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 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.

Prognosis and Prognostic Factors of Serous Borderline Tumor-Micropapillary Variant: Retrospective Study of 200 Patients with Long-Term Follow-Up.

Objective: To determine the oncofertility outcomes and prognostic factors in a large series of serous borderline ovarian tumor-micropapillary variant (SBOT-M) with a long-term follow-up. Methods: Consecutive patients with SBOT-Ms treated from two affiliated hospitals of the Chinese Academy of Medical Sciences were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free survival (DFS), and overall survival were analyzed, and outcomes of patients treated with conservative and radical surgery were compared. Results: From 2000 to 2020, 200 patients were identified and followed. After a median follow-up of 68 months, 81 patients relapsed. In the multivariate analyses, younger age at diagnosis and conservative surgery that preserved fertility potential were independently associated with worse DFS (p = 0.018 and <0.001, respectively). Twenty-three patients experienced invasive recurrence, and seven died of progressive disease. Multivariate analysis showed that nulliparous and advanced FIGO stage were independently adversely associated with lethal recurrence (p = 0.022 and 0.029, respectively). Only advanced FIGO stage at diagnosis was associated with worse overall survival at univariate analysis (p = 0.02). Among 61 patients attempting conception, 37 achieved 44 pregnancies and resulted in 32 live births. Conclusions: In this series, patients with SBOT-M have an acceptable oncofertility outcomes. The use of conservative surgery was independently associated with worse DFS, but without an impact on neither invasive relapse nor on overall survival. Patients with advanced FIGO stages had a significantly higher risk of lethal recurrence and worse overall survival, suggesting that adequate staging surgery and intensive postoperative surveillance should be warranted.

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.

Thoracic endometriosis presented as catamental hemoptysis: a case series of a rare disease.

OBJECTIVE: Thoracic endometriosis syndrome (TES) is a rare disease in which a functioning endometrial tissue is observed in the pleura, lung, parenchyma, airways, and/or diaphragm. The optimal management of this disease remains a matter of debate. We aimed to report TES cases and their effective hormonal treatment and management. METHODS: In this retrospective study, women presented as catamenial hemoptysis (CH) diagnosed with thoracic endometriosis were included. The main outcome of measure was cessation or recurrence of the clinical manifestations of thoracic endometriosis. RESULTS: The mean onset age of the 14 patients was 30.21 ± 5.40 years. CH was characteristic symptom of these patients. All patients underwent chest computed tomography (CT) scan during menstruation and 2 or 3 weeks after menstruation, which showed the obvious shrinking or disappearance of the lesions. All of the patients were given Gonadotropin releasing hormone agonists (GnRHa) for 3 to 6 months, eleven of them were administered with combined oral contraceptives (COC) cyclically after GnRHa. The median follow-up duration was 24 months. Hemoptysis recurrence was observed in one patient. CONCLUSIONS: CH is a rare clinical entity of thoracic endometriosis, the change of CT images during and after menstruation or the response to GnRHa were helpful for accurate diagnosis. Hormonal treatment with GnRHa followed by COCs cyclically could be employed for efficient management of thoracic endometriosis.

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.

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.

Establishment of endometriotic models: the past and future.

Endometriosis is a prevalent chronic disease that affects approximately 6% to 10% of reproductive-aged women. Although numerous researchers have endeavored to explore the etiology of endometriosis over a century, its etiology still remains an enigma. The exploration of pathophysiologic mechanism and novel therapy for endometriosis depends on ideal endometriotic models. In the previous decade, various endometriotic models have been established; therefore, we made a conclusion for available information on these models. This review summarized the common experimental models used in endometriotic studies, including their origins, characteristics, applications, and limitations. Endometriotic models played an important role in studying etiologies and novel treatments of endometriosis during the last decades. Among them, animal models and endometriotic cell lines were viewed as most common studying tools to explore the intrinsic entities of endometriosis. In addition, endometrial organoid also emerged and was regarded as an ideal studying tool for endometriosis research. Different research models collectively complement each other to advance the endometriosis research. The successful establishment of endometrial organoids means that organoids are expected to become an ideal model for studying endometriosis in the future.

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.

Oncofertility outcomes after fertility-sparing treatment of bilateral serous borderline ovarian tumors: results of a large retrospective study.

