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Background Scar endometriosis (EM) is defined by the presence of endometrial-like tissue outside the uterine cavity within the scar region after abdominal or pelvic surgery. It is a form of abdominal wall EM. This systematic review addresses the question of whether women after cesarean delivery (CD) are more frequently affected by scar EM than women after other pelvic surgical procedures. The primary aim is to analyze the distribution of previous operations in patients with scar EM. Secondarily, symptoms, diagnosis, and treatment are described. Methods A systematic literature search in MEDLINE (Pubmed) was performed. Twelve studies were included. Results The terminology of scar EM is unspecific and the descriptions are, therefore, of limited comparability among authors. In 64–96%, patients with scar EM had a history of CD, followed by laparoscopy, laparotomy, and episiotomy. The main symptoms were pain, often cyclical, and the presence of local swelling. For diagnosis ultrasound, CT scan and MR imaging were used. All patients had undergone surgical resection and the diagnosis was confirmed. Conclusion Most often scar EM develops after CD. Diagnosis and treatment are often delayed. As an objective classifications system is missing, we propose a simple objective descriptive tool for abdominal wall EM.

Gynecological ultrasonography plays a central role in the management of endometriosis. The rapid technical development as well as the currently increasing evidence for non-invasive diagnostic methods require an updated compilation of recommendations for the use of ultrasound in the management of endometriosis. The present work aims to highlight the accuracy of sonography for diagnosing and classifying endometriosis and will formulate the present list of key messages and recommendations. This paper aims to demonstrate the accuracy of TVS in the diagnosis and classification of endometriosis and to discuss the clinical applications and consequences of TVS findings for indication, surgical planning and assessment of associated risk factors. (1) Sophisticated ultrasound is the primary imaging modality recommended for suspected endometriosis. The examination procedure should be performed according to the IDEA Consensus. (2) Surgical intervention to confirm the diagnosis alone is not recommended. A preoperative imaging procedure with TVS and/or MRI is strongly recommended. (3) Ultrasound examination does not allow the definitive exclusion of endometriosis. (4) The examination is primarily transvaginal and should always be combined with a speculum and a bimanual examination. (5) Additional transabdominal ultrasonography may enhance the accuracy of the examination in case of extra pelvic disease, extensive findings or limited transvaginal access. (6) Sonographic assessment of both kidneys is mandatory when deep endometriosis (DE) and endometrioma are suspected. (7) Endometriomas are well defined by sonographic criteria. When evaluating the ovaries, the use of IOTA criteria is recommended. (8) The description of sonographic findings of deep endometriosis should be systematically recorded and performed using IDEA terminology. (9) Adenomyosis uteri has sonographically well-defined criteria (MUSA) that allow for detection with high sensitivity and specificity. MRI is not superior to differentiated skilled ultrasonography. (10) Classification of the extent of findings should be done according to the #Enzian classification. The current data situation proves the best possible prediction of the intraoperative situs of endometriosis (exclusive peritoneum) for the non-invasive application of the #Enzian classification. (11) Transvaginal sonographic examination by an experienced examiner is not inferior to MRI diagnostics regarding sensitivity and specificity in the prediction of the extent of deep endometriosis. (12) The major advantage of non-invasive imaging and classification of endometriosis is the differentiated planning or possible avoidance of surgical interventions. The recommendations represent the opinion of experts in the field of non-invasive and invasive diagnostics as well as therapy of endometriosis. They were developed with the participation of the following national and international societies: DEGUM, ÖGUM, SGUM, SEF, AGEM/DGGG, and EEL.

