OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).
Pregnancy ; Humans ; Female ; Fertilization in Vitro/methods* ; Single-Blind Method ; Embryo Transfer ; Pregnancy Rate ; Acupuncture Therapy ; Endometrium/blood supply*

OBJECTIVE: To compare the clinical efficacy between staged acupuncture based on "thoroughfare vessel is the sea of blood" theory combined with routine hormone replacement cycle treatment and routine hormone replacement cycle treatment for patients with recurrent implantation failure (RIF) of thin endometrium. METHODS: A total of 72 RIF patients with thin endometrium were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with routine hormone replacement cycle treatment. Based on the treatment of the control group, the patients in the observation group were treated with staged acupuncture based on "thoroughfare vessel is the sea of blood" theory. The main acupoints were Neiguan (PC 6) and Gongsun (SP 4), and the supplementary acupoints were selected according to the menstrual cycle and syndrome differentiation; the acupuncture was given once every other day, 3 times a week, for 3 consecutive menstrual cycles. The thickness and shape of endometrium, and Hamilton anxiety scale (HAMA) score were observed at implantation window before and after treatment; the clinical pregnancy rate, live birth rate and cycle cancellation rate were compared between the two groups; the correlation between endometrial thickness and HAMA score was analyzed. RESULTS: Compared before treatment, the endometrial thickness in the two groups and the proportion of type A+B endometrium in the observation group were increased (P<0.05), and the HAMA scores in the two groups were decreased (P<0.05) after treatment. The above indexes in the observation group were superior to those in the control group (P<0.05). The clinical pregnancy rate and live birth rate in the observation group were higher than those in the control group (P<0.05), and the cycle cancellation rate was lower than that in the control group (P<0.05). There was a negative correlation between endometrial thickness and HAMA score (P<0.05). CONCLUSION Based on the routine hormone replacement cycle treatment, the addition use of staged acupuncture based on "thoroughfare vessel is the sea of blood" theory could improve the thickness and shape of endometrium, relieve anxiety, increase the clinical pregnancy rate and live birth rate, and reduce the cycle cancellation rate in RIF patients with thin endometrium. The curative effect is superior to the routine hormone replacement cycle treatment alone.
Female ; Pregnancy ; Humans ; Anxiety ; Anxiety Disorders ; Acupuncture Therapy ; Endometrium ; Hormones

OBJECTIVES: Magnetic resonance diffusion-weighted imaging (DWI) has important clinical value in diagnosis and curative effect evaluation on endometrial carcinoma. How to improve the detection rate of endometrial small lesions by DWI is the research focus of MRI technology. This study aims to analyze the image quality of small field MRI ZOOMit-DWI sequence and conventional single-shot echo-planar imaging (SS-EPI) DWI sequence in the scanning of endometrial carcinoma, and to explore the clinical value of ZOOMit-DWI sequence. METHODS: A total of 37 patients with endometrial carcinoma diagnosed by operation and pathology in the Second Xiangya Hospital of Central South University from July 2019 to May 2021 were collected. All patients were scanned with MRI ZOOMit-DWI sequence and SS-EPI DWI sequence before operation. Two radiologists subjectively evaluated the anatomical details, artifacts, geometric deformation and focus definition of the 2 groups of DWI images. At the same time, the signal intensity were measured and the signal-to-noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) of the 2 DWI sequences were calculated for objective evaluation. The differences of subjective score, objective score and ADC value of the 2 DWI sequences were analyzed. RESULTS: The SNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (301.96±141.85 vs 94.66±41.26), and the CNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (185.05±105.45 vs 57.91±31.54, P<0.05). There was no significant difference in noise standard deviation between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). The subjective score of anatomical detail and focus definition in the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (both P<0.05). The subjective score of artifacts and geometric deformation of ZOOMit-DWI group was significantly lower than that of the SS-EPI DWI group (both P<0.05). ADC had no significant difference between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). CONCLUSIONS The image quality of ZOOMit-DWI is significantly higher than that of conventional SS-EPI DWI. In the MRI DWI examination of endometrial carcinoma, ZOOMit-DWI can effectively reduce the geometric deformation and artifacts of the image, which is more conducive to clinical diagnosis and treatment.
Female ; Humans ; Signal-To-Noise Ratio ; Endometrial Neoplasms/diagnostic imaging* ; Diffusion Magnetic Resonance Imaging/methods* ; Endometrium ; Echo-Planar Imaging/methods* ; Reproducibility of Results

