Predicting disease recurrence in patients with endometriosis: an observational study.

BACKGROUND: Despite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence. METHODS: This observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence. RESULTS: Several significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis. CONCLUSIONS: Following an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

Extensive heterogeneity in the expression of steroid receptors in superficial peritoneal endometriotic lesions.

RESEARCH QUESTION: Is the expression of steroid hormone receptors (oestrogen receptor-α and progesterone receptor A/B) and proliferative markers (Bcl-2 and Ki67) uniform among superficial peritoneal endometriotic lesions? DESIGN: A retrospective cohort study of 24 patients with surgically and histologically confirmed endometriosis. Immunofluorescence was used to determine the proportion of oestrogen receptor-α (ERα), progesterone receptor A/B, Bcl-2 and Ki67 positive cells in 271 endometriotic lesions (defined as endometriotic gland profile/s within an individual region of CD10 stromal immunostaining from a single biopsy) from 67 endometriotic biopsies from 24 patients. Data were analysed to examine associations related to menstrual cycle stage, lesion location and gland morphology. RESULTS: Oestrogen receptor-α and progesterone receptor A/B expression in superficial peritoneal endometriotic lesions was extremely heterogeneous. Bcl-2 immunostaining in endometriotic lesions was also variable, whereas Ki67 immunostaining was minimal. Menstrual cycle stage associations were limited in steroid hormone receptor and Bcl-2 expression in lesions. Patterns in progesterone receptor A/B and Bcl-2 immunostaining were associated with lesion location. Bcl-2 was differentially expressed, based on lesion gland morphology. CONCLUSIONS: These data demonstrate considerable diversity in the expression of steroid hormone receptors and Bcl-2 between lesions, even within an individual patient.

Distribution of smooth muscle actin and collagen in superficial peritoneal endometriotic lesions varies from the surrounding microenvironment.

RESEARCH QUESTION: Do different subtypes of superficial peritoneal endometriotic lesions exist, based on the presence and morphology of smooth muscle, collagen fibres and immune cell populations? DESIGN: A retrospective cohort study of 24 patients, from across the menstrual cycle, with surgically and histologically confirmed endometriosis. Immunofluorescence was used to delineate the CD10 stromal area of lesions (n = 271 lesions from 67 endometriotic biopsies), and then smooth muscle actin (SMA) positive tissue and immune cell populations (CD45+ and CD68+) were quantified within and adjacent to these lesions. Second harmonic generation microscopy was used to evaluate the presence and morphology of type-1 collagen fibres within and surrounding lesions. RESULTS: Overall, immune cell numbers and the area of SMA and collagen within endometriotic lesions tended to be low, but a spectrum of presentations significantly varied, particularly in the adjacent tissue microenvironment, based on lesion locations, the morphology of endometriotic gland profiles, or both. Lesions in which collagen fibres formed well aligned capsules around the CD10+ stromal border were identified compared with lesions in which collagen fibre distribution was random. Considerable inter- and intra-patient variability in the morphology of SMA and collagen was observed within and surrounding lesions. CONCLUSION: These data demonstrate considerable diversity in the presence of immune cells and morphology of SMA and collagen within, but even more so, surrounding endometriotic lesions, even within individual patients. This heterogeneity, especially within individual patients, presents a challenge to incorporating these cell and tissue types into any new endometriosis classification systems or prognostic approaches.

The impact of age and parity on the experience of relief and regret in women who have undergone hysterectomy for benign disease: A cross sectional survey.

OBJECTIVE: To investigate the impact of age and parity on the experience on relief and regret following elective hysterectomy for benign disease, and to explore the factors that impact relief and regret. DESIGN: Retrospective cross-sectional survey of a cohort. SETTING: Single-centre tertiary hospital in Melbourne, Australia. POPULATION: Patients who underwent elective hysterectomy for benign indications from 01 January 2008 - 31 July 2015 (inclusive) with age <51 years at time of admission. METHODS: Eligible participants completed a retrospective survey regarding their experience of relief and regret following hysterectomy. MAIN OUTCOME MEASURES: Regret was defined as a positive response to "Do you regret the decision to have a hysterectomy?". Relief was defined as responding "agree/strongly agree" to "I feel relieved I had a hysterectomy". RESULTS: 268 of 1285 (21%) eligible participants completed the study questionnaire. Of these, 29 were aged <36 years at the time of hysterectomy. Seven percent (n=18/262) reported regretting having a hysterectomy and 88% (n=230/262) reported experiencing relief. We did not observe associations between age at hysterectomy and regret (aOR 0.93; 95% CI 0.85, 1.03), age at hysterectomy and relief (aOR 1.01; 95% CI 0.93, 1.09), nulliparity and regret (aOR 0.32; 95% CI 0.06, 1.59) or nulliparity and relief (aOR 2.37; 95% CI 0.75, 7.51). Desire for future pregnancy at the time of hysterectomy was more frequently reported in those who experienced regret vs no regret (46.7% vs 12.1%, OR: 6.33; 95% CI: 2.12, 18.90; p=0.001). CONCLUSIONS: Age and parity are not associated with relief nor regret following elective hysterectomy for benign disease.

