIS) GHR, we aim to perform a systematic review and meta-analysis evaluating surgical outcomes comparing the approaches. Methods: Cochrane Central, Embase, and PubMed databases were systematically searched for studies comparing transection versus preservation of the RLU in MIS groin hernia surgeries. Outcomes assessed were operative time, bleeding, surgical site events, hospital stay, chronic pain, paresthesia, recurrence rates, and genital prolapse rates. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics. A review protocol for this meta-analysis was registered at PROSPERO (CRD 42023467146). Results: 1738 studies were screened. A total of six studies, comprising 1131 women, were included, of whom 652 (57.6%) had preservation of the RLU during MIS groin hernia repair. We found no statistical difference regarding chronic pain, paresthesia, recurrence rates, and postoperative complications. We found a longer operative time for the preservation group (MD 6.84 min; 95% CI 3.0–10.68; P = 0.0005; I2 = 74%). Conclusion: Transecting the RLU reduces the operative time during MIS GHR with no difference regarding postoperative complication rates. Although transection appears safe, further prospective randomized studies with long-term follow-up and patient-reported outcomes are necessary to define the optimal management of RLU during MIS GHR. [ABSTRACT FROM AUTHOR]

The new 2023 update of the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer incorporates the advances made in the understanding of the pathology and molecular classifications into the staging system. While the new staging system aids in precision medicine and may lead to better documentation of prognostic risk categories of endometrial cancer, it is complex and calls for an integrated approach and better communication between multiple disciplines involved in the management of endometrial cancer. In this review article, we address how the referral patterns to imaging services might change considering the updated staging system for endometrial cancer. We also discuss the practical aspects and nuances involved in the radiology service delivery and reporting practices as we adopt the new FIGO staging system for managing endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Deficiency of fumarate hydratase (FH) protein expression in uterine corpus leiomyomas may be attributable to either germline or somatic mutations of the FH gene, the former being definitional for the hereditary leiomyomatosis and renal cell cancer syndrome. The authors assess whether, using previously reported FH-associated morphologic features, FH protein-deficient uterine corpus leiomyomas associated with a pathogenic germline mutations of the FH gene (group 1) are distinguishable from FH protein-deficient uterine corpus leiomyomas without such mutations (and whose FH protein loss is presumed to be attributable to somatic/epigenetic inactivation or other unknown phenomena: group 2). Groups 1 and 2 were compared regarding a variety of clinicopathologic features, including 7 core "FH-associated" tumoral morphologic features: staghorn vasculature; alveolar-type edema; bizarre nuclei; chain-like tumor nuclei; hyaline cytoplasmic globules; prominent nucleoli, intranuclear inclusions, and perinucleolar halos; and prominent eosinophilic/fibrillary cytoplasm. Among 2418 patients diagnosed with uterine corpus leiomyoma during the study period, FH-associated morphologic features were reported in 1.5% (37 patients), and FH immunohistochemistry was performed in 29 (1.19%). Fourteen (48.27%) of the 29 patients showed FH protein deficiency by immunohistochemistry. Twelve patients underwent germline testing, of which 8 (66.7%) were classified as group 1 and 4 (33.3%) as group 2. FH protein-deficient tumors were larger (10.44 vs 4.08 cm, P = 0.01) and associated with younger patients (42.05 vs 47.97, P = 0.004) than 370 randomly selected uterine leiomyoma controls. Groups 1 and 2 showed no significant differences in patient age and tumor size. In group 1 tumors, the FH-associated morphologic features were generally present diffusely; all group 1 tumors displayed ≥5 FH-associated features, whereas all group 2 tumors displayed <5 FH-associated features (means 6.5 ± 0.53 vs 3.5 ± 1.00, P < 0.001). Notably, eosinophilic/fibrillary cytoplasm and alveolar-type edema were each significantly more prevalent in group 1 tumors than group 2 tumors (P = 0.018 for both). No single morphologic feature was found to be completely sensitive and specific in making the distinction between group 1 and 2 tumors. Our findings suggest that groups 1 and 2 are unlikely to be morphologically distinguishable by individual morphologic features. Whether there is a combination of features that can reliably make this distinction is unclear and will require additional studies with larger cohorts. [ABSTRACT FROM AUTHOR]

