Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

Pathophysiology and Clinical Implications of Ovarian Endometriomas.

Ovarian endometriomas affect many patients with endometriosis and have significant effects on quality of life, fertility, and risk of malignancy. Endometriomas range from small (1-3 cm), densely fibrotic cysts to large (20 cm or greater) cysts with varying degrees of fibrosis. Endometriomas are hypothesized to form from endometriotic invasion or metaplasia of functional cysts or alternatively from ovarian surface endometriosis that bleeds into the ovarian cortex. Different mechanisms of endometrioma formation may help explain the phenotypic variability observed among endometriomas. Laparoscopic surgery is the preferred first-line modality of diagnosis and treatment of endometriomas. Ovarian cystectomy is preferred over cyst ablation or sclerotherapy for enabling pathologic diagnosis, improving symptoms, preventing recurrence, and optimizing fertility outcomes. Cystectomy for small, densely adherent endometriomas is made challenging by dense fibrosis of the cyst capsule obliterating the plane with normal ovarian cortex, whereas cystectomy for large endometriomas can carry unique challenges as a result of adhesions between the cyst and pelvic structures. Preoperative and postoperative hormonal suppression can improve operative outcomes and decrease the risk of endometrioma recurrence. Whether the optimal management, fertility consequences, and malignant potential of endometriomas vary on the basis of size and phenotype remains to be fully explored.

Effectiveness and complication rates of high intensity focused ultrasound treatment for abdominal wall endometriosis: A systematic review.

In this review, a systematic literature search on the effectiveness and complication rates of ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USg-/MRgHIFU) for abdominal wall endometriosis (AWE) was conducted in six databases in May/June 2023. Original articles of (non)randomized trials, cohort studies, case-control studies and case series published in peer-reviewed journals were included. Of the included studies the level of evidence (LoE) and methodological quality using the ROBINS-I and IHE-QAT was assessed. Primary outcomes were non-perfused volume ratio (NPV%), lesion size, pain scores, side effects and complication rates according to Society of Interventional Radiology (SIR) guidelines. Secondary outcomes were recurrence and re-intervention rates. Seven cohort studies (one of good methodological quality) (LoE 3) on USgHIFU were included (n = 212, AWE lesions = 240-245). Six months after USgHIFU treatment, pain scores were reduced with 3.3-5.2 points (baseline: 5.1-6.8, n = 135). Self-limiting side effects were pain (85.7 % (114/133)) and swelling (34.6 % (46/133)) in the treatment area. Complications occurred in 17.7 % (32/181), all of which were minor. Recurrence occurred in 12.8 % (11/86). Three of these seven cohort studies compared USgHIFU (n = 61) with surgical excision (n = 74). Pooled results showed no significant differences in pain scores, complications (resp. 26.3 % (10/38) vs. 32.6 % (15/46) (p = 0.53)) and recurrences (resp. 4.9 % (3/61) vs. 5.4 % (4/74) (p = 0.90)). This systematic review suggests that HIFU is an effective and safe treatment option for AWE. USgHIFU treatment led to reduced pain scores and lesion size, was free of major complications and had a pooled recurrence rate of 12.8 %. Compared to surgical excision pooled results showed no significant differences in pain scores, complications and recurrences after USgHIFU. However, many of the included studies had limitations in their methodological quality and therefore the results should be interpreted with caution. Well-structured high-quality randomized controlled trials comparing HIFU to standard care should be conducted to provide more conclusive evidence.

Efficacy and influencing factor analysis of high-intensity focused ultrasound therapy for abdominal wall endometriosis: a case series.

