Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

PURPOSE: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. METHODS: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. RESULTS: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed. CONCLUSIONS: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Progress of the study of pericytes and their potential research value in adenomyosis.

Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.

Risk factors associated with changes in serum anti-Müllerian hormone levels before and after laparoscopic cystectomy for endometrioma.

Background: The objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements. Methods: Anti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change. Results: Pretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p<0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p<0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p<0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p>0.05). Conclusion: Laparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.

The pathogenesis of endometriosis and adenomyosis: insights from single-cell RNA sequencing†.

Endometriosis and adenomyosis are two similar gynecological diseases that are characterized by ectopic implantation and the growth of the endometrial tissue. Previous studies have reported that they share a common pathophysiology in some respects, such as a similar cellular composition and resistance to the progestogen of lesions, but their underlying mechanisms remain elusive. Emerging single-cell ribonucleic acid sequencing (scRNA-seq) technologies allow for the dissection of single-cell transcriptome mapping to reveal the etiology of diseases at the level of the individual cell. In this review, we summarized the published findings in research on scRNA-seq regarding the cellular components and molecular profiles of diverse lesions. They show that epithelial cell clusters may be the vital progenitors of endometriosis and adenomyosis. Subclusters of stromal cells, such as endometrial mesenchymal stem cells and fibroblasts, are also involved in the occurrence of endometriosis and adenomyosis, respectively. Moreover, CD8+ T cells, natural killer cells, and macrophages exhibit a deficiency in clearing the ectopic endometrial cells in the immune microenvironment of endometriosis. It seems that the immune responses are activated in adenomyosis. Understanding the immune characteristics of adenomyosis still needs further exploration. Finally, we discuss the application of findings from scRNA-seq for clinical diagnosis and treatment. This review provides fresh insights into the pathogenesis of endometriosis and adenomyosis as well as the therapeutic targets at the cellular level.

Clinical features of patients with previous spontaneous rupture of ovarian endometrioma operated electively: a case-control study.

BACKGROUND: The aim of the study is to investigate the proportion and clinical features of previous spontaneously ruptured ovarian endometrioma among women who underwent elective surgery for endometrioma. METHODS: This retrospective study was based on a cohort of elective surgeries for endometrioma performed by the same gynecologic team at Peking Union Medical College Hospital from January 2017 to October 2022. Patients diagnosed with previous spontaneously ruptured endometrioma during elective surgery were enrolled in the ruptured group. In the same cohort, patients with unruptured endometrioma treated during the same period were selected as the unruptured group by 1:2 matching according to age. Demographic and clinical information were collected and compared between two groups. RESULTS: A total of 422 patients in the cohort were diagnosed with endometrioma. There were 38 patients (9.0%) in ruptured group and 76 patients in unruptured group. All enrolled participants were treated by laparoscopic surgery. In ruptured group, 86.8% patients had a history of acute abdominal pain, which was only 13.2% in unruptured group (P < 0.001). Compared to unruptured group, patients diagnosed with ruptured endometrioma had a lower BMI (P = 0.021), larger maximum diameter of endometrioma (P = 0.040), higher proportion of cul-de-sac partial obliteration rather than complete obliteration (P = 0.003). CONCLUSIONS: Spontaneous rupture of endometrioma is not rare. The proportion of spontaneous rupture of endometrioma in our study was higher than that reported in the literatures. In women with endometrioma, the onset of acute abdominal pain should be considered a rupture of cyst, especially in patients with big cysts.

Effects of localization of uterine adenomyosis on clinical features and pregnancy outcome.

