Status and treatment of patients with uterine fibroids in hospitals in central China: a retrospective study from 2018 to 2021.

OBJECTIVE: To evaluate the hospitalised patients with uterine fibroids (UFs) and describe treatment patterns in hospital-treated patients in central China from 2018 to 2021. DESIGN: A retrospective analysis. SETTING: The gynaecology departments of class A and class B secondary and tertiary hospitals in Hubei Province, China. PARTICIPANTS: 101 008 patients diagnosed with UFs from 1 January 2018 to 31 December 2021. RESULTS: The hospitalised patients with UFs increased with age, reaching a peak at ages 45-49 years and then gradually decreasing. Among these patients, 19.05% had anaemia symptoms. Women aged 25-29 years were more likely to be treated with laparoscopic myomectomy (62.22%), while women aged 20-24 years tend to choose open myomectomy (34.58%). Women over age 45 years who had entered perimenopause tended to be treated with laparoscopic hysterectomy (64.85% for those aged 65-69 years). Patients with fibroid with moderate-to-severe anaemia mostly chose hysterectomy. As a whole, the proportion of patients who chose laparoscopic hysterectomy was similar to that of patients who chose laparoscopic myomectomy (31.38% vs 31.14%). Only 2.08% of UFs were treated with high-frequency MRI-guided focused ultrasound surgery (MRgFUS). The number of patients who choose laparoscopic surgery or MRgFUS treatment was increasing year by year. After stratifying by hospital grade, we found that women treated at class A tertiary hospitals were more likely to have laparoscopic than open surgery (66.12% vs 31.26%). At class B secondary hospitals, 61.9% of the patients underwent myomectomy. By contrast, hysterectomy was used to treat the majority of patients at class A secondary hospitals and class B tertiary hospitals (57.79% and 57.57%, respectively). Use of MRgFUS was mainly concentrated within class A tertiary hospitals. CONCLUSION: UFs affect mainly women in childbearing period. Most patients chose to receive treatment at class A tertiary hospitals, among which laparoscopic myomectomy was the mainstream surgical method for patients in Hubei Province. TRIAL REGISTRATION NUMBER: NCT05840042.

Automated Detection of Endometrial Polyps from Hysteroscopic Videos Using Deep Learning.

Endometrial polyps are common gynecological lesions. The standard treatment for this condition is hysteroscopic polypectomy. However, this procedure may be accompanied by misdetection of endometrial polyps. To improve the diagnostic accuracy and reduce the risk of misdetection, a deep learning model based on YOLOX is proposed to detect endometrial polyps in real time. Group normalization is employed to improve its performance with large hysteroscopic images. In addition, we propose a video adjacent-frame association algorithm to address the problem of unstable polyp detection. Our proposed model was trained on a dataset of 11,839 images from 323 cases provided by a hospital and was tested on two datasets of 431 cases from two hospitals. The results show that the lesion-based sensitivity of the model reached 100% and 92.0% for the two test sets, compared with 95.83% and 77.33%, respectively, for the original YOLOX model. This demonstrates that the improved model may be used effectively as a diagnostic tool during clinical hysteroscopic procedures to reduce the risk of missing endometrial polyps.

Oxidative stress on vessels at the maternal-fetal interface for female reproductive system disorders: Update.

Considerable evidence shows that oxidative stress exists in the pathophysiological process of female reproductive system diseases. At present, there have been many studies on oxidative stress of placenta during pregnancy, especially for preeclampsia. However, studies that directly focus on the effects of oxidative stress on blood vessels at the maternal-fetal interface and their associated possible outcomes are still incomplete and ambiguous. To provide an option for early clinical prediction and therapeutic application of oxidative stress in female reproductive system diseases, this paper briefly describes the composition of the maternal-fetal interface and the molecular mediators produced by oxidative stress, focuses on the sources of oxidative stress and the signaling pathways of oxidative stress at the maternal-fetal interface, expounds the adverse consequences of oxidative stress on blood vessels, and deeply discusses the relationship between oxidative stress and some pregnancy complications and other female reproductive system diseases.

Vaginal Microbiota Changes in Patients With Premature Ovarian Insufficiency and Its Correlation With Ovarian Function.