OBJECTIVE: The aim of this retrospective study was to investigate the short-term and long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for abdominal wall endometriosis (AWE) and explore its potential influencing factors. MATERIALS AND METHODS: A total of 80 patients with AWE who underwent HIFU therapy were retrospectively analyzed. Follow-ups were also conducted to evaluate the changes in lesion size and pain relief. Multivariate logistic regression analysis was applied to investigate factors influencing HIFU therapy for AWE. RESULTS: Among the 80 patients with AWE who received HIFU therapy, the effective rates were 76.3%, 80.5%, and 90.5% after 3, 12 and 24 months of follow-up, respectively. Multivariate logistic regression analysis revealed that the AWE lesion diameter and sonication intensity had statistically significant effects on the 3-month and 12-month efficacy of HIFU therapy for AWE, while age, BMI, disease duration, average sonication power and grey-scale changes did not have statistically significant effects. Four patients with AWE experienced recurrence after HIFU therapy, for a three-year cumulative recurrence rate of 6.3%. Furthermore, ten patients required reintervention after treatment, for a five-year cumulative reintervention rate of 13.9%. CONCLUSIONS: This study further confirmed the safety and effectiveness of HIFU therapy for AWE. Factors such as AWE lesion diameter and sonication intensity have been identified as key influencers affecting the short-term and long-term efficacy of HIFU therapy for AWE. The first two years following HIFU therapy constitute crucial periods for observation, and judiciously extending follow-up intervals during this timeframe is advised.

[Interest of multidisciplinary consultation meetings dedicated to endometriosis: From a series of 682 patients]. / Intérêt des réunions de concertation pluridisciplinaires dédiées à l'endométriose : à partir d'une série de 682 patientes.

OBJECTIVE: We decided to conduct a study based on these multidisciplinary team (MDT) in order to investigate their impact at the University Hospitals of Strasbourg and look for ways to improve this MDT. METHODS: This is a retrospective study of the 682 patients presented to endometriosis MDT from its inception in March 2017 to December 2020. RESULTS: The MDT decision was different from that initially proposed by the patient's referent for 406 patients (60%). Surgery was chosen for 417 patients (61%) and assisted reproduction for 261 patients (38%). A review of the MRI by a referring radiologist was carried out for 348 cases (51%), with a modification of the results for 255 patients (73%). Initial underestimation of lesions was noted in 198 cases. CONCLUSION: Our study has shown the importance of MDT in endometriosis since the therapeutic proposal was modified in 60% of cases. In addition, we supported the importance of radiologists specializing in this field since they made a modification in two-thirds of the MRIs reread. These results show the importance of collegial discussions, which can modify the decisions of medical teams. This underlines the importance of setting up endometriosis networks.

Efficacy and safety of a novel pain management device, AT-04, for endometriosis-related pain: study protocol for a phase III randomized controlled trial.

BACKGROUND: Endometriosis-related pain encompassing dysmenorrhea, dyspareunia, and chronic pelvic pain, reduces the quality of life in premenopausal women. Although treatment options for endometriosis alleviate this pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. The Angel Touch device (AT-04) is a portable magnetic fields irradiation device that incorporates a combination of mixed alternative magnetic fields at 2 kHz and 83.3 MHz. A phase III trial confirmed the efficacy and safety of AT-02, a prototype of AT-04, for pain relief in patients with fibromyalgia. METHODS: This is a phase III, multicenter, prospective, randomized, sham device-controlled, double-blind, parallel study. The participants will be premenopausal women aged > 18 years who have endometriosis-related pain with at least moderate severity. Considering dropouts, 50 participants have been deemed appropriate. Eligible women will be centrally registered, and the data center will randomly allocate them in a 1:1 ratio to the intervention and control groups. Women in the intervention group will receive electromagnetic wave irradiation generated by AT-04 and those who in the control group will wear a sham device for 16 weeks, and both groups will wear AT-04 for another 4 weeks. The primary outcome measure is the change in the Numeric Rating Scale score at 16 weeks compared with the baseline. Secondary outcome measures are efficacy for pelvic pain including dysmenorrhea and non-menstrual pain, and chronic pelvic pain not related to menstruation, dysmenorrhea, and dyspareunia, and improvement of quality of life during the study period. Safety will be evaluated by device defects and the frequency of adverse events. The study protocol has been approved by the Clinical Study Review Board of Chiba University Hospital, Chiba, Japan, and will be conducted in accordance with the principles of the Declaration of Helsinki and the Japanese Clinical Trials Act and relevant notifications. DISCUSSION: This study aims to develop a novel method of managing endometriosis-related pain. The AT-04 is an ultralow-invasive device that can be used without inhibiting ovulation, suggesting potential benefits to women of reproductive-age. Trial registration number Japan Registry of Clinical Trials (jRCTs032230278).

