OBJECTIVES: According to the World Health Organization (WHO), infertility rates have been steadily rising worldwide. Identifying risk factors for contrast agent reflux into the myometrium during hysterosalpingo-contrast sonography (HyCoSy) is of clinical significance in reducing this complication and improving infertility treatment. However, there is currently no standardized pre-evaluation method for predicting intra-myometrial contrast reflux, with clinical assessment often relying on physician experience and patient symptoms. This study aims to identify imaging risk factors for contrast agent reflux into the myometrium using four-dimensional (4D) HyCoSy and to construct a nomogram-based predictive model to assist in clinical decision-making. METHODS: A retrospective analysis was conducted on 1 274 infertile women who underwent 4D HyCoSy at the Women and Children's Hospital of Hunan and the the Third Xiangya Hospital of Central South University from January 1, 2020, to December 15, 2022. Patients were divided into a reflux group (n=234) and a non-reflux group (n=1 040) based on the presence of intra-myometrial contrast reflux. Univariate and multivariable Logistic regression analyses were used to identify significant predictors, which were then used to construct a nomogram model. Internal validation was performed using 500 bootstrap resamples. RESULTS: The age of the reflux group was significantly higher than that of the non-reflux group [(31.82±5.27) years vs (30.66±4.83) years, P=0.001 1]. Primary infertility was more common in the non-reflux group (50.96%), while secondary infertility dominated in the reflux group (76.50%), with 72.65% having a history of gynecological surgery (P<0.001). Abnormal menstrual volume and discomfort during the procedure were more common in the reflux group, while the non-reflux group tolerated higher contrast agent doses (P<0.001). Imaging differences included endometrial thickness, tubal wall smoothness, and peritoneal contrast dispersion, with the non-reflux group showing thicker endometrium and smoother, more patent tubes. The nomogram model yielded an area under the curve (AUC) of 0.854, indicating good predictive performance. The AUC of the decision curve analysis (DCA) for internal validation of the model was 0.737. When the threshold probability for contrast agent reflux into the myometrium ranged from 0.05 to 0.95, the maximum net benefit reached 0.18. The net benefit of applying the nomogram predictive model exceeded that of either full intervention or no intervention, indicating that the model demonstrates good clinical predictive performance. CONCLUSIONS The nomogram model, based on infertility type, endometrial thickness, contrast agent dose, and discomfort symptoms, effectively predicts intra-myometrial contrast agent reflux after 4D HyCoSy. It provides a valuable tool for clinicians to implement early preventive measures and reduce the risk of contrast leakage and associated complications.
Humans ; Female ; Nomograms ; Contrast Media/adverse effects* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Hysterosalpingography/methods* ; Infertility, Female/diagnostic imaging* ; Myometrium/diagnostic imaging* ; Risk Factors

A 66-year-old postmenopausal woman received routine gynecologic check-up. Transvaginal ultrasonography and abdominal and pelvic computed tomography showed about 5-cm cystic mass in uterus with solid component and the patient had thin endometrium and the serum level of CA 125 was normal. We performed a total hysterectomy and bilateral salpingo-oophorectomy and found tumor which had brownish cystic fluid and about 2 cm sized and colored in light yellowish, polypoid protruding solid mass, located within the myometrial wall. Histopathological examination of frozen section revealed malignancy. The tumor was confined within the myometrium and its histologic type was clear cell adenocarcinoma. Finally we identified that the myometrial mass was clear cell adenocarcinoma originated from adenomyosis pathologically. The malignant transformation of adenomyosis is very rare. When we find a cystic change with solid component in adenomyosis patients, clear cell adenocarcinoma should be suspected as a differential diagnosis and magnetic resonance imaging should be considered for further evaluation.
Adenocarcinoma, Clear Cell* ; Adenomyosis* ; Aged ; Animals ; Diagnosis, Differential ; Endometrium ; Female ; Frozen Sections ; Humans ; Hysterectomy ; Magnetic Resonance Imaging ; Mice ; Myometrium ; Ultrasonography ; Uterus