Endometriosis, a heterogeneous, inflammatory, and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus, affects approximately 5-10% of reproductive-age women, causing chronic pelvic pain and reduced fertility. Although the etiology of endometriosis is still elusive, emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris. Peritoneal macrophages and natural killer (NK) cells exhibit deficient cytotoxicity in the endometriotic microenvironment, leading to inefficient eradication of refluxed endometrial fragments. In addition, the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation, which contribute to endometriosis development. Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis, therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression. Here, we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment, focusing on their interactions with microbiota and endocrine and nervous systems, and how these interactions contribute to the etiology and symptomology of endometriosis.
Female ; Humans ; Endometriosis/metabolism* ; Killer Cells, Natural/metabolism* ; T-Lymphocytes/metabolism* ; Estrogens ; Endometrium/metabolism*

Objective: To investigate the value of uterine morphological parameters and endometrial T₂ signal intensity (T₂-SI) in evaluating the degree of the fibrotic repair secondary to endometrial injury. Methods: From Sep. 2018 to Feb. 2023, this study prospectively enrolled 29 patients with fibrotic repair secondary to severe endometrial injury (severe group), 17 patients with fibrotic repair secondary to mild to moderate endometrial injury (mild to moderate group), and 40 healthy women of reproductive age (control group) in Nanjing Drum Tower Hospital. The length of uterine cavity (LUC), length of cervix and isthmus (LCI), width of upper uterine cavity (WUUC) and width of lower uterine cavity (WLUC) were measured using magnetic resonance imaging. T₂-SI of endometrium and subcutaneous fat of buttocks were measured, and endometrial normalized T₂-SI (nT₂-SI; T₂-SI of endometrium/T₂-SI of subcutaneous fat of buttocks) was calculated. Statistical analyses of data were performed using one-way analysis of variance, Mann-Whitney U test, intraclass correlation coefficient, Spearman rho test, area under the receiver operating characteristic curve (AUC). Results: LUC, WUUC, WLUC and endometrial nT₂-SI of severe group [(19.7±3.5) mm, (26.9±6.4) mm, (7.9±1.4) mm, 0.73±0.11, respectively] were significantly lower than those of the control group (all P<0.01), while LCI and WUUC/LUC [(51.3±7.3) mm and 1.38±0.34] were significantly higher than those of the control group (all P<0.001). LUC and WLUC of severe group were significantly lower than those of mild to moderate group [(32.4±5.1) mm and (8.8±1.2) mm; all P<0.05], while LCI and WUUC/LUC were significantly higher than those of mild to moderate group [(41.8±8.6) mm and 0.94±0.16; all P<0.001]. LUC and endometrial nT₂-SI of mild to moderate group were significantly lower than those of the control group [ (32.4±5.1) vs (35.3±3.5) mm, 0.68±0.13 vs 0.80±0.12; all P<0.01]. LUC, WUUC, WLUC and endometrial nT₂-SI were significantly negatively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho:-0.794, -0.441, -0.471 and -0.316, respectively; all P<0.05), while LCI and WUUC/LUC were significantly positively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho: 0.481 and 0.674, respectively; all P<0.05). LUC and WUUC/LUC showed high value in distinguishing severe group from the control group or mild to moderate group (all AUC>0.9, all P<0.001). Conclusion: As noninvasive and quantitative biomarkers, uterine morphological parameters and endometrial nT₂-SI could evaluate the degree of the fibrotic repair secondary to endometrial injury.
Humans ; Female ; Uterus ; Endometrium ; Health Status ; Hospitals ; ROC Curve

OBJECTIVE: To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. METHODS: Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. RESULTS: No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). CONCLUSION A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.
Pregnancy ; Humans ; Female ; Infertility, Female/genetics* ; Endometrium/metabolism* ; Amino Acids/metabolism* ; Gene Expression ; Carnitine ; Alanine/metabolism* ; Valine/metabolism*

