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World Endometriosis Society consensus on the classification of endometriosis
Abstract
Study question:
What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis?
Summary answer:
We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis.
What is known already:
Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis.
Study design, size, duration:
A consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken.
Participants/materials, setting, methods:
A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.
Main results and the role of chance:
A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken.
Limitations, reasons for caution:
This consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements.
Wider implications of the findings:
This is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries - has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis.
Study funding/competing interests:
The World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca; G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie; Deborah Bush has received travel grants from Fisher & Paykel Healthcare and Bayer Pharmaceuticals; Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer; Lone Hummelshoj is an unpaid consultant to AbbVie; Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet; Jörg Keckstein has received a travel grant from AbbVie; Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma; Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms; Rulla Tamimi; Hugh Taylor.
Trial registration number:
N/A.
... Depending on the intraoperative findings, patients were either classified as endometriosis patients (n, number = 64) or controls (n = 38). Endometriosis was staged intraoperatively, using the revised rASRM score (revised American Society of Reproductive Medicine Score) [20,21] as well as the ENZIAN classification [20][21][22]. None of the patients included in this study suffered from intraand/or postoperative complications that might have changed their postoperative course. ...
... Depending on the intraoperative findings, patients were either classified as endometriosis patients (n, number = 64) or controls (n = 38). Endometriosis was staged intraoperatively, using the revised rASRM score (revised American Society of Reproductive Medicine Score) [20,21] as well as the ENZIAN classification [20][21][22]. None of the patients included in this study suffered from intraand/or postoperative complications that might have changed their postoperative course. ...
... While laparoscopy has been replaced as the gold-standard for the diagnosis of DIE, adenomyosis, and endometriomas, it allows the confirmation or exclusion of peritoneal lesions [45] and a more precise classification of the disease. In all endometriosis patients, the disease was intraoperatively scored by a member of our certified Endometriosis Centre according to rASRM and ENZIAN [20][21][22] classifications and all visible endometriotic lesions were resected. In contrast to other studies [28,46], our collective comprised all endometriosis subtypes (peritoneal, ovarian, DIE). ...
Background
Endometriosis is a chronic, estrogen-dependent, benign condition, affecting 10–15% of women of reproductive age. It is associated with a prevalence of sexual dysfunction that is nearly twice as high as that seen in women with other benign gynecological conditions. Our study aimed to assess the effect of surgical intervention on sexual function, as measured by the FSFI (Female Sexual Function Index) score, in women with endometriosis compared to those with other benign gynecological conditions, both before and after surgery.
Methods
A comparative analysis was conducted at the Medical University of Vienna from 2015 to 2020. The study included patients suspected of having endometriosis, fibroids, adnexal cysts, and/or infertility. Based on findings during surgery, patients were categorized into two groups: those with endometriosis (n = 64) and control patients (n = 38). All participants completed the FSFI questionnaire before surgery and again 8 to 18 weeks after the operation.
Results
No significant differences were observed in the preoperative FSFI scores between the endometriosis patients and the control group. Similarly, no significant differences were found between the two groups in postoperative scores. However, in women diagnosed with endometriosis, surgical removal of endometriotic lesions significantly increased their full-scale FSFI score, and resulted in a significant improvement in the areas “desire” and “satisfaction”. Improvements were noted in all other areas as well, though they were not statistically significant.
Conclusions
Our research indicates that the surgical removal of endometriotic lesions can lead to an improvement in sexual function, as measured by the FSFI, within 8 to 18 weeks post-surgery. This improvement was not observed in the control group, which underwent surgery for other benign gynecological issues.
... Endometriosis is an inflammatory disease process characterised by lesions of endometrial-like tissue outside of the uterus [1]. Common symptoms include dysmenorrhea, dyspareunia, and fatigue [2]. ...
... Endometriosis diagnosis was confirmed by medical examination or through medical record searching in two studies (5,8), while the remaining either relied on self-reports of a physician's diagnosis (1,3,4,7,(11)(12)(13) or did not report how the diagnosis was verified (2,6,9,10). Assessing overall disease interference across samples posed a challenge as only two studies addressed this (1,2), each utilizing distinct scales. ...
... Heterogeneity was observed in two analyses; however, the limited number of available effects for any random-effects model (k < 10) precluded the undertaking of meta-regression analyses to estimate potential sources of heterogeneity [94]. Seven studies were included in meta-analyses (1,(3)(4)(5)7,8,13), contributing cross-sectional data on three cognitive factors: pain-catastrophising, rumination, and illness perceptions of control and power. The most robust finding was for the relationship between pain-catastrophising and depression. ...
Objective: This meta-analytic review aimed to synthesise evidence on personality and cognitive factors related to depression and anxiety in endometriosis and determine whether sociodemographic and clinical variables moderate factor-symptom relations. Additionally, this review aimed to evaluate the quality of research and formulate recommendations for future research. Methods: A systematic search was conducted across databases (Medline, Embase, PsycInfo, Web of Science, ProQuest) through to February 2024. Search terms were used for endometriosis, depression, anxiety, cognitive factors and personality traits. Random-effects meta-analyses were conducted to produce pooled weighted effects (r) for factor-symptom relationships. Results: Thirteen studies (11 samples; N = 3287; M age 33.89 ± 2.48) were included in a narrative synthesis. One study provided evidence for a positive association between neuroticism and depression. Seven studies contributed to meta-analyses on three cognitive factors. Medium-to-large associations were identified between illness perceptions of low control/power (r = 0.35, 95 % CI: 0.01,0.62), rumination (r = 0.52, 95 % CI: 0.09, 0.78), pain-catastrophising (r = 0.37, 95 % CI: 0.28, 0.45) and higher levels of depression. The statistical power to detect significant effects was >80 %. Findings for anxiety were non-significant, although limited data were available. Quality appraisal revealed a high risk of within-study bias (4.69 ± 1.38, range: 3–7), with issues related to sample representativeness and measurement selection. Conclusion: Rumination, pain-catastrophising, and illness perceptions of low control/power are important in understanding depression in endometriosis. There is a lack of research on personality traits, necessitating further study. Findings highlight the importance of prioritising modifiable cognitive factors in psychological research and clinical practice in endometriosis.
... Estudos têm mostrado que a cirurgia pode ser eficaz na restauração da anatomia pélvica e na melhoria das taxas de gravidez espontânea (Marcoux et al., 1997). No entanto, a cirurgia também apresenta riscos e pode não ser eficaz para todas as pacientes (Johnson et al., 2013). ...
... Um estudo de Marcoux et al. (1997) mostrou que a remoção laparoscópica de lesões endometrióticas resultou em uma taxa de gravidez significativamente maior em comparação com a observação expectante. No entanto, outros estudos têm mostrado resultados mistos, com algumas mulheres não experimentando melhorias significativas na fertilidade após a cirurgia (Johnson et al., 2013). ...
... A cirurgia laparoscópica tem mostrado ser uma abordagem eficaz para a remoção de lesões endometrióticas e aderências, com estudos demonstrando melhorias nas taxas de gravidez espontânea após a cirurgia (Marcoux et al., 1997). No entanto, a eficácia da cirurgia pode variar entre as pacientes, e nem todas as mulheres experimentam melhorias significativas na fertilidade (Johnson et al., 2013). Estes achados sugerem que a cirurgia pode ser uma opção viável para algumas mulheres, mas não é uma solução universal para todas as pacientes com endometriose e infertilidade. ...
Introdução: A endometriose é uma condição ginecológica crônica que afeta cerca de 10% das mulheres em idade reprodutiva e é uma das principais causas de infertilidade feminina. A relação entre endometriose e infertilidade é complexa, envolvendo fatores anatômicos, inflamatórios, imunológicos e hormonais. Objetivo: Este artigo visa revisar a literatura existente sobre os mecanismos pelos quais a endometriose causa infertilidade e as abordagens terapêuticas disponíveis para tratar essa condição. Metodologia: Foi realizada uma revisão sistemática da literatura utilizando bases de dados como PubMed, Scopus e Web of Science. Foram incluídos estudos que abordam os mecanismos de infertilidade associados à endometriose e as intervenções terapêuticas, incluindo tratamentos médicos, cirúrgicos e técnicas de reprodução assistida. Resultados: A revisão identificou que a endometriose causa infertilidade através de mecanismos como obstrução das trompas de Falópio, formação de aderências pélvicas, alteração da qualidade dos oócitos e disfunção endometrial. Tratamentos médicos, como contraceptivos hormonais e agonistas do GnRH, são eficazes no manejo dos sintomas, mas têm limitações na restauração da fertilidade. Intervenções cirúrgicas, como a laparoscopia, são eficazes na remoção de lesões endometrióticas e na restauração da anatomia pélvica. Técnicas de reprodução assistida, como a fertilização in vitro (FIV), mostraram-se eficazes em melhorar as taxas de gravidez em mulheres com endometriose. Conclusão: A endometriose é uma causa significativa de infertilidade feminina, com múltiplos mecanismos subjacentes. As abordagens terapêuticas variam de acordo com a gravidade da doença e os objetivos reprodutivos da paciente. A combinação de tratamentos médicos, cirúrgicos e técnicas de reprodução assistida oferece a melhor chance de sucesso para mulheres com endometriose que desejam engravidar. Estudos futuros devem focar em terapias emergentes e na otimização das abordagens existentes.
... • Excision: Complete removal of endometriotic lesions is preferred over ablation to ensure thorough eradication of disease tissue and reduce recurrence [121]. • Adhesiolysis: Surgical removal of adhesions restores pelvic anatomy and improves organ function. ...
... Endometriosis is increasingly recognized as an inflammatory disease, with dysregulated immune responses playing a pivotal role. Peritoneal macrophages exhibit impaired phagocytic function but heightened cytokine production, creating a pro-inflammatory milieu [121]. Elevated levels of TNF-α, IL-1β, and IL-6, along with prostaglandins like PGE2, perpetuate inflammation and pain [108]. ...
Endometriosis is a complex gynecological disorder characterized by endometrial-like tissue growing outside the uterus, leading to chronic pain, infertility, and reduced quality of life. Its pathophysiology involves genetic, epigenetic, immune, and molecular factors. Theories such as retrograde menstruation, coelomic metaplasia, and stem cell involvement explain lesion formation. Endometrial mesenchymal stem cells (eMSCs) and epithelial progenitors (eEPs) contribute to lesion establishment by adhering to peritoneal surfaces, proliferating, and differentiating into ectopic tissue. Aberrant adhesion molecules, inflammatory cytokines, and molecular pathways like PI3K/Akt and Wnt/β-catenin drive proliferation, angiogenesis, and resistance to apoptosis. Elevated estrogen levels and progesterone resistance further promote lesion growth and immune evasion. Immune dysfunction, including altered macrophage activity and reduced natural killer (NK) cell function, contributes to inflammation and lesion persistence. Pain is linked to prostaglandin E2 (PGE2) and nerve infiltration, emphasizing the need for targeted pain management. Current therapies, such as GnRH agonists, suppress ovarian hormone production but face limitations in long-term efficacy and side effects. Integrating molecular insights into clinical practice may advance diagnostics and treatment, with emerging approaches focusing on molecular pathways, immune modulation, and hormonal regulation for more effective, personalized therapies. Future research should unravel the complex mechanisms driving endometriosis to improve patient outcomes.
... Our own prior research showed nearly a 30% reduction in fecundability or time to pregnancy (TTP) among a cohort of women undergoing laparoscopy/laparotomy regardless of clinical indication but no clear difference in TTP by rASRM stage (10). New staging systems that better correlate with infertility have been proposed, such as the Endometriosis Fertility Index, whose score is determined intraoperatively after surgical intervention describing the function of the tube, fimbria, and ovary on both sides (11). Although the Endometriosis Fertility Index has been found to correlate with infertility, the chief critique is that it may work only because the system includes important clinical variables, including age, years of infertility, and prior pregnancy, that affect fecundability independent of endometriosis (9,12). ...
