BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Humans ; Female ; Hysteroscopy/methods* ; Endometrial Neoplasms/therapy* ; Fertility Preservation/methods* ; Consensus ; China ; Endometrium/surgery* ; Hysterectomy

Humans ; Female ; Uterine Cervical Neoplasms/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Consensus ; Prognosis ; Neoplasm Staging ; Cervix Uteri/pathology*

Intrauterine adhesion(IUA) is a common gynecological disease that is difficult to treat, and there is a lack of specific effective drugs and measures to prevent endometrial fibrosis. In this study, the mechanism of endometrial oxidative stress and fibrosis regulation was studied in an IUA rat model constructed by Bushen Huoxue Formula intervention of mechanical injury combined with infection. A total of 72 SPF SD female rats aged 8-10 weeks were randomly divided into blank control group, model control group, low-dose, medium-dose, and high-dose groups of Bushen Huoxue Formula, and estrogen groups. The rats in the estrous cycle of the model control group and the positive control group were simulated with surgical injury and infection, and the sham operation group was treated with on-off abdominal treatment. After successful modeling, the model control group was administered intragastrically with purified water of 15 μL·g~(-1) every day. The low-dose group was administered intragastrically with Bushen Huoxue Formula of 7.8 g·kg~(-1); the medium-dose group was administered intragastrically with Bushen Huoxue Formula of 15.6 g·kg~(-1), and the high-dose group was administered intragastrically with Bushen Huoxue Formula of 31.2 g·kg~(-1). The estrogen group was administered intragastrically with estradiol valerate of 4.2 mg·kg~(-1). After continuous intervention for 28 days, all rats were deprived of water and killed to collect blood and tissue. Hematoxylin-eosin(HE) staining calculated the number of uterine glands; Masson staining calculated the area of uterine collagen fibers. Combined with HE and Masson staining, semi-quantitative scores were performed on the degree of endometrial fibrosis. Immunohistochemistry was performed to detect the vascular endothelial growth factor(VEGF), stromal cell-derived factor-1(SDF-1), and transforming growth factor-β1(TGF-β1) expression in rats' uterine tissue. Enzyme-linked immunosorbent assay(ELISA) dected angiopoietin 1(IFN-γ), interleukin-1α(IL-1α), TGF-β1, tumor necrosis factor-α(TNF-α), collagen type Ⅳ(Ⅳ-Col), leukemia inhibitory factor(LIF), superoxide dismutase(SOD)、glutathione peroxidase(GSH-Px);The mRNA expressions of Smad2, Smad3, adisintegrin and metalloproteinase(ADAM17) and TGF-β1 were determined by qPCR. Notch and ADAM17 protein expression in rat uterus were determined by Western blot. The results showed that the area of uterine fibrosis was significantly reduced and the conditions of edema and adhesion were effectively alleviated after high-dose intervention of Bushen Huoxue Formula. The levels of inflammatory factors and Ⅳ-Col were significantly decreased, and the levels of LIF and antioxidant enzymes were significantly increased. The mRNA expressions of Smad2, Smad3, ADAM17 and TGF-β1 were significantly down-regulated. Immunohistochemical results showed that Bushen Huoxu Formula could effectively increase the positive expression of SDF-1 and reduce the positive expression of VEGF and TGF-β1. Western blot results showed that the protein expressions of Notch and ADAM17 in high-dose, medium-dose and low-dose of Bushen Huoxu Formula groups were significantly down-regulated in a dose-dependent manner. These results suggest that Bushen Huoxue Formula may inhibit fibrosis process through ADAM17/Notch signaling pathway, suggesting that Bushen Huoxuet Formula is one of the potential therapeutic methods for IUA.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Endometrium/pathology* ; Rats ; Fibrosis/metabolism* ; Oxidative Stress/drug effects* ; Humans ; Uterine Diseases/genetics* ; Vascular Endothelial Growth Factor A/genetics*

Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans ; Toll-Like Receptors/genetics* ; Female ; Papillomavirus Infections/genetics* ; Papillomaviridae/immunology* ; Persistent Infection/genetics* ; Uterine Cervical Neoplasms/immunology* ; Animals ; Medicine, Chinese Traditional ; Cervix Uteri/immunology* ; Human Papillomavirus Viruses