The purpose of this study was to implore the association among clinical features, long-term fertility outcomes and the anatomical location of adenomyosis identified by ultrasound. We collected data of non-pregnant patients between 20 and 40 years old who had undergone surgical exploration for benign gynecological conditions at our institution between January 2010 and December 2017. A total of 158 women met the inclusion criteria and were allocated into three groups according to the ultrasound-determined adenomyosis anatomical location: anterior (Group A), posterior (Group B), both posterior and anterior (Group C). 44.3% (70/158) adenomyosis was located at the posterior side. History of miscarriage and parity were significantly higher in Group C (p = 0.036 and 0.001 respectively). Group C also had a higher concurrence rate of ovarian endometrioma (OEM) (80.4%, p = 0.002), pelvic adhesion (80.4%, P = 0.003) and the revised American Fertility Society (rAFS) Score (median64, range2-100, P < 0.001), while a significantly lower rate of concurrent peritoneal endometriosis (P = 0.01). Group B showed a relative higher rate of coexistent heavy menstrual bleeding (28.6%, p = 0.04) and oviduct obstruction (24.3%, P = 0.038). Group A had a higher proportion of coexistent leiomyoma (53.1%, P = 0.002). There were no significant differences between group A, B, and C in terms of pain symptoms, endometrial polyps, operation time, and endometriosis fertility index score and other basic characters (p > 0.05). During the follow-up, 59.2% (61/103) patients had clinical pregnancies, and 26.2% (16/61) of them experienced pregnancy loss. Total in vitro fertilization and embryo transfer pregnancy rate was 64.6% (42/65) and spontaneous pregnancy rate was 50.0% (19/38). The Kaplan-Meier curves demonstrated significant lower cumulative pregnancy rate in Group C than Group A and Group B (p = 0.01). Severe obstetric complications such as placenta previa, placenta accreta, preeclampsia, and preterm birth were only found in women with adenomyosis located in the posterior side. In conclusion, types of adenomyosis based on sonographic location had different clinical features and pregnancy outcome. Patients with adenomyosis lesion in both anterior and posterior sides had higher combination of OEM, pelvic adhesion and rAFS score.

Exploring the cellular and molecular differences between ovarian clear cell carcinoma and high-grade serous carcinoma using single-cell RNA sequencing and GEO gene expression signatures.

The two most prevalent subtypes of epithelial ovarian carcinoma (EOC) are ovarian clear cell carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC). Patients with OCCC have a poor prognosis than those with HGSC due to chemoresistance, implying the need for novel treatment target. In this study, we applied single-cell RNA sequencing (scRNA-seq) together with bulk RNA-seq data from the GEO (Gene Expression Omnibus) database (the GSE189553 dataset) to characterize and compare tumor heterogeneity and cell-level evolution between OCCC and HGSC samples. To begin, we found that the smaller proportion of an epithelial OCCC cell subset in the G2/M phase might explain OCCC chemoresistance. Second, we identified a possible pathogenic OCCC epithelial cell subcluster that overexpresses LEFTY1. Third, novel biomarkers separating OCCC from HGSC were discovered and subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) was preferentially expressed in OCCC over HGSC, while S100 calcium-binding protein A2 (S100A2) was detected less frequently in OCCC than in HGSC. In addition, we discovered that metabolic pathways were enriched in the epithelial compartment of the OCCC samples. In vitro experiments verified that inhibition of oxidative phosphorylation or glycolysis pathways exerted direct antitumor effects on both OCCC and HGSC cells, while targeting glutamine metabolism or ferroptosis greatly attenuated chemosensitivity only in OCCC cells. Finally, to determine whether there were any variations in immune cell subsets between OCCC and HGSC, data from scRNA-seq and mass cytometry were pooled for analysis. In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC.

The role of levonorgestrel-releasing intrauterine system for recurrence prevention after conservative surgery among patients with coexistent ovarian endometrioma and diffuse adenomyosis: A retrospective case control study with long-term follow up.

