Positron emission tomography in the evaluation of endometriosis: A systematic review.

Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported incidental uptake of 18F-FDG PET tracer in endometriotic lesions. However, the utility of PET imaging as a non-invasive diagnostic tool for endometriosis is currently unclear. The purpose of this systematic review was to summarise the existing evidence and determine the value of available PET scanning techniques in the detection and monitoring of endometriosis. MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science were searched from conception to 05/03/23. Eligible studies included participants with a history of known or suspected endometriosis who underwent a PET scan for any indication. All PET tracers and protocols were eligible. Outcomes included correlation of PET tracer uptake with the presence of endometriosis seen at laparoscopy or confirmed on histology, sensitivity of tracer uptake, specificity of tracer uptake, site of lesions with tracer uptake, stage of lesions with tracer uptake, SUVmax of endometriosis lesions and adverse reactions to PET imaging. The protocol for this review was registered with PROSPERO (ID: CRD42023405260). Eight studies describing 110 participants were eligible for inclusion. Six studies assessed 18F-FDG with combined PET-CT, one study assessed 18F-FDG PET alone, and the remaining study assessed PET-CT with an alternative tracer, 68Ga-DOTATATE. For 18F-FDG imaging, the correlation of PET avidity with lesions or sites of endometriosis ranged from 0-55 %. Pre-operative 68Ga-DOTATATE PET-CT detected endometriosis in 33 % of cases. All included studies were cohort studies, six were assessed to have low risk of bias, one with moderate risk and one with high risk of bias. Overall, 18F-FDG PET scanning does not appear to consistently identify endometriotic lesions, and therefore its reliability and usefulness in endometriosis diagnosis is limited. The utility of 68Ga-DOTATATE PET-CT remains uncertain. Findings are constrained by limited available evidence reporting outcomes of PET imaging for endometriosis. Other existing PET tracers with biological plausibility in the detection or monitoring of endometriosis warrant further investigation.

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 relationship between sleep disturbances and endometriosis: A systematic review.

OBJECTIVE: Endometriosis is associated with a range of symptoms that can negatively impact a person's quality of life. While pain and infertility have received at lot of attention, sleep disturbances in individuals with endometriosis has been overlooked in both clinical practice and research. Therefore, the primary aim of this systematic review was to gather evidence from the current literature to illustrate the association between sleep disturbances and endometriosis. STUDY DESIGN: A literature search was conducted using three electronic databases (OVID EMBASE, MEDLINE, and Web of Science). Observational studies, published in English, that involved participants aged 18 years or older that compared sleep outcomes between endometriosis patients and those without a history of endometriosis were included. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tools. RESULTS: Nine studies (six case-control and three cross-sectional) were included in this review; 7 with low risk of bias and 2 with moderate risk of bias. The studies demonstrated heterogeneity in the assessment of sleep disturbances. However, 7 studies reported a significant positive association between endometriosis and sleep disturbances. Moreover, this impact on sleep was further complicated by the complex interaction between pain, fatigue and quality of life. CONCLUSION: Current studies suggest an association between sleep disturbances and endometriosis, which may provide a blueprint for future clinical recommendations to screen and treat sleep disturbances in individuals with endometriosis to improve their quality of life. Future studies should aim to standardise the methods of assessing sleep disturbances and explore potential contributing factors.

Noninvasive diagnostic imaging for endometriosis part 2: a systematic review of recent developments in magnetic resonance imaging, nuclear medicine and computed tomography.