Objectives: To reveal the characteristics of vaginal microbiota in premature ovarian insufficiency (POI) patients and their relationship with ovarian function. Materials and Methods: In this case-control study, the vaginal bacterial composition of 30 POI patients and 26 healthy women of comparable age was assessed by 16S rRNA gene sequencing targeting the V3-V4 hypervariable regions. The metabolic functions of vaginal microflora were preliminarily predicted through the PICRUSt2 analysis. Redundancy analysis and Spearman's correlation analyzed the relationships between vaginal microbiota and ovarian function indicators. Results: Actinobacteria, Atopobium, and Gardnerella were significantly increased in POI patients. Their increments were significantly negatively correlated with anti-müllerian hormone (AMH) and inhibin B, and positively correlated with follicle-stimulating hormone (FSH) and luteinizing hormone (LH). While Bifidobacterium was significantly decreased in POI patients. Its relative abundance was significantly positively correlated with AMH and negatively correlated with FSH and LH. Then, POI patients included in this study were divided into POI (25 < FSH ≤ 40) (n = 9) and premature ovarian failure (POF) (FSH > 40) (n = 21) subgroups according to serum FSH levels. Compared with the controls, Firmicutes and Lactobacillus were significantly decreased only in POF (FSH > 40) patients, while no difference was observed in POI (25 < FSH ≤ 40) patients. Lactobacillus was negatively correlated with FSH. Firmicutes was significantly reduced and Actinobacteria was significantly increased in POF (FSH > 40) patients compared with POI (25 < FSH ≤ 40) patients. The key bacterial taxa Gardnerella and Atopobium showed potency in predicting POI. Conclusions: Here we demonstrated significant changes in the vaginal microbiota of POI patients, and these changes were significantly correlated with reduced ovarian reserve, endocrine disruption, and symptoms of perimenopausal syndrome. Differences in vaginal microbiota between POI (25 < FSH ≤ 40) and POF (FSH > 40) patients were also identified. These findings may provide new evidence for the relationship between vaginal microbiota and ovarian function.

Prediction of Endometrial Carcinoma Using the Combination of Electronic Health Records and an Ensemble Machine Learning Method.

Endometrial carcinoma (EC) is a common cause of cancer death in women, and having an early accurate prediction model to identify this disease is crucial. The aim of this study was to develop a new machine learning (ML) model-based diagnostic prediction model for EC. We collected data from consecutive patients between November 2012 and January 2021 at tertiary hospitals in central China. Inclusion criteria included women undergoing endometrial biopsy, dilation and curettage, or hysterectomy. A total of 9 features, including patient demographics, vital signs, and laboratory and ultrasound results, were selected in the final analysis. This new model was combined with three top optimal ML methods, namely, logistic regression, gradient-boosted decision tree, and random forest. A total of 1,922 patients were eligible for final analysis and modeling. The ensemble model, called TJHPEC, was validated in an internal validation cohort and two external validation cohorts. The results showed that the AUC values were 0.9346, 0.8341, and 0.8649 for the prediction of total EC and 0.9347, 0.8073, and 0.871 for prediction of stage I EC. Nine clinical features were confirmed to be highly related to the prediction of EC in TJHPEC. In conclusion, our new model may be accurate for identifying EC, especially in the early stage, in the general population of central China.

Analysis of Ovarian Injury Associated With COVID-19 Disease in Reproductive-Aged Women in Wuhan, China: An Observational Study.

Objective: This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women. Methods: Female COVID-19 patients of reproductive age were recruited between January 28 and March 8, 2020 from Tongji Hospital in Wuhan. Their baseline and clinical characteristics, as well as menstrual conditions, were recorded. Differentials in ovarian reserve markers and sex hormones (including anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], the ratio of FSH to luteinizing hormone [LH], estradiol [E2], progesterone [P], testosterone [T], and prolactin [PRL] were compared to those of healthy women who were randomly selected and individually matched for age, region, and menstrual status. Uni- and multi-variable hierarchical linear regression analyses were performed to identify risk factors associated with ovarian function in COVID-19 women. Results: Seventy eight patients agreed to be tested for serum hormone, of whom 17 (21.79%) were diagnosed as the severe group and 39 (50%) were in the basal level group. Menstrual status (P = 0.55), menstrual volumes (P = 0.066), phase of menstrual cycle (P = 0.58), and dysmenorrhea history (P = 0.12) were similar without significant differences between non-severe and severe COVID-19 women. Significant lower serum AMH level/proportion (0.19/0.28 vs. 1.12 ng/ml, P = 0.003/0.027; AMH ≤ 1.1 ng/ml: 75/70.4 vs. 49.7%, P = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, P < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, P < 0.001/0.001) levels were observed in basal level and the all-COVID-19 group compared with healthy age-matched control. When adjusted for age, menstrual status and parity variations in multivariate hierarchical linear regression analysis, COVID-19 disease was significantly associated with serum AMH (ß = -0.191; 95% CI: -1.177-0.327; P = 0.001), T (ß = 0.411; 95% CI: 11.154-22.709; P < 0.001), and PRL (ß = 0.497; 95% CI: 10.787-20.266; P < 0.001), suggesting an independent risk factor for ovarian function, which accounted for 3.2% of the decline in AMH, 14.3% of the increase in T, and 20.7% of the increase in PRL. Conclusion: Ovarian injury, including declined ovarian reserve and reproductive endocrine disorder, can be observed in women with COVID-19. More attention should be paid to their ovarian function under this pandemic, especially regarding reproductive-aged women. Clinical Trial Number: ChiCTR2000030015.