STUDY QUESTION: What are the oncofertility outcomes of young women (≤40 years old) with bilateral serous borderline ovarian tumors (SBOTs) after fertility-sparing surgery? SUMMARY ANSWER: Fertility preservation with the bilateral ovarian cystectomy procedure is feasible for bilateral SBOTs, with an acceptable oncological outcome and worthwhile pregnancy rates. WHAT IS KNOWN ALREADY: Fertility-sparing approaches are becoming the standard management of young patients with unilateral SBOTs and other borderline histological subtypes. However, there is a paucity of evidence to dictate the best management in bilateral SBOTs. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational study performed at the Peking Union Medical College Hospital in Beijing, China, between January 1999 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ninety-four women (≤40 years old) with pathologically confirmed bilateral SBOTs were included. Following preoperative counseling, patients self-selected into one of three treatment modalities: bilateral ovarian cystectomy (n = 48), unilateral adnexectomy plus contralateral cystectomy (UAC; n = 31), and radical surgery (n = 15). Univariate and multivariate analyses were used to determine the clinical and pathological features associated with disease-free survival and reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: During the median follow-up of 64 months (range, 4-243 months), 61 patients (65%) developed relapse, including 3 (20%) in the radical group, 26 (84%) in the UAC group and 32 (67%) in the bilateral cystectomy group. In the multivariate analyses, preoperative CA-125>300 U/mL, fertility preservation and micropapillary pattern were independently associated with adverse disease-free survival (P = 0.001, 0.03 and 0.026, respectively). Fourteen patients (15%) experienced invasive recurrence, and three (3%) died of progressive disease. The micropapillary pattern was significantly associated with invasive evolution risk (P = 0.006). Of the 49 patients who attempted to conceive, 23 (47%) achieved 27 pregnancies (24 spontaneous and three after IVF-ET), resulting in 19 live births. There was no significant difference in disease-free survival (P = 0.13) or pregnancy rate (41 vs. 50%, P = 0.56) between the UAC and bilateral procedures. LIMITATIONS, REASONS FOR CAUTION: As a retrospective study conducted in a referral center, inherent biases exist. The nonrandom allocation to treatment groups and relatively small number of patients attempt to conceive might limit the statistical power of our findings. Only 41 patients (43.6%) received complete staging during their initial surgeries, so an underestimation bias in terms of the FIGO stage and extraovarian implants might have occurred. WIDER IMPLICATIONS OF THE FINDINGS: The ultraconservative bilateral ovarian cystectomy procedure should be proposed in bilateral SBOTs when technically feasible. Invasive evolution occurs frequently in these women, and intense follow-up and oncofertility counseling are warranted, especially for those with micropapillary patterns. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Clinical Manifestations Of Adenomyosis Patients With Or Without Pain Symptoms.

PURPOSE: Our study aims to investigate the distribution of pain symptoms and the association between pain symptoms and clinical parameters in patients with adenomyosis. PATIENTS AND METHODS: The clinical and pathological data of 291 patients diagnosed with adenomyosis in the Obstetrics and Gynecology Department of Peking Union Medical College Hospital from March 2012 to September 2015 were collected, and analyzed in regard to the pain symptoms. RESULTS: The median age at disease onset was 34 years. 71.8% of the patients had pain symptoms (pain group) and 28.2% had no pain symptoms (painless group). Patients with symptoms accompanied by dysmenorrhea accounted for 68%, among which 30.3% were mild, 36.9% were moderate, and 32.8% severe, while 56.1% presented with progressive pain. Through comparison, significant differences were identified between the pain and painless groups with regard to age at diagnosis (P=0.009), age at onset of disease (P=0.008), and level of pre-surgical CA125 (P<0.001), as well as proportion of patients with rectal irritation (P=0.008), elevated CA125 level (P<0.001), thickened myometrial layer (P<0.001) and concurrent endometriosis (P=0.001). In the multivariable analysis, an elevated level of pre-surgical CA125 (P<0.001) and thickened posterior myometrial layer (P=0.023) were both independent risk factors for the morbidity of pain symptoms. Similar results except for the difference in rectal irritation were noticed when we made further comparison between the dysmenorrhea and non-dysmenorrhea groups in adenomyosis patients. CONCLUSION: Our research analyzes the clinical features related to pain symptoms in patients with adenomyosis, which may provide clues for the possible presurgical diagnosis of adenomyosis, as well as references for pain management of adenomyosis.

Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women.

OBJECTIVE: To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. METHODS: This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. RESULTS: The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615-0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054-1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008-2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072-3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175-2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460-0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. CONCLUSIONS: The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.

Safety and fertility outcomes after the conservative treatment of endometrioid borderline ovarian tumours.