Background: Differential diagnosis between uterine leiomyomas and sarcomas is challenging. Magnetic resonance imaging (MRI) represents the second‐line diagnostic method after ultrasound for the assessment of uterine masses. Objectives: To assess the accuracy of MRI in the differential diagnosis between uterine leiomyomas and sarcomas. Search Strategy: A systematic review and meta‐analysis was performed searching five electronic databases from their inception to June 2023. Selection Criteria: All peer‐reviewed observational or randomized clinical trials that reported an unbiased postoperative histologic diagnosis of uterine leiomyoma or uterine sarcoma, which also comprehended a preoperative MRI evaluation of the uterine mass. Data Collection and Analysis: Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve on summary receiver operating characteristic of MRI in differentiating uterine leiomyomas and sarcomas were calculated as individual and pooled estimates, with 95% confidence intervals (CI). Results: Eight studies with 2495 women (2253 with uterine leiomyomas and 179 with uterine sarcomas), were included. MRI showed pooled sensitivity of 0.90 (95% CI 0.84–0.94), specificity of 0.96 (95% CI 0.96–0.97), positive likelihood ratio of 13.55 (95% CI 6.20–29.61), negative likelihood ratio of 0.08 (95% CI 0.02–0.32), diagnostic odds ratio of 175.13 (95% CI 46.53–659.09), and area under the curve of 0.9759. Conclusions: MRI has a high diagnostic accuracy in the differential diagnosis between uterine leiomyomas and sarcomas. Synopsis: This meta‐analysis assesses the accuracy of MRI in the differential diagnosis between uterine leiomyomas and sarcomas, demonstrating a very high diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the magnetic resonance imaging (MRI) features that may help distinguish leiomyosarcomas from atypical leiomyomas (those presenting hyperintensity on T2-W images equal or superior to 50% compared to the myometrium). Materials and methods: The authors conducted a retrospective single-centre study that included a total of 57 women diagnosed with smooth muscle tumour of the uterus, who were evaluated with pelvic MRI, between January 2009 and March 2020. All cases had a histologically proven diagnosis (31 Atypical Leiomyomas—ALM; 26 Leiomyosarcomas—LMS). The MRI features evaluated in this study included: age at presentation, dimension, contours, intra-tumoral haemorrhagic areas, T2-WI heterogeneity, T2-WI dark areas, flow voids, cyst areas, necrosis, restriction on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) values, signal intensity and heterogeneity after contrast administration in T1-WI, presence and location of unenhanced areas. The association between the MRI characteristics and the histological subtype was evaluated using Chi-Square and ANOVA tests. Results: The MRI parameters that showed a statistically significance correlation with malignant histology and thus most strongly associated with LMS were found to be: irregular contours (p < 0.001), intra-tumoral haemorrhagic areas (p = 0.028), T2-WI dark areas (p = 0.016), high signal intensity after contrast administration (p = 0.005), necrosis (p = 0.001), central location for unenhanced areas (p = 0.026), and ADC value lower than 0.88 × 10−3 mm2/s (p = 0.002). Conclusion: With our work, we demonstrate the presence of seven MRI features that are statistically significant in differentiating between LMS and ALM. [ABSTRACT FROM AUTHOR]