BACKGROUND: When ovarian endometrioma coexist with adenomyosis, the risk of postoperative recurrence increased. How is the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on symptomatic recurrence for those patients was unknown. METHODS: This study retrospectively analyzed 119 women with coexistent endometrioma and diffuse adenomyosis who received laparoscopic excision of pelvic endometriosis from January 2009 to April 2013. Women were categorized into two groups: intervention group with LNG-IUS and control group with expectant observation after surgery. Data were compared in terms of preoperative history, laboratory and intraoperative findings, and clinical outcomes during follow-up, including pain regression, changes in uterine volume and recurrence. RESULTS: During a median 79 months (range, 6-107) of follow-up, patients with LNG-IUS experienced a significantly lower symptomatic recurrence of either ovarian endometrioma or dysmenorrhea (11.1% vs. 31.1%, p = 0.013), compared with women under expectant observation by Kaplan-Meier survival analysis (χ2 = 5.448, p = 0.020) and Cox univariate assessment (hazard ratio of 0.336, 95% confidence interval 0.128-0.885, p = 0.027). Patients treated with LNG-IUS demonstrated a more prominent reduction in uterine volume (-14.1 ± 20.9 vs. 8.7 ± 48.8, p = 0.003) and higher percentage of complete pain remission (95.6% vs. 86.5%). For multivariate analysis, use of LNG-IUS (aHR 0.159, 95%CI 0.033-0.760, p = 0.021) and severity of dysmenorrhea (aHR 4.238, 95%CI 1.191-15.082, p = 0.026) were two independent factors associated with overall recurrence. CONCLUSION: Postoperative insertion of LNG-IUS may prevent recurrence in symptomatic women with comorbidity of ovarian endometrioma and diffuse adenomyosis.

Clinical presentation of perineal endometriosis and prognostic nomogram after surgical resection.

BACKGROUND: This retrospective study evaluated the clinical features of perineal endometriosis (PEM) and established a prognostic nomogram for recurrence probability in patients treated with surgical resection. METHODS: This study enrolled 130 PEM patients who had received surgical treatment in Peking Union Medical College Hospital (PUMCH) between January 1992 and September 2020. We collected their clinical features and conducted outpatient or telephone follow-up. The predictive nomogram was constructed based on 104 patients who had completed follow-up by July 2021. The Cox proportional hazards regression model was used to evaluate the prognostic effects of multiple clinical parameters on recurrence. The Index of concordance (C-index) and calibration curves were used to access the discrimination ability and predictive accuracy of the nomogram respectively, and the results were further validated via bootstrap resampling. Calculating the area under the curve (AUC) via risk scores of patients aimed to further access the predictive power of the model. In addition, the survival curve was depicted using Kaplan-Meier plot and compared by log-rank method. RESULTS: Most PEM patients had been symptomatic for 24-48 months before the lesion resection. With a median 99.00 (interquartile range: 47.25-137.50) months of postoperative observation, there were 16 (15.1%) out of 104 cases who finished follow-up reported symptomatic recurrence. On multivariate analysis of derivation cohort, multiple lesions, microscopically positive margin (mPM) and anal sphincter involvement (ASI) were selected into the nomogram. The C-index of the nomogram for predicting recurrence was 0.84 (95% CI 0.77-0.91). The calibration curve for probability of recurrence for 36, 60 and 120 months showed great agreement between prediction by nomogram and actual observation. Furthermore, the AUCs of risk score for 36, 60 and 120 months were 0.89, 0.87 and 0.82 respectively. CONCLUSIONS: PEM is a rare kind of endometriosis and surgery is the primary treatment. Multiple lesions and ASI are independent risk factors for postoperative recurrence, and wide resection with more peripheral tissue could be preferred. The proposed nomogram resulted in effective prognostic prediction for PEM patients receiving surgical excision. In addition, this predictive nomogram needs external data sets to further validate its prognostic accuracy in the future.

Oral gonadotropin-releasing hormone antagonists for treating endometriosis-associated pain: a systematic review and network meta-analysis.