... Typology was assessed via the rASRM standardized form for women whose rASRM form had information on lesion location and size (n ¼ 180 [95%] out of the 190 women with an endometriosis diagnosis). Women with only superficial lesions on the ovary or peritoneum were considered to have SE, deep lesions (>5 mm invasion) (11), noted in the peritoneum or obliteration of posterior cul-de-sac were considered to be DIE, and deep lesions of any size noted in the ovary were considered to be OE; women who had deep ovarian and peritoneal lesions were considered to have OE þ DIE. Women without information on lesion location, size, and depth (n ¼ 10) were assumed to have SE. ...
Objective
To determine whether endometriosis typology, namely ovarian endometriomas (OE), deep infiltrating endometriosis (DIE), or superficial endometriosis (SE), correlates with fertility history.
Design
Prospective cohort.
Setting
One of fourteen surgical centers in Salt Lake City, Utah (n = 5) or San Francisco, California (n = 9).
Patient(s)
A total of 473 women (18–44 years) with no prior endometriosis diagnosis, undergoing laparoscopies/laparotomies, irrespective of indication, in Utah or California (2007–2009).
Exposure
Incident endometriosis.
Main Outcome Measure(s)
Before surgery, we queried women about time to become pregnant for prior planned pregnancies. Generalized linear models were used to calculate adjusted prevalence ratios (aPR) for association between endometriosis typology and infertility, defined as having ever tried >12 months (>6 months for women ≥35 years) to get pregnant. We also generated fecundability odds ratios (aFOR) to capture time to pregnancy.
Result(s)
Twenty-five percent (n = 116) of women were diagnosed with SE only, 5% (n = 23) with OE, 6% (n = 29) with DIE, and 5% (n = 22) with OE + DIE, and 60% (n = 283) with no endometriosis. Compared with women with no endometriosis, women with SE had a 1.58 higher aPR (95% confidence interval [CI], 1.16–2.14), although women with OE and/or DIE had a 2.41 higher aPR for subfertility after adjusting for women’s age, body mass index, and site. Compared with women with no endometriosis, women with OE and/or DIE had a 53% lower historic fecundability (aFOR, 0.47; 95% CI, 0.24–0.95); however, no association was found among women with SE (aFOR, 0.81; 95% CI, 0.49–1.33).
Conclusion(s)
Specific endometriosis typologies may be associated with fecundability, with OE and/or DIE associated with nearly a 150% higher prevalence of subfertility and over a 50% lower historic fecundability.
... Endometriosis is an inflammatory disease associated with pelvic pain and infertility that is characterized by lesions of endometrial-like tissue outside of the uterus [1]. It affects roughly 10 % (190 million) of reproductive age women and girls globally. ...
... It affects roughly 10 % (190 million) of reproductive age women and girls globally. In the field of endometriosis, more than 20 classifications, staging and descriptive systems have been developed, but none of the classification systems adequately classifies endometriosis [1,2]. The well accepted classification system for endometriosis is the revised American Society for Reproductive Medicine (r-ASRM) classification (1997), which classifies endometriosis in the peritoneum, ovary and tubes [3]. ...
Introduction and importance
Endometriosis is an inflammatory disease associated with pelvic pain and infertility that is characterized by lesions of endometrial-like tissue outside of the uterus. It affects roughly 10 % of reproductive age women and girls globally. Umbilical endometriosis is a rare pathology accounting for 0.5 to 1 % of all extra-pelvic endometriosis. Due to the varied presentations and rare incidence of endometriosis, it remains a diagnostic dilemma and challenge to treat it timely and properly.
Case presentation
A 32-year-old nulliparous lady who presented with umbilical lump, cyclical pain, and bleeding during menstrual cycle without any prior history of abdominal surgery of a year duration. Ultrasound and magnetic resonance imaging support the diagnosis of umbilical endometriosis and ruled out multifocal involvement. She was managed with surgical excision with free margin followed by umbilical reconstruction and the diagnosis was confirmed by biopsy.
Discussion
Umbilical endometriosis could be either secondary to endometrial tissue implantation during laparoscopic or open surgical procedures also called scar endometriosis or as a primary umbilical endometriosis with no previous surgery. The characteristic presentation for umbilical endometriosis is a brown to dark nodule in the umbilicus, which may be swollen, painful, and sometimes bleed during menstrual periods.
Conclusion
Umbilical endometriosis is a rare condition that should be considered as a differential diagnosis in women with umbilical lump, cyclical pain, and bleeding. The diagnosis is clinical and confirmed by histopathology. Surgical excision is the treatment of choice with a low risk of recurrence or malignancy.
... The first therapeutic approach is represented by pharmacological therapy, with the molecules used being: gonadotropin-releasing hormone agonist (leuprorelin), gonadotropin-releasing hormone antagonist (cetrorelix), progesterone, and gestrinone. In 2014, the European Society of Human Reproduction and Embryology issued a guideline with recommendations regarding the diagnosis and treatment of endometriosis, where gestrinone is the only anti-progestagen recommended for this pathology [1][2][3][4][5]. GTN, also known as ethyl-norgestrienone, chemical structure presented in Fig. 1, is a derivative of 19-nortestosterone which posses androgenic, weak estrogen-like, antiestrogen, weak progestin, and strong progesterone effects. ...
... Even if there are several papers dealing with the biopharmaceutical profile (including pharmacokinetics) [11] and biological activity of GTN [1][2][3][4][5], no references were found in the literature in our area of interest, namely, thermal stability and preformulation studies. ...
Gestrinone is an active pharmaceutical ingredient used in the treatment of endometriosis as capsules, with ongoing evaluation for intravaginal administration, while also having been studied for its potential antitumoral effects. The purpose of this study was to determine the compatibility of gestrinone with four excipients used in the development of solid pharmaceutical formulations (α-lactose monohydrate, magnesium stearate, starch, and talc) and to obtain a fully characterized thermoanalytical profile of gestrinone with the help of kinetic analysis. Preformulation studies were carried out on 1:1 mass/mass binary mixtures between gestrinone and each excipient by instrumental screening under ambient conditions using ATR-FTIR spectroscopy investigations, and later by studying the effect of thermal treatment over the samples (TG/DTG/DSC). The obtained results suggest that under ambient conditions, no chemical interactions take place between the active pharmaceutical ingredient and selected excipients, whereas under thermal stress incompatibilities are observed in all systems. The mechanism of decomposition was preliminary evaluated by the ASTM E698 and later completed by the isoconversional methods of Friedman, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa, which suggest similar mean activation energies. The mechanism of decomposition was elucidated in the last part of the study, by employing the modified NPK method. This method suggests that gestrinone is thermally degraded by the contribution of two individual processes, both consisting of superimposed physical transformations and chemical degradations.
... The Endometriosis Fertility Index (EFI) was created to predict the likelihood of spontaneous pregnancy in women three years after undergoing surgery for endometriosis. 12 This comprehensive score takes into account factors such as the patient's age, duration of infertility, pregnancy history, description of lesions observed during surgery (ASRM, AFS endometriosis score) and a post-operative functional score (LF score). ...
Endometriosis is a chronic inflammatory condition affecting women of reproductive age group, often resulting in subfertility and chronic pelvic pain. The multifactorial nature of endometriosis-associated infertility is influenced by a complex interplay of genetic, hormonal, menstrual, inflammatory and immunological factors, which together define the phenotypic presentation of the disease. These factors complicate natural conception and impact the success of Assisted Reproductive Technology (ART) cycles. While medical management, typically contraceptive, offers symptomatic relief, it may not address the underlying issues that impede natural conception. Surgical intervention, particularly for ovarian endometriosis, has the potential to enhance spontaneous conception rates but also carries the risk of reducing ovarian reserve. This presents a dilemma in fertility preservation, especially when considering assisted reproductive technologies (ART). The current evidence on the efficacy of surgery in improving ART outcomes remains inconclusive, underscoring the need for an individualized and holistic approach in treatment planning. Such an approach is crucial in optimizing reproductive outcomes for women with endometriosis. A systematic search of the literature was conducted to gather the latest evidence on endometriosis and subfertility. Databases searched included PubMed, Scopus, Web of Science and Cochrane Library. While excising endometriomas may help restore pelvic anatomy and increase spontaneous pregnancy rates, there is also a substantial risk of reducing ovarian reserve due to damage caused during the procedure. In particular, cystectomy has been associated with a significant reduction in anti-Müllerian hormone (AMH) levels, a key marker of ovarian reserve.
... 10,11 Recent studies have illuminated the high diagnostic accuracy of TVUS, particularly for endometriomas, deep endometriosis, and adhesion states such as pouch of Douglas (also known as rectouterine pouch or cul-de-sac) obliteration. 12,13 However, superficial endometriosis, the most common phenotype of endometriosis, present in 80% of all patients diagnosed, remains an elusive target when using noninvasive modalities, 5,14 though ultrasonographic features have been described previously. 5,14 In 2016, the IDEA (International Deep Endometriosis Analysis) group published a pioneering consensus to standardize ultrasound evaluation methods and nomenclature for diagnosing endometriosis. ...
OBJECTIVE:
To evaluate the diagnostic accuracy of transvaginal ultrasonography (TVUS) in detecting deep endometriosis, ovarian endometriosis, and superficial endometriosis using the IDEA (International Deep Endometriosis Analysis) consensus and novel International Terminology definitions for endometriosis phenotypes.
METHODS:
This prospective diagnostic accuracy study was conducted at McMaster University from November 2021 to January 2023. Participants included 125 individuals aged 18–50 years with suspected endometriosis who were undergoing TVUS followed by laparoscopic surgery. The index test, TVUS, was performed in accordance with the IDEA consensus, with results compared with laparoscopy and histopathologic findings, which served as the reference standard. Deep endometriosis was defined as endometriosis with any depth of infiltration, and superficial endometriosis was defined as endometriosis without any infiltration beyond the peritoneal surface. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated.
RESULTS:
The study demonstrated high diagnostic accuracy for endometriomas and deep endometriosis with TVUS, achieving a sensitivity of 95.0% for left ovarian endometrioma, 94.9% for right ovarian endometrioma, and sensitivity ranging from 84.3% to 100% for various deep endometriosis sites. Transvaginal ultrasonography showed high specificity for endometriomas (98.9%) and deep endometriosis (range 97.0–100%). However, TVUS showed lower sensitivity for superficial endometriosis (range 4.0–43.5%) but high specificity (99.0–100%) and PPV (90.0–100%). The accuracy of detecting superficial endometriosis improved when cases with ovarian endometriosis, deep endometriosis, and pouch of Douglas obliteration were excluded.
CONCLUSION:
Transvaginal ultrasonography demonstrates robust diagnostic accuracy for deep endometriosis and ovarian endometriosis, reaffirming its utility as a first-line diagnostic tool in endometriosis management despite changes in definitions of deep endometriosis and superficial endometriosis. However, its sensitivity for superficial endometriosis remains limited, suggesting the need for additional diagnostic techniques or refined ultrasound approaches for accurate detection of superficial endometriosis. The findings support the integration of TVUS in clinical practice while highlighting the need for further advancements in diagnosing superficial endometriosis to mitigate diagnostic delays.
... The American Society of Reproductive Medicine names endometriosis into four stages, with stage one being mild and stage four being sever. Infertility is a commonly known end result of endometriosis; however, the pathophysiology is thought to be different depending on the stage of the disease (Johnson et al., 2017;Rolla, 2019). In the first and second stages, infertility is assumed to be caused by inflammation, which is identified by greater level of prostaglandins, cytokines, macrophages, and Natural killer Cells (NKC). ...