Objective: To study the guiding significance of medical history on laparoscopic and vaginal cervical cerclage in the treatment of cervical incompetence and its influence on pregnancy outcome. Methods: A total of 53 cases by laparoscopic abdominal cervical cerclage (LAC group) before pregnancy and 73 cases by transvaginal cervix cerclage (TVC group) at 12–14 weeks of pregnancy were collected. Multivariate logistic regression analysis was performed on the influencing factors of delivery gestational weeks. Furthermore, the gestational weeks after cervical cerclage were compared between the two groups with high- and low-risk grades. Results: The number of previous uterine cavity operations in LAC group was more than that TVC group, and the costs of operation were more than TVC group. At the same time, the hospitalization days and operation time were longer than those in TVC group, and the delivery rate of cesarean section was higher than TVC group, but the total hospitalization times were less than TVC group (P < 0.05). The rate of delivery before 34 weeks of pregnancy and the incidence of premature rupture of membranes or premature labor in LAC group were lower than those in TVC group (P < 0.05). In TVC group, the increased number of prior PTB or STL and the history of cervical cerclage failure would increase the risk of premature delivery before 34 weeks of pregnancy. There was no increased risk of preterm delivery before 34 weeks of pregnancy in LAC group (P > 0.05). According to the risk level, in the high-risk group, the delivery rate of LAC group at gestational weeks < 37 weeks, < 34 weeks and < 28 weeks was lower than that of TVC group. Conclusion: Laparoscopic cervical cerclage might be more effective in preventing premature delivery before 34 weeks of gestation, and its influence on delivery gestational weeks was not affected by related medical history. For high-risk patients with the history of prior PTB or STL and failed cerclage, laparoscopic cervical cerclage might be more effective than vaginal cervical cerclage in preventing extremely preterm before 28 weeks, premature delivery before 34 weeks and premature delivery before 37 weeks. Therefore, our limited experience suggested that LAC can be a recommended option for patients with high-risk history. [ABSTRACT FROM AUTHOR]

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20–30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency 'slow wave' which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings. [ABSTRACT FROM AUTHOR]

Objective To investigate the therapeutic effect of total flavonoids of Sarsaparilla on chronic pelvic inflammatory disease (CPID) model rats. Methods CPID rat model were performed by injecting phenol mucilage into the right uterus. The SD rats were divided into the model control group, the high dose group [32. 4 g/ (kg·d)], the medium dose group [16. 2 g/ (kg·d)], the low dose group [8. 1 g/ (kg·d)], the Jingangteng capsule group, the dexamethasone group according to the random number table method, with ten animals each. Rats treated with sham operation were divided into the sham operation group and the background control group according to the random number table method, with ten animals each. In addition, the blank control group (ten animals) was estabished without any treatment. The hemorheology and routine blood indexes of each group were detected 14 days after administration. The morphological changes of the left and right sides of the uterus were observed, the swelling rate and swelling inhibition rate of the uterus were calculated, and the pathological changes of the uterus were observed by hematoxylin-eosin (HE) and Masson staining. The expression of interleukin-1β (IL-1β), IL-4, IL-6 and IL-10 in uterine tissue of rats was detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the model control group and the Jingangteng capsule group, all dose groups of total flavonoids from Sarsaparilla can significantly reduce the number of white blood cells, lymphocytes, neutrophils, and various hemorheological indicators in the blood of CPID model rats, reduce the rate of uterine swelling in rats, and inhibit the expression of L-1β and IL-6 in rat uterine tissue, and promote the expression of IL-4 and IL-10 and can significantly reduce uterine congestion and edema, reduce inflammatory cell infiltration, alleviate fibrous connective tissue proliferation around glands, and improve endometrial hyperplasia and fibrosis, with statistical significance (P＜0. 01). Conclusion Total flavonoids of Sarsaparilla can improve the symptoms of CPID model rats, enhance blood flow, improve local blood circulation, and inhibit uterine inflammation and fibrotic hyperplasia in CPID model rats. [ABSTRACT FROM AUTHOR]

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by the absence or underdevelopment of the uterus and upper part of the vagina. It is usually diagnosed during adolescence, and the present study investigates how women experience and negotiate to live with MRKH syndrome long-term. From January to March 2021, eighteen Danish women with MRKH syndrome participated in semi-structured interviews via video conference. The mean time since diagnosis was 11.5 years. A thematic analysis using the life course framework as a theoretical approach was applied. The analysis identified the diagnosis as a turning point, that dramatically altered the women's imagined futures. Not conforming to dominant social norms regarding sexuality and pregnancy meant that the women continuously managed and negotiated the meaning and impact of MRKH syndrome in relation to the five principles of the life course perspective: (1) Lifelong development, (2) Timing, (3) Human agency, (4) Linked lives, and (5) Historical time and place. Using the life course framework contributed to a holistic understanding of life with MRKH syndrome by showing how the meaning and consequences of the congenital condition changed over time and in adaptation to gendered and age-related social norms and expectations. The perceived meaning and impact of living with Mayer-Rokitansky-Küster-Hauser syndrome change over time, and women's information and support needs thus change accordingly Sensitive, clinical communication is essential when discussing treatment options Online communities may provide support and reduce feelings of loneliness [ABSTRACT FROM AUTHOR]