Endometriosis is a chronic inflammatory disorder that negatively impacts reproductive health via endometriosis-related pain, infertility, and endometriosis-associated ovarian cancer. Although current therapeutic options for endometriosis are effective for the endometriosis-related pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. This is the first randomized controlled trial to investigate the efficacy and safety of a novel portable pain management device, AT-04, that incorporates a combination of mixed alternating magnetic fields, for endometriosis-related pain. This is a multicenter, prospective, sham device-controlled, double-blind, parallel study. Enrolled women will have undergone standard hormonal treatment for endometriosis at baseline, and this allows for assessing whether the device remains effective when used in conjunction with existing treatment methods. The study also will explore the impact of AT-04 on reducing the size of ovarian endometriotic cysts that reflect the activity of endometriosis. The study reflects the strong desire by physicians to liberate women from the unbearable pain associated with endometriosis. The sole efficacy of AT-04 in treating endometriosis-related pain is difficult to evaluate as there is a possibility that menstrual cycles may influence the assessment of pain and quality of life. However, the study findings regarding the effectiveness of AT-04 for the treatment of endometriosis-related pain may benefit women with endometriosis who have pain that is not effectively relieved by other treatments. Consequently, it may contribute to the improvement of reproductive health within society.

Treatment of adenomyosis, abdominal wall endometriosis and uterine leiomyoma with interventional radiology: A review of current evidences.

Interventional radiology shows promises in the field of women's health, particularly in pelvic interventions. This review article discusses the latest advancements in interventional radiology techniques for pelvic conditions affecting women including adenomyosis, abdominal wall endometriosis and uterine leiomyoma. Extraperitoneal endometriosis involving the abdominal wall may be treated by percutaneous thermal ablation, such as cryoablation, whereas uterine leiomyoma and adenomyosis can be managed either using percutaneous thermal ablation or using uterine artery embolization. Continued research and development in interventional radiology will further enhance the minimally-invasive interventions available for women's health, improving outcomes and quality of life for this large patient population of women.

Diagnostic and therapeutic approaches for endometriosis: a patent landscape.

OBJECTIVE: The aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field. METHODOLOGY: Patent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords "Endometriosis OR Adenomyosis" AND "Diagnostic OR Therapeutics" were used along with wildcard search queries in the "Title", "Abstract" and "Descriptions" fields. RESULTS: A patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories. CONCLUSION: Efforts are being made to improve current diagnostic instruments. Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years.

Nonsurgical approaches to the diagnosis and evaluation of endometriosis.

An inability to make the diagnosis of endometriosis or evaluate lesion response to treatment without surgery is a clear impediment to understanding the disease and to developing new therapies. The need is particularly strong for rASRM Stage 1 or 2 disease, since higher stage (rASRM Stage 3 or 4) endometriosis can often be diagnosed by ultrasound or other imaging techniques. Despite promising findings in association studies, no biomarkers or nonsurgical diagnostic or evaluation methods for Stage 1 or Stage 2 endometriosis has yet been clinically validated. Admittedly, validation is difficult, since surgery is required as a gold standard diagnostic method for comparison. This manuscript is aimed as a succinct review of what is known about nonsurgical approaches to detect and assess endometriosis, with an emphasis on Stage 1 and 2.

Changing the "scope" of diagnosing endometriosis: the new frontier of noninvasive markers.

