Lysine acetyltransferase 14 mediates TGF-ß-induced fibrosis in ovarian endometrioma via co-operation with serum response factor.

BACKGROUND: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-ß (TGF-ß), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-ß remain poorly understood. METHODS: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-ß-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. RESULTS: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-ß-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-ß-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-ß treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. CONCLUSION: Our results shed light on KAT14 as a key effector of TGF-ß-induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.

Ethanol endometrioma sclerotherapy: safety through 8 years of experience.

STUDY QUESTION: What are the complications of transvaginal ethanol sclerotherapy for the treatment of endometriomas? SUMMARY ANSWER: Sclerotherapy is a reliable, minimally invasive method applicable in outpatient procedures but with specific and potential life-threatening complications that need to be identified and prevented. WHAT IS KNOWN ALREADY: There are currently few data on the use of transvaginal ethanol sclerotherapy, and we mainly note septic complications. STUDY DESIGN, SIZE, DURATION: A retrospective observational cohort study was carried out. The study was conducted at an academic hospital and included 126 women aged 31.9 ± 5.5 years (mean ± SD), between November 2013 and June 2021. We analyzed a total of 157 ethanol sclerotherapy treatment (EST), treated by 131 EST procedures, in 126 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with an indication for transvaginal ethanol sclerotherapy. Indications were women with at least one endometrioma over 10 mm, isolated or associated with other endometriosis locations, requiring treatment for pain or infertility before assisted reproductive treatment. We followed a standardized transvaginal ethanol sclerotherapy procedure consisting of an ultrasound-guided transvaginal puncture of one or more endometriomas under general anesthesia. The cyst content was completely removed and flushed with saline solution. Ethanol (96%) was injected at 60% of the initial volume of the endometrioma, remained in the cyst for 10 min and was then completely removed. Ethanol loss was defined as a loss of 5 ml or more than 10% of the initial volume of the injected ethanol. Failure was defined by the contraindication of endometrioma puncture because of interposition of the digestive tract, ethanol loss in the previous endometrioma treated (in case of multiple ESTs), failure to aspirate the endometriotic fluid, contraindication to start ethanol injection owing to saline solution leakage, or contraindication to continue ethanol injection owing to suspicions of ethanol leakage at sonography. Intraoperative complications were defined by ethanol loss, positive blood alcohol level, and ethanol intoxication. Postoperative complications were defined by fever, biological inflammatory syndrome, and ovarian abscess. Complications were classified according to the Clavien and Dindo surgical classification, which is a system for classifying postoperative complications in five grades of increasing severity. MAIN RESULTS AND THE ROLE OF CHANCE: We reported a total of 17/157 (10.8%) transvaginal ethanol sclerotherapy failures during 14/131 (10.7%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. In the same sets of data, complication was reported for 15/157 (9.5%) transvaginal ethanol sclerotherapy in 13/131 (9.9%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. Nine of 126 women (7.1%) had a grade I complication, one (0.8%) had a grade II complication (medical treatment for suspicion of pelvic infection), two (1.6%) had a grade III complication (ovarian abscess) and one (0.8%) had a grade IV complication (ethanol intoxication). We did not observe any grade V complications. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study and pain assessment not considered. The benefit-risk balance of endometrioma transvaginal ethanol sclerotherapy was not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: Our study is the first to evaluate the complications of transvaginal ethanol sclerotherapy with such a large cohort of women in a standardized protocol. Transvaginal ethanol sclerotherapy seems to be an effective alternative to laparoscopic surgery in the management of endometriomas and limits the alteration of ovarian reserve. Transvaginal ethanol sclerotherapy is a reliable, minimally invasive method applicable on an outpatient basis. The majority of complications are Clavien-Dindo ≤IV, for which preventative measures, or at least early diagnosis and treatment, can be easily performed. The risk of ethanol intoxication is rare, but it is a life-threatening risk that must be avoided by appropriate implementation and promotion of the sclerotherapy procedures. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Aix Marseille University's ethics committee registration number 2021-06-03-01.

The role of regulatory T-cells in the development of endometriosis.

Endometriosis is a benign disease of the female reproductive tract, characterized by the process of chronic inflammation and alterations in immune response. It is estimated to affect 2-19% of women in the general population and is commonly associated with symptoms of chronic pelvic pain and infertility. Regulatory T cells (Treg) are a subpopulation of T lymphocytes that are potent suppressors of inflammatory immune response, essential in preventing destructive immunity in all tissues. In endometriosis, several studies have investigated the possible role of Treg cells in the development of the disease. Most studies to date are heterogeneous in methodology and are based on a small number of cases, which means that it is impossible to define their exact role at present. Based on current knowledge, it seems that disturbed Treg homeostasis, leading to increased systemic and local inflammation within ectopic and eutopic endometrium, is present in women who eventually develop endometriosis. It is also evident that different subsets of human Treg cells have different roles in suppressing the immune response. Recent studies in patients with endometriosis have investigated naive/resting FOXP3lowCD45RA+ Treg cells, which upon T cell receptor stimulation, differentiate into activated/effector FOXP3highCD45RA- Treg cells, characterized by a strong immunosuppressive activity. In addition, critical factors controlling expression of Treg/effector genes, including reactive oxygen species and heme-responsive master transcription factor BACH2, were found to be upregulated in endometriotic lesions. As shown recently for cancer microenvironments, microbial inflammation may also contribute to the local composition of FOXP3+ subpopulations in endometriotic lesions. Furthermore, cytokines, such as IL-7, which control the homeostasis of Treg subsets through the tyrosine phosphorylation STAT5 signalling pathway, have also been shown to be dysregulated. To better understand the role of Treg in the development of endometriosis, future studies should use clear definitions of Tregs along with specific characterization of the non-Treg (FOXP3lowCD45RA-) fraction, which itself is a mixture of follicular Tregs and cells producing inflammatory cytokines.