Endometriosis affects 1 in 9 women, taking 6.4 years to diagnose using conventional laparoscopy. Non-invasive imaging enables timelier diagnosis, reducing diagnostic delay, risk and expense of surgery. This review updates literature exploring the diagnostic value of specialist endometriosis magnetic resonance imaging (eMRI), nuclear medicine (NM) and computed tomography (CT). Searching after the 2016 IDEA consensus, 6192 publications were identified, with 27 studies focused on imaging for endometriosis. eMRI was the subject of 14 papers, NM and CT, 11, and artificial intelligence (AI) utilizing eMRI, 2. eMRI papers describe diagnostic accuracy for endometriosis, methodologies, and innovations. Advantages of eMRI include its: ability to diagnose endometriosis in those unable to tolerate transvaginal endometriosis ultrasound (eTVUS); a panoramic pelvic view, easy translation to surgical fields; identification of hyperintense iron in endometriotic lesions; and ability to identify super-pelvic lesions. Sequence standardization means eMRI is less operator-dependent than eTVUS, but higher costs limit its role to a secondary diagnostic modality. eMRI for deep and ovarian endometriosis has sensitivities of 91-93.5% and specificities of 86-87.5% making it reliable for surgical mapping and diagnosis. Superficial lesions too small for detection in larger capture sequences, means a negative eMRI doesn't exclude endometriosis. Combined with thin sequence capture and improved reader expertise, eMRI is poised for rapid adoption into clinical practice. NM labeling is diagnostically limited in absence of suitable unique marker for endometrial-like tissue. CT studies expose the reproductively aged to radiation. AI diagnostic tools, combining independent eMRI and eTVUS endometriosis markers, may result in powerful capability. Broader eMRI use, will optimize standards and protocols. Reporting systems correlating to surgical anatomy will facilitate interdisciplinary preoperative dialogues. eMRI endometriosis diagnosis should reduce repeat surgeries with mental and physical health benefits for patients. There is potential for early eMRI diagnoses to prevent chronic pain syndromes and protect fertility outcomes.

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.

Evidence for the role of multidisciplinary team care in people with pelvic pain and endometriosis: A systematic review.

BACKGROUND: Endometriosis is a chronic, inflammatory condition characterised by the presence of endometrial-like tissue outside the uterine cavity. Given the multi-system nature of the disease and the potential for significant negative impact on quality of life, there has been a long-standing recognition of the need for multidisciplinary care for people with endometriosis. However, there is paucity to the data supporting this approach, and much of the evidence is anecdotal. AIM: This systematic review aims to describe recent evidence-based models and patient-centred perspectives of multidisciplinary care for endometriosis, to improve understanding of the role of an integrated, multidisciplinary team in effectively addressing patients' care needs. MATERIALS AND METHODS: PubMed, Medline, Embase and Web of Science were searched for relevant articles published between 1 January 2010 to 7 July 2022. RESULTS: Nineteen studies met the inclusion and exclusion criteria and pinpointed a multidisciplinary team consisting of gynaecologists, pain specialists, nurses, physiotherapists, psychologists, sex therapists, nutritionists, complementary medicine practitioners, and social workers to be most commonly utilised in holistically managing people with pelvic pain and endometriosis. Furthermore, patient perspectives on care highlighted the need for reliable information, respect and validation of experiences or preferences, discussion of long-term treatment plans and social and emotional supports. CONCLUSION: The trend for multidisciplinary team care for people with endometriosis is growing. Further consumer-driven clinical studies and outcome evaluations need to be conducted to determine the effect of multidisciplinary care on improvements to quality of life for people living with endometriosis and or pelvic pain.

Using a Quantitative High-Throughput Screening Platform to Identify Molecular Targets and Compounds as Repurposing Candidates for Endometriosis.

Endometriosis, defined as the growth of hormonally responsive endometrial-like tissue outside of the uterine cavity, is an estrogen-dependent, chronic, pro-inflammatory disease that affects up to 11.4% of women of reproductive age and gender-diverse people with a uterus. At present, there is no long-term cure, and the identification of new therapies that provide a high level of efficacy and favourable long-term safety profiles with rapid clinical access are a priority. In this study, quantitative high-throughput compound screens of 3517 clinically approved compounds were performed on patient-derived immortalized human endometrial stromal cell lines. Following assay optimization and compound criteria selection, a high-throughput screening protocol was developed to enable the identification of compounds that interfered with estrogen-stimulated cell growth. From these screens, 23 novel compounds were identified, in addition to their molecular targets and in silico cell-signalling pathways, which included the neuroactive ligand-receptor interaction pathway, metabolic pathways, and cancer-associated pathways. This study demonstrates for the first time the feasibility of performing large compound screens for the identification of new translatable therapeutics and the improved characterization of endometriosis molecular pathophysiology. Further investigation of the molecular targets identified herein will help uncover new mechanisms involved in the establishment, symptomology, and progression of endometriosis.

Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations.

This review leads the 2023 Call for Papers in MHR: 'Cyclical function of the female reproductive tract' and will outline the complex and fascinating changes that take place in the reproductive tract during the menstrual cycle. We will also explore associated reproductive tract abnormalities that impact or are impacted by the menstrual cycle. Between menarche and menopause, women and people who menstruate living in high-income countries can expect to experience ∼450 menstrual cycles. The primary function of the menstrual cycle is to prepare the reproductive system for pregnancy in the event of fertilization. In the absence of pregnancy, ovarian hormone levels fall, triggering the end of the menstrual cycle and onset of menstruation. We have chosen to exclude the ovaries and focus on the other structures that make up the reproductive tract: uterine tubes, endometrium, myometrium, and cervix, which also functionally change in response to fluctuations in ovarian hormone production across the menstrual cycle. This inaugural paper for the 2023 MHR special collection will discuss our current understanding of the normal physiological processes involved in uterine cyclicity (limited specifically to the uterine tubes, endometrium, myometrium, and cervix) in humans, and other mammals where relevant. We will emphasize where knowledge gaps exist and highlight the impact that reproductive tract and uterine cycle perturbations have on health and fertility.

Radiotherapy exposure directly damages the uterus and causes pregnancy loss.

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma-/-) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Gene expression of the endocannabinoid system in endometrium through menstrual cycle.

Endocannabinoids mediate cellular functions and their activity is controlled by a complex system of enzymes, membrane receptors and transport molecules. Endocannabinoids are present in endometrium, a cyclical regenerative tissue requiring tightly regulated cellular mechanisms for maturation. The objective of this study was to investigate the gene expression of key elements involved in the endocannabinoid system across the menstrual cycle. RNA was isolated from endometrial tissue and genome-wide gene expression datasets were generated using RNA-sequencing. An a priori set of 70 genes associated with endocannabinoid system were selected from published literature. Gene expression across the menstrual cycle was analyzed using a moderated t test, corrected for multiple testing with Bonferroni's method. A total of 40 of the 70 genes were present in > 90% of the samples, and significant differential gene expression identified for 29 genes. We identified 4 distinct regulation patterns for synthesizing enzymes, as well as a distinct regulation pattern for degradations and transporting enzymes. This study charts the expression of endometrial endocannabinoid system genes across the menstrual cycle. Altered expression of genes that control endocannabinoid may allow fine control over endocannabinoid concentrations and their influence on cellular function, maturation and differentiation as the endometrium matures through the menstrual cycle.

Is there a role for small molecule metabolite biomarkers in the development of a diagnostic test for endometriosis?

Endometriosis is a disease defined by the presence of benign lesions of endometrial-like glands and stroma outside the endometrial cavity. Affecting an estimated 11.4% of Australian women, symptoms include chronic pelvic pain, dysmenorrhea and infertility. The current gold standard of diagnosis requires an expensive and invasive laparoscopic surgery, resulting in delayed time to treatment. The identification of a non-invasive endometriosis biomarker - a measurable factor correlating with disease presence or activity - has therefore become a priority in endometriosis research, although no biomarker has yet been validated. As small molecule metabolites and lipids have emerged as a potential focus, this review with systematic approach, aims to summarize studies examining metabolomic biomarkers of endometriosis in order to guide future research. EMBASE, PubMed and Web of Science were searched using keywords: lipidomics OR metabolomics OR metabolome AND diagnostic tests OR biomarkers AND endometriosis, and only studies written in English from August 2000 to August 2020 were included. Twenty-nine studies met inclusion and exclusion criteria and were included. These studies identified potential biomarkers in serum, ectopic tissue, eutopic endometrium, peritoneal fluid, follicular fluid, urine, cervical swabs and endometrial fluid. Glycerophospholipids were identified as potential biomarkers in all specimens, except urine and cervical swab specimens. However, no individual molecule or metabolite combination has reached clinical diagnostic utility. Further research using large study populations with robust patient phenotype and specimen characterisation is required if we are to make progress in identifying and validating a non-invasive diagnostic test for endometriosis.

In-Hospital Patient Harm Across Linguistic Groups: A Retrospective Cohort Study of Home Care Recipients.