Year 2023 is the 100-year anniversary of the discovery in guinea pigs that the lifespan of the corpus luteum (CL) is controlled by the uterus. The CL is the gatekeeper between two fundamental reproductive events — the estrous cycle and pregnancy. Uteroluteal research for the initial 33 years was productive but limited to laboratory species until the inclusion of farm animals in 1956. In the early 1960s, it was found that uterine luteolysin in sows travels unilaterally from a uterine horn to the adjacent CL which likely accounted for the heyday of uteroluteal research in the 1960s–70s. The luteolytic properties of PGF2α were demonstrated in rats in 1969. In 1971, (1) surgical separation of the lengthwise adherence between the uteroovarian vein and ovarian artery interfered with luteolysis in ewes, (2) species with primarily unilateral vs systemic uterine-induced luteolysis have a strong vs an absent or weak unilateral venoarterial transfer pathway, and (3) vascular infusions identified PGF2α as a uterine luteolysin. Vascular and PGF2α studies were beginning to merge. In 1973, a venoarterial pathway was firmly demonstrated in ewes and later in heifers by surgical anastomosis of a uterine vein or ovarian artery from a uterine-intact side to the corresponding vessel on the unilaterally hysterectomized side. More recent studies described how prostaglandins likely transfer through the walls of uterine and ovarian vessels using concentration gradients in sows and a prostaglandins transporter system in cows. • Uterine-induced luteolysis was discovered in guinea pigs in 1923. • The subject was extended to farm animals in 1965. • Surgical anastomoses of uterine veins or ovarian arteries documented the pathway. • PGF2α was identified as the uterine luteolytic factor in 1972. • A local venoarterial pathway is used for passage of messages in many body systems. [ABSTRACT FROM AUTHOR]

During placental development, autophagy has an important role at the molecular level, especially in cases such as trophoblast cell proliferation and cell death. Abnormal placental development due to trophoblast dysfunction causes serious gynaecological diseases and various fetal malformations. In the study conducted to investigate autophagy on the 5th day of pregnancy, in the pregnant and non pregnant group uterus tissues, uterine glands LC3 and Beclin 1 (+), in the evaluation of myometrium and perimetrium, weak (+) was observed in myometrium cells in pregnancy, while (+) reaction could not be distinguished in perimetrium. In this study, it was concluded that the immunohistochemical increase in LC3 and Beclin 1 intensity in the uterus, especially in the endometrial areas in the first trimester of pregnancy compared to the control group tissues is related to the physiology of pregnancy, homeostasis in pregnancy and hormonal mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. Method: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). Results: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. Conclusions: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels. [ABSTRACT FROM AUTHOR]

The Ex Utero Intrapartum Treatment (EXIT) procedure has long been an invaluable tool in managing complex fetal conditions requiring airway interventions during the transition from intrauterine to extrauterine life. This technical note offers an in-depth examination of the EXIT procedure, emphasizing the refinements and innovations introduced at our center. The technique focuses on meticulous preoperative assessment and uses distinctive techniques and anesthetic methodologies. A multidisciplinary team assembles to plan the EXIT procedure, emphasizing patient communication and risk discussion. Our technique involves atraumatic access to the uterine cavity, achieved through the application of a uterine progressive distractor developed for this purpose. Following the use of this distractor, vascular clamps and a stapling device (Premium Poly Cs-57 Autosuture®, Medtronic) are employed. Our anesthetic approach employs general anesthesia with epidural catheter placement. Maternal operation involves low transverse laparotomy and intraoperative ultrasonography-guided hysterotomy. Fetal exposure includes gentle extraction or external version, ensuring airway access. After securing fetal airway access, umbilical cord clamping and maternal abdominal closure conclude the procedure. By revisiting the core principles of EXIT and incorporating center-specific advancements, we enhance our understanding and technical expertise. To our knowledge, this is the first time a detailed description of the technique has been published. [ABSTRACT FROM AUTHOR]