The most impactful endometriosis symptom: An international, cross-sectional, two-round survey study.

INTRODUCTION: There is considerable variation in the types of symptoms experienced by people living with endometriosis, and it is unclear which symptoms impact people the most. This study aimed to identify the specific symptoms that are "most impactful" to people living with the condition. MATERIAL AND METHODS: Two sequential online surveys were conducted. Women aged over 18 years with a diagnosis of endometriosis were eligible to participate. Participants first provided a free-text list of all the endometriosis symptoms they experienced (Survey 1, Australian only). Responses were condensed into a shorter list by grouping symptom types and selecting the top 20 most common and most impactful. Survey 2 (international) participants reviewed the list and selected all that they had experienced in the last 3 months, nominated one as their single "most impactful symptom", and rated its impact on one of five randomized scale types. RESULTS: Survey 1 and Survey 2 had 195 and 983 responses, respectively. The mean age of respondents was 30.8 ± 7.9 years. There were 275 separate symptom descriptions from Survey 1, which were condensed into 104 groups, of which 25 met criteria for inclusion in Survey 2. The most commonly experienced symptoms were abdominal pain (93% of respondents), bloating (92%), and fatigue (90%), and the symptoms nominated as causing the most impact were pelvic pain (20%), abdominal pain (15%), and cramps (7%). Nearly everyone (99.7%) in Survey 2 reported experiencing at least one pain symptom. The symptoms that generated the highest impact scores were infertility (99.8/100), irregular menstrual cycles (95.3/100), and constipation (92/100). The average impact score was 87.5/100. CONCLUSIONS: There was substantial variation in the symptom selected as causing the most impact, and the level of impact was high. A focus on measuring the "most impactful symptom" in future research may enable us to better capture and measure the true symptom experience.

The "most bothersome symptom" construct: A qualitative study of Australians living with endometriosis.

INTRODUCTION: "Improvement in the most bothersome symptom" was recently selected as a core outcome for endometriosis intervention trials. This study aimed to explore the applicability of the construct of "symptom bother" in representing the lived experiences of people with endometriosis. MATERIAL AND METHODS: Semi-structured interviews were conducted to understand the meaning of "symptom bother" and related constructs. Eighteen interviews were conducted: 14 among people with a surgical diagnosis of endometriosis who were recruited from the community, and four with people who were recruited from a private gynecology clinic who had either a confirmed diagnosis or a high suspicion of the disease. All interviews were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: Three primary themes were identified: (1) endometriosis symptoms and priorities vary with time and context, (2) endometriosis symptoms impair normal daily functioning, (3) endometriosis symptoms are more than just a "bother." The concept of "bother" to describe endometriosis symptoms did not resonate with most participants. Whilst "bother" was familiar language, it did not encompass the broader implications of living with endometriosis. Participants felt "bother" implied emotional distress, lacking a full understanding of the consequences of the disease. Instead, "symptom impact" was endorsed, allowing participants to quantify and objectively assess their symptoms, free from negative connotations. CONCLUSIONS: This was the first qualitative study to explore "symptom bother" among people living with endometriosis. Instead of "bother," "impact" was widely endorsed as a suitable construct. This term more appropriately captured the broad ways in which endometriosis symptoms impair daily functioning.

Constipation After Elective Laparoscopy for Benign Gynecological Indications-A Prospective Observational Study.