OBJECTIVE: Research examining the impact of language barriers on patient safety is limited. We conducted a population-based study to determine whether patients whose primary language is not English are more likely to experience harm when admitted to hospitals in Ontario, Canada. METHODS: We used linked administrative health records to establish a retrospective cohort of home care recipients (from 2010 to 2015) who were subsequently admitted to hospital. Patient language (obtained from home care assessments) was coded as English, French, or other. Harmful events were identified using the Hospital Harm Indicator developed by the Canadian Institute for Health Information. RESULTS: We included 190,724 patients (156,186 Anglophones, 5,110 Francophones, and 29,428 Allophones). There was no significant difference in the unadjusted risk of harm for Francophones compared with Anglophones (relative risk [RR], 0.94; 95% confidence interval [CI], 0.87-1.02). However, Allophones were more likely to experience harm when compared with Anglophones (RR, 1.14; 95% CI, 1.10-1.18). The risk of harm was even greater for Allophones with low English proficiency (RR, 1.18; 95% CI, 1.13-1.24). After adjusting for potential confounders, Anglophones and Allophones were equally likely to experience harm of any type, but Allophones more likely to experience harm from infections and procedures. CONCLUSIONS: Patients whose primary language was not English or French were more likely to experience harm after admission to hospital, especially if they had low English proficiency. For these patients, the risk of harm from infections and procedures persisted in the adjusted analysis, but the overall risk of harm did not.

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.

Anticipating the monsoon: the necessity and impossibility of the seasonal weather forecast for South Asia, 1886-1953.

This article examines the most controversial of the activities of the India Meteorological Department (IMD): long-term seasonal forecasting for the South Asian subcontinent. Under the pressure of recurrent famines, in 1886 the imperial IMD commenced annual issue of monsoon predictions several months in advance, focused on one variable: rainfall. This state service was new to global late nineteenth-century meteorology, attempted first and most rigorously in India. Successive IMD leaders adapted the forecast in light of scientific and infrastructural developments, continuously revising the underlying methods of its production. All methods failed to achieve accurate prevision. Nevertheless, the imperatives of economic administration, empire and public demand compelled IMD scientists to continue annual publication of this unreliable product. This article contends that the seasonal forecast is best understood as an enduring ritual of good governance in a monsoonal environment. Through analysis of newspaper controversies, it suggests that although the seasonal forecast was the most compelling justification for the IMD's imperial and global importance, its limitations undercut popular trust in modern meteorology. Finally, this case illustrates the centrality of 'tropical meteorology' to the historical development of modern atmospheric science.

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.

Evidence for an Association Between Endometriosis and Allergic and Non-allergic Food Hypersensitivity Is Lacking.

Endometriosis effects up to 1 in 9 women, and can be a severe and debilitating disease. It is suggested that there is a link between endometriosis and allergic hypersensitivities, including allergic and non-allergic food hypersensitivity. Best practice for managing endometriosis symptoms is holistic and includes broad multi-disciplinary care. Therefore, improving our understanding of common endometriosis comorbidities, including allergic and non-allergic food hypersensitivity, will assist in improving patient quality of life. This mini-review with systematic approach aims to explore the literature for evidence surrounding an association between endometriosis and allergic and/or non-allergic food hypersensitivity from the last 20 years. Of the 849 publications identified, five fulfilled the inclusion criteria. Only one publication reported a statistically significant increased risk for non-allergic food hypersensitivity in patients with endometriosis (P = 0.009), however, the endometriosis group was not uniform in diagnostic criteria and included individuals without laparoscopically visualized disease. No studies elucidated a statistically significant link between allergic food hypersensitivity alone and endometriosis. Therefore, based on a small number of studies with limited research quality, evidence does not support the existence of a link between endometriosis and allergic or non-allergic food hypersensitivity. Sufficiently powered evidence-based research is required, including information which better characterizes the patient's endometriosis symptoms, importantly the gastrointestinal sequalae, as well as specific allergic and non-allergic food hypersensitivities and method of diagnoses. Unequivocally confirming a link between endometriosis and food hypersensitivities is an essential step forward in dispelling the many myths surrounding endometriosis and improving management of disease.

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.