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China.

BACKGROUND: Recent studies have indicated that females with coronavirus disease 2019 (COVID-19) have a lower morbidity, severe case rate, and mortality and better outcome than those of male individuals. However, the reasons remained to be addressed. METHODS: To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at 3 branches of Tongji Hospital (N = 1902), and analyzed the correlation between menstrual status (n = 509, including 68 from Mobile Cabin Hospital), female hormones (n = 78), and cytokines related to immunity and inflammation (n = 263), and the severity/clinical outcomes in female patients <60 years of age. RESULTS: Nonmenopausal female patients had milder severity and better outcome compared with age-matched men (P < .01 for both). Menopausal patients had longer hospitalization times than nonmenopausal patients (hazard ratio [HR], 1.91 [95% confidence interval {CI}, 1.06-3.46]; P = .033). Both anti-Müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (adjusted HR, 0.146 [95% CI, .026-.824], P = .029 and 0.304 [95% CI, .092-1.001], P = .05, respectively). E2 levels were negatively correlated with interleukin (IL) 2R, IL-6, IL-8, and tumor necrosis factor alpha in the luteal phase (P = .033, P = .048, P = .054, and P = .023) and C3 in the follicular phase (P = .030). CONCLUSIONS: Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19 severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation.

CCL5 secreted by senescent theca-interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis.

As a fundamental aging mechanism, cellular senescence causes chronic inflammation via the senescence-associated secretory phenotype (SASP). Theca-interstitial cells are an essential but little-studied component of follicle development in the ovarian microenvironment. In the present study, we observed significant cellular senescence in theca-interstitial cells and secretion of chemokine (C-C motif) ligand 5 (CCL5) by these cells during aging. Furthermore, we aimed to investigate whether and how senescence-associated secretory phenotype (SASP)-associated CCL5 may be involved in follicle development. Increased levels of CCL5 in the microenvironment of follicles attenuated preantral follicle growth, survival, and estradiol secretion. Oocyte maturation and the expression of zona pellucida 3 and differentiation factor 9 (GDF9) were also inhibited by CCL5. Granulosa cell apoptosis in follicles was promoted by CCL5, accompanied by the phosphorylation of nuclear factor-κB by CCL5 and inhibition of the PI3K/AKT pathway. These results suggest that SASP-associated CCL5 produced by senescent theca-interstitial cells may impair follicle development and maturation during ovarian aging by promoting granulosa cell apoptosis.

Suppression of SEMA6C promotes preantral follicles atresia with decreased cell junctions in mice ovaries.

Mammalian oocytes go through a long and complex developmental process, while acquiring the competencies that are required for fertilization and embryogenesis. Recent studies revealed that the communication between oocytes and granulosa cells (GCs) is a critical process for female follicle development. In the current study, we aimed to study whether and how semaphorin 6C (Sema6c) regulated the cell junctions between oocytes and GCs in mice preantral follicles. The attenuation of SEMA6C expression by siRNA decreased the cell-cell junctions and accelerated follicle atresia in vitro. PI3K-AKT pathway was activated when SEMA6C expression was downregulated. And the LY294002, a PI3K inhibitor, could reverse the effect of low SEMA6C expression on cell junctions in preantral follicles. Our findings revealed that Sema6c was involved in follicle development, and the suppression of SEMA6C led to cell junction defection by activating the PI3K/AKT pathway, which might also provide valuable information for understanding premature ovarian failure and ovarian aging.

Low expression of SEMA6C accelerates the primordial follicle activation in the neonatal mouse ovary.