STUDY OBJECTIVE: Discover the rate of post-operative constipation in participants undergoing elective laparoscopy for benign gynecological indications DESIGN: Prospective observational study SETTING: Single site, tertiary level gynecology unit with a focus on pelvic pain and endometriosis. PATIENTS: Recruited participants were patients of the institution over the age of 18 who had planned to undergo an elective laparoscopy for benign gynecological indications prior to enrolment in the study. Participants were excluded if they were not English speaking, had a chronic bowel condition (with the exception of irritable bowel syndrome), were planned to have bowel surgery, hysterectomy, or converted to laparotomy. INTERVENTION: In this prospective study, participants completed 3 consecutive surveys. One prior to surgery, one a week post-surgery, and a third 3 months post-surgery. The surveys collected data regarding the participant's bowel habits, pain relief used, laxatives used, and the distress or bother caused by their bowels. MEASUREMENT AND MAIN RESULTS: Constipation was defined by a modified ROME IV criteria. Opiate use and laxative use were defined by patient-reported tablet counts. The level of distress was measured as a continuously variable scale from 0 to 100. Variables adjusted for included subject's demographics, pre-operative constipation, indication for surgery, duration of surgery, estimated blood loss, opiate use (preoperative, peri-operative, and post-operative), laxative use, and length of stay. A total of 153 participants were recruited, of which 103 completed both the pre-operative and post-operative survey. Post-operative constipation was present in 70% of participants. The mean length of time to first bowel motion was 3 days, with 32% of participants having their first bowel motion after the third post-operative day. The level of bother caused by their bowel habit was higher in the constipation group compared to those without constipation. Post-operatively opiates were used in 84.9% of participants, and laxatives were used in 47.1%. Visits to the general practitioner for constipation occurred in 5.8% of participants. CONCLUSION: Post-operative constipation is common and bothersome in participants who undergo elective laparoscopy for benign gynecological indications. Analysis of individual variables failed to identify any factors that influenced the rate of constipation.

Sexual Function of Women With Deep Endometriosis Before and After Surgery: A Prospective Study.

BACKGROUND: Deep endometriosis (DE) may significantly affect women's quality of life. Limited data exists on the effect of surgery on the several domains of sexual function. AIM: To prospectively compare various domains of sexual function before and after laparoscopic surgery for DE. METHODS: A prospective observational cohort study in a tertiary university-affiliated referral center. Patients with suspected DE who were planned to undergo laparoscopic surgery completed the Female Sexual Function Index questionnaire before surgery. The same questionnaire was completed by the participants 6 weeks, 6 months, and 12 months after surgery. Rate of sexual dysfunction over time was compared using multilevel logistic regression. Summary scores were then compared at each time point to the corresponding score before surgery using multilevel linear regression. Multivariable analysis was performed of potential confounders. OUTCOMES: Change in desire, arousal, orgasm, lubrication, satisfaction and pain summary scores as well as in the full-scale score between before and after surgery. RESULTS: We followed 149 patients with surgically confirmed DE. Sexual dysfunction rate as per the full-scale score was 75.5% before surgery and remained over 60% to 12 months after. The full-scale sexual function score improved at 6 (change in score = 2.8 ± 9.5, P = .004) and 12 months (change in score = 2.1 ± 9.9, P = .03). None of the summary scores improved at 6 weeks. Desire score (P < .001), arousal score (P = .02), and pain score (P = .01) improved at 6 months. Desire score (P = .03) and pain score (P = .01) also improved at 12 months, as compared to before surgery. On multivariable multilevel analysis, scores before surgery significantly contributed to the scores after surgery (P < .001). CLINICAL TRANSLATION: While sexual function improved after surgery, dysfunction rate remained substantial. Proper preoperative counseling should address sexual function measures and clinical and research attention should be given to seek ways to further reduce sexual dysfunction. STRENGTHS AND LIMITATIONS: The main strengths of our study are the prospective design, the relatively long follow-up and the use of a detailed validated questionnaire allowing assessment of a large variety of clinically relevant sexual function domains and scores as well as a full-scale score. Among our limitations are the lower response rate at 12 months and the limited generalizability as this is a single center study. CONCLUSION: Sexual function is a major and often under reported domain of quality of life. Further research is needed to identify the specific populations who may improve, not change or experience deterioration in their sexual functioning after surgery. Dior UP, Reddington C, Cheng C, et al. Sexual Function of Women With Deep Endometriosis Before and After Surgery: A Prospective Study. J Sex Med 2022;19:280-289.

Urinary Function after Surgery for Deep Endometriosis: A Prospective Study.

