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Norah Spears University of Edinburgh – Biomedical Sciences, Edinburgh, UK

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Andrew W Horne University of Edinburgh – MRC Centre for Reproductive Health, Edinburgh, UK

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Kevin KW Kuan Edinburgh Medical School, University of Edinburgh, Edinburgh, UK

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Aileen R Neilson Usher Institute, Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK

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Andrew W Horne MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK

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Lucy HR Whitaker MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK

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Abstract

Patients with chronic pelvic pain (CPP) may experience pain exacerbations requiring hospital admissions. Due to the effects of backlogged elective surgeries and outpatient gynaecology appointments resulting from the COVID-19 pandemic, we hypothesised that there would be an increased number of women admitted with CPP flares. We conducted a retrospective review of all acute gynaecology admissions at the Royal Infirmary of Edinburgh from July to December 2018 (pre-COVID) and 2021 (post-COVID lockdown). We collected information on the proportion of emergency admissions due to CPP, inpatient investigations and subsequent management. Average total indicative hospital inpatient costs for women with CPP were calculated using NHS National Cost Collection data guidance. There was no significant difference in the number of emergency admissions due to pelvic pain before (153/507) and after (160/461) the COVID-19 pandemic. As high as 33 and 31% had a background history of CPP, respectively. Across both timepoints, investigations in women with CPP had low diagnostic yield: <25% had abnormal imaging findings and 0% had positive vaginal swab cultures. Women with CPP received significantly more inpatient morphine, pain team reviews and were more likely to be discharged with strong opioids. Total yearly inpatient costs were £170,104 and £179,156 in 2018 and 2021, respectively. Overall, emergency admission rates for managing CPP flares was similar before and after the COVID-19 pandemic. Inpatient resource use for women with CPP remains high, investigations have low diagnostic yield and frequent instigation of opiates on discharge may risk dependence. Improved community care of CPP is needed to reduce emergency gynaecology resource utilisation.

Lay summary

Existing treatments for chronic pelvic pain (CPP) and endometriosis focus on surgery or hormone medication, but these are often ineffective or associated with unacceptable side-effects. As a result, women continue to experience chronic pain and often have ‘flares’ of worsening pain that may lead to hospital admission. The COVID-19 pandemic resulted in backlogged gynaecology clinics and surgeries. The aim of this study was to compare the management of emergency pelvic pain admissions for women with CPP before and after COVID-19. We also aimed to better understand their in-hospital management and estimate their hospital length of stay costs. We did not find an increase in CPP patients admitted for pelvic pain flares after the COVID-19 lockdown. Women with CPP often undergo multiple hospital tests and are often prescribed with strong pain medications which can cause long-term problems. Efforts are needed to improve long-term pain management for women with CPP.

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Francesca Hearn-Yeates F Hearn-Yeates, Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland

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Andrew W Horne A Horne, Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland

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Siobhain O’Mahony S O’Mahony, Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

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Philippa T K Saunders P Saunders, Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland

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Endometriosis is a chronic inflammatory condition affecting one in 10 women and those assigned female at birth, defined by the presence of endometrial-like tissue outside the uterus. It is commonly associated with pain, infertility, and mood disorders, and often comorbid with other chronic pain conditions, such as irritable bowel syndrome. Recent research has identified a key role for the microbiota-gut-brain axis in health and a range of inflammatory and neurological disorders, prompting an exploration of its potential mechanistic role in endometriosis. Increased awareness of the impact of the gut microbiota within the patient community, combined with the often-detrimental side effects of current therapies, has motivated many to utilise self-management strategies, such as dietary modification and supplements, despite a lack of robust clinical evidence. Current research has characterised the gut microbiota in endometriosis patients and animal models. However, small cohorts and differing methodology has resulted in little consensus in the data. In this narrative review, we summarise research studies that have investigated the role of gut microbiota and their metabolic products in the development and progression of endometriosis lesions, before summarising insights from research into co-morbid conditions and discussing the reported impact of self-management strategies on symptoms of endometriosis. Finally, we suggest ways in which this promising field of research could be expanded to explore the role of specific bacteria, improve access to ‘microbial’ phenotyping, and to develop personalised patient advice for reduction of symptoms such as chronic pain and bloating.

