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Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (25 September 2021) | Viewed by 45867

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Special Issue Editors

Dr. Vered H. Eisenberg

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Guest Editor

1. Sheba Medical Center, Tel Hashomer 5265601, Israel
2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Interests: endometriosis; early diagnosis; non-invasive diagnosis; healthcare resource utilization; quality of care; outcome measures; process measures; health-related quality of life; ultrasound diagnosis; patient-reported outcomes and experiences.

Prof. Dr. Arnaud L. Fauconnier

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Guest Editor

1. Université Paris-Saclay, UVSQ, Unité de recherche 7285 « Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), 78180 Montigny-le-Bretonneux, France
2. Centre Hospitalier Intercommunal de Poissy-Saint-Germain-en-Laye, Service de gynecologie & obstétrique, 78303 Poissy CEDEX, France
Interests: endometriosis; early diagnosis; non-invasive diagnosis; healthcare resource utilization; quality of care; outcome measures; process measures; health-related quality of life; ultrasound diagnosis; patient-reported outcomes and experiences.

Special Issue Information

Dear Colleagues,

The gold standard for the diagnosis of endometriosis has traditionally been surgery. Over the past decade, considerable progress has been made in non-invasive diagnosis using ultrasound or magnetic resonance imaging. Despite this, the delay in diagnosis remains long, averaging eight years worldwide, and contributes to a significant utilization of healthcare resources and burden of care. Once a diagnosis is reached, a solution that improves quality of life is not always available, and many women experience distress.

Improvement in access to quality care for women with endometriosis is a challenge. The goal of early diagnosis of endometriosis and its primary or secondary prevention is a solution desired by patients and associations. Achieving these objectives raises many preliminary issues, such as our knowledge of the natural history and pathogenesis of endometriosis. The actual prevalence and severity of endometriosis in the general population is another challenge, because most studies to date are based on cohort studies of patients undergoing surgery, frequently from referral centers, which may distort the true prevalence of the disease. Timely access to quality care relies on early referral to specialized endometriosis centers and wider access to non-invasive diagnostic methods taking into account the risks associated with overdiagnosis or the risks associated with a delay in diagnosis. Therapeutic strategies applicable in primary care, for mild to moderate endometriosis that does not necessitate invasive procedures or treatment in a referral center, need to be developed. Simple first-line therapies are available, as is supportive care.

The objective of this Special Issue is to develop and evaluate the concepts, strategies, and outcomes necessary to improve access to quality care for women suffering from endometriosis by taking into account the impact of primary care and patient empowerment. We will focus on non-invasive diagnosis, early diagnosis and prediction of endometriosis, patient-reported outcomes and experiences, and laboratory diagnosis, such as biomarkers.

Dr. Vered H. Eisenberg
Prof. Dr. Arnaud L. Fauconnier
Guest Editors

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Keywords

endometriosis
early diagnosis
non-invasive diagnosis
healthcare resource utilization
quality of care
outcome measures
process measures
health-related quality of life
ultrasound diagnosis
patient-reported outcomes and experiences

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Published Papers (7 papers)

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Research

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10 pages, 780 KiB

Open AccessArticle

Burden of Endometriosis: Infertility, Comorbidities, and Healthcare Resource Utilization

by Vered H. Eisenberg, Dean H. Decter, Gabriel Chodick, Varda Shalev and Clara Weil