Infertility is a term used to describe a pathological condition that can affect married relationship in more than one line, it means the women don't have pregnancy after twelve months of successful sexual relationship. Infertility could be primary or secondary and the main causes include ovulation fault, ovum transport problems, and implantation failure. There are many mean to early diagnose infertility and specialize it cause to decide proper treatment intervention. Infertility can result from men or women causes and for each case suitable treatment options are present now. Now a day, there are different interventions that can help couples to have successful conceive such as Intra-Uterine Insemination, In-vitro fertilization, Donor egg and sperm in addition to the medications. Finally, infertility could result in a health, social, and economic complication if not diagnosed and treated early. Kerbala Journal of Pharmaceutical Sciences ISSN: 2221-7207(Print) / ISSN: 3006-7189 (Online)
... Endometriosis is an inflammatory disease characterized by lesions of endometrial-like tissue outside the uterus, commonly in the pelvic cavity [1]. This condition is estimated to affect 10% of reproductive age women and an unmeasured number of gender-diverse people, however, incidence varies geographically [2]. ...
Background
We recognized a paucity of accessible, evidence-based, empowering patient-centred resources for those with endometriosis-associated dyspareunia. Affecting more than 50% of people with endometriosis, dyspareunia can significantly impact relationships, chronic pain and the ability to have a family. We aimed to develop a patient-centred educational website for those affected by endometriosis-associated dyspareunia.
Methods
To develop a functional and meaningful website for endometriosis-associated dyspareunia, we utilized a Knowledge to Action framework, supplemented with a patient-centred research design and technology-enabled knowledge translation. Our patient partners influenced the direction and scope of the project, provided critical feedback throughout the development process, and approved website revisions prior to launch. The website was developed in five phases; (1) needs assessment interviews and focus groups with key stakeholders, (2) landscape analysis of pre-existing websites, (3) development, (4) usability testing and qualitative interviews, and (5) revisions and launch.
Results
Phase 1 and 2 emphasized a need for comprehensive yet plain language explanations of pain mechanisms and strategies for pain management. Rigorous consultation with key stakeholders informed the creation of the preliminary website in phase 3. Usability testing in phase 4 identified five main categories of usability problems, most of which were considered minor. Phase 4 qualitative interviews identified users’ overall impressions of the preliminary website, including that the website could help people understand their pain and describe their pain to partners and healthcare providers, as well as feel empowered to seek healthcare and validated in their experiences. User suggestions, combined with usability testing, informed revisions in phase 5.
Conclusion
We developed an educational website for endometriosis-associated painful sex where people can find evidence-based etiologies for pain, pain management options, and actionable resources. Based on the data collected through qualitative interviews with patients, this website can potentially empower people to seek health care. The strength of the website development approach used was the inclusion of qualitative user insights in addition to the commonly completed user tests. The patient interviews provided insights into the potential impact of the website and, thus, ensured that we not only created a functional website that meets end users’ needs, but a website that is also meaningful to those affected by this condition.
... Quality parameters calculated for the test set using different supervised classification algorithms to distinguish women with endometriosis and the healthy control women. 1 AC, accuracy in % 2 SENS, sensitivity in % 3 SPEC, specificity in % 4 PCA, principal component analysis. 5 SPA, successive projections algorithm. 6 GA, genetic algorithm. ...
Endometriosis is a common benign gynecological condition characterized by the growth of endometrial gland and stroma located outside the uterine cavity, which the current approaches for its detection are invasive and expensive, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the diagnosis of this disease. Attenuated total reflection Fourier-transform infrared and near infrared spectroscopy combined with multivariate classification were applied as a new tool to analyze blood plasma samples from women with endometriosis (n = 41) and healthy individuals (n = 34). In addition, the use of advanced data fusion strategies and multivariate analysis techniques improved the classification models and facilitated diagnostics segregation of both sample categories in a fast and non-destructive way, generating high levels of accuracy, sensitivity and specificity. 2D correlation analysis revealed strong positive correlations between the spectrochemical biomarkers identified in both IR regions. To the best of our knowledge, this is the first study demonstrating the efficacy of a new tool for fast and non-invasive diagnosis of endometriosis using blood plasma samples analyzed with IR spectroscopy combined with multivariate classification.
... The current standard for diagnosis is using laparoscopic surgery to visualize the peritoneum for ectopic lesions which then must be histologically confirmed for at least two of the three hallmark characteristics 9 . The most common histological hallmarks for a positive diagnosis are the presence of endometrial glands, organized stroma, and hemosiderin-laden macrophages 10 . An additional histological hallmark being included for characterizing ectopic lesions is firbosis 11 . ...
... Современные варианты лечения эндометриоза включают в себя лекарственную терапию, которая подавляет функцию яичников и хирургическое иссечение эктопических очагов эндометриоза. Однако, высокая частота рецидивов после хирургического лечения приводит к неоднократным повторным оперативным вмешательствам, несмотря на заключение консенсуса всемирного общества эндометриоза, о необходимости единственной операции в жизни женщины [16]. ...
Endometriosis is a chronic multifactorial disease that affects more than 170 million women of reproductive age worldwide, causing pelvic pain syndrome, dyspareunia, and symptoms of gastrointestinal dyspepsia, thereby having a negative impact on the psycho-emotional state of patients. Despite a wide range of medical and surgical treatments, the relapse rate reaches 50%, which is a global economic and social problem.
The purpose of the study. to evaluate the mutual influence of clinical manifestations of intestinal disorders and the state of the intestinal microbiota in patients with deep endometriosis.
Materials and methods. The study included 83 patients of reproductive age who underwent surgical treatment of common forms of external genital endometriosis. The first group consisted of 32 patients of reproductive age who underwent repeated surgical treatment due to relapse of deep infiltrative endometriosis, the second group — 51 patients without relapse of the disease one year after the primary operation, due to deep infiltrative endometriosis, the third group — 30 patients of reproductive age. not suffering from external genital endometriosis. An analysis of the somatic anamnesis was carried out, as well as questionnaire data on pelvic pain on a visual analogue scale (VAS) and functional bowel disorders in patients with deep infiltrating endometriosis, depending on the status of relapse of the disease. The composition of the intestinal microbiota was assessed by quantitative real-time PCR using a test system for determining the DNA of intestinal-associated microorganisms.
Results and discussion. The results of the study demonstrate bidirectional relationships between clinical and microbiological parameters and the recurrent course of deep endometriosis. Patients of the main group significantly more often suffered from functional diseases of the gastrointestinal tract, the spectrum of which was represented by chronic gastritis and irritable bowel syndrome. Correlation relationships between indicators of the Bacillota domain of the intestinal microbiota and clinical and anamnestic indicators of gastrointestinal pathology, the values of questionnaire scales in patients with deep endometriosis demonstrate moderate positive relationships between the weight of patients and the number of Lachnospiraceae (r = 0.63299), symptoms of bloating and the number Streptococcus spp (r=0.67402). Correlation relationships between indicators of the Bacteroidota domain of the intestinal microbiota and corresponding indicators demonstrate strong positive relationships between the amount of E.Coli in the intestinal microbiota and the level of pain assessed on the VAS scale after 1 (r = 0.62366) and 3 months (r = 0. 72598) after surgery. Moderate positive correlations were revealed between the number of Enterobacterales in the intestinal microbiota and the level of pain assessed on the VAS scale 1 (r=0.58169) and 3 months (r=0.57706) after surgery.
Conclusions. The recurrent course of endometriosis is accompanied by functional intestinal disorders, the manifestations of which persist after surgical treatment, which is mediated by changes in the intestinal microbiota. In patients with recurrent deep endometriosis, a decrease in the species and taxonomic diversity of the intestinal microbiota was found, due to an increase in the Bacillota/Bacteroidota ratio, the number of pathobionts, and a decrease in the number of commensal bacteria of the genus Bifidobacterium spp. These clinical and microbiological parallels demonstrate the need to harmonize the intestinal microbiota as a comprehensive prevention of disease relapse.
... Studies have shown that utilizing a pelvic trainer and the Da Vinci Robotic Surgical System permits surgeons to get robotic -assisted laparoscopic abilities more rapidly and with more prominent accuracy than manual laparoscopic abilities (68). Besides, experience in laparoscopic surgery significantly further develops performance in robotic surgery, demonstrating that surgeons can adjust to robotic systems all the more rapidly assuming they as of now have essential laparoscopic abilities (69). Accordingly, robotic surgery offers clinical benefits as well as works with quicker and more powerful preparation for surgeons, at last working on careful results and extending the capacities of minimally invasive surgery. ...
Endometriosis is a persistent condition influencing roughly 10% of women of reproductive age, prompting huge physical and emotional pressure. Therapies incorporate medical management and surgical interventions, with laparoscopic medical procedure being the highest quality level for eliminating endometrial tissue. The approach of robotic assisted laparoscopic surgery (RALS) has empowered more complex methods to be performed minimally invasively, expanding its utilization in high-difficulty surgeries. Created in the late twentieth century, Systems like the Da Vinci Careful Framework have changed a surgical procedure by upgrading accuracy, dexterity, and visualization. The most recent models, including the Da Vinci Xi and SP, offer high level elements, for example, upgraded arm mobility, fluorescence imaging, and single-port abilities. Comparative studies of RALS and conventional laparoscopy (LPS) for endometriosis show mixed results. While certain studies show no huge differences in complications or recovery results, others feature longer operative times and hospital stays for RALS. In spite of these disadvantages, RALS isn't second rate compared to LPS in general. The clinical advantages of RALS incorporate more prominent accuracy and exactness, diminished surgeon fatigue, and a quicker learning curve worked with by cutting edge ergonomic and control systems. Be that as it may, the significant expenses and broad foundation prerequisites limit the availability and accessibility of robotic surgery medical, especially in smaller or rural hospitals. The shortfall of tactile sensation stays a test, however impending advancement mean to address this. Proceeded with innovative work are crucial to make robotic surgery procedure more financially savvy and comprehensively open, guaranteeing its advantages can arrive at a more extensive patient populace. This theoretical exemplifies the vital parts of robotic surgery procedure's turn of events, comparative studies with conventional methods, and its clinical advantages and constraints, featuring the requirement for progressing upgrades and exploration.
... Laparoscopic surgery is the most common intervention for EMT (3) . Since 1996, the revised American Society for Reproductive Medicine (r-ASRM) classification system has been widely used worldwide for the staging of EMT lesions via laparoscopic visualization, categorizing EMT in the pelvic area into four stages: minimal (stage I), mild (stage II), moderate (Stage III), and severe (stage IV) EMT (4) . However, r-ASRM classification is done after laparoscopic surgery, which also indicates that the necessity of laparoscopic surgery should be effectively evaluated. ...
... Endometriosis is an inflammatory disorder characterized by the presence of endometrial tissue outside of the uterine cavity [1]. Women with endometriosis may experience a range of gynecological symptoms, including pelvic pain, dysmenorrhea, dyspareunia, and fertility issues [2]. ...
Objectives: The purpose of this study was to evaluate the impact of endometriosis on various outcomes of in vitro fertilization (IVF), including live birth rates, clinical pregnancy rates, fertilization rates, and implantation rates, through a systematic review and meta-analysis. Methods: Systematic searches were carried out using PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, EMBASE, and Web of Science from January 2010 to November 2023. Studies comparing IVF outcomes in women with and without endometriosis were included. The primary outcome was live birth rate; secondary outcomes included clinical pregnancy, fertilization, and implantation rates. Data were extracted and analyzed using odds ratio (OR) and 95% confidence interval (CI) with fixed or random-effects models, depending on heterogeneity. Results: From 1340 studies initially identified, 40 studies met the inclusion criteria, encompassing 8970 women with endometriosis and 42,946 control participants. There were no significant differences between the endometriosis and control groups in terms of live birth rate (OR 1.03, 95% CI 0.75–1.41, p = 0.84), clinical pregnancy rate (OR 0.86, 95% CI 0.72–1.02, p = 0.1), or fertilization rate (OR 0.96, 95% CI 0.79–1.15, p = 0.64). However, endometriosis was associated with a significantly lower implantation rate (OR 0.85, 95% CI 0.74–0.97, p = 0.02). Conclusions: Endometriosis significantly negatively affects implantation rates in women undergoing IVF, despite the absence of significant differences in live birth, clinical pregnancy, and fertilization rates. Further research is needed to evaluate the impact of different stages of endometriosis on IVF outcomes and to develop optimized management protocols for these patients.
