Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

BACKGROUND: Endometrial cancer (EC) is the most common gynecological malignancy. Accurate preoperative staging is essential for guiding treatment. The depth of myometrial invasion is a key prognostic factor. This prospective study aimed to evaluate the added benefit of diffusion-weighted imaging (DWI) compared to T2-weighted imaging (T2WI) and dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative assessment of myometrial invasion in EC.
OBJECTIVE: The aim of this prospective study was to evaluate the added benefit of DWI in the preoperative assessment of myometrial invasion in EC, in comparison with T2WI and DCE-MRI. The objectives were to assess the imaging characteristics of endometrial carcinoma on T2WI, DCE, and DW MR, to assess the depth of myometrial invasion and overall stage in EC patients, to compare the diagnostic performance of DCE-MRI with that of DW-MRI combined with T2WI, to describe how MR imaging findings can be combined with tumor histologic features and grading to guide treatment planning, and to evaluate the pitfalls and limitations of DCE and DW MR in the assessment of EC.
METHODS: Thirty-one patients with histologically confirmed EC underwent preoperative pelvic MRI on a 1.5T scanner. T2WI, DWI (b-values 0, 1000 s/mm2), and DCE-MRI were performed. Two radiologists independently assessed myometrial invasion on T2WI, T2WI + DWI, and T2WI + DCE-MRI. Histopathology after hysterectomy was the reference standard. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each MRI protocol, with separate analyses for superficial (<50%) and deep (≥50%) myometrial invasions.
RESULTS: The accuracy for assessing superficial invasion was 61.3% for T2WI, 87.1% for T2WI + DWI, and 87.1% for T2WI + DCE-MRI. For deep invasion, accuracy was 64.5% for T2WI, 90.3% for T2WI + DWI, and 90.3% for T2WI + DCE-MRI. Sensitivity, specificity, PPV, and NPV for T2WI + DWI and T2WI + DCE-MRI were high and comparable (88.9-91.7%) for both superficial and deep invasions. T2WI had markedly lower sensitivity and specificity. The differences between T2WI and the functional MRI protocols were statistically significant (p < 0.01).
CONCLUSIONS: DWI and DCE-MRI significantly improve the diagnostic performance of MRI for the preoperative assessment of myometrial invasion depth in EC compared to T2WI alone. DWI + T2WI and DCE-MRI + T2WI demonstrate comparable high accuracy. DWI may be preferable since it is faster and avoids contrast administration.

Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA sequencing (RNA-seq) data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by ultra-high performance liquid chromatography-mass spectrometry identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic subtype. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression, and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort.

UNASSIGNED: The resolution of factors linked to the recurrence of cesarean section defects can be accomplished through a comprehensive technique that effectively addresses the dehiscent area, eliminates associated intraluminal fibrosis, and establishes a vascularized anterior wall by creating a sliding myometrial flap.
UNASSIGNED: Propose a comprehensive surgical repair for recurrent and large low hysterotomy defects in women seeking pregnancy or recurrent spotting.
UNASSIGNED: A retrospective cohort analysis included 54 patients aged 25-41 with recurrent large cesarean scar defects treated at Otamendi, CEMIC, and Valle de Lili hospitals. Comprehensive surgical repair was performed by suprapubic laparotomy, involving a wide opening of the vesicouterine space, removal of the dehiscent cesarean scar and all intrauterine abnormal fibrous tissues, using a glide myometrial flap, and intramyometrial injection of autologous platelet-rich plasma. Qualitative variables were determined, and descriptive statistics were employed to analyze the data in absolute frequencies or percentages. The data obtained were processed using the InfostatTM statistic program.
UNASSIGNED: Following the repair, all women experienced normal menstrual cycles and demonstrated an adequate lower uterine segment thickness, with no evidence of healing defects. All patients experienced early ambulation and were discharged within 24 h. Uterine hemostasis was achieved at specific points, minimizing the use of electrocautery. The standard duration of the procedure was 60 min (skin-to-skin), and the average bleeding was 80-100 ml. No perioperative complications were recorded. A control T2-weighted MRI was performed six months after surgery. All patients displayed a clean, unobstructed endometrial cavity with a thick anterior wall (Median: 14.98 mm, IQR 13-17). Twelve patients became pregnant again, all delivered by cesarean between 36.1 and 38.0 weeks, with a mean of 37.17 weeks. The thickness of the uterine segment before cesarean ranged between 3 and 7 mm, with a mean of 3.91 mm. No cases of placenta previa, dehiscence, placenta accreta spectrum (PAS), or postpartum hemorrhage were reported.
UNASSIGNED: The comprehensive repair of recurrent low-large defects offers a holistic solution for addressing recurrent hysterotomy defects. Innovative repair concepts effectively address the wound defect and associated fibrosis, ensuring an appropriate myometrial thickness through a gliding myometrial flap.