(1) Background: Synchronous tumors are defined as tumors that occur at the same time, appearing within 2 months, according to the Surveillance Epidemiology and End Results Program, with a frequency of tertiary tumors of 0.5%. The purpose of this presentation is to report a case of three synchronous tumors of the female genital tract, given the fact that it represents a challenge both therapeutically and in demonstrating that the malignant lesions are completely different from each other. (2) Methods: We report the case of a 45 year-old patient diagnosed with three synchronous tumors developed in the genital tract: clear-cell ovarian carcinoma, uterine endometrioid adenocarcinoma, and cervical adenosquamous carcinoma. (3) Results: Total hysterectomy with bilateral anexectomy was performed and accompanied by a biopsy of the greater omentum. The evolution of the patient was favorable during chemotherapy, but she died two weeks after the completion of this treatment, from a cause secondary to the adverse effects determined by it, namely, severe thrombopenia which caused a massive lower digestive hemorrhage. (4) Conclusions: This case demonstrates the maximum importance of the involvement of adjuvant diagnostic techniques, especially when it comes to a diagnostic challenge with direct implications in the subsequent therapy of the patient. [ABSTRACT FROM AUTHOR]

Introduction: Intravasation on hysterosalpingogram (HSG) is defined by the flow of injected contrast from the uterine cavity into adjacent myometrial vessels. Evidence suggests intravasation can result in consequences such as pulmonary and cerebral embolisms. However, adverse events are poorly reported across published studies. Reported intravasation ranges from 0.0% to 13%, with higher rates attributed to oil‐soluble contrast medium (OSCM) use. Recent reviews of OSCM's fertility‐enhancing benefits have prompted rapid clinical uptake by fertility specialists worldwide. This instigates increased concern for intravasation and its associated sequelae. We aim to assess the prevalence of intravasation in fluoroscopic HSGs and its reporting in Western Australia (WA). Methods: A two‐year retrospective analysis of all fluoroscopic HSGs in one public teaching hospital within WA was conducted. All HSGs were retrieved from the public radiology information system and a blinded method was utilised to verify the presence and grading of intravasation in captured HSG images. Grading of intravasation was attributed by anatomical spread: 1 to myometrium, 2 to parametrium and 3 to para‐iliac vessels. Results were subsequently compared with reported intravasation to assess for discrepancies. Results: Of 308 successful HSGs, an intravasation rate of 7.1% was identified. Of these cases, 45% were reported and 32% were graded. Majority (73%) of intravasation events were classified as grade 1, with 9.0% and 18% of cases classified as grade 2 and 3, respectively. Conclusion: Under‐reporting of intravasation emphasises a need for increased vigilance of radiologists. Standardised classification can provide interpretational consistency and should be considered to improve safety in future practice. [ABSTRACT FROM AUTHOR]