Background: The International Endometrial Tumor Analysis (IETA) group developed a catalog of standardized terms to describe findings that may be associated with uterine pathology. However, there is a lack of reliability studies for these descriptors in the literature. Objective: The objective of this study was to estimate interobserver and intraobserver reliability with regard to the IETA group descriptors for endometrial vascular characteristics in women with abnormal uterine bleeding. Materials and Methods: Five nonexpert and five expert raters assessed stored still images of transvaginal ultrasound examinations obtained from 68 women with abnormal uterine bleeding and endometrial thickening. Endometrial vascularity was evaluated using the IETA group descriptors for color flow and vascular pattern. Interobserver agreement was estimated by comparing the assessments of the nonexpert and expert raters. Intraobserver agreement was estimated by repeating the raters’ assessment after 4 weeks. Interrater agreement to the subjective assessment of an expert investigator was also computed. Results and Conclusion The reproducibility of assigning IETA color score is good regardless of the degree of expertise of the rater, although the experts displayed better interobserver reliability (κ = 0.74 vs. 0.57) and intraobserver reliability (κ = 0.84 vs. 0.63). However, the reproducibility of describing IETA vascular patterns is significantly worse for both expert and nonexpert raters in both interobserver reliability (experts κ = 0.49 vs. 0.34) and intraobserver reliability (experts κ = 0.65 vs. 0.42). Both expert and nonexpert raters exhibited acceptable agreement with the reference standard, with experts performing better for both color score (κ = 0.79 vs. 0.70) and vascular pattern (κ = 0.63 vs. 0.44).
Endometrium

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.
Female ; Humans ; Middle Aged ; Adult ; Aged ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; China ; Adenocarcinoma/pathology* ; Endometrium/pathology* ; Gastrointestinal Neoplasms/pathology* ; Biomarkers, Tumor/analysis*

Corded and hyalinized endometrioid carcinoma (CHEC) is a morphologic variant of endo-metrioid adenocarcinoma. The tumor exhibits a biphasic appearance with areas of traditional low-grade adenocarcinoma merging directly with areas of diffuse growth composed of epithelioid or spindled tumor cells forming cords, small clusters, or dispersed single cells. It is crucial to distinguish CHEC from its morphological mimics, such as malignant mixed mullerian tumor (MMMT), because CHECs are usually low stage, and are associated with a good post-hysterectomy prognosis in most cases while the latter portends a poor prognosis. The patient reported in this article was a 54-year-old woman who presented with postmenopausal vaginal bleeding for 2 months. The ultrasound image showed a thickened uneven echo endometrium of approximately 12.2 mm and a detectable blood flow signal. Magnetic resonance imaging revealed an abnormal endometrial signal, considered endometrial carcinoma (Stage Ⅰ B). On hysterectomy specimen, there was an exophytic mass in the uterine cavity with myometrium infiltrating. Microscopically, most component of the tumor was well to moderately differentiated endometrioid carcinoma. Some oval and spindle stromal cells proliferated on the superficial surface of the tumor with a bundle or sheet like growth pattern. In the endometrial curettage specimen, the proliferation of these stromal cells was more obvious, and some of the surrounding stroma was hyalinized and chondromyxoid, which made the stromal cells form a cord-like arrangement. Immunostains were done and both the endometrioid carcinoma and the proliferating stroma cells showed loss of expression of DNA mismatch repair protein MLH1/PMS2 and wild-type p53 protein. Molecular testing demonstrated that this patient had a microsatellite unstable (MSI) endometrial carcinoma. The patient was followed up for 6 months, and there was no recurrence. We diagnosed this case as CHEC, a variant of endometrioid carcinoma, although this case did not show specific β-catenin nuclear expression that was reported in previous researches. The striking low-grade biphasic appearance without TP53 mutation confirmed by immunohistochemistry and molecular testing supported the diagnosis of CHEC. This special morphology, which is usually distributed in the superficial part of the tumor, may result in differences between curettage and surgical specimens. Recent studies have documented an aggressive clinical course in a significant proportion of cases. More cases are needed to establish the clinical behaviors, pathologic features, and molecular profiles of CHECs. Recognition of the relevant characteristics is the prerequisite for pathologists to make correct diagnoses and acquire comprehensive interpretation.
Female ; Humans ; Middle Aged ; Carcinoma, Endometrioid/surgery* ; Endometrial Neoplasms/pathology* ; Endometrium/metabolism* ; Adenocarcinoma/pathology* ; Stromal Cells/pathology*

Female ; Humans ; Uterine Cervical Neoplasms ; Uterus ; Endometrium ; Ichthyosis ; Carcinoma, Squamous Cell ; Squamous Intraepithelial Lesions