OBJECTIVE: To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of endometriosis-associated pain. DESIGN: Systematic review and network meta-analysis. SETTING: Not applicable. PATIENT(S): Premenopausal women with endometriosis who had experienced moderate or severe pain. INTERVENTION(S): The Web of Science, Embase, Scopus, and MEDLINE were searched until April 10, 2022. Only randomized controlled trials were included. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool 2. A Bayesian random-effects network meta-analysis was used to perform indirect comparisons. I2 was used to assess the global heterogeneity. Relative treatment estimates were performed. Treatment ranking was performed through the surface under the cumulative ranking curve. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. MAIN OUTCOME MEASURE(S): Endometriosis-associated pain, dysmenorrhea, dyspareunia, and noncyclic pelvic pain reduction. RESULT: (s): Five studies and 6 randomized controlled trials, including a total of 2,796 women and 10 different doses of oral GnRH antagonist treatments, were eligible for inclusion. All studies were considered to have a low risk of bias. Almost all efficacy- and safety-related outcomes showed a dose-response relationship. Regarding endometriosis-associated pain, the top 3 treatments were elagolix 400 mg, linzagolix 75 mg, and linzagolix 200 mg, with mean differences of -1.26 (95% credible interval [CrI], -1.70 to -0.79), -0.98 (95% CrI, -1.84 to -0.15), and -0.98 (95% CrI, -1.90 to -0.064), respectively. The top 3 treatments to decrease dysmenorrhea were relugolix 40 mg, elagolix 400 mg, and relugolix 20 mg, with mean differences of -1.60 (95% CrI, -2.07 to -1.14), -1.25 (95% CrI, -1.56 to -0.95), and -1.10 (95% CrI, -1.59 to -0.62), respectively. However, only high-dose treatments were significantly associated with most quality of life- and adverse effect-related outcomes. Relugolix 40 and 20 mg and elagolix 400 mg, with odds ratios of 6.88 (95% CrI, 2.18-24.58), 1.60 (95% CrI, 0.62-4.13), and 1.85 (95% CrI, 1.05-3.30), had a significantly increased incidence of adverse events. CONCLUSION: (s): Oral GnRH antagonists are effective for endometriosis-associated pain and dysmenorrhea and the patient global impression. The incidence of ovarian hypoestrogenic effects in a short-term duration was significant in a dose-effect response, particularly the highest dose. CLINICAL TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews registration number CRD42022332904.

Does Dysmenorrhea Affect Clinical Features and Long-Term Surgical Outcomes of Patients With Ovarian Endometriosis? A 12-Year Retrospective Observational Cohort Study.

Background: To examine and compare the differences in clinical characteristics and long-term postoperative outcomes of ovarian endometriomas (OMA) patients with and without dysmenorrhea, including data from at least 8 years of postoperative follow-up examinations. Methods: Retrospective analysis of 334 OMA patients, including their demographic and clinical data. Long-term follow-up record was also collected. All laparoscopic cystectomy procedures were performed by the same surgeon at Peking Union Medical College Hospital between January 2009 and April 2013. Patients were divided into the dysmenorrhea and non-dysmenorrhea groups to perform the analysis of their preoperative characteristics, relevant surgical findings, and postoperative outcomes at the follow-up. Results: Out of 334 OMA patients, 257 (76.9%) patients were allocated to the dysmenorrhea group, while the rest 77 (23.1%) patients were included in the non-dysmenorrhea group. Compared with the dysmenorrhea group, the non-dysmenorrhea group exhibited a reduced proportion of chronic pelvic pain (CPP) (P = 0.003), dyspareunia (P < 0.001), tenesmus (P < 0.001), concurrency of deep infiltrating endometriosis (DIE) (P < 0.001), and adenomyosis (P = 0.032). Preoperative infertility was significantly higher in the dysmenorrhea group (P = 0.001). The mean operating time in the dysmenorrhea vs. the non-dysmenorrhea group was 68.0 vs. 56.0 min (P < 0.001). According to the revised American Fertility Society (rAFS) scoring system, the mean scores of the two groups were 52.1 vs. 44.6 (P = 0.033). During follow-up, the dysmenorrhea group showed a higher rate of disease relapse (P < 0.001). A minimum postoperative follow-up period of 8 years was required to evaluate the pregnancy outcomes. Successful pregnancies were identified in 97/257 (37.7%) cases in the dysmenorrhea group and 36/77(46.8%) cases in the non-dysmenorrhea group (P = 0.157), respectively. Though the dysmenorrhea group had a higher rate of postoperative infertility, differences were not significant between the two groups. Conclusions: Compared with the dysmenorrhea group, OMA patients without dysmenorrhea exhibited lower proportions of CPP, dyspareunia, tenesmus, lower concurrency of DIE and adenomyosis, shorter mean operating time, lower mean rAFS scores, and lower infertility rates. During the long-term follow-up, a lower recurrence rate was observed in the non-dysmenorrhea group. Regarding fertility outcomes, non-dysmenorrhea patients had a higher likelihood of successful pregnancy after surgery. Postoperative management needs to be evaluated separately according to dysmenorrhea pathology.