STUDY OBJECTIVE: To compare urinary function before and after surgery in patients undergoing laparoscopy for deep endometriosis and to measure the rate of postoperative deterioration in urinary function after surgery. DESIGN: Prospective questionnaire-based observational cohort study. SETTING: Tertiary university-affiliated hospital. PATIENTS: Included were 149 women who underwent surgery for deep endometriosis. INTERVENTIONS: Participants completed the international consultation on incontinence female lower urinary tract symptoms long-form questionnaire before surgery and 6 weeks, 6 months, and 12 months after surgery. MEASUREMENTS AND MAIN RESULTS: Bladder filling, voiding, and urinary incontinence summary scores were compared before and after surgery with mixed-effects linear regression analysis (correlated observations). Individual domains comprising the summary scores and their bother scores were also compared before and after surgery. Filling score at 6 weeks (3.7 ± 2.6), 6 months (3.2 ± 2.2), and 12 months (3.4 ± 2.2) improved from presurgery scores (4.2 ± 2.6) (p-value for the difference between before and after surgery: p <.001, p = .009, and p = .02 for 6 weeks, 6 months, and 12 months, respectively). No change was observed after surgery in bladder voiding score. Incontinence score improved at 6 weeks after surgery (presurgery and 6-week scores: 2.5 ± 3.3 and 1.6 ± 2.2, respectively, p <.001) but not thereafter. Patients with low preoperative summary scores had higher summary scores (worse function) after surgery, and patients with high preoperative scores had lower summary scores (improved function) after surgery. CONCLUSION: Urinary function improved after laparoscopy for deep endometriosis. Greatest improvement was found in patients with worse preoperative function, whereas postoperative deterioration in urinary function was found for patients with initially normal function. More research is needed to better identify the subpopulations in whom surgical intervention provides symptomatic benefit or deterioration.

Central sensitisation in pelvic pain: A cohort study.

BACKGROUND: Central sensitisation (CS) leads to pain amplification and impacts on the management of pelvic pain (PP). Identification of CS in patients with PP may provide additional treatment pathways and improve patient outcomes. AIMS: The aims are to quantify the prevalence of questionnaire-predicted CS (QPCS) in patients presenting with PP and investigate associations between QPCS and clinical variables. MATERIALS AND METHODS: This was an observational, cross-sectional study. Subjects with PP completed a questionnaire comprising four validated tools: the Central Sensitisation Inventory (CSI) for QPCS, Pain Catastrophising Scale for Catastrophising Trait, Bladder Pain/Interstitial Cystitis Symptom Score for bladder pain syndrome (BPS) and the Rome IV criteria for irritable bowel syndrome (IBS). RESULTS: One hundred and eleven women were enrolled in the study; 74.8% (n = 83) had a CSI score of >40, indicating the presence of QPCS. Subjects with QPCS were more likely to screen positive for catastrophising trait (odds ratio (OR) 3.57, 95% CI 1.19-10.76, P = 0.02), BPS (OR 11.77, 95% CI 2.13-64.89, P = 0.005) and IBS (OR 2.6, 95% CI 1.05-6.43, P = 0.04). They were more likely to experience pain for more than two years (OR 4.98, 95% CI 1.94-12.82, P = 0.001) and other pain symptoms involving bladder (OR 9.87, 95% CI 2.52-38.67, P = 0.001), bowel (OR 3.13, 95% CI 1.31-7.48, P = 0.01), back (OR 4.17, 95% CI 1.66-10.51, P = 0.002) and vulva (OR 3.61, 95% CI 1.21-10.82, P = 0.02). They also had higher previous diagnoses of mental health disorder (OR 3.5, 95% CI 1.5-8.4, P = 0.005) or IBS (OR 8.9, 95% CI 1.6-49.1, P = 0.01). CONCLUSIONS: QPCS occurs frequently in patients with PP, and subjects with QPCS experience more prolonged and complex pain.

The use of the myometrial-cervical ratio in the ultrasound diagnosis of adenomyosis - A validation study.

BACKGROUND: Adenomyosis is a benign disorder defined by ectopic endometrial glands within the uterine myometrium. A study by Mooney et al reported the myometrial-cervical ratio (MCR), a novel ultrasound measurement that was found to improve the preoperative diagnosis of adenomyosis. AIMS: To validate the association between sonographic MCR and adenomyosis confirmed on histopathology in an independent patient group. MATERIALS AND METHODS: Single-centre retrospective cohort study including women who underwent hysterectomy between 1 January 2016 and 31 December 2018 for a benign, non-obstetric indication with an ultrasound at the study centre prior to surgery. Clinical details and histopathology were extracted. Ultrasound images were reviewed by a gynaecology ultrasound subspecialist blinded to histological findings. RESULTS: Eight hundred eighty-seven patients underwent hysterectomy in the study period for eligible indications; 317 had an ultrasound at the study centre and were included. There was no statistically significant association between the MCR and adenomyosis on histology when all patients were included; however, increased MCR was associated with adenomyosis when those with fibroids on ultrasound were excluded. The area under the receiver operating characteristic for this model was 0.614 (95% CI: 0.53 to 0.69). The optimal MCR cut-point in this subgroup was 1.79, which achieved 55.6% sensitivity and 62.8% specificity, with 58.5% correctly classified. There was no significant difference in MCR compared to traditional ultrasound markers of adenomyosis. CONCLUSIONS: In a population undergoing hysterectomy for benign and non-obstetric indications, the MCR applied to preoperative ultrasound was only weakly associated with a histological diagnosis of adenomyosis.