BACKGROUND: Because of the rarity of endometrioid borderline ovarian tumours (EBOTs), there is a paucity of data concerning the natural history and prognosis of this condition. Thus, the objective of our study was to establish the feasibility of fertility preservation in young women with EBOTs, as well as their oncological and reproductive outcomes. METHODS: Consecutive patients with EBOTs, treated at a tertiary referral centre during a span of 22 years, were retrospectively analysed. Recurrence-free interval, as well as its association with the type of surgery and with other clinical and pathological features, was assessed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: Of the 59 patients studied, the median follow-up time was 30 months (range, 6-177 months). Nine (15.3%) patients developed 13 recurrences 6-137 months after the initial surgeries, including three patients (5.1%; n = 3/59) who developed six invasive recurrences 8, 18 and 68 months after their initial surgeries. Conservative surgery showed a tendency towards a high recurrence rate (17.2% versus 13.3%); however, this difference was not significant (p = 0.45). The 5-year recurrence-free survival rate was significantly higher in the oophorectomy group than in the cystectomy group (p = 0.001). Cox regression analysis showed that none of the variables assessed were associated with an increased hazard ratio for recurrence, except for a younger age at diagnosis (p = 0.021). Of 20 patients who attempted to conceive, three pregnancies among two patients (10.0%) resulted in two live births. CONCLUSIONS: Conservative surgery with unilateral adnexectomy can be proposed for young women with EBOTs with fertility desire; however, the reproductive result is not satisfactory. In addition, careful evaluations of the endometria should be offered during the initial surgery and follow-up period. TRIAL REGISTRATION: Retrospectively registered.

Risk Factors for Recurrence of Ovarian Endometriosis in Chinese Patients Aged 45 and Over.

BACKGROUND: When considering the issue of recurrence, perimenopausal women may have more dilemma during management comparing with young women, for example, whether to retain the uterus and ovary during surgery, whether it is necessary to add adjuvant medicine treatment after operation, and there is no evidence for reference about using of gonadotropin-releasing hormone agonist. This study aimed to study the risk factors for the recurrence of ovarian endometriosis (EM) in patients aged 45 and over. METHODS: This is a retrospective nested case-control study. We reviewed the medical records of patients aged over 45 years who underwent surgical treatments for ovarian EM from 1994 to 2014, in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences. By following up to January 2016, 45 patients were found to have relapses and regarded as the recurrence group. The patients with no recurrence during the same follow-up period were randomly selected by the ratio of 1:4 as the nonrecurrence group (180 patients in total). Stratified Cox regression was used to analyze the risk factors of the recurrence. RESULTS: Univariate analysis showed that there was a significant difference in the postoperative treatment (the percentage of patients who received postoperative treatment in non-recurrence group and recurrence group, 23.9% vs. 40.0%, χ2 = 4.729, P = 0.030) and ovarian preservation (the percentage of patients who received surgery of ovarian preservation in non-recurrence group and recurrence group, 25.0 % vs. 44.4%, χ2 = 19.462, P < 0.001) between the nonrecurrence group and the recurrence group. There was no correlation between recurrence and the following factors including patient's age, menarche age, gravidity, parity, CA125 level, ovarian lesions, menopausal status, combined benign gynecological conditions (such as myoma and adenomyoma) and endometrial abnormalities, and surgical approach or surgical staging (all P > 0.05). Multivariate analysis indicated that whether to retain the ovary was the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM (odds ratio: 5.594, 95% confidence interval: 1.919-16.310, P = 0.002). CONCLUSION: Ovarian preservation might be the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM.

Risk of synchronous endometrial disorders in women with endometrioid borderline tumors of the ovary.

BACKGROUND: Synchronous endometrial disorders have been poorly studied in women with endometrioid borderline ovarian tumors (EBOT). The aims of this study were to investigate the risk of endometrial disorders among women with EBOT and associated factors, as well as their oncological and fertility outcomes. RESULTS: This retrospective study included 33 women with EBOT. Their mean age was 41.9 years, and endometria were evaluated in 25 of these patients. The prevalence of synchronous endometrial disorders was 52.0% (n = 13/25) and this incidence was 41.4% (n = 46/111) after systematic analysis. Univariable analysis showed that EBOT patients who were younger, nulliparous, and had experienced abnormal vaginal bleeding were more likely to have synchronous endometrial disorders. The median follow-up was 54 months (range: 14-250 months), and three patients (10.3%) developed recurrences. No deaths due to EBOT were recorded. Among the nine nulliparous women treated conservatively who were attempting to conceive, only one (11.1%) pregnancy resulted in a live birth. CONCLUSIONS: Synchronous endometrial disorders are common in women with EBOT, especially in those who are younger, nulliparous, and have experienced abnormal vaginal bleeding. Thus, endometrial sampling should be performed in women with EBOT undergoing conservative surgery, and a hysterectomy should be performed in cases requiring radical treatment.

Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis.

BACKGROUND: Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment. METHODS: A total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions. RESULTS: Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752-0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571-0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network. CONCLUSIONS: This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.