Congenital malformations of the uterus are rare. Pregnancies in these uterine abnormalities are usually associated with poor reproductive outcomes such as recurrent pregnancy losses, preterm birth and intrauterine growth restriction. Presented here is the case of a 21-year old G2P1(1001), who was diagnosed intraoperatively with a septate bicornuate uterus during her second Cesarean delivery. She had to undergo abdominal delivery for both her pregnancies due to malpresentation, and delivered live healthy babies with no gross structural defects. Pathophysiology and classification of congenital uterine malformations are discussed in the case, as well as the diagnostics and management for such conditions.
Human ; Female ; Young Adult: 19-24 yrs old ; Bicornuate uterus ; Septate Uterus ; Uterine anomalies

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

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

Retained products of conception (RPOC) represent a common pregnancy-related condition that may lead to complications such as abnormal uterine bleeding, infection, secondary arteriovenous fistula, intrauterine adhesions, and infertility. Currently, the main clinical treatments for RPOC include surgical intervention, medical therapy, and expectant management, sometimes supplemented by high-intensity focused ultrasound or uterine artery embolization when necessary. However, no standardized treatment guidelines exist. Medical and expectant management may help some patients avoid or reduce the need for surgery, though these approaches often involve a prolonged disease course. While surgery yields rapid results, patients with large lesions may require multiple procedures, increasing the risk of endometrial damage and intrauterine adhesions. There is still a lack of robust evidence-based guidance for selecting the optimal or individualized treatment approach. This review explores recent advances in the management of RPOC, with an emphasis on strategies that effectively preserve the endometrium, safeguard fertility, and support more precise, minimally invasive, and efficient personalized treatment.
Humans ; Female ; Pregnancy ; Placenta, Retained/surgery* ; Uterine Artery Embolization/methods* ; Tissue Adhesions ; Endometrium ; High-Intensity Focused Ultrasound Ablation

OBJECTIVES: Transcervical resection of adhesions (TCRA) under hysteroscopy is the mainstay treatment for intrauterine adhesions (IUA), but its effectiveness varies depending on the surgical approach. This study aims to investigate the impact of different surgical techniques on endometrial repair and pregnancy outcomes in patients with secondary infertility and moderate-to-severe IUA. METHODS: A retrospective analysis was conducted on 225 patients who underwent TCRA followed by in vitro fertilization and embryo transfer between January 2021 and December 2022. Patients were grouped based on the surgical method: A cold knife group (n=127) and an electrosurgical group (n=98). Adhesions were separated using either cold knife or electrosurgical instruments. Postoperative visualization of uterine angle and tubal ostia, endometrial restoration, vascular endothelial growth factor (VEGF) expression in adhesion tissues, and clinical pregnancy outcomes were compared. Univariate and multivariate Logistic regression analyses were performed to identify factors influencing pregnancy outcomes. A LightGBM model was constructed to predict pregnancy outcomes. RESULTS: Compared with the electrosurgical group, patients in the cold knife group had significantly greater postoperative endometrial thickness [(8.86±0.53) mm vs (8.10±0.87) mm, P<0.05], higher live birth rates (64.57% vs 30.61%, P<0.05), and lower VEGF expression (1.31±0.09 vs 1.53±0.16, P<0.05). Logistic regression analyses identified age, number of visible tubal ostia postoperatively, and surgical method as significant factors affecting pregnancy outcomes (P<0.05). The LightGBM model based on surgical method had an area under the curve (AUC) of 0.882 (0.838-0.926), with internal validation AUC of 0.817 (0.790-0.840). CONCLUSIONS Cold knife surgery promotes faster recovery of the endometrial microenvironment and earlier improvement of fertility in patients with secondary infertility and IUA Surgical method is a key factor influencing pregnancy outcomes, and the LightGBM model based on surgical approach shows good predictive performance for pregnancy outcomes in patients with moderate-to-severe IUA.
Humans ; Female ; Pregnancy ; Tissue Adhesions/surgery* ; Retrospective Studies ; Adult ; Pregnancy Outcome ; Uterine Diseases/surgery* ; Hysteroscopy/methods* ; Infertility, Female/etiology* ; Electrosurgery/methods* ; Fertilization in Vitro ; Endometrium/surgery* ; Embryo Transfer ; Vascular Endothelial Growth Factor A/metabolism*