J. Clin. Med. 2022, 11(4), 1133; https://doi.org/10.3390/jcm11041133 - 21 Feb 2022

Cited by 32 | Viewed by 5445

Abstract

The goal of our study was to evaluate the burden of endometriosis in the community by comparing healthcare resource utilization, total direct medical costs, infertility, and comorbidity rates of women with and without a diagnosis of endometriosis. A retrospective case–control study was performed using the databases of a 2.1 million-member nationwide healthcare plan. The study population included women aged 15–55 years enrolled in the healthcare plan. Women with a diagnosis (ICD-9) of endometriosis were compared to controls without diagnosed endometriosis. Women were individually matched (1:4) on age and residence area. Patient characteristics were described, including infertility, comorbidities, and annual healthcare resource utilization. Total direct medical costs were analyzed in a generalized linear model adjusting for age. Women with endometriosis (n = 6146, mean age ± SD: 40.4 ± 8.0 y) were significantly more likely than controls (n = 24,572) to have a lower BMI and a higher socioeconomic status. After adjusting for BMI and socioeconomic status, endometriosis was significantly associated with infertility (OR = 3.3; 95% CI 3.1–3.5), chronic comorbidities, higher utilization of healthcare services (hospitalization: OR = 2.3; 95% CI 2.1–2.5), pain medications, and antidepressants. Women aged 15–19 y with endometriosis had substantially higher utilization of primary care visits (57.7% vs. 14.4%) and oral contraceptive use (76.9% vs. 9.6%). Direct medical costs associated with endometriosis were higher than those for controls (OR = 1.75; 95% CI 1.69–1.85). Endometriosis is associated with a high burden of comorbidities, increased healthcare resource utilization, and excess costs, particularly for younger patients whose healthcare needs may differ widely from the older population. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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13 pages, 820 KiB

Open AccessArticle

The ENDOPAIN 4D Questionnaire: A New Validated Tool for Assessing Pain in Endometriosis

by Anne Puchar, Pierre Panel, Anne Oppenheimer, Joseph Du Cheyron, Xavier Fritel and Arnaud Fauconnier

J. Clin. Med. 2021, 10(15), 3216; https://doi.org/10.3390/jcm10153216 - 21 Jul 2021

Cited by 12 | Viewed by 5063

Abstract

Objectives: To study the measurement properties, the responsiveness and the minimal clinically important difference of the ENDOPAIN-4D: a new questionnaire for assessing pain in endometriosis. Methods: A prospective, observational, multicentre study was conducted including all women ≥18 years consulting for symptomatic proven endometriosis between 1 January 2017 and 30 June 2018 and volunteering to participate. Each patient had to answer a new self-administered patient-reported outcome (PRO) questionnaires (the ENDOPAIN-4D) at inclusion (T0) and 12 months after medical or surgical treatment (T1). Criteria defined by COSMIN were used to validate the questionnaire’s measurement properties. The minimal clinically important difference was estimated by the anchor-based method. Results: The study included 199 women. The ENDOPAIN-4D score had a four dimensional structure with good internal consistency (measured by Cronbach α): (I) pain-related disability (α = 0.79), (II) painful bowel symptoms (α = 0.80), (III) dyspareunia (α = 0.83), and (IV) painful urinary tract symptoms (α = 0.77). They produced four subscores that can be summed to obtain a single score (α = 0.61). The ENDOPAIN-4D total score ranged from 0 to 94.00 (mean ± SD: 46.7 ± 22). The total score was significantly correlated with the PROs used in endometriosis. Sensitivity to change was good with large effect sizes (ES) (mean of the differences: 36.3 p = 1.8 10⁻⁷, ES 0.76). The minimal clinically important difference of the global score was determined to be 10.9. Conclusions: The ENDOPAIN-4D questionnaire is easy to use, valid, and effective in assessing patient reported pain symptoms in women treated for endometriosis. This new instrument can be used as the primary outcome for future clinical trials and as a tool for routine patient follow-up. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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13 pages, 9071 KiB

Open AccessArticle

External Validation of the IOTA Classification in Women with Ovarian Masses Suspected to Be Endometrioma