Predictive factors of ovarian carcinoma for women with ovarian endometrioma aged 45 years and older in China.

BACKGROUND: To explore the risk factors of endometriosis-associated ovarian cancer (EAOC) in women with ovarian endometriosis (OEM) aged 45 years and above in China. METHODS: This study reviewed the medical records of 1038 women in total who were aged 45 years and above, surgical-pathologically diagnosed with ovarian endometriosis, and were treated at Peking Union Medical College Hospital between December 1996 and December 2016. Histology evaluation was used to determine whether the ovarian endometriosis specimen was with (n = 30) or without (n = 1008) ovarian cancer. RESULTS: 2.9% (30/1038) of women with the surgical-pathological diagnosis of ovarian endometriosis were found to have EAOC. Those patients with EAOC were prone to be in the postmenopausal status at the time of the diagnosis (OR 5.50, 95%CI 2.54-11.90, P < .001) and larger size of tumor (≥8 cm, OR 7.19, 95% CI 3.34-15.50, P < .001), and higher prevalence of coexisting with endometrial disorders (OR 4.11, 95%CI 1.73-9.73, P = .003). This study showed that patients of an older age when diagnosed with OEM, were at a higher risk of developing EAOC, respectively measuring of 1.7% (13/751) at 45-49 years, 5.6% (12/215) at 50-54 years, and 10.0%(5/50) at 55-59 years (P < 0.001). CONCLUSIONS: This study showed that for women aged 45 years and above who were diagnosed with OEM, the independent risk factors of EAOC were menopausal status, tumor size of 8 cm or greater in diameter, and coexisting endometrial disorders. Therefore, intensive follow-ups or active interventions should be considered for them.

Menorrhagia and Uterine Volume Associated with Lower Urinary Tract Symptoms in Patients with Adenomyosis.

BACKGROUND: Adenomyosis is a gynecological disorder with symptoms most presenting as dysmenorrhea and heavy menstrual bleeding. However, the presence of lower urinary tract symptoms (LUTS) among women with adenomyosis remains unclear. This study was designed to determine the prevalence of LUTS and factors related to the severity of these symptoms in this population. METHODS: From July 2016 to November 2016, a total of 298 untreated symptomatic adenomyosis patients and 280 age-matched controls were enrolled. Demographics, LUTS, pain symptoms, ultrasonographic uterine size, and serum CA125 level were recorded. LUTS were evaluated using the International Prostate Symptom Score (IPSS) questionnaire. Factors related to the severity of LUTS were detected using the logistic regression analysis presented as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Compared with the control group, patients with adenomyosis had a greater IPSS total (4 [2-8] vs. 2 [0-3], Z = -8.159, P 0.001), IPSS storage (2 [1-4] vs. 1[0-2], Z = -7.361 P 0.001), and IPSS voiding (2 [0-4] vs. 0 [0-1], Z = -7.194, P 0.001). Of the patients with adenomyosis, 30.2% had moderate-to-severe lower urinary tract symptoms (IPSS ≥8). The most prevalent LUTS were daytime frequency (40.9%), followed by nocturia (24.8%), weak stream (24.2%), and incomplete emptying (23.5%). In study group, patients with an IPSS total score ≥8 had higher proportion of menorrhagia (51.1% vs. 30.8%, χ2= 11.162 P= 0.025) and larger uterine volumes (183.3 [109.8-273.8] cm3 vs. 148.5 [96.4-262.7] cm3, Z = -1.441, P= 0.150) compared to patients with an IPSS total score <8. On multivariate logistic regression analysis, patients with menorrhagia were associated with an increased risk of an IPSS total score ≥8 (OR: 2.309, 95% CI: 1.310-4.070, P= 0.004), an IPSS storage subscore ≥4 (OR: 2.422, 95% CI: 1.395-4.206, P= 0.002), and an IPSS voiding subscore ≥5 (OR: 1.971, 95% CI: 1.176-3.302, P= 0.010). However, patients with uterine volume more than 180 cm3 had more than 2-fold risk of bearing IPSS total score ≥8 (OR: 2.437, 95% CI: 1.381-4.300, P= 0.002), IPSS storage subscore ≥4 (OR: 2.486, 95% CI: 1.433-4.314, P= 0.001), and IPSS voiding subscore ≥5 (OR: 2.700, 95% CI: 1.485-4.908, P= 0.001). CONCLUSIONS: Lower urinary tract symptoms are prevalent in patients with symptomatic adenomyosis and greatly affect patients' quality of life. Menorrhagia and large uterine volume could be potential risk factors that increase the occurrence of moderate-to-severe LUTS.