Background: The application of high throughput technologies has enabled unravelling of unique differences between healthy mares and mares with endometritis at transcriptomic and proteomic levels. However, differences in the uterine microbiome are yet to be investigated. Objectives: The present study was aimed at evaluating the differences in uterine microbiome between healthy mares and mares with endometritis. Methods: Low‐volume lavage (LVL) samples were collected from the uterus of 30 mares classified into healthy (n = 15) and endometritis (n = 15) based on their reproductive history, intrauterine fluid accumulation, gross appearance of LVL samples, endometrial cytology and bacterial culture. The samples were subjected to 16S rRNA sequencing. Results: Notable differences in the uterine microbiome were observed between healthy mares and mares with endometritis at various taxonomic levels. In healthy mares, the most abundant phylum, class, order and family were Firmicutes, Bacilli, Bacillales and Paenibacillaceae, respectively. In contrast, the most abundant corresponding taxonomic levels in mares with endometritis were Proteobacteria, Gammaproteobacteria, Enterobacterales and Enterobacteriaceae, respectively. At the genus level, Brevibacillus and Paenibacillus were more abundant in healthy mares, whereas Escherichia, Salmonella and Klebsiella were more abundant in mares with endometritis. In healthy mares, Brevibacillus brevis was the most abundant species, followed by Brevibacillus choshinensis and Paenibacillus sp JDR‐2. However, in mares with endometritis, Escherichia coli was the most abundant species, followed by Salmonella enterica and Klebsiella pneumoniae. Conclusions: These results confirmed the previously reported presence of a uterine microbiome in healthy mares and helped unravel some alterations that occur in mares with endometritis. The findings can potentially help formulate new approaches to prevent or treat equine endometritis. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of Müllerian duct anomalies (MDA) remains a clinical challenge even by direct surgical inspection. Although obstetrical complications are more frequent in women with MDA, some subtypes allow normal reproduction, further delaying the diagnosis. Unicornuate uterus with a rudimentary non-communicating functioning horn is a rare form of MDA, susceptible to many gynecologic and obstetric complications such as miscarriages, premature birth, hematosalpinx, endometriosis, and chronic pelvic pain. We present an entire case pictorial assay including preoperative imaging as well as the surgical correction of the uterine anomaly and the associated complication of an occult unicornuate right uterus with rudimentary non-communicating functioning left horn (Class U4aC0V0/ European Society of Human Reproduction and Embryology/European Society of Gastrointestinal Endoscopy Classification) and its natural evolution following a previous incomplete surgical treatment. The patient had an emergency left adnexectomy for hematosalpinx and ovarian endometrioma at her local county hospital. After five years, the patient presented with severe dysmenorrhea and abdominal endometriosis due to blocked retrograde menstruation from a rudimentary, non-communicating functioning horn. Surgical treatment with the resection of the rudimentary uterine horn, together with the abdominal wall endometriosis lesions, was carried out with good outcomes. [ABSTRACT FROM AUTHOR]

The enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms. Using siRNA, HO-1 was knocked down in JEG-3 and BeWo cells and trophoblastic spheroids were generated with or without CO treatment. Adhesion assays were performed after transferring the spheroids to RL-95 endometrial epithelial cell layers. Additionally, angiogenesis, stress, and toxicity RT2-Profiler™ PCR SuperArray and PCR analyses were performed in uterine murine samples. HO-1 knockdown by siRNA impeded implantation in the 3D culture model, but this effect could be reversed by CO. Uteruses from virgin Hmox1−/− females exhibited altered expression of angiogenesis and stress markers. Furthermore, there was a distinct expression pattern of cytokines and chemokines in uteruses from gestation day 14 in Hmox1−/− females compared to Hmox1+/+ females. This study strongly supports the essential role of HO-1 during implantation. Moreover, CO appears to have the potential to compensate for the lack of HO-1 during the spheroid attachment process. The absence of HO-1 results in dysregulation of angiogenesis and stress-related genes in the uterus, possibly contributing to implantation failure. [ABSTRACT FROM AUTHOR]

Objective: The pathophysiology of uterine scar dehiscence is not yet clear. The aim of this study was to investigate whether preoperative hemogram parameters can be used as predictive markers of uterine scar dehiscence, thus improving prediction and contributing to management of repeat Cesarean section. Material and Methods: Between 2015 and 2020, 36670 (47.6%) cesarean sections were delivered in our hospital and 16943 of them had a previous Cesarean section. All cases of uterine scar rupture detected during Cesarean section were identified, and a total of 40 patients were included after excluding cases with impairment of the systemic inflammatory response (SIR). Controls consisted of 40 randomly selected, ageand body mass index (BMI)-matched patients, and the groups were compared. Results: Age, BMI, and gravidity were similar (p>0.05). Although the gestational week and Apgar scores were similar between the groups (p>0.05), the birth weight amongst controls was significantly higher than the uterine dehiscence group (p=0.028). Platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and other hemogram values were similar in both groups (p>0.05). Mean platelet volume (MPV) in the control group was significantly higher than in the uterine rupture group (p=0.049). Regression analysis found no significant result between hemogram parameters, birth weight, and dehiscence. Conclusion: In this study, which set out to identify predictors of the risk of uterine scar dehiscence with SIR parameters, only the MPV value was lower in the dehiscence group. [ABSTRACT FROM AUTHOR]