by Lee Cohen Ben-Meir, Roy Mashiach and Vered H. Eisenberg

J. Clin. Med. 2021, 10(13), 2971; https://doi.org/10.3390/jcm10132971 - 1 Jul 2021

Cited by 7 | Viewed by 3782

Abstract

The study aimed to perform external validation of the International Ovarian Tumor Analysis (IOTA) classification of adnexal masses as benign or malignant in women with suspected endometrioma. A retrospective study including women referred to an endometriosis tertiary referral center for dedicated transvaginal ultrasound (TVUS). Adnexal masses were evaluated using the IOTA classification simple descriptors, simple rules and expert opinion. The reference standard was definitive histology after mass removal at laparoscopy. In total, 621 women were evaluated and divided into four groups: endometrioma on TVUS and confirmed on surgery (Group 1 = 181), endometrioma on TVUS but other benign cysts on surgery (Group 2 = 9), other cysts on TVUS but endometrioma on surgery (Group 3 = 2), masses classified as other findings or suspicious for malignancy on TVUS and confirmed on surgery (Group 4 = 5 potentially malignant, 11 benign). This gave a sensitivity 98.9%, specificity 64%, positive 95.3% and negative 88.9% predictive values, positive 2.74 and negative 0.02 likelihood ratios and 94.7% overall accuracy. The surgical diagnosis for the five masses suspected to be malignant was: borderline serous tumor (2), borderline mucinous tumor (2), and endometrioid lesion with complex hyperplasia without atypia (1). The conclusions were that the IOTA classification simple descriptors, simple rules and expert opinion performs well for classifying adnexal masses suspected to be endometrioma. The most common potentially malignant masses in these women were borderline ovarian tumors. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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12 pages, 776 KiB

Open AccessArticle

The Underestimated Prevalence of Neglected Chronic Pelvic Pain in Women, a Nationwide Cross-Sectional Study in France

by François Margueritte, Xavier Fritel, Marie Zins, Marcel Goldberg, Henri Panjo, Arnaud Fauconnier and Virginie Ringa

J. Clin. Med. 2021, 10(11), 2481; https://doi.org/10.3390/jcm10112481 - 3 Jun 2021

Cited by 10 | Viewed by 3818

Abstract

Dysmenorrhoea, dyspareunia, and non-menstrual chronic pelvic pain (NMCPP) are symptoms that are probably underreported and neglected. This study aimed to assess the prevalence and overlapping relations between these symptoms among a general population of French women of reproductive age. A cross-sectional study among the nationwide CONSTANCES cohort study recruiting a representative sample of women within different French areas was constructed. Women aged 18–49 years (n = 21,287) who reported periods in the previous three months and experienced intercourse at least once were asked about prevalence of three types of chronic pelvic pain: mild, moderate and severe dysmenorrhea; dyspareunia assessed according to its frequency; NMCPP from a binary question. Between the start of 2012 through the end of 2017, 21,287 women were enrolled, 39.8% of them (95% confidence interval (CI), 39.2–40.5) reported moderate to severe dysmenorrhea; 20.3% (95% CI, 18.7–21.9) of the youngest group (18–24 years) reported severe dysmenorrhea. Dyspareunia was reported to happen often or always by 7.9% (95% CI, 7.5–8.2) and peaked among the youngest women at 12.8% (95% CI, 11.5–14.1). NMCPP was reported by 17.0% (95% CI, 16.5–17.5). Moreover, 7.5% (95% CI, 6.4–8.6) of the women reported two or more types of severe or frequent pain. More attention should be paid to this substantial proportion (7.5%) of French women of reproductive age who experience multiple, severe and frequent pelvic pain symptoms. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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10 pages, 1746 KiB

Open AccessArticle

Sonographic Signs of Adenomyosis in Women with Endometriosis Are Associated with Infertility

by Dean Decter, Nissim Arbib, Hila Markovitz, Daniel S. Seidman and Vered H. Eisenberg