Endometriosis affects 1 in 9 women, and diagnosis is often delayed using conventional laparoscopy. Noninvasive markers of endometriosis have the potential to enable earlier diagnosis, leading to more timely treatment and better surgical planning. This issue's Views and Reviews seek to summarize the current status of noninvasive markers of endometriosis. Experts in reproductive medicine with prior work in this field summarize the key literature on endometrial biomarkers, blood biomarkers, and advanced imaging, including ultrasound and magnetic resonance imaging. At present, there is no single definitive biomarker that can diagnose endometriosis with high sensitivity and specificity. Advancing endometriosis biomarkers beyond the discovery phase is challenging, and more work is needed. Clinicians who have an improved understanding of noninvasive imaging and biomarkers will be able to identify endometriosis earlier and more easily, allowing for prompt consideration of treatment options. We believe that continued research, innovation, and development will lead to improved diagnostic accuracy and guidance toward the best treatments for endometriosis-related pain and infertility.

IVF stimulation protocols and outcomes in women with endometriosis.

Endometriosis is a complex medical condition with a high prevalence in women of reproductive age. Fertility is compromised in patients with endometriosis, and success in IVF treatments has been a challenge leading to evaluation of different stimulation protocols. The long-standing debate between GnRH agonist long protocols and short GnRH antagonist protocols is being resolved in favor of the latter, since in addition to presenting equivalent results with respect to the traditional option, they have the additional benefit of safety. The good results derived from vitrification techniques have led to the development of new stimulation strategies, such as progestin-primed ovarian stimulation (PPOS), with a greater degree of approval among patients. None of the stimulation protocols currently applied in women with endometriosis has been shown to be superior, so early intervention with an Assisted Reproduction treatment, regardless of the chosen protocol, can provide these women with good chances of motherhood. Women with endometrioma should be counseled for fertility preservation before planned ovarian endometrioma excision. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.

Endometriosis and adenomyosis: Similarities and differences.

Deep endometriosis and uterine adenomyosis are two frequently encountered conditions affecting approximately 200 million women worldwide. They are closely related, showing similar histological patterns and multiple common pathogenic features, and share the same symptoms. It is therefore not surprising that they are often thought to have a common developmental origin. Indeed, both deep endometriosis and adenomyosis appear to derive from estrogen-dependent overproliferation of endometrial tissue and its subsequent implantation in ectopic sites. Although the scientific community has shown increasing interest in these diseases over recent years, neither pathogenesis has yet been elucidated, so there are currently no efficient treatment options. Understanding the mechanisms underlying disease development, as well as discerning their relationship, are key to improving clinical management for millions of patients. The aims of this review are to summarize current knowledge on deep endometriosis and adenomyosis pathogeneses and discuss the possibility that these two entities are actually differential phenotypes of the same disease.

Endometriosis: Classification, pathophysiology, and treatment options.

The human endometrium is a complex hormone-target tissue consisting of two layers: the lower basalis, and the upper functionalis. The latter of the two goes through a cycle of thickening and shedding without residual scarring or loss of function. This cycle, known as the menstrual cycle, occurs on a monthly basis in most of healthy reproductive-age women. It is, however, associated with a number of reproductive diseases, endometriosis being one of them. Endometriosis is defined as the presence of endometrium at ectopic sites within the peritoneum or, more rarely, other locations outside the abdominal area. It affects around 6-10% of reproductive-age women in the world and causes debilitating pain, heavy menstrual bleeding, pain during penetrative sex, and infertility. The etiology of the disease is not yet fully understood but the generally accepted theory is that the endometriotic lesions originate from viable eutopic endometrial cells that flow back into the peritoneum through the process of retrograde menstruation. Endometriosis is usually classified into four stages: minimal, mild, moderate, and severe, though it is important to note that the presentation of symptoms does not necessarily correspond to the disease progression. The immune system plays an important role in supporting the viability and growth of ectopic endometriotic tissue, all the while promoting chronic inflammation at the lesion sites, which causes prolonged pain. There is no definitive cure for endometriosis, but there are several options for symptom management, including laparoscopy, hormonal therapy, the use of NSAIDs, dietary changes, exercise, and, in cases when all conservative treatments fail, hysterectomy.