... It can be classified into three forms according to the location of the lesions in the abdomen: superficial endometriosis (i.e. peritoneal lesions extending up to 5 mm below the peritoneal pelvic surface and/or the serosa of the pelvic viscera), ovarian endometriosis, and deep infiltrating endometriosis (DIE, i.e. penetration of endometrial-like tissue into pelvic structures, resulting in lesions that invade the peritoneum beyond a depth of 5 mm) [1,3]. Among these, DIE represents the most severe and challenging form, with invasive lesions that can lead to adhesions and anatomical distortion, contributing to the significant morbidity associated with the disease [4,5]. ...
Objective
To assess the prevalence and the characteristics of pelvic floor dysfunction (PFD) in women with endometriosis.
Methods
This is a methodological paper that describes the ‘Endometriosis and Pelvic Floor Dysfunction’ (EndoPFD) multicenter study protocol. It involves three sites: the University Hospital of Pisa, the San Raffaele Hospital of Milan and the Vanvitelli University Hospital of Naples. Women are recruited through web links and are asked whether they want to participate to the clinical evaluation or only to the web survey. The web survey gathers personal history, endometriosis history and symptoms, and performs a subjective evaluation of PFD through questionnaires: Urinary Distress Inventory 6, Colorectal-Anal Distress Inventory 8, Wexner Scale for Fecal Incontinence, Wexner Constipation Scoring System, and Female Sexual Function Index. Those interested in the clinical evaluation will add to the questionnaires the following exams: gynecological and proctological exam, pelvic ultrasound, urodynamic test, and anorectal manometry.
Preliminary results
Recruitment for the web survey was completed. A total of 1,149 women signed the electronic consent, 329 were excluded due to inclusion/exclusion criteria; hence, 525 completed all the questionnaires (response rate of 64.02%). Recruitment for the clinical evaluation is ongoing.
Discussion
This study protocol offers the possibility to define the prevalence of PFD in endometriosis patients with a subjective and an objective assessment of signs and symptoms. This may pave the way for changing the approach to patients with endometriosis. Moreover, it demonstrates the validity of the method used (online survey and recruitment) to reach a high number of patients.
... Additionally, infertility treatments can be financially burdensome, with median per-person costs ranging from USD 1182 for medications alone to USD 24,373 for an infertility treatment service such as in vitro fertilization [6]. Common individual risk factors for female infertility include genetic disorders, chromosomal abnormalities, ovulatory disorders, tubal factors, endometriosis, lifestyle choices, and advanced age [7][8][9][10][11][12]. Low fertility rates can also be Int. ...
Environmental chemical exposure has been rising over the past few decades but its impact on fertility remains uncertain. We assessed exposures to 23 common chemicals across a range of sociodemographic characteristics and their relationship with self-reported infertility. The analytic sample was non-pregnant women aged 18–49 years without a history of hysterectomy or oophorectomy (n = 2579) from the National Health and Nutrition Examination Survey (2013–2016). Environmental chemical exposure was assessed with biospecimens and dichotomized as high and low levels of exposure based on the median. Logistic regression models estimated the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for the association between high levels of exposure and infertility, adjusted for age, race, education level, family income, and smoking status. We observed associations between infertility and cadmium [aOR: 1.88; 95% CI: 1.02–3.47] and arsenic [aOR: 1.88 (1.05–3.36)]. Two pesticides hexachlorobenzene [OR: 2.04 (1.05–3.98)] and oxychlordane [OR: 2.04 (1.12–3.69)] were also associated with infertility in unadjusted analyses. There were negative associations with two Per- and polyfluoroalkyl substances with n-perfluorooctanoic acid [aOR: 0.51: (0.30–0.86)] and n-perfluorooctane sulfonic acid [aOR: 0.51: (0.26–0.97). Specific chemicals may contribute to infertility risk, highlighting the need for targeted public health strategies to mitigate exposure.
... 1 Se presenta clínicamente como dismenorrea, dolor pélvico crónico e infertilidad. 2 mujeres en todo el mundo 2, Afecta aproximadamente al 10% de las mujeres en edad reproductiva. Se encuentra en el 20% -50% de las mujeres con infertilidad y el 90% con dolor pélvico crónico y es la tercera entidad ginecológica más frecuente en edad reproductiva con una incidencia del 32.4%. ...
Objetivo: Determinar el efecto de la peritonectomía sobre el dolor pélvico en pacientes con endometriosis. Pacientes y método: Estudio prospectivo, longitudinal y observacional en pacientes con endometriosis peritoneal y dolor pélvico sometidas a peritonectomía en la Clínica de Excelencia de Endometriosis en Guadalajara, Jalisco. Se evaluó la intensidad del dolor mediante la escala visual análoga (EVA) antes y 12 meses después del procedimiento. También se clasificó el estadio de la enfermedad con ASRM y AAGL, y se analizaron variables secundarias como gestaciones, evolución de la dismenorrea, cirugías previas, manejo médico, duración del procedimiento, pérdida sanguínea y complicaciones. Resultados: Se realizaron 213 procedimientos, con una edad media de 32.9 años (rango 15-54). De las pacientes, 106 (49.8%) estaban casadas y 107 (50.2%) solteras. Las nuligestas fueron 147 (69.01%) y el 46.4% de las pacientes estuvo libre de dismenorrea entre 2 y 4 años tras la cirugía. Los estadios de enfermedad fueron: rASM (I: 4.69%, II: 22.5%, III: 30.04%, IV: 42.7%) y AAGL (I: 4.69%, II: 14.55%, III: 16.43%, IV: 64.31%). La pérdida sanguínea osciló entre 10 y 700 ml, y el tiempo quirúrgico promedio fue de 177.5 minutos. La media de dolor antes y después de la cirugía fue de 9.0 y 1.0, respectivamente, con una reducción promedio de 7.9 puntos en la EVA (p<0.001). Conclusiones: La peritonectomía laparoscópica es efectiva en el manejo de la endometriosis peritoneal, con un 46.4% de ausencia de dismenorrea a 2 años y una disminución media de 7.9 puntos en la intensidad del dolor. Palabras clave: Endometriosis, laparoscopia, dismenorrea, recurrencia.
... Peritoneal, ovarian, and deep infiltrating endometriosis are the three forms of endometriosis that have been histologically Omar K. Naser identified. Deep infiltrating endometriosis is defined as penetrating the surrounding tissues by more than 5 mm (1) In the painful abdominopelvic region, endometriosis patients also exhibit enhanced responsiveness to noxious and benign somatic stimulation (referred to as "hyperalgesia" and "allodynia," respectively), such that a significant negative correlation is seen between patient-rated abdominopelvic pain intensity (e.g., visual analogue scale) and pressure (or "force") threshold (2). ...
... Современные варианты лечения эндометриоза включают в себя лекарственную терапию, которая подавляет функцию яичников и хирургическое иссечение эктопических очагов эндометриоза. Однако, высокая частота рецидивов после хирургического лечения приводит к неоднократным повторным оперативным вмешательствам, несмотря на заключение консенсуса всемирного общества эндометриоза, о необходимости единственной операции в жизни женщины [14]. ...
Background . Endometriosis is a chronic multifactorial disease that affects more than 170 million women of reproductive age worldwide, causing pelvic pain syndrome, dyspareunia, and symptoms of gastrointestinal dyspepsia, thereby having a negative impact on the psycho-emotional state of patients. Despite a wide range of medical and surgical treatments, the relapse rate reaches 50%, which is a global economic and social problem.
The purpose of the study . To determine the spectrum of clinical features of the gastrointestinal tract in women with recurrent deep infiltrative endometriosis.
Materials and methods . The study included 113 patients of reproductive age who underwent surgical treatment of common forms of external genital endometriosis. The main group consisted of 32 patients who underwent repeated surgical treatment due to relapse of deep infiltrative endometriosis, the comparison group — 51 patients without relapse of the disease one year after the primary operation, the control group — 30 patients of reproductive age who did not suffer from external genital endometriosis. An analysis of the somatic anamnesis was carried out, as well as questionnaire data on pelvic pain on a visual analogue scale (VAS) and functional bowel disorders in patients with deep infiltrating endometriosis, depending on the status of relapse of the disease.
Results and discussion . Patients of the main group suffered significantly more often from functional diseases of the gastrointestinal tract (71.9% (23/32) versus 51.3% (26/51) in the comparison group; p = 0.006, the spectrum of which was represented by chronic gastritis and irritable bowel syndrome. In the main group, the clinical manifestations of gastrointestinal dyspepsia before surgical treatment correspond to a moderately severe degree of 17.706 (4.601) points. A significantly higher initial level of functional intestinal disorders was established during subjective assessment in the main observation group: 17.706 (4.601) points versus 10.66 (3.61) points in the comparison group; p=0.001. In women of the main observation group, one month after surgical treatment, there was a significant decrease in subjective assessment of the severity of functional intestinal disorders (from 17.71 (4.60) points to 9.86 (4.73) points; p = 0.001). The integral VAS pain score in the main group was 6.65 (1.53) points, which is significantly higher than in patients in the comparison group without relapse of the disease.
Conclusions . The identified clinical and anamnestic predictors of the recurrent course of deep infiltrative endometriosis will allow us to formulate a personalized approach at the pre- and postoperative stage, aimed at preventing relapse of the disease, which will directly improve the psycho-emotional state and quality of life of women.
... The classification created by the American Society for Reproductive Medicine (ASRM) determines the advancement of the disease, taking into account the extent and depth of endometriosis foci and the involvement of the peritoneum, fallopian tubes and ovary, as well as the presence and type of adhesions. ASRM has distinguished four stages of the disease, which are marked from I to IV [8,9]. ...
Objectives:
Endometriosis is a complex, chronic inflammatory disease in which immune system disorders play an important role. Soluble mediators of the immune and inflammatory response, including cytokines, are involved in these processes. Therefore, the aim of the conducted research was to understand the role of selected cytokines belonging to the Interleukin-1(IL-1) family, including IL-36α, IL-36β, IL-36γ, IL-36R, IL-37 and IL-38, in the onset and development of endometriosis by analysing the concentration of the tested molecules and to determine whether their concentration depends on the stage of the disease.
Material and methods:
The study group included 60 women who had pelvic endometriosis diagnosed during laparoscopy and subsequently confirmed by histopathology. The reference group consisted of 20 women who had no endometriosis or other pelvic lesions during laparoscopy.
Results:
Immunoenzymatic assays were used to determine the concentration of the cytokines studied. In the peritoneal fluid of women with endometriosis, a statistically significant increase in the concentrations of all parameters tested was observed: IL-36α, IL-36β, IL-36γ, IL-36R, IL-37 and IL-38. The concentration of these cytokines depended on the severity of the disease.
Conclusions:
Disturbances of the immune system involving the network of cytokines belonging to the IL-1 family occurring in the peritoneal fluid environment testify to the involvement of these molecules in the development of the disease and are one of many factors involved in the pathogenesis of endometriosis. The use of some of them in the treatment of endometriosis may be a hope for effective causal treatment of this disease, but this requires further, more advanced research.
... EMs is a common gynecological disease with a trend of increasing incidence yearly. Pain and infertility caused by EMs are severe threats to women's physical and mental health (Johnson et al., 2017). The natural pregnancy rate of patients with EMs decreases annually with increasing postoperative time, and ART also leads to low implantation rates due to the poor quality of oocytes and embryos in patients with EMs (Bailey and Coe, 2002;Flores et al., 2012). ...
Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics.
... At the global consensus in 2021, the following classifications for clinical use in endometriosis were recommended: rASRM (revised American Society for Reproductive Medicine), the EFI scale (Endometriosis Fertility Index), and the #Enzian classification. These classifications not only allow for staging the pathological process but also for evaluating the reproductive prognosis of the patients [7,8]. Of particular interest for our study are the #Enzian classification, which completely describes all possible forms of DIE, and the EFI, which provides a precise reproductive prognosis and allows for specific recommendations regarding fertility management for patients in the postoperative period [9][10][11]. ...
Introduction Deep infiltrating endometriosis (DIE) is the most severe form of endometriosis, contributes to pelvic pain syndrome, extragenital symptoms, fertility problems, and diminished reproductive prognosis for affected individuals. It is recommended to use the Endometriosis Fertility Index (EFI) to assess reproductive prognosis and conduct clinical research to compare reproductive prognosis in different forms of endometriosis. Objective Comparison of the impact of the DIE and others forms of endometriosis on EFI, patients' fertility and on reproductive prognosis to understand the management approach. Materials and methods A cohort study included 190 reproductive-age women, divided according to the #Enzian classification: the main group - 85 patients with DIE, the control group - 105 women with other forms of endometriosis. The EFI was utilized for reproductive prognosis. Pain was evaluated with Visual Analog Scale (VAS). Statistical analyses were performed using SPSS, with calculation of the Mann-Whitney U and Pearson's chi-square test (χ²). Results In main group, the frequency of infertility was 83.5% compared to the control group's 71.4% (p > 0.05). The EFI in main group was 7.18±0.25 points vs the control group's 7.13±0.28 points (p = 0.852). Patients in the main group suffered from intense pelvic pain (>7 points by the VAS, p < 0.01), including severe dyspareunia (7.85±0.33 points vs 2.18±0.46 points in control group, p < 0.01). Conclusions Our results suggest that infertility in women with DIE may be more often associated with sexual abstinence due to significant dyspareunia rather than organic impairments. Thus, EFI in patients with DIE does not reflect all aspects of infertility and has reservations, and consideration of both physical symptoms and sexual health is crucial in managing DIE to optimize fertility outcomes. These findings open the way to the feasibility of surgical treatment of DIE to improve sexual quality of life, which will reduce the need for IVF and increase the chances of spontaneous pregnancy in patients, but this conclusion requires further investigation in randomized clinical trials.
... Endometriosis lesions seem to develop due to the frequent occurrence of retrograde menstruation, combined with neuroangiogenic factors that allow endometrial cells to attach to peritoneal surfaces, proliferate, and form endometriosis lesions [2] . It is estimated that 176 million women globally are affected by endometriosis, with 1.5% to 10% of them being of reproductive age [3,4] . The average age at which endometriosis is first diagnosed is 28 years [5] . ...
... The widely accepted rASRM classification of endometriosis differentiates between four stages of disease advancement (I-IV), based on lesion size, location, degree of involvement, and presence of adhesions [12]. Notably, there is no correlation between pain intensity and advancement of the disease classified with the help of the rASRM scale [13,14]. ...
... Este nuevo sistema de clasificación de la endometriosis establece diferentes categorías que describen de manera fiable el nivel de complejidad de la cirugía necesaria para tratar completamente la enfermedad y se correlaciona también con los síntomas de dolor preoperatorio y la infertilidad. La nueva clasificación sí tiene en cuenta todos los tipos de endometriosis: la peritoneal, la ovárica y la profunda (5,11). ...
Objective: To study the relationship that exists between some predisposing factors to develop endometriosis and the most frequent symptoms manifested by patients. Methods: Longitudinal, retrospective and descriptive observational study, through the review of 455 records taken from 560 patients who attended the endometriosis consultation and made a definitive diagnosis at the “Dr. Ángel Larralde” and private consultation, in Venezuela, Carabobo state, in the period from January 2006 to May 2023. Results: The diagnosis was made in 47.1% of the patients aged between 26 and 35 years. Menarche occurred between 8 and 12 years of age (69%). 63% did not have pregnancies. Primary dysmenorrhea was more frequent in 63.07%. Pelvic pain and dyspareunia in 48%, digestive symptoms in 21%. The most frequent location was in the ovary (78.7%). Conclusion: Endometriosis, a benign, estrogen-dependent inflammatory disease, is characterized by the presence of ectopic endometrial glands and stroma, usually accompanied by fibrosis. It manifests itself in the reproductive period, its main symptom is pain. It is located most frequently in the pelvis and from this in the ovaries, intestine, bladder, liver, lungs, brain, abdominal wall and perineum. There is no treatment to cure it, but there is treatment for the symptoms and slowing its progress. Its diagnosis due to its multifactorial development and clinical manifestations is often made late. Keywords: endometriosis, pelvic pain, endometrioma, fertility, dysmenorrheal
Endometriosis, a prevalent gynecological condition affecting 10–15% of reproductive-age women, involves the growth of endometrial-like tissue outside the uterine cavity. This chronic inflammatory disease can significantly impact fertility by disrupting ovulation, tubal transport, and implantation. Clinical manifestations vary widely, ranging from asymptomatic cases to severe pelvic pain, dysmenorrhea, and dyspareunia. Accurate diagnosis remains challenging, often requiring a combination of patient history, clinical examination, and imaging studies. This paper will discuss the clinical approach to endometriosis during a first-line gynecological appointment, focusing on patient history, including detailed assessment of menstrual, pelvic, and bowel symptoms, and clinical examination; thorough gynecological examination, including abdominal and pelvic palpation, speculum examination, and bimanual examination; imaging evaluation (particularly of the role of ultrasound in identifying and characterizing endometriotic lesions, including the use of the #ENZIAN classification for deep infiltrating endometriosis and evaluation of fertility impact); and discussion of the Endometriosis Fertility Index (EFI) as a tool for assessing fertility potential. This comprehensive approach aims to guide clinicians in identifying and managing endometriosis effectively, improving patient outcomes and optimizing fertility management strategies. Methods: A literature search for suitable articles published from January 1974 to 2024 in the English language was performed using PubMed. Results: Endometriosis is associated with infertility rates ranging from 20% to 68%, with mechanisms including pelvic adhesions, chronic inflammation, and immune dysregulation. The revised American Society for Reproductive Medicine (rASRM) classification and #ENZIAN classification were identified as essential tools for staging and characterizing the disease. Transvaginal ultrasound (TVS) demonstrated high diagnostic accuracy for deep infiltrating endometriosis, with a sensitivity of up to 96% and specificity of 99%. EFI emerged as a valuable predictor of natural conception post-surgery. Additionally, the review underscores the frequent co-occurrence of adenomyosis in women with endometriosis, which may further compromise fertility. Despite advancements in imaging techniques and classification systems, the variability in symptom presentation and disease progression continues to challenge early diagnosis and effective management. Conclusions: Endometriosis is a prevalent gynecological condition affecting women of reproductive age and is associated with infertility. This paper describes the diagnostic approach to endometriosis during a first-line gynecological appointment, focusing on clinical history, physical examination, and the role of imaging, particularly ultrasound, in identifying and characterizing endometriosis lesions. The adoption of standardized classification systems such as #ENZIAN and EFI enhances disease staging and fertility prognosis, allowing for tailored treatment strategies. Despite improvements in non-invasive diagnostic methods, challenges persist in correlating symptom severity with disease extent, necessitating continued research into biomarkers and novel imaging techniques. Additionally, the frequent coexistence of adenomyosis further complicates fertility outcomes, underscoring the need for comprehensive management strategies. Further research is needed to enhance early detection strategies and optimize fertility preservation techniques for affected women.
Endometriosis is an enigmatic disease whose diagnosis and management are being transformed through innovative surgical, molecular, and computational technologies. Integrating single-cell and other omic disease data with clinical and surgical metadata can identify multiple disease subtypes with translation to novel diagnostics and therapeutics. Herein, we present real-world perspectives on endometriosis and the importance of multidisciplinary collaboration in informing molecular, epidemiologic, and cell-specific data in the clinical and surgical contexts.
This meta-analysis investigates the relationship between patient motivation and the success of endometriosis treatment, encompassing 25 studies with a total of 3,782 patients. A strong positive correlation was found (r = 0.68, p < 0.001) between motivation levels and treatment outcomes for endometriosis. Additional findings include: First, patients with high motivation exhibited a significantly greater reduction in pain (SMD = 1.24, 95% CI [0.98, 1.50]) and a more substantial improvement in quality of life (SMD = 0.89, 95% CI [0.67, 1.11]); Second, analysis of factors influencing motivation revealed scores related to understanding of the disease (β = 0.41, p < 0.001), social support (β = 0.38, p < 0.001), and the quality of the doctor-patient relationship (β = 0.45, p < 0.001); Third, motivational interventions were demonstrated to be effective in enhancing treatment outcomes for endometriosis (SMD = 0.94, 95% CI [0.73, 1.15], p < 0.001). Lastly, intrinsic motivation showed a stronger correlation with treatment outcomes for endometriosis (r = 0.73, 95% CI [0.65, 0.79]) compared to extrinsic motivation (r = 0.54, 95% CI [0.45, 0.62]). These findings extend the results of Facchin et al. (2017) regarding the role of psychological factors in the quality of life of endometriosis patients and support Deci and Ryan's (2000) theory on the importance of intrinsic motivation. Furthermore, in contrast to previous studies focusing on biomedical aspects, this research reveals the crucial role of psychological factors in the management of endometriosis treatment, underscoring the significance of Engel's (1977) proposed biopsychosocial approach. Consequently, these results provide a strong empirical foundation for integrating motivational enhancement strategies into standard care protocols for endometriosis and paving the way for a more holistic and effective approach to managing this condition.
Endometriosis is a debilitating disease affecting one in ten women worldwide. Due to several reasons the diagnosis is delayed for 7–11 years. Currently, the ultimate diagnostic procedure is laparoscopy followed by histological examination. The need for non-invasive biomarker is placed as a top priority according to the World Endometriosis Society. The present study includes 45 females – 30 patients with endometriosis at different stages and 15 healthy controls. An expression analysis of 84 circulating miRNAs was performed comparing between different groups of participants. Ten miRNAs with the most significant expression difference between females at early stage of endometriosis, advanced stage of endometriosis and healthy controls were nominated as a potential diagnostic and prognostic biomarker using a panel of miRNAs.
Study question:
How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?
Summary answer:
For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.
What is known already:
Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high inter- and intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.
Study design, size, duration:
In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents.
Participants/materials, setting, methods:
The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records.
Main results and the role of chance:
For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99).
Limitations, reasons for caution:
Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time, which may limit generalizability to some US states. Additionally, given that participants whose administrative health records we utilized were also part of the ENDO Study, the surgeons may have been more vigilant in diagnostic coding due to the operative forms they completed for the ENDO Study, which may have led to increased validity. However, the codes compared in the UPDB would have been entered by medical coders as part of standard clinical practice.
Wider implications of the findings:
We observed substantial agreement between administrative health data and surgically confirmed endometriosis diagnoses overall, and for superficial and ovarian endometrioma subtypes. These findings may provide reassurance to researchers using administrative healthcare records to assess risk factors and long-term health outcomes of endometriosis. Our findings corroborate prior research that demonstrates high specificity but low sensitivity for deep infiltrating endometriosis, indicating deep infiltrating endometriosis is not reliably annotated in administrative healthcare data. This suggests that medical record-based deep infiltrating endometriosis diagnoses may be suitable for etiologic studies but not for surveillance or detection studies.