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Nick Wheelhouse School of Applied Sciences, Edinburgh Napier University, Sighthill Court, Edinburgh, UK
Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

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Sadie Kemp School of Applied Sciences, Edinburgh Napier University, Sighthill Court, Edinburgh, UK

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Jo E B Halliday Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

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Efstathios Alexandros Tingas School of Engineering & the Built Environment, Edinburgh Napier University, Merchiston Campus, Edinburgh, UK

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W Colin Duncan MRC Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh Bioquarter, Edinburgh, UK

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Andrew W Horne MRC Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh Bioquarter, Edinburgh, UK

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Lay summary

Q fever is a bacterial disease that passes between animals and humans and causes disease in both. The disease has been associated with pregnancy complications including miscarriage. This study was undertaken to identify if Q fever exposure was correlated with miscarriage in 369 women attending a pregnancy support unit in Edinburgh. The women in the study were in two groups, the miscarriage group with 251 women who had experienced a miscarriage and a control group of 118 women who had not experienced miscarriage. Three women were found to be positive for Q fever antibodies, suggesting that they had previously been exposed to the infection and all of them were from the group who had experienced miscarriage. The study indicates that Q fever is relatively rare in women attending an urban Scottish hospital suggesting that the infection is not a major cause of miscarriage in this population. However, as Q fever antibodies could only be found in women within the miscarriage group, it suggests that the infection cannot be ruled out as a potential cause of miscarriage in individual cases.

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Scott C Mackenzie MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK

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Catherine A Moakes Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK

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W Colin Duncan MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK

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Stephen Tong Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia

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Andrew W Horne MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK

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Lay summary

An ectopic pregnancy occurs when an embryo implants outside of the uterus, usually in a fallopian tube. When detected early, treatment is often with a medication called methotrexate. When methotrexate does not work, surgery is required. A recent clinical trial of ectopic pregnancy treatment (called GEM3) found that adding a drug called gefitinib to methotrexate did not reduce the need for surgery. We have used data from the GEM3 trial, combined with data collected 12 months after the trial finished, to investigate post-methotrexate pregnancy outcomes. We found no difference in pregnancy rates, pregnancy loss rates and recurrent ectopic pregnancy rates between those treated medically only and those who subsequently also needed surgery. The surgical technique used also did not affect pregnancy rates. This research provides reassurance that women with ectopic pregnancies treated medically who need surgery have similar post-treatment pregnancy outcomes to those treated successfully medically.

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Douglas A Gibson Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

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Frances Collins Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

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Bianca De Leo Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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Andrew W Horne MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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Philippa T K Saunders Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

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Endometriosis is a chronic neuroinflammatory pain condition affecting ~180 million women worldwide. Surgical removal or hormonal suppression of endometriosis lesions only relieves pain symptoms in some women and symptomatic relapse following treatment is common. Identifying factors that contribute to pain is key to developing new therapies. We collected peritoneal fluid samples and clinical data from a cohort of women receiving diagnostic laparoscopy for suspected endometriosis (n = 52). Peritoneal fluid immune cells were analysed by flow cytometry and data compared with pain scores determined using the pain domain of the Endometriosis Health Profile Questionnaire (EHP-30) in order to investigate the association between peritoneal immune cells and pain symptoms. Pain scores were not different between women with or without endometriosis, nor did they differ according to disease stage; consistent with a poor association between disease presentation and pain symptoms. However, linear regression and correlation analysis demonstrated that peritoneal macrophage abundance correlated with the severity of pelvic pain. CD14high peritoneal macrophages negatively correlated with pain scores whereas CD14low peritoneal macrophages were positively correlated, independent of diagnostic outcome at laparoscopy. Stratification by pain subtype, rather than endometriosis diagnosis, resulted in the most robust correlation between pain and macrophage adundance. Pain score strongly correlated with CD14high (P = 0.007) and CD14low (P = 0.008) macrophages in patients with non-menstrual pain and also in patients who reported dysmennorhea (CD14high P = 0.021, CD14low P = 0.019) or dysparunia (CD14high P = 0.027, CD14low P = 0.031). These results provide new insight into the association between peritoneal macrophages and pelvic pain which may aid the identification of future therapeutic targets.

Lay summary

Endometriosis is a common condition where cells similar to those that line the womb are found elsewhere in the body. It is associated with inflammation and pain in the pelvis and affects ~180 million women worldwide. Current treatments are not effective for all patients and we, therefore, need to understand what causes pain in order to develop new treatments. We investigated the types of immune cells present within the pelvis of women undergoing investigation for suspected endometriosis. Disease diagnosis and stage (I–IV) was recorded along with pain score determined by questionnaire. We characterised the immune cells present and compared them to disease stage and pain score. We found that pelvic pain was linked to the abundance of immune cells but, surprisingly, not to disease stage. These findings suggest that immune cells are closely associated with pain severity in endometriosis and may be good targets for future endometriosis treatments.