The Efficiency of Sclerotherapy for the Management of Endometrioma: A Systematic Review and Meta-Analysis of Clinical and Fertility Outcomes.

Background and Objectives: The most common sites of implantation of endometriotic tissue are the ovaries. Endometriomas are present in most cases of endometriosis (up to 45%). Although laparoscopic cystectomy is the standard of care in endometrioma, new strategies have been set up to minimize iatrogenic injuries to ovarian tissue. Sclerotherapy consists of injecting alcohol into the endometrioma to denature the amino acidic components of its pseudocapsule. The aim of this systematic review and meta-analysis is to compare clinical and pregnancy outcomes in surgery and sclerotherapy. Materials and Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched PubMed, EMBASE, Scopus, Google Scholar, Clinical-trials.gov, and the Cochrane Central Register of Controlled Trials databases in January 2023, adopting the string "Endometriosis and sclerotherapy". We made no limitations on the country and year of publication. We included the studies containing Success Rate (SR), Recurrence Rate (RR), Pregnancy Rate (PR) before and after the procedure. We used comparative studies for meta-analysis. Results: A total of 29 studies fulfilled inclusion criteria, 7 retrospective observational studies and 22 prospective studies. Eight comparative studies were enrolled in meta-analysis. Patients were analyzed concerning the number of recurrences and pregnancies in surgery, and compared with sclerotherapy. Four studies showed SR > 80.0%, and only two had SR < 80.0%, of which one consisted of tetracycline instillation. Only 1 study had 100% PR, the other 14 reported PR > 30.0%, whereas six had PR < 30.0%, of which one showed 0.0% PR with ethanol injection at two-thirds of the cyst fluid volume. Meta-analysis highlighted a non-significant lower incidence of recurrence in the surgery group compared to the sclerotherapy group (p = 0.87). In parallel, the surgery group showed a non-significant better PR than the sclerotherapy group (p = 0.08). Conclusions: Despite sclerotherapy having a minor incidence of postoperative complications compared to surgery, the latter is associated with a lower RR and better PR. However, those data assert the importance of a targeted therapy according to preoperative conditions and reproductive potential.

Engineered extracellular vesicles in female reproductive disorders.

Biologically active and nanoscale extracellular vesicles (EVs) participate in a variety of cellular physiological and pathological processes in a cell-free manner. Unlike cells, EVs not only do not cause acute immune rejection, but are much smaller and have a low risk of tumorigenicity or embolization. Because of their unique advantages, EVs show promise in applications in the diagnosis and treatment of reproductive disorders. As research broadens, engineering strategies for EVs have been developed, and engineering strategies for EVs have substantially improved their application potential while circumventing the defects of natural EVs, driving EVs toward clinical applications. In this paper, we will review the engineering strategies of EVs, as well as their regulatory effects and mechanisms on reproductive disorders (including premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), recurrent spontaneous abortion (RSA), intrauterine adhesion (IUA), and endometriosis (EMS)) and their application prospects. This work provides new ideas for the treatment of female reproductive disorders by engineering EVs.

Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics.

Endometriosis is a prevalent gynecological condition associated with pelvic pain and infertility. Despite more than a century of research, the etiology of endometriosis still eludes scientific consensus. This lack of clarity has resulted in suboptimal prevention, diagnosis, and treatment options. Evidence of genetic contributors to endometriosis is interesting but limited; however, significant progress has been made in recent years in identifying an epigenetic role in the pathogenesis of endometriosis through clinical studies, in vitro cell culture experiments, and in vivo animal models. The predominant findings include endometriosis-related differential expression of DNA methyltransferases and demethylases, histone deacetylases, methyltransferases, and demethylases, and regulators of chromatin architecture. There is also an emerging role for miRNAs in controlling epigenetic regulators in the endometrium and endometriosis. Changes in these epigenetic regulators result in differential chromatin organization and DNA methylation, with consequences for gene expression independent of a genetic sequence. Epigenetically altered expression of genes related to steroid hormone production and signaling, immune regulation, and endometrial cell identity and function have all been identified and appear to play into the pathophysiological mechanisms of endometriosis and resulting infertility. This review summarizes and critically discusses early seminal findings, the ever-growing recent evidence of epigenetic contributions to the pathophysiology of endometriosis, and implications for proposed epigenetically targeted therapeutics.