Prostaglandin (PG) E plays critical roles during pregnancy and parturition. Emerging evidence indicates that human labour is an inflammatory event. We sought to investigate the effect of PGE on the output of proinflammatory cytokines in cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and elucidate the role of subtypes of PGE receptors (EP, EP, EP and EP). After drug treatment and/or transfection of each receptor siRNA, the concentrations of inflammatory secreting factors in HUSMCs culture medium were detected by the corresponding ELISA kits. The results showed that, PGE increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) output, decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent manner, but had no effect on IL-1β and chemokine (c-c motif) ligand 2 (CCL-2) secretion of HUSMCs. EP/EP agonist 17-phenyl-trinor-PGE stimulated IL-6 and TNFα whilst suppressing IL-1β and CXCL8 output. The effects of 17-phenyl-trinor-PGE on IL-1β and CXCL8 secretion were remained whereas its effect on IL-6 and TNFα output did not occur in the cells with EP knockdown. The stimulatory effects of 17-phenyl-trinor-PGE on IL-6 and TNFα were remained whereas the inhibitory effects of 17-phenyl-trinor-PGE on IL-1β secretion was blocked in the cells with EP knockdown. Either of EP and EP agonists stimulated IL-1β and TNFα output, which was reversed by EP and EP siRNA, respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked EP/EP modulation of TNFα and CXCL8 output. PI3K inhibitor LY294002 and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE-induced IL-1β and IL-6 output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP and EP stimulation of IL-1β and TNFα output, whereas PLC and PKC inhibitors blocked EP- and EP-induced TNFα output but not IL-1β output. Our data suggest that PGE receptors exhibit different effects on the output of various cytokines in myometrium, which can subtly modulate the inflammatory microenvironment in myometrium during pregnancy.
Cells, Cultured ; Chromones ; pharmacology ; Cytokines ; metabolism ; Female ; Humans ; Imidazoles ; pharmacology ; Inflammation ; Morpholines ; pharmacology ; Myocytes, Smooth Muscle ; cytology ; Myometrium ; cytology ; Phosphatidylinositol 3-Kinases ; Pregnancy ; Pyridines ; pharmacology ; Receptors, Prostaglandin E ; physiology

The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of α-bisabolol (560, 860, 1,200 and 1,860 µM) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to α-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of α-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. α-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p < 0.05). α-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p < 0.05) and a concentration-dependent decrease in LPS-induced TNFα and IL-1β production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by α-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place α-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.
Adenosine Monophosphate ; Animals ; Colforsin ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans* ; Immunomodulation ; In Vitro Techniques ; Inflammation ; Interleukin-10 ; Interleukins ; Mice ; Myometrium ; Necrosis ; Obstetric Labor, Premature ; Pregnancy ; Premature Birth ; Uterine Contraction ; Uterus*