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Ezekiel O Mecha Department of Biochemistry, University of Nairobi, Nairobi, Kenya

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Joseph N Njagi Marple Grove Gynecological Centre, Kerugoya, Kenya

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Roselydiah N Makunja Department of Biochemistry, University of Nairobi, Nairobi, Kenya

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Charles O A Omwandho Department of Biochemistry, University of Nairobi, Nairobi, Kenya
Kirinyaga University, Kerugoya, Kenya

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Philippa T K Saunders EXPPECT Centre, Queen’s Medical Research Institute, Edinburgh Bioquarter, The University of Edinburgh, Edinburgh, UK

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Andrew W Horne EXPPECT Centre, Queen’s Medical Research Institute, Edinburgh Bioquarter, The University of Edinburgh, Edinburgh, UK

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Endometriosis has long been wrongly perceived to be rare among women of African descent. The misconception about the prevalence of endometriosis among African women has significantly contributed to long diagnostic delays, limited access to diagnosis and care, and a scarcity of research on the condition among African women. In this commentary, we highlight the prevalence of endometriosis among African women, the state of endometriosis care in Africa, and the gaps in knowledge that need to be addressed. Based on the available data, the prevalence of endometriosis in Africa is likely higher than previously thought, with varying subtypes. There is a long diagnostic delay of endometriosis among African women. Additionally, endometriosis care in Africa from the general population and health practitioners is poor; this can be attributed to the high diagnostic cost, scarcity of trained specialists, as well as patients’ inability to express their symptoms due to societal taboos surrounding menstrual health. Public sensitization on endometriosis may help improve endometriosis diagnosis and care in Africa.

Lay summary

Endometriosis is a condition in which tissue like the uterine lining is found outside the uterus, causing women to experience pain especially before, during, or after menstruation. Although endometriosis affects an estimated 176 million women worldwide, it has been wrongly reported that endometriosis is a rare condition among African women, mainly due to lack of awareness among healthcare providers and historical bias. In the current commentary, we discuss the prevalence of endometriosis, the diagnostic delays, and the care of endometriosis among black African women living in the African continent. Much of the literature has demonstrated (falsely) that endometriosis is rare in Black women compared to White ethnicity. African women experience a long diagnostic delay and do not receive appropriate care. Public awareness of endometriosis may help improve diagnosis delay and endometriosis care in Africa.

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Elizabeth Ball Department of Obstetrics and Gynaecology, The Royal London Hospital, Barts Health NHS Trust, London, UK
Women’s Health Research Unit, Queen Mary University of London, London, UK

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Babu Karavadra Department of Gynecology, Norfolk & Norwich University Hospital, Norwich, UK

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Bethany Jade Kremer-Yeatman Poole Hospital NHS Foundation Trust, UK

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Connor Mustard Barts and the London Pragmatic Clinical Trials Unit, Queen Mary University of London, London, UK

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Kim May Lee Barts and the London Pragmatic Clinical Trials Unit, Queen Mary University of London, London, UK

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Sharandeep Bhogal Women’s Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Julie Dodds Women’s Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Andrew W Horne MRC Centre for Reproductive Health, University of Edinburgh, UK

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John Allotey Institute of Metabolism and Systems Research and Institute of Applied Health Research, University of Birmingham, Birmingham, UK

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Carol Rivas UCL Social Research Institute, University College London, London, UK

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Background

Up to 28% of endometriosis patients do not get pain relief from therapeutic laparoscopy but this subgroup is not defined.

Objectives

To identify any prognostic patient-specific factors (such as but not limited to patients’ type or location of endometriosis, sociodemographics and lifestyle) associated with a clinically meaningful reduction in post-surgical pain response to operative laparoscopic surgery for endometriosis.

Search strategy

PubMed, Cochrane and Embase databases were searched from inception to 19 May 2020 without language restrictions. Backward and forward citation tracking was used.

Selection criteria, data collection and analysis:

Cohort studies reporting prognostic factors, along with scores for domains of pain associated with endometriosis before and after surgery, were included. Studies that compared surgeries, or laboratory tests, or outcomes without stratification were excluded. Results were synthesised but variation in study designs and inconsistency of outcome reporting precluded us from doing a meta-analysis.

Main results

Five studies were included. Quality assessment using the Newcastle–Ottawa scale graded three studies as high, one as moderate and one as having a low risk of bias. Four of five included studies separately reported that a relationship exists between more severe endometriosis and stronger pain relief from laparoscopic surgery.

Conclusion

Currently, there are few studies of appropriate quality to answer the research question. We recommend future studies report core outcome sets to enable meta-analysis.

Lay summary

Endometriosis is a painful condition caused by displaced cells from the lining of the womb, causing inflammation and scarring inside the body. It affects 6–10% of women and there is no permanent cure. Medical and laparoscopic surgical treatments are available, but about 28% of patients do not get the hoped-for pain relief after surgery. Currently, there is no way of predicting who gets better and who does not. We systematically searched the world literature to establish who may get better, in order to improve counselling when women choose treatment options. We identified five studies of variable quality showing: More complex disease (in specialist hands) responds better to surgery than less, but more studies needed.

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