The primordial follicle assembly, activation and the subsequent development are critical processes for female reproduction. A limited number of primordial follicles are activated to enter the growing follicle pool each wave, and the primordial follicle pool progressively diminishes over a woman's life-time. The number of remaining primordial follicles represents the ovarian reserve. Identification and functional investigation of the factors involved in follicular initial recruitment will be of great significance to the understanding of the female reproduction process and ovarian ageing. In this study, we aimed to study whether and how semaphorin 6C (Sema6c) regulated the primordial follicle activation in the neonatal mouse ovary. The attenuation of SEMA6C expression by SiRNA accelerated the primordial follicle activation in the in vitro ovary culture system. PI3K-AKT-rpS6 pathway was activated when SEMA6C expression was down-regulated. And the LY294002 could reverse the effect of low SEMA6C expression on primordial follicle activation. Our findings revealed that Sema6c was involved in the activation of primordial follicles, and the down-regulation of SEMA6C led to massive primordial follicle activation by interacting with the PI3K-AKT-rpS6 pathway, which might also provide valuable information for understanding premature ovarian failure and ovarian ageing.

Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes.

Circular RNAs (circRNAs) are a unique class of endogenous RNAs which could be used as potential diagnostic and prognostic biomarkers of many diseases. Our study aimed to investigate circRNA profiles in human granulosa cells (GCs) during maternal aging and to uncover age-related circRNA variations that potentially reflect decreased oocyte competence. CircRNAs in GCs from in vitro fertilization (IVF) patients with young age (YA, ≤ 30 years) and advanced age (AA, ≥ 38 years) were profiled by microarray, and validated in 20 paired samples. The correlation between circRNAs expression and clinical characteristics was analyzed in additional 80 samples. Chip-based analysis revealed 46 up-regulated and 11 down-regulated circRNAs in AA samples (fold change > 2.0). Specifically, circRNA_103829, circRNA_103827 and circRNA_104816 were validated to be up-regulated, while circRNA_101889 was down-regulated in AA samples. After adjustment for gonadotropin treatment, only circRNA_103827 and circRNA_104816 levels were positively associated with maternal age (partial r = 0.332, P = 0.045; partial r = 0.473, P = 0.003; respectively). Moreover, circRNA_103827 and circRNA_104816 expressions in GCs were negatively correlated with the number of top quality embryos (r = -0.235, P = 0.036; r = -0.221, P = 0.049; respectively). Receiver operating characteristic (ROC) curve analysis indicated that the performance of circRNA_103827 for live birth prediction reached 0.698 [0.570-0.825], with 77.2% sensitivity and 60.9% specificity (P = 0.006), and that of circRNA_104816 was 0.645 [0.507-0.783] (P = 0.043). Bioinformatics analysis revealed that both circRNAs were potentially involved in glucose metabolism, mitotic cell cycle, and ovarian steroidogenesis. Therefore, age-related up-regulation of circRNA_103827 and circRNA_104816 might be potential indicators of compromised follicular micro-environment which could be used to predict IVF prognosis, and improve female infertility management.

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway.

Follicular atresia is the main process responsible for the loss of follicles and oocytes from the ovary, and it is the root cause of ovarian aging. Apoptosis of granulosa cells (GCs) is the cellular mechanism responsible for follicular atresia in mammals. Recent advances have highlighted fundamental roles for EGR1 in age-related diseases via the induction of apoptosis. In the present study, we found that the expression of EGR1 was significantly increased in aged mouse ovaries compared with young ovaries. Immunohistochemical analysis revealed strongly positive EGR1 staining in atretic follicles, especially in apoptotic granulosa cells. We further showed that EGR1 up-regulation in mouse primary granulosa cells inhibited cell proliferation and promoted apoptosis. In addition, the promotion of apoptosis in GCs by EGR1 increases over time and with reactive oxygen species (ROS) stimulation. Our mechanistic study suggested that EGR1 regulates GC apoptosis in a mitochondria-dependent manner and that this mainly occurs through the NF-κB signaling pathway. In conclusion, our results suggested that age-related up-regulation of EGR1 promotes GC apoptosis in follicle atresia during ovarian aging.

Down-regulation of coxsakie and adenovirus receptor during embryo implantation.

In this study, real-time PCR and immunohistochemistry were used to detect coxsakie and adenovirus receptor (CAR) expression. Both localization and quantity were evaluated in the uteri obtained at days post coitus (dpc) 2.5, 4.5, 6.5, 8.5. Outcome of PCR was assessed by 2(-ΔΔCt) method. Image Pro-Plus 6.0 software was used for quantifying mean density of CAR expression in immunohistochemical sections. We found relatively weak CAR expression in the mouse uteri during implantation window. PCR and immunohistochemistry revealed highest CAR expression was detected on dpc 2.5 followed by down-regulation of CAR at dpc 4.5 and 6.5 (with significant difference). At dpc 8.5, CAR expression was increased slightly again. It is concluded that during implantation, the expression of CAR mRNA and protein is declined, resulting in the impairment of tight junction between cavity epithelium cells. After implantation window closure, CAR appears again to maintain epithelium stability. CAR might play an important role during embryo implantation procedure.