OBJECTIVE: We compared the expression levels of Müllerian inhibiting substance (MIS)/anti-Müllerian hormone type II receptor (AMHRII) in uterine myoma and adenomyosis to evaluate the possibility of using MIS/anti-Müllerian hormone (AMH) as a biological regulator or therapeutic agent in patients with uterine leiomyoma and adenomyosis. METHODS: We studied normal uterine myometrium, leiomyoma, endometrial tissue, and adenomyosis from 57 patients who underwent hysterectomy for uterine leiomyoma (22 cases) or adenomyosis (28 cases) and myomectomy for uterine myoma (7 cases). Immunohistochemical staining was used to confirm the MIS/AMHRII protein expression level in each tissue. Reverse transcription-polymerase chain reaction was performed to quantify MIS/AMHRII mRNA expression. RESULTS: The MIS/AMHRII protein was more strongly expressed in uterine myoma (frequency of MIS/AMHRII expressing cells: 51.95%±13.96%) and adenomyosis (64.65%±4.85%) tissues than that in the normal uterine myometrium (3.15%±1.69%) and endometrium (31.10%±7.19%). In the quantitative analysis of MIS/AMHRII mRNA expression, MIS/AMHRII mRNA expression levels in uterine myoma (mean density: 4.51±0.26) and adenomyosis (6.84±0.20) tissues were higher than that in normal uterine myometrial tissue (0.08±0.09) and endometrial tissue (1.63±0.06). CONCLUSION: This study demonstrated that MIS/AMHRII was highly and strongly expressed on uterine myoma and adenomyosis. Our data suggest that MIS/AMH may be evaluated as a biological modulator or therapeutic agent on MIS/AMHRII expressing uterine myoma and adenomyosis.
Adenomyosis ; Animals ; Endometrium ; Female ; Humans ; Hysterectomy ; Leiomyoma ; Mice ; Myoma ; Myometrium ; RNA, Messenger

OBJECTIVE: Corticotropin-releasing hormone (CRH) is a crucial regulator of human pregnancy and parturition. Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels are important for regulating myometrial quiescence during pregnancy. We investigated regulatory effects of different concentrations of CRH on KATP channel expression in human myometrial smooth muscle cells (HSMCs) in in vitro conditions. METHODS: After treating HSMCs with different concentrations of CRH (1, 10, 102, 103, 104 pmol/L), mRNA and protein expression of KATP channel subunits (Kir6.1 and SUR2B) was analyzed by reverse transcription-polymerase chain reaction and western blot. We investigated which CRH receptor was involved in the reaction and measured the effects of CRH on intracellular Ca2+ concentration when oxytocin was administered in HSMCs using Fluo-8 AM ester. RESULTS: When HSMCs were treated with low (1 pmol/L) and high (103, 104 pmol/L) CRH concentrations, KATP channel expression significantly increased and decreased, respectively. SUR2B mRNA expression at low and high CRH concentrations was significantly antagonized by antalarmin (CRH receptor-1 antagonist) and astressin 2b (CRH receptor-2 antagonist), respectively; however, Kir6.1 mRNA expression was not affected. After oxytocin treatment, the intracellular Ca2+ concentration in CRH-treated HSMCs was significantly lowered in low concentration of CRH (1 pmol/L), but not in high concentration of CRH (103 pmol/L), compared to control. CONCLUSION: Our data demonstrated the regulatory effect was different when HSMCs were treated with low (early pregnancy-like) and high (labor-like) CRH concentrations and the KATP channel expression showed significant increase and decrease. This could cause inhibition and activation, respectively, of uterine muscle contraction, demonstrating opposite dual actions of CRH.
Adenosine Triphosphate ; Adenosine ; Animals ; Blotting, Western ; Corticotropin-Releasing Hormone ; Female ; Humans ; In Vitro Techniques ; KATP Channels ; Mice ; Myocytes, Smooth Muscle ; Myometrium ; Oxytocin ; Parturition ; Potassium Channels ; Potassium ; Pregnancy ; Receptors, Corticotropin-Releasing Hormone ; RNA, Messenger

Background: The Lead Vessel and Infitrating Vessels are findings in endometrial cancer that are well visualized by three-dimensional power Doppler angiography. Vessel diameter and length may be utilized as markers for deep myometrial and or cervical involvement. Objective: To determine the accuracy of Lead vessel and Infiltrating vessel dimensions in assessing the depth of myometrial invasion in endometrial cancer and its cervical involvement. Participants and Methods All women histopathologically diagnosed with endometrial cancer, undergoing surgical staging, with informed consent were included. Sonography using GE Voluson S8 system for describing the uterus and endometrial thickness were followed by a 3D power Doppler Angiography to analyze the depth of myometrial invasion and presence or absence of cervical involvement. Vessel diameter and length in transverse and sagittal plane were measured by calipers. Predictive values and operating characteristics (sensitivity, specificity, positive and negative predictive values) were computed.
Myometrium ; Endometrial Neoplasms ; Angiography ; Ultrasonography, Doppler

