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.

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.

Combined proteomics and transcriptomics identifies serpin family C member 1 associated protein as a biomarker of endometriosis.

OBJECTIVE: To explore potential biomarkers indicating endometriosis (EM). MATERIALS AND METHODS: A proteomics method and combined quantitative transcriptomics were adopted to highlight markers in the EM. Venn analysis was used to integrate the ribonucleic acid sequencing (RNA-seq) and protein profiles. Promising candidate markers were tested by enzyme-related immunosorbent assay. RESULTS: A sum of 979 mRNAs and 39 proteins were tested to be significantly differentially expression in the standard cluster compared with the EM cluster. Venn analysis showed a filtered signature of only two down-regulated molecules in the EM group, i.e. fetuin B (FETUB) and serpin family C member 1 (SERPINC1); the latter showed a big variance between the control category and the EM set in the authentication test. CONCLUSION: SERPINC1 may be a useful possible biomarker for the analysis of EM.

The clinical features and long-term surgical outcomes of different types of abdominal wall endometriosis.

PURPOSE: To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. METHODS: In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. RESULTS: Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. CONCLUSION: Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.

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.

IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression.

Rationale: N6-methyladenosine (m6A) mRNA methylation is the most abundant chemical posttranscriptional modification in mRNA and is involved in the regulation of a number of biological processes. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has recently been reported as having the capacity to recognize m6A sites in mRNA and plays a role in regulating mRNA metabolization. However, it is unclear which genes IGF2BP1 targets to identify m6A sites and what are their respective functions in endometrial cancer (EC). Methods: Quantitative PCR, western blot and immunohistochemistry were used to measure IGF2BP1 expression in EC cell lines and tissues. Xenograft experiments were performed to examine the in vivo role of IGF2BP1 in EC cell growth. RNA-binding protein immunoprecipitation sequencing, methylated RNA-binding protein immunoprecipitation sequencing and RNA-sequencing were also conducted to identify potential IGF2BP1 targets involved in EC regulation. Co-immunoprecipitation and mass spectrometry were used to identify IGF2BP1-interacting proteins. Results: IGF2BP1 expression increased in EC, and high expression of this protein correlated with poor prognosis. IGF2BP1 overexpression/knockdown can promote (and inhibit) cell proliferation and regulate the tumor cell cycle and cancer progression, both in vivo and in vitro. Mechanistically, IGF2BP1 can recognize m6A sites in the 3' untranslated region (3'UTR) of Paternally Expressed Gene 10 (PEG10) mRNA and recruits polyadenylate-binding protein 1 (PABPC1) to enhance PEG10 mRNA stability, which consequently promotes PEG10 protein expression. Additionally, it would appear that a large number of PEG10 proteins bind p16 and p18 gene promoter sequences, thereby repressing expression and accelerating the cell cycle. Conclusion: This investigation found that IGF2BP1 has a crucial role in the m6A-dependent regulatory mechanism for endometrial cancer. This study provides new insights into our understanding of disease progression and provides another potential route for understanding biological functions.

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.

Microbiome of the lower genital tract in Chinese women with endometriosis by 16s-rRNA sequencing technique: a pilot study.

BACKGROUND: Endometriosis is a benign, chronic, gynecological disease which affect the women in reproductive age. The dysfunction of immune system is associated with endometriosis and the diversity of microbiota in genital tract. According to previous studies, microbiota significantly contributes to multi-systemic function, but the evidence of relationship between microbiota and endometriosis remains insufficient. METHODS: There are 68 participants were included in this study and 134 samples obtained from the cervical canal, posterior fornix and uterine cavity were analyzed by 16s-rRNA sequencing. The raw data was filtered, analyzed, and visualized, and bio-information methods were used to identify the characteristics of microbiota. RESULTS: Two different locations near the cervix, cervical canal, and posterior fornix, exhibited no differences in alpha diversity. The microbiota profile of adenomyosis with endometriosis patients is different from control group through PCoA. Among the different disease groups, five microbiotas were distinctive in the genus level, and Atopobium presented with the greatest significance in adenomyoisis-endometriosis patients. The LeFSe analysis failed to identify the special biomarkers, while several characteristic functions were identified through PICRUSt. CONCLUSIONS: Lactobacillus is the predominant genus in the female lower genital tract, and Atopobium is higher in patients with endometriosis combined with adenomyosis. Several different functions of microbiota were explored, some of them are found to be associated with endometriosis or adenomyosis, other functions are needed to be further verified. These findings may provide a new concept of microbiota/immune system/endometriosis system.

Endometrial Organoids: A New Model for the Research of Endometrial-Related Diseases†.

An ideal research model plays a vital role in studying the pathogenesis of a disease. At present, the most widely used endometrial disease models are cell lines and animal models. As a novel studying model, organoids have already been applied for the study of various diseases, such as disorders related to the liver, small intestine, colon, and pancreas, and have been extended to the endometrium. After a long period of exploration by predecessors, endometrial organoids (EOs) technology has gradually matured and maintained genetic and phenotypic stability after long-term expansion. Compared with cell lines and animal models, EOs have high stability and patient specificity. These not only effectively and veritably reflects the pathophysiology of a disease, but also can be used in preclinical drug screening, combined with patient derived xenografts (PDXs). Indeed, there are still many limitations for EOs. For example, the co-culture system of EOs with stromal cells, immune cell, or vascular cells is not mature, and endometrial cancer organoids have a lower success rate, which should be improved in the future. The investigators predict that EOs will play a significant role in the study of endometrium-related diseases.