Study funding/competing interest(s):
The original ENDO Study was funded by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02). We acknowledge partial support for the UPDB through grant P30 CA2014 from the National Cancer Institute, University of Utah and from the University of Utah's program in Personalized Health and Center for Clinical and Translational Science. This research was also supported by the NCRR grant, 'Sharing Statewide Health Data for Genetic Research' (R01 RR021746, G. Mineau, PI) with additional support from the Utah Department of Health and Human Services, University of Utah. Additionally, this research was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's SEER Program, Contract No. HHSN261201800016I, the US Centers for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP007131, with additional support from the University of Utah and Huntsman Cancer Foundation. Research reported in this publication was also supported by the National Institutes of Health (Award Numbers R01HL164715 [to L.V.F., K.C.S., and A.Z.P.] and K01AG058781 [to K.C.S.]), by the Huntsman Cancer Institute's Breast and Gynecologic Cancers Center, and by the Doris Duke Foundation's COVID-19 Fund to Retain Clinical Scientists funded by the American Heart Association. A.C.K. was supported by Training Grant Number 5T15LM007124 from the National Library of Medicine to K.E. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. There are no competing interests among any of the authors.
Trial registration number:
N/A.
Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its antiangiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the
multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions.
Background:
Endometrioma are endometriotic deposits within the ovary. Laparoscopic management of endometriomas is associated with shorter hospital stay, faster recovery, and decreased hospital costs compared with laparotomy. The previous version of this systematic review (2008), including randomised controlled trials (RCTs) of surgical interventions for endometrioma, concluded that laparoscopic cystectomy (excision) was preferable to drainage and ablation of endometrioma. We aimed to update the evidence comparing excision with drainage and ablation for improving pain and fertility-related outcomes.
Objectives:
To evaluate the safety and efficacy of laparoscopic excision (cystectomy) compared with laparoscopic drainage and ablation of endometrioma in women of reproductive age.
Search methods:
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycInfo, two trials registries, grey literature sources, and conference proceedings on 19 December 2022. We also checked the reference lists of relevant papers and contacted leaders in the field of endoscopic surgery for any additional trials.
Selection criteria:
Eligible studies were RCTs that compared excision with drainage and ablation of endometriomas.
Data collection and analysis:
Two review authors independently assessed study eligibility, extracted data, assessed risk of bias, and applied the GRADE approach to rate the certainty of evidence.
Main results:
We identified nine studies (involving 578 women) that investigated laparoscopic excision versus drainage and ablation of endometriomas measuring at least 3 cm in diameter. Participants were women of reproductive age who presented to an outpatient gynaecology clinic with pain, infertility, or both. For most outcomes, we downgraded the certainty of evidence for risk of bias due to lack of blinding and for imprecision due to low participant numbers. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dysmenorrhoea recurrence (OR 0.25, 95% CI 0.12 to 0.52; 2 studies, 140 women; low-certainty evidence;). Recurrence of dysmenorrhoea may occur in 49% of women after ablative surgery compared with 10% to 34% after excisional surgery. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dyspareunia recurrence (OR 0.09, 95% CI 0.03 to 0.22; 2 studies, 131 women; low-certainty evidence). Recurrence of dyspareunia may occur in 58% of women after ablative surgery compared with 4% to 23% after excisional surgery. At one year after surgery, excisional surgery may reduce the risk of endometrioma recurrence compared with ablative surgery (OR 0.17, 95% CI 0.09 to 0.34; 4 studies, 264 women; low-certainty evidence). Recurrence of endometrioma may occur in 37% of women after ablative surgery compared with 5% to 17% after excisional surgery. At one year after surgery, excisional surgery may reduce the need for further endometrioma surgery compared with ablative surgery (OR 0.16, 95% CI 0.07 to 0.41; 2 studies, 178 women; low-certainty evidence). Our results suggest that 32% of women require further endometrioma surgery after ablative surgery compared with 3% to 16% after excisional surgery. There may be little or no difference between excisional surgery and ablative surgery in terms of their effect on spontaneous pregnancy during the first year after surgery (OR 1.27, 95% CI 0.33 to 4.87; 3 studies, 101 women; low-certainty evidence). Five studies reported that there were no conversions to laparotomy. No studies provided data about any other surgical complications or adverse effects.
Authors' conclusions:
Surgical management of endometrioma with excision (cystectomy) may be more effective than drainage and ablation for reducing painful menstrual periods, pain during sexual intercourse, endometrioma recurrence, and the need for further endometrioma surgery. However, there may be little or no difference between the techniques in their effect on subsequent pregnancy rates. We found limited evidence on the safety of excisional surgery compared with ablative surgery. Future trials should recruit adequate numbers of women and measure outcomes relating to adverse events and clinical pregnancy.
STUDY QUESTION
What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)?
SUMMARY ANSWER
Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels.
WHAT IS KNOWN ALREADY
Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development.
STUDY DESIGN, SIZE, DURATION
This is a cross-sectional study aimed to elucidate the molecular mechanisms underlying the impact of OEM on follicular development. Initially, miRNA expression profiles in follicular fluid (FF) samples were sequenced from patients with infertility related to OEM (N = 3) and male factor (MF) infertility (N = 3), with the latter serving as the control group. Differentially expressed miRNAs were validated in additional samples from each group (N = 55 in OEM group and N = 45 in MF group) to confirm candidate miRNAs. The study also investigated indicators associated with GCs dysfunction in vitro on rat GCs. Subsequently, rat models of OEM were established through endometrial allogeneic transplantation, and fertility experiments were conducted to assess the let-7/IGF1R axis response to OEM in vivo. Patient samples were collected between May 2018 and April 2019, and the mechanistic study was conducted over the subsequent three years.
PARTICIPANTS/MATERIALS, SETTING, METHODS
FF and GC samples were obtained from infertile patients undergoing IVF treatment for OEM and MF related infertility. miRNA expression profiles in FF samples were analyzed using second-generation high-throughput sequencing technology, and candidate miRNAs were validated through quantitative PCR (qPCR). In the in vitro experiments conducted with rat GCs, cell proliferation was assessed using the CCK-8 assay, while steroid hormone concentrations were measured using chemiluminescence. ATP content was determined with an ATP assay kit, and levels of ROS were quantified using flow cytometry. A dual luciferase reporter gene assay was employed to identify the target gene of let-7 based on the construction of a IGF1R reporter gene plasmid using 293T cells. Western blotting was utilized to evaluate the expression of IGF1R in GCs, as well as its downstream proteins, and changes in signaling pathways following let-7 agomir/antagomir transfection and/or Igf1r silencing. In the in vivo OEM rat models, alterations in ovarian structure and cyst morphology were observed using hematoxylin and eosin staining. The expressions of let-7 and Igf1r in GCs were evaluated through qPCR, while variations in IGF1R expression were investigated with immunohistochemistry.
MAIN RESULTS AND THE ROLE OF CHANCE
The cohort of patients with ovarian OEM in this study exhibited significantly decreased antral follicle counts, oocyte retrieval numbers, and normal fertilization rates compared to the control group with MF. The expression of the let-7 miRNA family was markedly upregulated in the FF and GCs of OEM patients. Transfection of rat GCs with let-7 agonists diminished the functions of GCs, including disrupted cell proliferation, mitochondrial oxidative phosphorylation, and steroid hormone secretion, while transfection of rat GCs with let-7 antagonists caused the opposite effects. Luciferase reporter gene experiments confirmed that let-7 complementarily bound to the 3′-untranslated regions of IGF1R. Stimulation of let-7 expression in rat GCs led to a significant decrease in IGF1R expression, while inhibition of let-7 increased IGF1R expression. The expression of IGF1R in the GCs of OEM patients was also significantly reduced compared to MF patients. Silencing of Igf1r led to the dysfunction of GCs, similar to the effects of let-7 agonization, as demonstrated by the downregulation of key proteins involved in cell proliferation (CCND2 and CCND3) and oestradiol synthesis, as well as an increase in progesterone synthesis (StAR), while implicating the PI3K-Akt and MAPK signaling pathways. The antagonistic effect of let-7 on GCs was ineffective when Igf1r was silenced. Conversely, the agonistic effect of let-7 on GCs could be reversed by stimulation with the IGF1R ligand IGF-1. These findings suggested that let-7 regulated the proliferation, differentiation, and ATP synthesis of GCs through targeting IGF1R. The OEM rat model demonstrated alterations in ovarian morphology and structure, along with reduced fertility. Let-7 expression was significantly upregulated in GCs of OEM rats compared to normal rats, while Igf1r and IGF1R expression in pre-ovulatory follicular GCs were notably downregulated, supporting the notion that elevated let-7 expression in the follicular microenvironment of OEM inhibited IGF1R, leading to abnormal GC function and impacting fertility at the molecular level.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
The synthesis and secretion mechanisms of steroid hormones are intricate and complex. Some enzymes that regulate oestrogen synthesis also play a role in progesterone synthesis. Moreover, certain receptors can respond to multiple hormone signals. Therefore, in this study, the expression patterns of key enzymes such as CYP17A, CYP11A1, HSD3B2, StAR, and receptors including AR, LHCGR, FSHR, ESR2, might be influenced by various factors and might not demonstrate complete consistency.
WIDER IMPLICATIONS OF THE FINDINGS
Future research will concentrate on investigating the potential impact of ovarian stromal cells on the external microenvironment of follicle growth. Additionally, screening for small molecule drugs that target let-7 and IGF1R actions can be conducted to intervene and modify the ovarian microenvironment, ultimately enhancing ovarian function.
STUDY FUNDING/COMPETING INTEREST(S)
This study received funding from the National Natural Science Foundation of China (grant number 82301851 to L.B.S., grant numbers U23A20403 and U20A20349 to S.Y.Z., and grant number 82371637 to Y.D.D.) and the Natural Science Foundation of Zhejiang Province (grant LTGY23H040010 to F.Z.). The authors have no conflicts of interest to declare.
Objective
To assess the association between adenomyosis volume, as a reflection of its severity, and the risk of adverse perinatal outcomes.
Methods
This multicenter retrospective cohort study was conducted at a comprehensive tertiary care institution and a tertiary maternal and child healthcare hospital, which are the main types of hospital providing maternal medical care in China. The study included pregnant women without adenomyosis (non‐AD cohort) who delivered between 1 January 2021 and 31 December 2021, and women with pregnancy complicated by adenomyosis (AD cohort) who delivered between 1 January 2020 and 31 December 2022. Adenomyosis was diagnosed and measured using transvaginal or transabdominal ultrasound up to 14 weeks of gestation. The adenomyosis volume (V) was calculated based on the sonographic measurement of three dimensions, using the formula V = (length × width × thickness) × 4/3π. Univariate and multivariate logistic regression analyses were conducted to assess the association between adenomyosis and the risk of pregnancy complications. We also performed a sensitivity analysis among 226 pregnancies complicated by adenomyosis that had volume measurements available and 10 507 pregnancies without adenomyosis, using as a threshold for severe adenomyosis the 3 rd quartile of adenomyosis volume.
Results
The study group included 10 507 pregnant women in the non‐AD cohort and 321 in the AD cohort. Pregnancies complicated by adenomyosis had an increased risk of preterm birth < 37 weeks of gestation (adjusted odds ratio (aOR), 2.39 (95% CI, 1.65–3.48)), spontaneous preterm birth < 37 weeks of gestation (aOR, 2.57 (95% CI, 1.54–4.28)), placenta previa (aOR, 2.57 (95% CI, 1.41–4.67)), cervical incompetence (aOR, 9.70 (95% CI, 4.00–23.55)) and abnormal fetal presentation (aOR, 2.04 (95% CI, 1.39–3.00)), and there was also a non‐significant trend toward increased risk of pre‐eclampsia (aOR, 1.64 (95% CI, 0.94–2.85)). Sensitivity analysis revealed there was a greater risk in pregnancies with severe (≥ 757.5 cm ³ ) vs mild adenomyosis of preterm birth < 37 weeks of gestation (aOR, 5.50 (95% CI, 2.80–10.82) vs aOR, 1.73 (95% CI, 0.98–3.05)), pre‐eclampsia (aOR, 4.94 (95% CI, 2.11–11.58) vs aOR, 1.03 (95% CI, 0.41–2.58)), placenta previa (aOR, 6.37 (95% CI, 2.39–17.04) vs aOR, 1.58 (95% CI, 0.60–4.19)) and cervical incompetence (aOR, 12.79 (95% CI, 2.87–56.93) vs aOR, 4.97 (95% CI, 1.25–19.77)) compared to pregnancies without adenomyosis. The risk of spontaneous preterm birth < 37 weeks and the risk of abnormal fetal presentation was similar between the two subgroups.