Oophorectomy for ovarian torsion - should this be abandoned?

BACKGROUND: Management of ovarian torsion ranges from de-torsion to oophorectomy and is dependent on various factors. Oophorectomy can have significant implications for fertility and general health, thus requiring careful consideration. AIMS: We evaluate the management of ovarian torsion at a tertiary hospital over a ten-year period and identify the predictors of oophorectomy in ovarian torsion cases. MATERIALS AND METHODS: Inpatient notes of patients who underwent surgical management for acute ovarian torsion at a tertiary hospital in Victoria, Australia, were reviewed, from January 2008 to June 2018. We reported the incidence and predictors of oophorectomy and ovarian ischaemia and current practices in oophoropexy. RESULTS: Our analysis included 159 patients. The incidence of oophorectomy was 47%. After confounders were adjusted, increasing age was the only significant predictor for oophorectomy. The adjusted odds ratio of having an oophorectomy based on age alone was 1.10 for each year increase in age between the ages of 15 and 68 (P = 0.001, 95% confidence interval 1.04-1.16). Of those with oophorectomy, 57% had ischaemia confirmed histologically. There were no significant predictors for ischaemia. CONCLUSION: The incidence of oophorectomy in this audit is comparable to reported incidences in current literature. However, with increasing evidence to support ongoing ovarian function even in cases where ischaemia is histologically confirmed, this incidence could be lowered. Age was the only variable that was found to have a significant effect on the incidence of oophorectomy.

The role of social media in management of individuals with endometriosis: A cross-sectional study.

BACKGROUND: To better understand the potential role of social media (SM) as a self-management tool for individuals with endometriosis and to assess its current use by endometriosis patients. AIMS: The primary outcome was use of SM for health in patients with endometriosis. Secondary outcomes included preferred SM platforms for health information sharing and factors that influenced use, positive and negative experiences and reported impacts on health. MATERIALS AND METHODS: A single-centre, cross-sectional study performed within benign gynaecology units at a tertiary hospital in Melbourne, Australia. One hundred patients with a confirmed diagnosis of endometriosis participated. Individuals did not have to be users of SM. Data were collected through an electronic third-party survey tool (SurveyMonkey® ). Analysis methods included descriptive statistical analysis, frequency counts, as well as cross-tabulation to examine statistical association between variables. Free-text responses were qualitatively analysed using deductive-inductive semantic thematic analysis. RESULTS: Social media was used for health by 76% of patients with endometriosis in this study. SM users were younger, had pelvic pain for more than six months and reported higher rates of psychosocial impact and symptoms from endometriosis. Respondents reported overall positive impacts on psychological, social and cognitive health outcomes (76%) from SM use. CONCLUSION: In our cohort, a high number of people with endometriosis are using SM for health. These individuals are more likely to suffer both physical and psychosocial impacts from endometriosis. Hospitals and health organisations may consider support of the endometriosis community through SM.

Elucidating the role of long intergenic non-coding RNA 339 in human endometrium and endometriosis.