Collagen is an essential constituent of the uterine extracellular matrix that provides biomechanical strength, resilience, structural integrity, and the tensile properties necessary for the normal functioning of the uterus. Cross-linking is a fundamental step in collagen biosynthesis and is critical for its normal biophysical properties. This step occurs enzymatically via lysyl oxidase (LOX) or non-enzymatically with the production of advanced glycation end-products (AGEs). Cross-links found in uterine tissue include the reducible dehydro-dihydroxylysinonorleucine (deH-DHLNL), dehydro-hydroxylysinonorleucine (deH-HLNL), and histidinohydroxymerodesmosine (HHMD); and the non-reducible pyridinoline (PYD), deoxy-pyridinoline (DPD); and a trace of pentosidine (PEN). Collagen cross-links are instrumental for uterine tissue integrity and the continuation of a healthy pregnancy. Decreased cervical cross-link density is observed in preterm birth, whereas increased tissue stiffness caused by increased cross-link density is a pathogenic feature of uterine fibroids. AGEs disrupt embryo development, decidualization, implantation, and trophoblast invasion. Uterine collagen cross-linking regulators include steroid hormones, such as progesterone and estrogen, prostaglandins, proteoglycans, metalloproteinases, lysyl oxidases, nitric oxide, nicotine, and vitamin D. Thus, uterine collagen cross-linking presents an opportunity to design therapeutic targets and warrants further investigation in common uterine disorders, such as uterine fibroids, cervical insufficiency, preterm birth, dystocia, endometriosis, and adenomyosis. [ABSTRACT FROM AUTHOR]

Summary: A population of Xiphinema artemisiae was recovered from Iran, representing the first report after its original description from a meadow pasture in northern Caucasus, Russia. The Iranian population was recovered from the rhizosphere of grasses in the Damavand region, Tehran province. The females of the recovered populations are characterised by a lip region separated from the rest of body by a depression, a 5.1-5.6 mm long body, a 129-138 μ m long odontostyle, 76-85 μ m long odontophore, a uterus having a pseudo-Z-organ and crystalloid bodies observed in some specimens, and a short, rounded, dorsally more convex tail with a subcentral mucron, four juvenile developmental stages (the first stage was not recovered) and functional males. The Iranian population is morphologically and morphometrically similar to the type population and minor morphological differences can be attributed to geographical interpopulation differences. Molecular phylogenetic relationships of the Iranian population of X. artemisiae with other species were reconstructed using sequences of three genomic ribosomal markers, viz. small, large subunit D2-D3 and internal transcribed spacer (SSU, LSU D2-D3 and ITS) rDNA. [ABSTRACT FROM AUTHOR]

Early gestational loss occurs in approximately 20% of all clinically recognized human pregnancies and is an important cause of morbidity. Either embryonic or maternal defects can cause loss, but a functioning and receptive uterine endometrium is crucial for embryo implantation. We report that the switch/sucrose nonfermentable (SWI/SNF) remodeling complex containing polybromo-1 (PBRM1) and Brahma-related gene 1 (BRG1) is essential for implantation of the embryonic blastocyst on the wall of the uterus in mice. Although preimplantation development is unaffected, conditional ablation of Pbrm1 in uterine stromal cells disrupts progesterone pathways and uterine receptivity. Heart and neural crest derivatives expressed 2 (Hand2) encodes a basic helix-loop-helix (bHLH) transcription factor required for embryo implantation. We identify an enhancer of the Hand2 gene in stromal cells that requires PBRM1 for epigenetic histone modifications/coactivator recruitment and looping with the promoter. In Pbrm1cKO mice, perturbation of chromatin assembly at the promoter and enhancer sites compromises Hand2 transcription, adversely affects fibroblast growth factor signaling pathways, prevents normal stromalepithelial crosstalk, and disrupts embryo implantation. The mutant female mice are infertile and provide insight into potential causes of early pregnancy loss in humans. [ABSTRACT FROM AUTHOR]