J. Clin. Med. 2021, 10(11), 2355; https://doi.org/10.3390/jcm10112355 - 27 May 2021

Cited by 8 | Viewed by 9057

Abstract

We compared the prevalence of ultrasound signs of adenomyosis in women with endometriosis who underwent surgery to those who were managed conservatively. This was a retrospective study of women evaluated at a tertiary endometriosis referral center who underwent 2D/3D transvaginal ultrasound. Adenomyosis diagnosis was based on the presence of at least three sonographic signs. The study group subsequently underwent laparoscopic surgery while the control group continued conservative management. Statistical analysis compared the two groups for demographics, symptoms, clinical data, and sonographic findings. The study and control groups included 244 and 158 women, respectively. The presence of any, 3+, or 5+ sonographic signs of adenomyosis was significantly more prevalent in the study group (OR = 1.93–2.7, p < 0.004, 95% CI; 1.24–4.09). After controlling for age, for all findings but linear striations, the OR for having a specific feature was higher in the study group. Women in the study group with ≥ 5 sonographic signs of adenomyosis had more than twice the risk of experiencing infertility (OR = 2.31, p = 0.012, 95% CI; 1.20–4.45). Sonographic signs of adenomyosis are more prevalent in women with symptomatic endometriosis who underwent surgery compared with those who continued conservative management. Women with 5+ findings have a significantly increased risk of infertility. Adenomyosis on ultrasound should be considered in the management decisions regarding these patients. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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Review

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24 pages, 767 KiB

Open AccessReview

Patient-Reported Outcome Measures in Endometriosis

by Alba Nicolas-Boluda, Anne Oppenheimer, Jerome Bouaziz and Arnaud Fauconnier

J. Clin. Med. 2021, 10(21), 5106; https://doi.org/10.3390/jcm10215106 - 30 Oct 2021

Cited by 17 | Viewed by 5910

Abstract

Patient Reported Outcome Measures (PROM) evoke measurements that allow capturing patients’ perspectives on their condition. In endometriosis care, physicians’ understanding of the effect of the disease and the treatment on patients is often poor. The use of PROMs in endometriosis clinical practice can facilitate patient-provider communication and the implementation of patient-centered care, improve patients’ quality of life, as well as provide a tool for patients’ self-management of the disease. Today, PROMs are extensively used in research and clinical trials, however they are barely used in clinical practice. The development of digital tools facilitating capturing PROMs can contribute to their use by physicians in routine endometriosis care. However, all PROMs are not adapted to be used in routine care in the context of endometriosis. The objective of this study was to present a catalogue of available PROMs for routine endometriosis care and evaluate them according to selected criteria. To do so, we explored the different PROMs currently in the literature. Consequently, 48 PROM were identified as tools used to evaluate various dimensions of the impact of endometriosis on patients. The selected PROMs were evaluated for their potential to be used as a standard in clinical practice in endometriosis. The selected catalogue of PROMs is the starting point for the integration of digital tools to capture PROMs and the development of patient-centered dashboards to be used by patients and clinicians in endometriosis care and self-management to improve care processes, patient satisfaction, quality of life, and outcomes. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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16 pages, 1113 KiB

Open AccessReview

The Potential of Non-Invasive Biomarkers for Early Diagnosis of Asymptomatic Patients with Endometriosis

by Żaneta Kimber-Trojnar, Aleksandra Pilszyk, Magdalena Niebrzydowska, Zuzanna Pilszyk, Monika Ruszała and Bożena Leszczyńska-Gorzelak

J. Clin. Med. 2021, 10(13), 2762; https://doi.org/10.3390/jcm10132762 - 23 Jun 2021

Cited by 27 | Viewed by 11419

Abstract

Endometriosis is a disease that affects women of reproductive age and has a significantly negative impact on their well-being. The main symptoms are dysmenorrhoea, chronic pelvic pain and infertility. In many patients the diagnostic process is very long and can take up to 8–12 years. Laparoscopy, an invasive method, is still necessary to confirm the diagnosis. Therefore, development of more effective diagnostic markers appears to be of the utmost importance for early diagnosis of endometriosis and provision of appropriate treatment. From a clinical point of view, detection of early-stage endometriosis in asymptomatic patients is an ideal situation since early diagnosis of endometriosis may delay the onset of symptoms as well as prevent progression and complications. In the meantime, Cancer Antigen 125 (CA-125) is still the most frequently studied and used marker. Other glycoproteins, growth factors and immune markers seem to play an important role. However, the search for an ideal endometriosis marker is still underway. Further studies into the pathogenesis of endometriosis will help to identify biomarkers or sets of biomarkers with the potential to improve and speed up the diagnostic process in a non-invasive way. Full article

(This article belongs to the Special Issue Endometriosis: Epidemiology, Non-invasive Diagnosis, Prediction, and Clinical Management)

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