Endometriosis is a complex disease, influenced by genetic factors. Genetic markers associated with endometriosis exist at chromosome 1p36.12 and lead to altered expression of the long intergenic non-coding RNA 339 (LINC00339), however, the role of LINC00339 in endometriosis pathophysiology remains unknown. The aim of this work was to characterize the expression patterns of LINC00339 mRNA in endometrium and endometriotic lesions in situ and to determine the functional role of LINC00339 in human endometrium. We employed RNA-sequencing (RNA-seq), quantitative RT-PCR and in situ hybridization to investigate the abundance of LINC00339 transcripts in endometrium and endometrial cell lines and to describe the pattern and localization of LINC00339 expression in endometrium and endometriotic lesions. LINC00339 mRNA expression was manipulated (overexpressed and silenced) in endometrial stromal cell lines and RNA-seq data from overexpression models were analysed using online bioinformatics platforms (STRING and Ingenuity Pathway Analysis) to determine functional processes. We demonstrated the expression of LINC00339 in endometriotic lesions for the first time; we found LINC00339 expression was restricted to the lesion foci and absent in surrounding non-lesion tissue. Furthermore, manipulation of LINC00339 expression in endometrial stromal cell lines significantly impacted the expression of genes involved in immune defence pathways. These studies identify a novel mechanism for LINC00339 activity in endometrium and endometriosis, paving the way for future work, which is essential for understanding the pathogenesis of endometriosis.

Comparing endometriotic lesions with eutopic endometrium: time to shift focus?

Endometriosis is a heterogeneous disease in terms of patient symptoms, treatment responsiveness and the presentation of endometriotic lesions. This article explores the histological features of endometriotic lesions, highlighting their sometimes underappreciated heterogeneity. We note the variability in evidence for and against the menstrual cycle responsiveness of lesions and consider the utility of drawing parallels between endometriotic lesions and eutopic endometrium. We ask whether histopathologic features beyond just the presence/absence of endometrial-like glands and/or stroma could help improve disease stratification. At the same time, we acknowledge the desire of many clinicians and patients to avoid invasive surgery thereby limiting the ability to histologically phenotype lesions. The ability to derive clinically useful histological information from endometriotic lesions, in association with patient data, would be invaluable to clinicians to help improve treatment options in such a diverse group of patients. However, in suggesting that a shift in focus may enable the development of a better patient stratification system, we recognise that our wish for a single comprehensive stratification system may be beyond reach for a disease of such diverse presentation.

Associations between body mass index and the surgical phenotype and location of endometriotic lesions.

RESEARCH QUESTION: Is there a relationship between body mass index (BMI) and endometriotic lesions, specifically surgical phenotype and lesion location? DESIGN: An observational retrospective cohort study at the Royal Women's Hospital, Melbourne, Australia, including 471 histologically confirmed endometriosis patients. Statistical analyses included multivariate logistic regression and multivariate modelling, correcting for multiple testing. Outcomes were the presence or absence of surgically classified lesion phenotypes, as per revised American Society for Reproductive Medicine criteria including superficial or deep, peritoneal or ovarian, and adhesions (Study I); and lesions at specific anatomical locations (including pelvic side wall, uterosacral ligament, pouch of Douglas, ovarian, uterovesical fold, bladder, and pararectal endometriosis) (Study II). RESULTS: In Study I, patients with higher BMI were more likely to have superficial peritoneal lesions (odds ratio [OR] 1.070, 95% confidence interval [CI] 1.004-1.144; P = 0.044), and less likely to have deep ovarian lesions (OR 0.928, 95% CI 0.864-0.993; P = 0.034). In Study II, patients with higher BMI were less likely to have uterovesical fold lesions (OR 0.927, 95% CI 0.867-0.985; P = 0.021) or anterior compartment lesions (OR 0.940, 95% CI 0.888-0.989; P = 0.023). After correcting for multiple testing, the relationship between BMI and lesion phenotypes did not persist (P > 0.01). CONCLUSIONS: This analysis does not conclusively support an influence of BMI on endometriotic lesion phenotype based on surgical classification or location. Further investigation of the physiological disturbances underlying BMI and the promotion of endometriotic lesion phenotypes and their location is warranted, but any effect is likely to be small.

New Diagnosis of Endometriosis is Less Common in Women over Age Forty Presenting with Pelvic Pain.