Objective: To compare contained and free manual vaginal morcellation of large uteruses after total laparoscopic hysterectomy (TLH) in women at low risk of uterine malignancy in terms of feasibility and safety. Methods: A single‐center, observational, retrospective, cohort study was carried out including all patients undergoing TLH requiring manual vaginal morcellation for specimen extraction of large uteruses from January 2015 to August 2021 at the Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero‐Universitaria of Bologna, Bologna, Italy. Patients were divided into two groups according to the type of manual vaginal morcellation (contained or free), and compared in terms of demographic, clinical, and perioperative data. Results: In all, 271 patients were included: 186 (68.6%) in the contained morcellation group and 85 (31.4%) in the free morcellation group. The mean operative time was significantly lower in the contained morcellation group compared with the free morcellation group (median [interquartile range] 130 [45] vs. 155 [60] min; P < 0.001). No significant difference was found in complications related to the morcellation step, overall, intraoperative and postoperative complications, estimated blood loss, length of hospital stays, uterine weight, and rate of occult malignancy between the two groups. Conclusion: Contained vaginal manual morcellation of the uterus after total laparoscopic hysterectomy using a specimen retrieval bag appears to be a safe procedure with significantly lower operative time than free vaginal manual morcellation. SYNOPSIS: Contained vaginal morcellation of the uterus after total laparoscopic hysterectomy seems to be a safe procedure associated with reduced operative times. [ABSTRACT FROM AUTHOR]

Background: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. Purpose: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. Methods: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. Results: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. Conclusions: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists. [ABSTRACT FROM AUTHOR]

Standard of care radiotherapy for locally advanced cervical cancer includes large margins to ensure the uterocervix remains within the treatment fields over the course of treatment. Daily online cone-beam adaptive radiotherapy corrects for interfractional changes by adjusting the plan to match the target position during each treatment session, thus allowing for significantly reduced clinical target volume (CTV) to planning target volume (PTV) margins. We hypothesise that reduced margins from daily online adaptive radiotherapy will reduce organ at risk dose without compromising target coverage. Ten patients with cervical cancer (stage IIB–IIIC2) were treated with definitive chemoradiation using daily online cone-beam adaptive radiotherapy in 25–27 fractions. Initial and all adapted treatment plans were generated with CTV to PTV margins versus standard of care image-guided radiotherapy (IGRT) plans as follows: cervix/uterus/gross tumour volume (0.5 versus 1.5 cm), parametria/vagina (0.5 versus 1.0 cm) and nodal chains and gross nodes (0.5 versus 0.5 cm). IGRT plans were created and copied to synthetic computed tomography scans and contours generated from each daily adapted fraction. The dosimetry of each clinically treated online adapted fraction was compared with emulated IGRT plans. Statistical significance was defined as P < 0.05. Daily online cone-beam adaptive radiotherapy significantly improves bowel bag dosimetry compared with IGRT, with a reduction in V40 by an average of 91.3 cm3 [V40 (–6.2%) and V45 (–6.1%)]. The daily adapted plans showed significant improvements in bladder and rectum [V40 (–25.2% and –36.0%) and V30 (–9.7% and –17.1%), respectively]. Additionally, bone marrow had a significantly reduced dose [V10 (–2.7%) and V20 (–3.3%)]. Daily online cone-beam adaptive radiotherapy improved uterocervix CTV coverage and reduced hotspots compared with IGRT [D95% (+1.6%) and Dmax (–0.9%)]. Reduced CTV to PTV margins achievable with daily online adaptive radiotherapy improves organ at risk dosimetry and target coverage when compared with standard of care IGRT for locally advanced cervical cancer. The clinical impact of improved dosimetry is currently undergoing investigation. • Adaptive radiotherapy accounts for changes in anatomy and improves radiation delivery. • Daily online adaptive radiotherapy allows for reduced CTV to PTV margins. • Daily online adaptive radiotherapy improves CTV coverage and OAR sparing. • Daily online adaptive therapy takes about 41 min on average. [ABSTRACT FROM AUTHOR]