Conclusion
Pregnancies complicated by adenomyosis, particularly those with severe adenomyosis, have an increased risk of pregnancy complications, including preterm birth, spontaneous preterm birth, placenta previa, cervical incompetence and abnormal fetal presentation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
Ovarian endometrioma (OE), also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+ macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+ and KLF2+ epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.
Endometriosis is an estrogen-dependent condition that can lead to significant morbidity, including chronic pelvic pain, multiple surgeries, and infertility. Recent discoveries regarding its genetics, the potential influence of environmental factors and the immune system, along with intrinsic abnormalities in the endometrium of affected women and the secretions from endometriotic lesions, have provided new insights into the disease's pathogenesis. These findings form the basis for developing new treatments aimed at managing disease-related pain and infertility. It was possible to observe a case of remission of symptoms and complete disappearance of lesions on ultrasound images after anthroposophic treatment. Certainly, more cases need to be followed up in the long term to verify whether there has been a real cure for the disease. Case: Brazilian woman in the reproductive period with endometriosis presented remission of symptoms with disappearance of the lesions after anthroposophic treatment
A endometriose é uma condição ginecológica crônica que afeta aproximadamente 10% das mulheres em idade reprodutiva, sendo uma das principais causas de infertilidade no mundo. O manejo da doença é complexo e requer uma abordagem individualizada, dado o espectro variado de sintomas e a resposta variável ao tratamento. Diversas opções terapêuticas estão disponíveis no mercado hoje. Além disso, inovações como terapias imunomoduladoras e tratamentos baseados na biologia molecular estão sendo exploradas. O objetivo da pesquisa consistiu em analisar aspectos gerais e atuais sobre a endometriose, assim como sua fisiopatologia e suas principais formas de tratamento, desde as mais antigas até as mais atuais. Para tanto, a metodologia utilizada consistiu na realização de buscas em bases de dados reconhecidas, resultando na seleção inicial de 26 artigos. Desses, 11 atenderam aos critérios previamente estabelecidos. A personalização do tratamento, levando em conta a gravidade dos sintomas e os objetivos reprodutivos da paciente, é essencial, destacando a necessidade de uma abordagem multidisciplinar e contínuas pesquisas para desenvolver terapias mais eficazes e duradouras.
Introduction:
This study aims to examine the effect of full thickness discoid resection (FTDR) and modified, limited nerve-vessel sparing segmental bowel resection (NVSSR) in symptomatic patients with low rectal deep endometriosis (DE) within 7 cm from the anal verge. Presurgical and postsurgical evaluation of gastrointestinal (GI) function reflected by low anterior resection syndrome (LARS) and gastrointestinal function-related quality of life index (GIQLI) scores, complication rates, pain scores/visual analog scale (VAS) and endometriosis health profile (EHP-30) was performed.
Methods:
In this prospective multicenter cohort study, 63 premenopausal patients with symptomatic low (within 7 cm from the anal verge) colorectal endometriosis, undergoing low modified limited nerve vessel sparing rectal segmental bowel resection (NVSSR) and full thickness discoid resection (FTDR) were evaluated. Presurgery and postsurgery lower anterior resection syndrome (LARS) scores, gastrointestinal function-related quality of life index (GIQLI), pain symptoms, endometriosis health profile (EHP-30) parameters compared between two groups.
Results:
Out of 63 women, 49 (77.8%) underwent NVSSR while 14 (22.2%) underwent FTDR. LARS-like symptoms were observed presurgically in 24/63 (38.1%) patients. Postsurgical LARS was observed in 14/63 (22.2%) of the patients (10/49, 20.4% in NVSSR vs. 4/14, 28.5% in the FTDR group). The LARS-like symptoms significantly decreased following surgery in the FTDR group (p = 0.049) and showed a trend for decrease in the NVSSR group (p = 0.077). Postsurgical de novo LARS was only observed in 5/63 (8%) of the patients (NVSSR 4/49, 8.1%, FTDR 1/14, 7.1%). Postsurgical GIQLI scores improved in both groups (p < 0.001) with comparable changes in the NVSSR and FTDR cohorts (p = 0.490). Postoperative grade III complication rates between NVSSR and FTDR did not vary significantly (6/49, 12.2% vs. 3/14, 21.4% p = 0.26). Pain/VAS scores and EHP-30 scores significantly decreased after a mean follow-up of 29.6 ± 11 months and 30.6 ± 11 months in the NVSSR and FTDR groups, respectively (EHP-30; p < 0.001; dysmenorrhea, dyspareunia, dyschezia all p < 0.05 for both cohorts).
Discussion:
When comparing low colorectal surgery by either NVSSR or FTDR in a high-risk group for surgical complications, both techniques confer improvement of GI function reflected by LARS and GIQLI with non-significant differences in major complication rates, reduced pain and EHP-30 scores.
Endometriosis is a prevalent gynecological disease, leading to chronic pain and inflammation, affecting 1 in 10 individuals presumed female at birth. The diagnostic journey is often arduous, marked by neglect of the right diagnosis and prolonged wait times, significantly compromising the quality of life among those affected. This review provides a nuanced exploration of endometriosis-associated pain management, encompassing medical, surgical, and holistic approaches, all guided by accurate and refined diagnostics. Our paramount goal is to empower physicians as key figures in confronting this intricate challenge with a patient-centric approach, ultimately aiming to improve treatment and quality of life. Acknowledging each patient’s unique needs, we emphasize the importance of tailoring a spectrum of options informed by current literature and insights gleaned from our experience in a high-volume tertiary endometriosis center. It is imperative to recognize endometriosis as a complex and chronic disease, often occurring with co-morbid conditions and nuanced complexities, necessitating a long-term personalized multimodal approach for each case. In addition, incorporating principles such as patient autonomy, profound respect for diverse experiences, and practical education on treatment choices is pivotal in enhancing treatment outcomes and overall patient satisfaction.
Objective: To consider of the surgery of the endometriotic cyst multifacedly, and to investigate the significance of performing resection of the median pelvic endometriosis (RME).
Design: Retrospective observational study.
Setting: Regional medical support hospital
Patients: A total of 885 patients who underwent laparoscopic surgery for the endometriotic cysts from 2005 to 2016 at Japanese Red Cross Maebashi Hospital were included.
Intervention: Under the diagnosis of endometriotic cyst based on physical findings, ultrasonography, MRI, etc., the cyst was operated by laparoscopic surgery, along with uterine fibroid enucleation or hysterectomy/supracervical hysterectomy, depending on the case. Of those, 420 underwent RME.
Main Outcomes: Pain symptoms were assessed with a 10 cm visual analogue scale (VAS), and the status of pain relief and recurrence after surgery were investigated. Additionally, recurrence of cysts, occurrence of premature menopause, pregnancy, delivery, perinatal complications, ovarian cancer, complications of other organ diseases were investigated.
Results: Resection of endometriotic cysts was effective in improving postoperative menstrual pain and chronic pelvic pain. Pain symptoms were relieved more effectively by performing RME. Postoperative pain recurrence was not related to the RME, and hormone therapy significantly suppressed pain recurrence. Recurrence of ovarian cysts was found in 4.6％. Premature menopause before 40 years of age occurred in 1.53％. Thirty-one ％ of those who wished to have children had at least one pregnancy. Eight patients (0.94％) were found to have ovarian cancer, 7 patients survived on disease free, of those three patients became pregnant and delivered after surgery.
Conclusions: In surgery for endometriotic cysts, combined RME improved pain more effectively.
Endometriosis is a chronic inflammatory disease that causes debilitating pelvic pain in women. Macrophages are considered to be key players in promoting disease progression, as abundant macrophages are present in ectopic lesions and elevated in the peritoneum. In the present study, we examined the role of GATA6⁺ peritoneal macrophages on endometriosis-associated hyperalgesia using mice with a specific myeloid deficiency of GATA6. Lesion induction induced the disappearance of TIM4hi MHCIIlo residential macrophages and the influx of increased Ly6C⁺ monocytes and TIM4lo MHCIIhi macrophages. The recruitment of MHCIIhi inflammatory macrophages was extensive in Mac Gata6 KO mice due to the severe disappearance of TIM4hi MHCIIlo residential macrophages. Ki67 expression confirmed GATA6-dependent proliferative ability, showing different proliferative phenotypes of TIM4⁺ residential macrophages in Gata6f/f and Mac Gata6 KO mice. Peritoneal proinflammatory cytokines were elevated after lesion induction. When cytokine levels were compared between Gata6f/f and Mac Gata6 KO mice, TNFα at day 21 in Gata6f/f mice was higher than in Mac Gata6 KO mice. Lesion induction increased both abdominal and hind paw sensitivities. Gata6f/f mice tended to show higher sensitivity in the abdomen after day 21. Elevated expression of TRPV1 and CGRP was observed in the dorsal root ganglia after ELL induction in Gata6f/f mice until days 21 and 42, respectively. These results support that peritoneal GATA6⁺ macrophages are involved in the recruitment and reprogramming of monocyte-derived macrophages. The extensive recruitment of monocyte-derived macrophages in Mac Gata6 KO mice might protect against inflammatory stimuli during the resolution phase, whereas GATA6 deficiency did not affect lesion initiation and establishment at the acute phase of inflammation. GATA6⁺ residential macrophages act to sustain local inflammation in the peritoneum and sensitivities in the neurons, reflecting endometriosis-associated hyperalgesia.
Introdução: A endometriose é uma doença inflamatória e estrogênio-dependente que afeta 10% das mulheres em idade reprodutiva, causando dor crônica e infertilidade. Envolve fatores genéticos, hormonais e imunológicos. O diagnóstico inclui ultrassonografia, ressonância magnética e laparoscopia. O tratamento é multidisciplinar, combinando terapias hormonais, cirúrgicas e apoio psicossocial para melhorar a qualidade de vida das pacientes. Metodologia: Buscas online em Google Scholar, PubMed, BVS e SCIELO utilizaram palavras-chave dos DeCS. Foram incluídos artigos originais, acessíveis integralmente, publicados entre 2015 e 2024, sobre manejo multidisciplinar da endometriose. Excluíram-se publicações com mais de 10 anos. A análise crítica dos dados avaliou a qualidade metodológica, resultados e aplicabilidade prática dos estudos. Resultados: A endometriose é uma condição inflamatória crônica que afeta cerca de 10% das mulheres em idade reprodutiva, caracterizada pela presença de tecido semelhante ao endometrial fora do útero, causando inflamação, dor crônica e infertilidade. O diagnóstico inclui avaliação clínica, ultrassonografia transvaginal, ressonância magnética e laparoscopia. O manejo é multifacetado, integrando tratamentos médicos, cirúrgicos, apoio psicossocial e terapias complementares, como dietas específicas, yoga e acupuntura, visando melhorar a qualidade de vida das pacientes. Considerações Finais: A endometriose é uma doença crônica que causa dor severa e infertilidade em mulheres em idade reprodutiva. O manejo requer uma abordagem multidisciplinar, incluindo diagnósticos precisos, tratamentos médicos e cirúrgicos, e terapias complementares. Métodos como ultrassonografia transvaginal e laparoscopia melhoram a identificação da doença. Tratamentos hormonais e intervenções cirúrgicas são essenciais, complementados por dietas, yoga, meditação e acupuntura para melhorar a qualidade de vida.