Acupuncture and moxibustion for endometriosis: A systematic review and analysis.

OBJECTIVES: This study aimed to examine the effect of acupuncture on symptoms and health-related quality of life in patients with endometriosis. METHODS: Nine biomedical databases were searched to April 2022 to identify randomized controlled trials of acupuncture and/or moxibustion used alone or as adjunct to guideline-recommended pharmacotherapy for the treatment of endometriosis. One reviewer extracted data and another verified the data. A random effects model was used to calculate mean differences. RESULTS: Fifteen trials involving 1018 patients met the inclusion criteria, but diversity in comparisons and outcome measures prevented meta-analysis. Compared to sham acupuncture, manual acupuncture was more effective at reducing dysmenorrhea VAS pain score (mean difference [MD] - 2.40, 95 % CI [- 2.80, - 2.00]; moderate certainty evidence), pelvic pain VAS score (MD - 2.65, 95 % CI [- 3.40, - 1.90]; high certainty evidence) and dyspareunia VAS scores (MD - 2.88, [- 3.83, - 1.93]), lessened the size of ovarian cyst (MD - 3.88, 95 % CI [- 7.06, - 0.70]), and improved quality of life. Compared to conventional therapy, manual acupuncture plus conventional therapy and warm needle alone resulted in greater improvements in quality of life than conventional therapy. Among the six studies that reported safety, fewer adverse events were reported in participants who received acupuncture or moxibustion. CONCLUSIONS: Low to moderate certainty evidence from single studies showed that manual acupuncture may improve pain-related symptoms and quality of life; however, there is insufficient evidence on the overall effectiveness of acupuncture and moxibustion for endometriosis.

A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility.

Introduction: Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis. Methods: ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA). Results: Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation. Conclusion: ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.

Investigating the efficacy of ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on pro-inflammatory cytokine levels: A single-arm clinical trial.

BACKGROUND: Endometriosis is a chronic inflammatory disease affecting about 10% of women of reproductive age. Endometrioma is the most common presentation of endometriosis in ovaries. OBJECTIVES: Herein, the authors study the effect of the ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on the plasma levels of pro-inflammatory cytokines. MATERIALS AND METHODS: Each endometrioma was aspirated and washed with 0.9% saline until clearance and then 2/3 of the cyst volume was filled with ethanol 98%. Patients were followed for 3 months. After that, changes in their cyst diameter, dyspareunia, dysmenorrhea, and antral follicular count were assessed. Also, the sera levels of Interleukin 1ß (IL-ß), IL-6, and IL-8 were assayed before and after the treatment. The primary sera levels were also compared with a control group. RESULTS: In the treatment and control groups, 23 and 25 individuals (respectively) with a matched mean age (p-value = 0.680) were enrolled in the study. Among the laboratory variables, IL-1ß (p-value = 0.035), as well as AMH (p-value = 0.002), were lower, and IL-6 (p-value = 0.011) was higher in the endometriosis group compared to the controls. Following the treatment, dysmenorrhea, dyspareunia, and the mean diameter of all cysts were significantly (p-values < 0.001) decreased in the treatment group. Also, right (p-value = 0.022) and left (p-value = 0.002) ovaries' antral follicular counts were increased following the treatment. No significant change was found among any of the investigated laboratory levels (p-value > 0.05). CONCLUSION: Ethanol retention method is proven to be safe and could improve the clinical status of patients with endometrioma. Although further studies are necessary.