The Development of Predictive Nomogram of Recurrence for Patients With Endometrioma After Cystectomy Who Were Younger Than 45 Years Old and Received Postoperative Therapy.

Objective: This study aimed to establish an effective prognostic nomogram for the postoperative recurrence of endometrioma or endometriosis-related pain for patients with endometrioma after long-term follow-up, who were younger than 45 years old and received postoperative therapy. Methods: The predictive nomogram was based on 323 patients who underwent cystectomy for endometrioma at Perking Union Medical College Hospital from January 2009 to April 2013, and the last follow-up occurred in September 2018. We collected information on all included patients, including preoperative data, intraoperative data, and long-term follow-up data after surgery. The Cox proportional hazards regression model was used to evaluate the prognostic effects of multiple clinical parameters on recurrence. The survival curve was depicted based on Kaplan-Meier method and compared by log-rank method. The Index of concordance (C-index) and calibration curves were used to access the discrimination ability and predictive accuracy of the nomogram respectively, and the results were further validated via bootstrap resampling. In addition, calculating the area under the curve (AUC) via risk scores of patients aimed to further access the prediction ability of the model. Results: On multivariate analysis of derivation cohort, independent factors for recurrence such as dysmenorrhea degree, sum of both cyst diameters, presence of adenomyosis, and other essential factors for recurrence such as age at surgery, presence of uterine fibroids were all selected into the nomogram. The C-index of the nomogram for predicting recurrence was 0.683 (95% CI, 0.610- 0.755). The calibration curve for probability of recurrence for 7 years and 9 years showed great agreement between prediction by nomogram and actual observation. Furthermore, the AUCs of risk score for 7-year and 9-year were 0.680 and 0.790 respectively. Conclusion: This research tried to develop the predictive nomogram of recurrence for patients with endometrioma after cystectomy. The C-index and calibration curve of nomogram, as well as the AUC of the nomogram was potential to predict the recurrence probability. In addition, this predictive nomogram needs external data sets to further validate its prognostic accuracy in the future.

Technique integration of single-cell RNA sequencing with spatially resolved transcriptomics in the tumor microenvironment.

BACKGROUND: The tumor microenvironment contributes to tumor initiation, growth, invasion, and metastasis. The tumor microenvironment is heterogeneous in cellular and acellular components, particularly structural features and their gene expression at the inter-and intra-tumor levels. MAIN TEXT: Single-cell RNA sequencing profiles single-cell transcriptomes to reveal cell proportions and trajectories while spatial information is lacking. Spatially resolved transcriptomics redeems this lack with limited coverage or depth of transcripts. Hence, the integration of single-cell RNA sequencing and spatial data makes the best use of their strengths, having insights into exploring diverse tissue architectures and interactions in a complicated network. We review applications of integrating the two methods, especially in cellular components in the tumor microenvironment, showing each role in cancer initiation and progression, which provides clinical relevance in prognosis, optimal treatment, and potential therapeutic targets. CONCLUSION: The integration of two approaches may break the bottlenecks in the spatial resolution of neighboring cell subpopulations in cancer, and help to describe the signaling circuitry about the intercommunication and its exact mechanisms in producing different types and malignant stages of tumors.