OBJECTIVE: To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model.
METHODS: Thunbergia laurifolin L. leaves were subjected to ethanolic extraction. In vivo study, 50 pregnant rats were randomly divided into 5 groups (10 for each): non-GDM group, GDM induced by streptozotocin (STZ, 60 mg/kg i.p.), metformin (MET) 100 mg/kg, TLE 50, and 500 mg/kg groups. Administration was performed on gestation day 7 until term (day 21). The effects of TLE on blood glucose, insulin levels, lipid profiles, liver enzymes, and maternal performances were assessed. In in vitro study, the effect of TLE was examined using the organ bath for uterine force measurement.
RESULTS: In in vivo study, TLE significantly reduced blood glucose as compared to GDM (P<0.05) with gradually increased insulin level. This effect was consistent with islets of Langerhans restoration. Histologically, the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM (P<0.05). Additionally, TLE significantly reduced total cholesterol, triglyceride, and alanine transaminase levels (P<0.05). Intriguingly, TLE also led to a notable augmentation in gravid uterus size, live fetuses count, and implantation numbers, while significantly reducing the post-implantation loss rate associated with fetal classification (P<0.05). Thus, GDM improvements were close to those produced by MET. In in vitro study, TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility (half-maximal inhibition concentration=1.2 mg/L). This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions. When combined with its major constituent, rosmarinic acid, TLE produced an enhanced inhibitory effect (P<0.05).
CONCLUSIONS: TLE ameliorated blood glucose levels, enhanced uterine muscular structure, and improved maternal and fetal performance in GDM. TLE also displayed tocolytic properties. These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.

OBJECTIVE: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST.
METHODS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed.
RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4).
CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined ex vivo using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually.

Fibroids are the most common benign tumours of the uterus, often requiring surgery when symptomatic. This study aims to investigate the impact of surgery using two methods, laparoscopy and laparotomy, on the thickness and vascularity of the uterine myometrium at the site of myomectomy scar (comparing sonographic features at the surgical scar site, including thickness, vascularity, and the extent of fibrotic tissue, in both open and laparoscopic surgical approaches). In this clinical trial, 100 women with type 2-5 fibroids and clinical symptoms, seeking surgery et al. Zahra Hospital, were enrolled in two groups: laparoscopy and laparotomy. Inclusion criteria were a maximum fibroid size of 8 cm and, in the case of multiple fibroids, a maximum of three, with the largest being 8 cm. 6 months post-surgery, sonographic assessments of the myomectomy scar site were compared between both groups. Participants showed no significant differences in demographic and obstetric factors. The most common clinical symptom (87%) in both groups was abnormal uterine bleeding (AUB). The mean hospital stay duration was statistically significantly lower in the laparoscopy group at 1.64 (SD 0.56) compared to 1.89 (SD 0.58) in the laparotomy group (p = 0.028). Additionally, the decrease in haemoglobin levels was 0.89 (SD 0.92) and 1.87 (SD 2.24) units, respectively, which showed a statistically significant difference (p = 0.003). The duration of surgery was significantly shorter in the laparotomy group (p = 0.001). Abdominal pressure was not observed in the laparoscopy group, while 12% of the laparotomy group reported complaints (p = 0.013). Based on the results obtained in this study, it can be concluded that there was no difference between these two methods in terms of improving uterine thickness and associated complications. However, the decrease in haemoglobin levels and the length of hospital stay were lower in patients undergoing laparoscopy.

OBJECTIVE: To study the differences in immune cell profile in uterine fibroids (Fib) and matched myometrium (Myo).
METHODS: Observational Study SETTING: Laboratory Study PATIENTS: The study included tissue that was collected from ten pairs of fibroid and matched myometrium from women, not on hormonal medications, undergoing hysterectomy and myomectomy.
METHODS: None MAIN OUTCOME MEASURES: Differences in immune cell and cytokine composition between fibroid and matched myometrium RESULT(S): The mass cytometry analysis indicated that fibroids had a significantly higher number of NK cells, total macrophages, M2 macrophages, and conventional dendritic cells when compared to matched myometrium from the same patient. In contrast, fibroids had significantly fewer CD3 and CD4 T cells when compared to myometrium. The mass cytometry analysis did not show any significant difference in the number of resting mast cells. IFC and IHC imaging confirmed the CytoF results, showing a significantly higher (p<0.05) number of NK, tryptase-positive mast cells indicative of mast cell activation, total macrophage, and M2 cells in Fibroids and a significantly lower (p<0.05) number of CD3 and CD4 T cells. The cytokine assay revealed significantly increased (p<0.05) levels of IFNA2, Il-1α, and PDGF-AA and significantly lower levels of M-CSF and IL-1RA in Fib.
CONCLUSIONS: Our results show significant differences in immune cell populations and cytokine levels between Fib and Myo. There was a significant increase in total number of macrophages, M2 macrophages, NK cells, and dendritic cells and a significant decrease in CD3 and CD4 T cells in Fib. IHC confirmed no differences in total resting mast cell count, but a significant increase in tryptase-positive mast cells in Fib. Fibs also expressed significantly higher levels of IFNA2, IL-1α, and PDGF-AA and significantly lower levels of IL-1RA and M-CSF as compared with matched myometrium. These findings provide a foundation for further studies exploring the role of immune cells in Fib development.

Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76-11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11-9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10-13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.