STUDY OBJECTIVE: To investigate the incidence of new diagnosis of endometriosis in women at or above the age of 40 who present with previously undiagnosed pelvic pain and no previous surgical or sonographic evidence of endometriosis to a tertiary care clinic specializing in pelvic pain and endometriosis. DESIGN: Retrospective cohort study (on the basis of the Strengthening the Reporting of Observational Studies in Epidemiology guidelines) of the incidence of laparoscopically proven endometriosis in women presenting with previously undiagnosed pelvic pain on the basis of age category (age <40 years or ≥40 years). Adjusted odds ratios and 95% confidence intervals were calculated using a multivariable logistic regression model. SETTING: Pelvic pain focused gynecology clinic at a tertiary care hospital. PATIENTS: Premenopausal women between 18 to 51 years who presented with pelvic pain and were booked for laparoscopy for the diagnosis and the possible treatment of endometriosis between the years 2012 to 2016. Patients who had had previous laparoscopy and those who had sonographic evidence of endometriosis were excluded from the study. INTERVENTIONS: Laparoscopic visual evaluation and treatment was carried out in all patients by specialized gynecologists focusing on endometriosis surgery. MEASUREMENTS AND MAIN RESULTS: Presence or absence of visualized endometriosis at laparoscopy. We evaluated 174 women who met the inclusion criteria. Endometriosis was diagnosed in 35% (19/55) of patients aged 40 years and above and in 67% (80/119) of patients below the age of 40 years. Odds ratio adjusted for body mass index and parity was 2.38 (1.09-5.00; p = .03). When assessed as a continuous curvilinear variable without division to age categories, age was significant even in the more comprehensive model including more potential confounders. Secondary outcome analysis demonstrated that deep infiltrating endometriosis was diagnosed in 5% (3/55) of the women at or above 40 years and in 8% (10/119) of women below 40 years (p = .76). In addition, a curvilinear relationship was found with age, and there was also a lower incidence of endometriosis of 50% (19/38) in the youngest cohort of women aged 18 to 25 years. CONCLUSION: The likelihood of a new diagnosis of endometriosis in women with pelvic pain, no previous laparoscopy and a normal sonogram in our referral center was lower in women aged 40 and above. Careful counseling and consideration of the risks and yield of surgery is recommended before performing a laparoscopy for investigation of pelvic pain in this age group.

Risk Factors and Outcomes of Conversion to Open Surgery in Benign Gynecologic Laparoscopies: A Case-Control Study.

STUDY OBJECTIVE: To describe cases of conversion from gynecologic laparoscopy to open surgery and to assess risk factors for conversion and conversion outcomes. DESIGN: A retrospective case-control study. SETTING: Tertiary referral hospital in Melbourne, Australia. PATIENTS: Eighty-five cases of conversion from laparoscopy to laparotomy and 170 controls matched by age, surgical date, and gynecologic unit from 2006 to 2017. INTERVENTIONS: Demographic, clinical, and surgical data were collected and compared between the study groups. Logistic regression was performed to identify preoperative and intraoperative risk factors for conversion. MEASUREMENTS AND MAIN RESULTS: Rate of conversion during the study period was 0.7%. The most common indication for conversion was unexpected surgical complexity (67% of cases), which included severe adhesive disease, specimen size, severe pathology, and inadequate views. Factors that were significantly associated with risk of conversion in multivariate analysis were previous pelvic inflammatory disease (adjusted odds ratio [aOR] 5.16; 95% confidence interval [CI], 1.35-19.71; p = .02), previous open surgery (aOR 3.62; 95% CI, 1.52-8.58; p <.01), history of endometriosis (aOR 2.96; 95% CI, 1.17-7.50; p = .02), and elevated body mass index (aOR 1.07; 95% CI, 1.01-1.13; p = .02). As compared with current surgery for endometriosis, odds of conversion were higher in surgeries for emergency indications (aOR 5.40; 95% CI, 1.53-18.98; p <.01), uterine pathologies (aOR 3.34; 95% CI, 1.10-10.12; p = .03), and adnexal pathologies (aOR 2.76; 95% CI, 1.19-6.40; p = .02). With the inclusion of intraoperative factors, surgical adhesions were also found to be associated with conversion (aOR 3.19; 95% CI, 1.30-7.85; p = .01). Most skilled laparoscopic surgeon level as defined by the Australasian Gynaecological Endoscopy and Surgery Society was not associated with conversion risk. Conversion to laparotomy was associated with a higher rate of intraoperative and postoperative complications and prolonged length of stay. CONCLUSION: Conversion to laparotomy is a rare but very important clinical outcome measure of laparoscopic surgery. Understanding the factors contributing to conversion and perioperative outcomes may help clinicians to identify and counsel patients before surgery and to reduce surgical morbidity.

Tissue specific regulation of transcription in endometrium and association with disease.