Clinical Features and Long-Term Outcomes After Laparoscopic Surgery in Patients Co-existing With Endometriosis and Adenomyosis.

Objective: To investigate the difference of clinical features and outcomes between EM patients with and without AM after following up for at least 6 years after surgery. Methods: We retrospectively analyzed 358 EM patients who had a minimum of 6 years follow-up after laparoscopic cystectomy, which was performed by one single doctor at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into AM group and non-AM group and analysis was performed in preoperative characteristics, surgical findings and postoperative outcomes during follow-up. Results: A total of 358 EM patients were recruited, of which 142 (39.7%) were in the AM group and the rest 216 (60.3%) in the non-AM group. Between the two group, the mean age was 34.6 vs. 32.2 years (P < 0.001). The mean operating time in the AM and non-AM group was 73.2 vs. 61.9 min (P < 0.001). According to the revised AFS classification, the mean score of the two group were 60.3 vs. 45.5 (P < 0.001). At the end of the follow-up, though the AM group was with higher rate of disease relapse, yet no significant difference was found between the two groups in statistical comparison (34/142 [23.9%] vs. 34/216 [15.7%], P = 0.053). With a minimum follow-up of 6 years after laparoscopic cystectomy, failed and successful pregnancy were seen in 107/142(75.4%) and 35/142 (24.6%) patients in the AM group vs. 114/216(52.8%) and 102/216 (47.2%) patients in the non-AM group (P < 0.05). As for the successfully pregnant patients, live births, including spontaneous pregnancy and IVF-ET, were seen in 34/35 (97.1) vs. 99/102 (97.1) patients between AM and non-AM groups, while others ended in spontaneous abortion. No significant associations were found between the two groups in infertility, leiomyoma presence, the size of ovarian endometrioma, type of deep infiltrating endometriosis (DIE) or type of recurrence (P > 0.05). Conclusion: Compared with non-AM group, EM patients with concurrent AM may have higher age, longer mean operating time and higher mean AFS score. In terms of fertility outcomes, patients in the AM group were with lower likelihood of pregnancy after surgery during the long-time follow-up.

Pregnancy outcomes in women with infertility and coexisting endometriosis and adenomyosis after laparoscopic surgery: a long-term retrospective follow-up study.

BACKGROUND: Adenomyosis (AM) and endometriosis (EM) often coexist. Laparoscopic surgery is one of the main methods for diagnosing and treating these conditions. This study aims to investigate the pregnancy outcomes of women with infertility with both AM and EM after laparoscopic surgery and to identify the relevant associated factors. METHODS: This is a retrospective study involving women with infertility diagnosed with EM and AM. All patients had undergone laparoscopic surgery and were divided into two groups according to their pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected. RESULTS: A total of 226 female patients with infertility diagnosed with both AM and EM underwent laparoscopic surgery. Of these, a total of 176 patients completed follow-up. Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The clinical pregnancy and live birth rates were 67.4 and 55.11%, respectively. One hundred thirty-five patients received in vitro fertilization (IVF), with 70 (51.85%) of these patients having live births. Age, endometrioma size, and uterus size were significantly lower in those who had a successful delivery. There was no statistically significant difference in symptoms, except that those who achieved live birth had a lower rate of anaemia (13.40% vs. 25.32%, p = 0.044). The group that did not proceed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (p < 0.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434-0.932, p = 0.020) and endometriosis fertility index (EFI) (OR: 1.299, 95% CI: 1.101-1.531, p = 0.002) were significantly correlated with live birth in the multivariable analysis. CONCLUSIONS: Endometriosis and adenomyosis appear to have an adverse effect on pregnancy outcome. These might be related to the size of the uterus and EFI. Obstetricians and gynaecologists should be alert to this potential adverse effect and manage these patients accordingly.