PurposeTo analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility.MethodsUsing our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in minimal invasive surgery, and included a suspended hormonal pretreatment for 2 months. Postoperative outcomes including complications, fertility and recurrence rates were analysed.ResultsLaparoscopic peritonectomy was performed on 94 women. Follow-up data were available in 87% of these cases. At the time of surgery, almost all patients tested showed signs of stage I or II endometriosis (44.7 and 48.9%, respectively). More than three-quarters of the women reported pain relief, inter alia, due to the post-surgical hormonal therapy. About one-third of the patients wanted to have children after the procedure. 62% of them became pregnant and the majority did so without the need for assisted reproductive therapy. In seven women a re-operation was performed.ConclusionAccording to our data, a consistent excision of altered peritoneum followed by adjuvant hormonal therapy and multimodal concepts results in better outcomes for the patient, particularly in regards to pregnancy and recurrence rates.

PurposeEpithelial–mesenchymal transition (EMT) endows cells with migratory and invasive properties, a prerequisite for the establishment of endometriotic lesions. However, the role EMT might play in the pathophysiology of endometriosis is still unknown. Therefore, we examined five recognized markers for EMT in endometrium and endometriosis: E-cadherin, N-cadherin, Twist, Snail and Slug.MethodsImmunohistochemistry was used for peritoneal, ovarian and rectovaginal endometriotic lesions (n = 27) and endometrium (n = 13). Reverse transcription polymerase chain reaction was applied to tissue samples and primary cell cultures of endometriotic lesions (n = 9) and endometrium (n = 8).ResultsIn endometriosis and endometrium E-cadherin, N-cadherin, Twist, Snail and Slug were expressed on protein and mRNA level. E-cadherin expression was strong in epithelial cells, but single E-cadherin-negative cells were frequently present in endometriosis. In endometriosis N-cadherin, Twist and Snail expression were upregulated in comparison with endometrium. The expression of E- and N-cadherin was inversely correlated, while that of N-cadherin and Twist was positively correlated.ConclusionThis study strongly suggests that EMT may be regulated differently in endometriosis and the endometrium. Future research should further elucidate the regulation of EMT in the endometrium and endometriosis.

Objective To identify and characterize endometriosis-associated immune cell infiltrates (EMaICI). Furthermore, to define occurrence and size of EMaICI in various types of endometriosis. Methods Immune cells were characterized in samples of 60 premenopausal women with histological proven endometriosis. Therefore, immunohistochemical staining with monoclonal antibodies for CD3, CD4, CD8, CD45RO, CD25, CD56, CD68, and CD20 on sections of paraffin-embedded endometriotic tissue was performed. Results EMaICI were observed in all the types of endometriosis, and characterized as T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), antigen-experienced T lymphocytes”memory cells” (CD45RO+), macrophages (CD68+), and B lymphocytes (CD20+). The maximum frequency of EMaICI and their distribution per endometriotic lesion (EML) was observed in peritoneal endometriosis (pEM) and in ovarian endometriosis (Ov. EM). In myometrium from adenomyosis (M/AM), EMaICI occurrence was lower and smaller in size in comparison with EMaICI seen in other forms of endometriosis. EMaICI were negative for regulatory T cells (CD25+ high, FoxP3+) and natural killer cells (NK cells, CD56+). Conclusion Numerous and brisk EMaICI comprising several types of immune cells in all endometriosis forms suggest acute immunological reactions within the microenvironment of endometriosis lesions.

Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

Background It is known that various chronic pain conditions lead to maladaptive changes in the central nervous system. Endometriosis is frequently associated with chronic pelvic pain (CPP). Its sufficient treatment remains a clinical challenge. Transcranial direct current stimulation (tDCS) has been shown to be a powerful method to reduce chronic pain. Therefore, this study aimed to investigate pain reduction via anodal tDCS in patients with endometriosis and CPP. Methods This clinical phase II, placebo-controlled, randomized, parallel-design study included 36 patients with endometriosis and CPP. All patients had CPP, defined as a score of ≥3/10 on the visual analog scale for ≥3 months in the prior 6 months. Anodal or placebo tDCS (18 patients per arm) was applied over the primary motor cortex for 10 days. The primary outcome measure was the pressure pain threshold (objective pain measure), and secondary outcomes were the numerical rating scale score (subjective pain measure), Von Frey monofilaments, and disease- and pain-related questionnaires. Data were collected at baseline, after the 10-day stimulation, and at a follow-up session, which took place 1 week after the tDCS had ended. Statistical analyses were performed with analyses of variance and t tests. Results Significant decreased pain perception in both pain measurements (pressure pain threshold and numerical rating scale score) was found for the active tDCS group compared with the placebo group. This proof-of-concept study shows that tDCS is a helpful supporting pain therapy for patients with endometriosis and CPP. Moreover, further analyses revealed that 1 week after the stimulation had ended, pain reduction as indexed by pressure pain threshold remained significantly decreased, which indicates possible long-term analgesic effects. Conclusion The present study provides evidence that tDCS is an effective therapy for pain reduction in endometriosis-associated CPP. The results support the notion that CPP is developed and maintained in the central nervous system, making a multimodal pain therapy necessary. Trial registration www.ClinicalTrials.gov ID: NCT05231239.

Endometriosis (EM) is an oestrogen-dependent disease affecting 10–15 % of women during reproductive age. It is characterised by the presence of endometrial glands, stromal- and smooth muscle-like cells outside of the uterine cavity. Fifty to sixty per cent of women and teenage girls with pelvic pain suffer from EM. EM causes disability and compromises the quality of life in women and young girls significantly. Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments.

Nervenfasern konnten im eutopen Endometrium von Patientinnen mit Endometriose sowie in ektopen Endometrioseläsionen nachgewiesen werden. Zwei pathophysiologische Hypothesen werden hinsichtlich des Vorkommens von Nervenfasern sowohl im Endometrium als auch in ektopen Läsionen kontrovers diskutiert: Ist das Vorkommen von Nervenfasern ein rein endometrioseabhängiges oder auch ein schmerzabhängiges Phänomen? Diese Diskussion basiert auf unterschiedlichen Beobachtungen. Einerseits werden Nervenfasern ausschließlich im Endometrium von Patientinnen mit Endometriose beschrieben, unabhängig von deren Beschwerden. Andererseits wurden Nervenfasern im Endometrium von Patientinnen mit Schmerzen gefunden, wie sie auch bei anderen gynäkologischen Erkrankungen wie Myomen auftreten können. Diese Frage hat hohe Klärungsrelevanz, da in diesem Zusammenhang postuliert wurde, dass das Vorkommen von endometrialen Nervenfasern als nichtinvasive Testmethode für das Vorliegen einer Endometriose gewertet werden könnte. Fest steht, dass Endometriose neuromodulierende Eigenschaften aufweist, ob nun endometrioseabhängig oder durch Schmerzfaktoren verursacht. Eine Nerveninvasion in Endometrioseläsionen bietet eine schlüssige Erklärung hinsichtlich der bislang unklaren Pathogenese der mit Endometriose assoziierten Beschwerden.

Endometriosis is a disease that is becoming more and more challenging for the medical community. The current therapeutic concepts (surgical therapy and/or hormonal therapies) often do not lead to sufficient pain control, and late diagnosis and high recurrence rates mean that women affected by the disease can suffer for decades before receiving proper treatment. Although the introduction of certified endometriosis centers has created contact points for surgical therapies performed by endometriosis experts, these centers are not sufficient to offer the affected patients the all-encompassing long-term support they need. In recent years, new findings regarding the pathogenesis and correlations of the pain phenomena caused by endometriosis have shown that conventional therapy strategies are not adequate and individual long-term concepts must be developed. Not only can endometriosis cause nociceptive pain, but it can also lead to a nociplastic reaction with central sensitization. Hence, aside from the classic cyclic complaints, patients increasingly suffer from atypical pain. Due to the high number of affected patients who are treated inadequately, it is necessary for gynecologists in private practices to become familiar with multimodal treatment concepts since they are the central point of contact of their patients. The following article will provide an overview of treatment strategies for chronic symptomatic endometriosis.