STUDY QUESTION: Are genetic effects on endometrial gene expression tissue specific and/or associated with reproductive traits and diseases? SUMMARY ANSWER: Analyses of RNA-sequence data and individual genotype data from the endometrium identified novel and disease associated, genetic mechanisms regulating gene expression in the endometrium and showed evidence that these mechanisms are shared across biologically similar tissues. WHAT IS KNOWN ALREADY: The endometrium is a complex tissue vital for female reproduction and is a hypothesized source of cells initiating endometriosis. Understanding genetic regulation specific to, and shared between, tissue types can aid the identification of genes involved in complex genetic diseases. STUDY DESIGN, SIZE, DURATION: RNA-sequence and genotype data from 206 individuals was analysed and results were compared with large publicly available datasets. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA-sequencing and genotype data from 206 endometrial samples was used to identify the influence of genetic variants on gene expression, via expression quantitative trait loci (eQTL) analysis and to compare these endometrial eQTLs with those in other tissues. To investigate the association between endometrial gene expression regulation and reproductive traits and diseases, we conducted a tissue enrichment analysis, transcriptome-wide association study (TWAS) and summary data-based Mendelian randomisation (SMR) analyses. Transcriptomic data was used to test differential gene expression between women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: A tissue enrichment analysis with endometriosis genome-wide association study summary statistics showed that genes surrounding endometriosis risk loci were significantly enriched in reproductive tissues. A total of 444 sentinel cis-eQTLs (P < 2.57 × 10-9) and 30 trans-eQTLs (P < 4.65 × 10-13) were detected, including 327 novel cis-eQTLs in endometrium. A large proportion (85%) of endometrial eQTLs are present in other tissues. Genetic effects on endometrial gene expression were highly correlated with the genetic effects on reproductive (e.g. uterus, ovary) and digestive tissues (e.g. salivary gland, stomach), supporting a shared genetic regulation of gene expression in biologically similar tissues. The TWAS analysis indicated that gene expression at 39 loci is associated with endometriosis, including five known endometriosis risk loci. SMR analyses identified potential target genes pleiotropically or causally associated with reproductive traits and diseases including endometriosis. However, without taking account of genetic variants, a direct comparison between women with and without endometriosis showed no significant difference in endometrial gene expression. LARGE SCALE DATA: The eQTL dataset generated in this study is available at http://reproductivegenomics.com.au/shiny/endo_eqtl_rna/. Additional datasets supporting the conclusions of this article are included within the article and the supplementary information files, or are available on reasonable request. LIMITATIONS, REASONS FOR CAUTION: Data are derived from fresh tissue samples and expression levels are an average of expression from different cell types within the endometrium. Subtle cell-specifc expression changes may not be detected and differences in cell composition between samples and across the menstrual cycle will contribute to sample variability. Power to detect tissue specific eQTLs and differences between women with and without endometriosis was limited by the sample size in this study. The statistical approaches used in this study identify the likely gene targets for specific genetic risk factors, but not the functional mechanism by which changes in gene expression may influence disease risk. WIDER IMPLICATIONS OF THE FINDINGS: Our results identify novel genetic variants that regulate gene expression in endometrium and the majority of these are shared across tissues. This allows analysis with large publicly available datasets to identify targets for female reproductive traits and diseases. Much larger studies will be required to identify genetic regulation of gene expression that will be specific to endometrium. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Health and Medical Research Council (NHMRC) under project grants GNT1026033, GNT1049472, GNT1046880, GNT1050208, GNT1105321, GNT1083405 and GNT1107258. G.W.M is supported by a NHMRC Fellowship (GNT1078399). J.Y is supported by an ARC Fellowship (FT180100186). There are no competing interests.

Obesity does not alter endometrial gene expression in women with endometriosis.

RESEARCH QUESTION: Does obesity affect endometrial gene expression in women with endometriosis, specifically women with stage I disease? DESIGN: Differential gene expression analysis was conducted on endometrium from women with and without endometriosis (n = 169). Women were diagnosed after surgical visualization and staged according to the revised American Society for Reproductive Medicine (stage I-IV). Women were grouped by body mass index (BMI) (kg/m2) as underweight, normal, pre-obese or obese. After accounting for menstrual cycle stage, endometrial gene expression was analysed by BMI (continuous and grouped) in women with endometriosis, and in non-endometriosis controls. RESULTS: No significant interaction effect was found between BMI and endometriosis status on endometrial gene expression. We have previously reported that obese women with endometriosis have a reduced incidence of stage I disease; however, stratifying our analysis into stage I endometriosis versus combined II, III and IV endometriosis failed to reveal any differentially expressed endometrial genes between normal, pre-obese and obese patients. CONCLUSIONS: Despite obesity having deleterious effects on endometrial gene expression in other gynaecological pathologies, e.g. endometrial cancer and polycystic ovary syndrome, our results do not support an association between BMI and altered endometrial gene expression in women with or without endometriosis.