Effects of green waste addition on waste activated sludge and fat, oil and grease co-digestion in mesophilic batch digester.

Anaerobic digestion (AD) is regarded as an effective method to treat waste activated sludge (WAS) and fat, oil and grease (FOG). Co-digestion of WAS/FOG could promote the methane yield but it will cause acid and salinity inhibition. Green waste (GW) was added into the digesters, and its effects on co-digestion of WAS and FOG in the mesophilic batch digester were investigated. Digestive performances (such as hydrolysis, acidogenesis and methanogenesis) were studied emphatically. The results showed that digester L6 (WAS:FOG:GW = 1:2:1, VS basis) presented the highest specific methane yield (SMY, 341.5 mL/g VS). The results of kinetics study verified that there was a slower hydrolysis rate when GW was applied as a co-substrate, which could reduce the potential of acid inhibition. Volatile fatty acid (VFA) and electrical conductivity analysis showed that GW addition could keep moderate VFA concentrations and alleviate the negative effects of high-salinity substrates on the digestive systems. The microbial community and diversity analysis proved that GW addition was beneficial to keep the balance of hydrolytic bacteria, acidogens and acetogens. The results of this study indicated that GW addition could enhance the energy recovery and system stability in the WAS/FOG co-digestive system.

Preventive therapeutic options for postoperative recurrence of ovarian endometrioma: gonadotropin-releasing hormone agonist with or without levonorgestrel intrauterine system insertion.

PURPOSE: Here, we compared endometrioma recurrence rates in patients who have undergone a laparoscopic cystectomy and treated with a gonadotropin-releasing hormone agonist (GnRHa) alone or a GnRHa combined with a levonogestrel intrauterine system (LND-IUS). METHODS: We enrolled endometrioma patients who underwent laparoscopic cyst enucleation and divided them into two groups according to postoperative management: GnRHa alone and GnRHa in combination with LND-IUS. We compared preoperative history, perioperative parameters, postoperative endometrioma recurrence, and symptoms between these two groups. RESULTS: A total of 320 patients were included in the final analysis. With a median 84.6 months of follow-up, we detected significant differences between the two groups with respect to age at surgery (31.6 ± 4.8 vs. 37.6 ± 4.2 years, χ2 = 1.978, p < 0.001), gravida (0 vs. 2, χ2 = 4.391, p < 0.001), parity (0 vs. 1, χ2 = 0.035, p < 0.001), body mass index (21.0 ± 2.5 vs. 21.9 ± 2.4, χ2 = 0.0096, p = 0.009), r-AFS score (48 vs. 64, χ2 = 4.888, p = 0.001), and operation time (60 vs. 75 min, χ2 = 9.119, p = 0.003). Patients treated with both GnRHa and LND-IUS achieved significantly less endometrioma recurrence (23.6 vs. 11.5%, χ2 = 5.202, p = 0.023) and higher rates of pain remission (92.1 vs. 100%, χ2 = 6.511, p = 0.011), while those with GnRHa alone suffered more recurrent and painful symptoms (χ2 = 9.280, p = 0.026). Multivariate analysis using a Cox regression demonstrated that combined GnRHa and LNG-IUS treatment correlated with a decreased endometrioma recurrence rate after laparoscopic cystectomy (RR 0.369, 95% CI 0.182-0.749, p = 0.006). CONCLUSIONS: Combination treatment of GnRHa and LNG-IUS exhibited superior pain relief and recurrence prevention among endometrioma patients after fertility-sparing surgery. Thus, combination treatment is a preferable long-term option for patients without intent for pregnancy in the near future.

Silencing of circular RNA ANRIL attenuates oxygen-glucose deprivation and reoxygenation-induced injury in human brain microvascular endothelial cells by sponging miR-622.

BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Clinical characteristics difference between early and late recurrence of ovarian endometriosis after laparoscopic cystectomy.

BACKGROUND: Ovarian endometriosis is the most frequent type of endometriosis. Despite the use of surgery and medication, many patients suffer from recurrence within near future. Currently, there are no effective clinical characteristics available to predict the time to recurrence in ovarian endometriosis patients. PURPOSE: To identify the effective clinical indicators for early and late endometrioma recurrence, we compared the clinical characteristics of early and late recurrence after treatment. METHODS: We collected 358 patients with ovarian endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing a laparoscopic excision of ovarian endometrioma performed at Peking Union Medical College Hospital from January 2009 to April 2013. RESULTS: A total of 358 patients were recruited in the validation set, with a median follow-up time of 83 months (60-120 months). Till the last follow-up, 68 patients exhibited recurrence. Three-year and 5-year recurrence rates were 9.2% and 15.4%, respectively. Univariate analysis in our study showed that patient with endometrioma surgery history had higher incidence of recurrence in 3 years after re-surgery (OR: 5.594, P = 0.029). Univariate and multivariate analyses using the logistic regression showed that the presence of tenesmus before surgery affected the incidence of early recurrence with a ratio of 57.9% (11/19) and 89.5% (17/19) in 3 years and 5 years after surgery, respectively. CONCLUSIONS: Presence of tenesmus before surgery may be linked to the early recurrence of endometrioma.

Fertility Outcomes After Laparoscopic Cystectomy in Infertile Patients with Stage III-IV Endometriosis: a Cohort with 6-10 years of Follow-up.

INTRODUCTION: Ovarian endometriosis is the most common type of endometriosis (EM), affecting more than 40% of women with EM. Currently, surgical intervention is still controversial in infertile patients with ovarian endometriosis, especially in those with stage III-IV EM. Very few studies have been done to analyze long-term pregnancy results in patients with endometrioma more than 5 years after surgery. Therefore, the aim of this study was to explore the pregnancy outcomes and the related factors in patients with endometrioma and stage III-IV endometriosis during a long-term follow-up postoperatively. METHODS: We collected 347 patients with ovarian endometriosis, which included 59 infertile patients with stage III-IV endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing laparoscopic excision of ovarian endometriomas performed by a single doctor at the Peking Union Medical College Hospital from January 2009 to April 2013. RESULTS: A total of 59 infertile patients were recruited. The mean age was 31.8 ± 3.6 years. The mean size of the endometriomas was 6.8 ± 3.3 cm. Before surgery, dysmenorrhea was present in 88.1% (52/59) of the cases, while chronic pelvic pain was reported in nine cases (15.3%). A total of 20.3% (12/59) of cases were concurrent with leiomyoma, 52.5% (31/59) with deep infiltrating endometriosis (DIE), and 39.0% (23/59) with adenomyosis. During laparoscopy, 21 cases were diagnosed as stage III (35.6%) and 38 as stage IV (64.4%) EM according to the revised American Fertility Society (AFS) classification. After laparoscopic cystectomy, 38 (64.4%) patients became successfully pregnant by the 5th year. All the patients were divided into two groups according to the postoperative pregnancy outcomes. In univariate analysis, the higher mean age and concurrent diagnosis of adenomyosis were seen to be related to poor postoperative pregnancy outcomes (p < 0.05). In multivariate analysis, however, the mean age, chronic pelvic pain (CPP), and adenomyosis were independent risk factors of pregnancy outcomes between the two groups (p < 0.05). With a minimum follow-up of 6 years, 23.7% (14/59) of recurrence was observed in the entire study cohort. CONCLUSION: Infertile patients with endometrioma and stage III-IV EM may have lower pregnancy rates after laparoscopic cystectomy if they are older and present with CPP and adenomyosis. Our data showed a lower rate of recurrence but a higher rate of pregnancy after surgery.