Endometriosis affects an estimated 176 million women worldwide during the prime years of their lives. Yet many clinical questions remain unanswered, treatment failures are common, and there is little investment in investigating disease mechanisms. The World Endometriosis Research Foundation (WERF) has been created to provide a global platform where resources and intelligence are pooled to enable international collaboration in order to find answers so that treatments for endometriosis can be improved and prevention can become reality in future generations of women. WERF is now working with 30 centres in 19 countries conducting prospective studies investigating the impact of endometriosis, disease predictability, and personal and societal cost. (Journal of Endometriosis 2010; 2: 3-6).
Objective
To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis.
Design
An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents.
Setting
In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world.
Patient(s)
None.
Intervention(s)
Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds.
Main Outcome Measure(s)
Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research.
Result(s)
We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results.
Conclusion(s)
The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect.
Objective
To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration.
Design
An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents.
Setting
In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research.
Patients
None.
Intervention(s)
Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds.
Main Outcome Measure(s)
Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data.
Result(s)
The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information.
Conclusion(s)
The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and—after a first review after 1 year—triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect.
Objective: To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. Design: An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Setting: Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. Patient(s): None. Intervention(s): A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. Main Outcome Measure(s): The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. Result(s): SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. Conclusion(s): This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition.
Study question:
Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis?
Summary answer:
It was possible to produce an international consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis.
What is known already:
Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence.
Study design, size, duration:
A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken.
Participants/materials, setting, methods:
A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.
Main results and the role of chance:
A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis.
Limitations, reasons for caution:
This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements.
Wider implications of the findings:
This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.
Several endometriosis classifications were proposed, based on the assumption that endometriosis is a progressive disease,
and designed to score severity of visible lesions. In addition, several specific classifications, e.g., for deep endometriosis,
were proposed. None of these classifications however, have been validated to be predictive for diagnosis, treatment prognosis,
recurrence, progression or for the associated infertility or pain. The difficulties derive from the fact that pathophysiology
and the natural history are still uncertain. A classification should avoid assumptions. It seems established beyond reasonable
doubt that endometriosis presents as subtle, typical, cystic, and deep lesions and that severity of each lesion is related
to size or volume. By pathology, these four lesions present as active, burnt-out, inactive, and active lesions, respectively.
Besides this, there are many uncertainties. It is unclear whether endometriosis is one disease progressing ultimately into
severe endometriosis or whether typical, cystic, and deep endometriosis represents three different diseases, each being an
end stage. It is unclear whether endometriotic cells are different from endometrial cells or whether only the environment
is different. It is unclear how adenomyosis, Müllerianosis, and peritoneal pockets should be considered. We therefore suggest
a descriptive classification with the severity of Subtle, Typical, Cystic, Deep, Adenomyotic, and peritoneal pocket lesions,
estimated by their area or volume. This classification should permit to evaluate the actual uncertainties in order to build
subsequently a validated classification. The similarity of the classes for superficial and cystic lesions with the rAFS classification
is considered an advantage. It is discussed why adhesions need not to be scored. In conclusion, a simple classification scoring
separately severity of subtle, typical, cystic, deep, adenomyotic, and peritoneal pocket lesions is suggested. This will permit
to confirm or reject statistically many of the actual uncertainties on endometriosis and to evaluate what the predictive power
of the severity of each type of lesion is, both essential elements for a validated endometriosis classification.
KeywordsClassification–Endometriosis–Adenomyosis–Peritoneal pockets–Müllerianosis
Background:
Ovarian hyperstimulation syndrome is an important condition with considerable morbidity and a small risk of mortality, which most commonly results as an iatrogenic condition following follicular stimulation of the ovaries.
Aim:
To produce evidence-based and consensus statements on the prevention and detection of ovarian hyperstimulation syndrome (OHSS).
Method:
The CREI Consensus Group met in 2008 and identified issues for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted.
Results:
The group considered that there is a need for standardisation of the definition and classification of the clinical syndrome of OHSS to allow further conclusive research. Interventions with evidence of effect in reducing OHSS include the use of metformin in women with PCOS, use of GnRH antagonist rather than GnRH agonist and use of GnRH agonist triggers in GnRH antagonist stimulation cycles. The consensus view was that reducing the dose of FSH, freezing all embryos and transferring a single embryo were appropriate interventions to reduce OHSS. Agreement could not be reached on coasting, the lowest number of oocytes to consider freezing all embryos and management after cancellation of oocyte collection.
Conclusion:
OHSS is a serious condition for which there are a number of proven preventative strategies. OHSS is an area requiring ongoing research and development of a universally agreed definition will allow development of optimal prevention strategies and facilitate improved early detection of women at risk.
Objective
To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis.
Design
An international collaboration involving 34 clinical/academic centers and 3 industry collaborators from 16 countries on 5 continents.
Setting
In 2013, 2 workshops were conducted, followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing worldwide.
Patient(s)
None.
Intervention(s)
Consensus SOPs were based on: [1] systematic comparison of SOPs from 18 global centers collecting fluid samples from women with and without endometriosis on a medium/large scale (publication on >100 cases), [2] literature evidence where available, or consultation with laboratory experts otherwise, and [3] several global consultation rounds.
Main Outcome Measure(s)
Standard recommended and minimum required SOPs for biofluid collection, processing, and storage in endometriosis research.
Result(s)
We developed recommended standard and minimum required SOPs for the collection, processing, and storage of plasma, serum, saliva, urine, endometrial/peritoneal fluid, and menstrual effluent, and a biospecimen data-collection form necessary for interpretation of sample-derived results.
Conclusion(s)
The Endometriosis Phenome and Biobanking Harmonisation Project SOPs allow endometriosis research centers to decrease variability in biofluid sample results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other female conditions involving biofluid samples subject to cyclic reproductive influences. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback, and through systematic tri-annual follow-up. Updated versions will be made available at: endometriosisfoundation.org/ephect.
To assess the extent to which the Enzian classification correlates with the revised American Society for Reproductive Medicine (rASRM) score and clinical symptoms in women with deeply infiltrating endometriosis.
Retrospective cohort study (Canadian Task Force classification II-2).
Endometriosis competence center specializing in minimally invasive surgery.
Between 1 January 2009 and 31 December 2011, a total of 194 women underwent surgery due to deeply infiltrating endometriosis. After histological confirmation, they were classified using the rASRM and Enzian systems. Clinical symptoms were recorded preoperatively.
Operative laparoscopy to treat endometriosis.
A clear correlation was seen between grades of severity in the rASRM score and the Enzian classification (p < 0.001). In addition, the rASRM severity grade and clinical symptoms correlated with the locations in the Enzian classification in relation to deeply infiltrating endometriosis. Pain and dysmenorrhea correlated strongly (p = 0.002, p < 0.001) with the severity grade in the Enzian classification.
Deeply infiltrating endometriosis is well characterized using the Enzian classification as a supplement to the rASRM score. There is also a clear correlation between the rASRM and Enzian classifications, because of the way in which the disease crosses morphological boundaries. The locations in the Enzian classification correlate partially with clinical symptoms, and the classification's severity grades correlate substantially with pain and dysmenorrhea. In view of these clinical results, use of the Enzian classification can be recommended as a supplement to the rASRM score for detailed description of endometriosis.
Endometriosis is common in women with infertility but its management is controversial and varied. This article summarises the consensus developed by a group of Australasian subspecialists in reproductive endocrinology and infertility (the Australasian CREI Consensus Expert Panel on Trial evidence group) on the evidence concerning the management of endometriosis in infertility. Endometriosis impairs fertility by causing a local inflammatory state, inducing progesterone resistance, impairing oocyte release and reducing sperm and embryo transport. Medical treatments have a limited role, whereas surgical and assisted reproductive treatments improve pregnancy rates. The role of surgery for deep infiltrative endometriosis and repeat surgery requires further evaluation and there is insufficient evidence for the use of anti-adhesives to improve fertility. Intrauterine insemination (IUI) and in vitro fertilisation (IVF) improve pregnancy rates but women with endometriosis have lower pregnancy rates than those with other causes of infertility. The decision about whether to operate or pursue assisted reproduction will depend on a variety of factors such as the patient's symptoms, the presence of complex masses on ultrasound, ovarian reserve and ovarian access for IVF, risk of surgery and cost. Some women with infertility and endometriosis may benefit from a combination of assisted reproduction and surgery.
Fibroid management is surrounded by considerable controversy and uncertainty. This paper summarises the consensus developed by a group of Australasian subspecialists in reproductive endocrinology and infertility (the ACCEPT group) on the evidence concerning the impact and management of fibroids in infertility. The location of a fibroid within the uterus influences its effect on fertility. Subserosal fibroids do not appear to impact on fertility outcomes. Intramural (IM) fibroids may be associated with reduced fertility and an increased miscarriage rate (MR); however, there is insufficient evidence to inform whether myomectomy for IM fibroids improves fertility outcomes. Submucosal fibroids are associated with reduced fertility and an increased MR, and myomectomy for submucosal fibroids appears likely to improve fertility outcomes. The relative effect of multiple or different sized fibroids on fertility outcomes is uncertain, as is the relative usefulness of myomectomy in these situations. It is recommended that fibroids with suspected cavity involvement are defined by magnetic resonance imaging, sonohysterography or hysteroscopy because modalities such as transvaginal ultrasound and hysterosalpingography lack appropriate sensitivity and specificity. Medical management of fibroids delays efforts to conceive and is not recommended for the management of infertility associated with fibroids. Newer treatments such as uterine artery embolisation, radiofrequency ablation, bilateral uterine artery ligation, magnetic resonance-guided focussed ultrasound surgery and fibroid myolysis require further investigation prior to their establishment in the routine management of fibroid-associated infertility.
Endometriosis remains an enigmatic disease for many reasons, not the least being a continued inability to stage its clinical presentation so that prognosis and treatment for both pain and infertility patients can be facilitated. This article reviews issues with current staging systems.
The revised American Fertility Society (rAFS) classification system has historically been the only classification system. Recently, the ENZIAN classification system, developed as an adjunct to the rAFS to describe more severe disease, has been introduced but is rarely used. More recently, the Endometriosis Fertility Index (EFI) that has been validated to predict pregnancy rates in infertility patients following surgical diagnosis and treatment of endometriosis was published. Currently, the AAGL is developing a categorization system that will be more focused on pain. Novel research in imaging, biomarkers, histology, and the human genome may provide useful information to develop future classification systems.
The only validated endometriosis classification system that predicts a clinical outcome is the EFI. It is to be hoped that renewed interest in the importance and utility of classification systems will result in novel classification systems that are clinically useful.
To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception.
Prospective data collection on 579 patients and comprehensive statistical analysis to derive a new staging system--the endometriosis fertility index (EFI)--from data rather than a priori assumptions, followed by testing the EFI prospectively on 222 additional patients for correlation of predicted and actual outcomes.
Private reproductive endocrinology practice.
A total of 801 consecutively diagnosed and treated infertile patients with endometriosis.
Surgical diagnosis and treatment followed by non-IVF fertility management.
The EFI and life table PRs.
A statistically significant variable used to create the EFI was the least function score (i.e., the sum of those scores determined intraoperatively after surgical intervention that describe the function of the tube, fimbria, and ovary on both sides). Sensitivity analysis showed that the EFI varies little, even with variation in the assignment of functional scores, and predicted PRs.
The EFI is a simple, robust, and validated clinical tool that predicts PRs after endometriosis surgical staging. Its use provides reassurance to those patients with good prognoses and avoids wasted time and treatment for those with poor prognoses.