OBJECTIVE: To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration (MI) in endometrial carcinoma. METHODS: An extensive search of papers comparing TVS and MRI in assessing MI in endometrial cancer was performed in MEDLINE (PubMed), Web of Science, and Cochrane Database from January 1989 to January 2017. Quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: Our extended search identified 747 citations but after exclusions we finally included in the meta-analysis 8 articles. The risk of bias for most studies was low for most 4 domains assessed in QUADAS-2. Overall, pooled estimated sensitivity and specificity for diagnosing deep MI were 75% (95% confidence interval [CI]=67%–82%) and 82% (95% CI=75%–93%) for TVS, and 83% (95% CI=76%–89%) and 82% (95% CI=72%–89%) for MRI, respectively. No statistical differences were found when comparing both methods (p=0.314). Heterogeneity was low for sensitivity and high for specificity for TVS and MRI. CONCLUSION: MRI showed a better sensitivity than TVS for detecting deep MI in women with endometrial cancer. However, the difference observed was not statistically significant.
Animals ; Bias (Epidemiology) ; Endometrial Neoplasms* ; Female ; Humans ; Magnetic Resonance Imaging* ; Mice ; Myometrium ; Population Characteristics ; Sensitivity and Specificity ; Ultrasonography*

OBJECTIVE: To report our 15-year institutional experience of fertility-sparing treatment in young patients with early endometrial cancer (EC) treated by combined hysteroscopic resection and progestin therapy. METHODS: Twenty-eight patients (stage IA, G1 and 2 endometrioid EC) wishing to preserve their fertility were enrolled into this prospective study. Hysteroscopic resection was used to resect the tumor, endometrium adjacent to the tumor and myometrium underlying the tumor. Adjuvant hormonal therapy consisted of oral megestrol acetate or levonorgestrel intrauterine device for 6 months or more. RESULTS: After 3 months from the progestin start date, 25 patients (89.3%) showed a complete regression (median time to complete regression, 3 months [range, 3-9 months]), two (7.1%) showed persistent disease, while one patient (3.6%) presented with progressive disease and underwent definitive surgery (stage IA, G3 endometrioid). At 6 months, one of the two patients with persistent disease underwent definitive surgery (stage IA, G1 endometrioid), while the other one was successfully re-treated. Two recurrences were observed (7.7%) both involving the endometrium and synchronous ovarian cancer. The median duration of complete response was 94.5 months (range, 8-175 months). More than half of the responders (57.7%) attempted to conceive with 93.3% and 86.6% pregnancy and live birth rates, respectively. CONCLUSION: The addition of a standardized three-step resectoscopy to progestin would seem to improve the efficacy of progestin alone. High pregnancy and live birth rates were observed in women attempting to conceive.
Animals ; Endometrial Neoplasms* ; Endometrium ; Female ; Fertility Preservation ; Fertility* ; Humans ; Hysteroscopy ; Intrauterine Devices ; Levonorgestrel ; Live Birth ; Megestrol Acetate ; Mice ; Myometrium ; Ovarian Neoplasms ; Pregnancy ; Prospective Studies ; Recurrence

Uterine leiomyomas are benign tumors arising from the myometrium and largely prevalent in the woman's reproductive years. The majority of women with leiomyomas either remain asymptomatic or develop symptoms gradually over time. When patients are symptomatic, the nature of their complaints is often attributable to the number, size, and/or location of their fibroids. Depending on a patient's symptomatology and reproductive plans, treatment options include expectant management, medical management (hormonal and non-hormonal), or surgical management (myomectomy or hysterectomy).
Animals ; Female ; Humans ; Leiomyoma* ; Mice ; Myometrium