Indirect markers of oocyte quality in patients with ovarian endometriosis undergoing IVF/ICSI: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF, compared with women without anatomical or functional ovarian abnormalities. The search spanned original randomized controlled trials, case-control studies and cohort studies published in MEDLINE, the Cochrane Controlled Trials Register and the ClinicalTrials.gov database up to October 2023. Thirty-one studies were included in the meta-analysis, showing no significant differences in fertilization (OR 1.10, 95% CI 0.94-1.30), blastulation (OR 0.86, 95% CI 0.64-1.14) and cancellation (OR 1.06, 95% CI 0.78-1.44) rates. However, patients with OMA exhibited significantly lower numbers of total and mature (metaphase II) oocytes retrieved (mean difference -1.59, 95% CI -2.25 to -0.94; mean difference -1.86, 95% CI -2.46 to -1.26, respectively), and lower numbers of top-quality embryos (mean difference -0.49, 95% CI -0.92 to -0.06). The Ovarian Sensitivity Index was similar between the groups (mean difference -1.55, 95% CI -3.27 to 0.18). The lack of data published to date prevented meta-analysis on euploidy rate. In conclusion, although the presence of OMA could decrease the oocyte yield in patients undergoing IVF/intracytoplasmic sperm injection, it does not appear to have an adverse impact on oocyte quality.

Ultrasound study of natural progression of ovarian endometrioma.

OBJECTIVE: To determine the natural progression of ovarian endometrioma in women who are managed expectantly. METHODS: This was a retrospective cohort study of 83 women with evidence of ovarian endometrioma who were managed expectantly between April 2007 and May 2022. The study was conducted in the Department of Women's Health, University College London Hospitals and The Gynecology Ultrasound Centre, London, UK. We searched our ultrasound clinic databases to identify women aged 18 years or older with evidence of ovarian endometrioma who were managed expectantly for ≥ 6 months. All women attended for a minimum of two ultrasound scans performed by a single expert ultrasound operator. In addition to patient demographics, we recorded the number, mean diameter and location of each cyst. The cyst growth rate was expressed as annual change in the mean diameter. RESULTS: A total of 1922 women who attended our gynecology clinic during the study period were found to have evidence of moderate or severe endometriosis on pelvic ultrasound examination. Of those, 83 women had evidence of ovarian endometrioma and were managed expectantly. The median age of women was 39 (range, 26-51) years at the initial visit. Each woman had at least two ultrasound scans performed by a single expert operator at a minimum interval of ≥ 6 months. Of 83 women diagnosed with endometrioma, 50 (60% (95% CI, 49-71%)) had a single cyst and the remainder had multiple cysts. The median number of endometriomas per patient was 1 (range, 1-5) and the median follow-up time was 634 (range, 187-2984) days. A total of 39/83 (47% (95% CI, 36-58%)) women experienced an overall reduction in size of cysts, in 18/83 (22% (95% CI, 13-32%)) the cysts increased in size and in 26/83 (31% (95% CI, 22-42%)) women, no meaningful change in size was observed. The median change in mean cyst diameter per woman during the study period was -2.7 (range, -57.7 to 39.3) mm, with a median annual regression rate of -1.7 (range, -24.6 to 42.0) mm/year/woman. Overall, when compared with the initial visit, cysts were significantly smaller at follow-up (median diameter, 22.3 (range, 6.7-77.0) mm vs 18.5 (range, 5.0-72.0) mm; P = 0.009). We did not identify any clinical characteristics that could reliably predict the chance of endometrioma progression. CONCLUSIONS: In the majority of women with an ultrasound diagnosis of ovarian endometrioma, the cysts do not increase in size significantly over time and they could be managed expectantly. This evidence may help clinicians when counseling asymptomatic or minimally symptomatic women about management of ovarian endometrioma. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Quality of life and symptoms of pain in patients with endometriomas compared to those with other endometriosis lesions: a cross-sectional study.

BACKGROUND: Endometriomas are genetically distinct from other endometriosis lesions and could be associated with a predisposition to excessive inflammation. However, differences in clinical presentation between types of endometriosis lesions have not been fully elucidated. This study aimed to investigate the quality of life and pain scores of patients with endometriomas compared to those with other types of endometriosis lesions. METHODS: A cross-sectional observational study was conducted between January 2020 and August 2023. Patients diagnosed with endometriosis completed the Endometriosis Health Profile 30 pain subscale questionnaire for their quality of life score and rated their endometriosis-associated pain symptoms using an 11-point numerical rating scale. The data were analyzed for comparison through multivariate linear regression models. RESULTS: A total of 248 patients were included and divided into endometrioma (81, 33%) and nonendometrioma (167, 67%) groups. The mean age of the patients was 37.1 ± 7.5 years. Most participants were Canadian or North American (84%). One-third of the patients reported experiencing up to four concurrent pain symptoms. The most reported pain included deep dyspareunia (90%), chronic pelvic pain (84%) and lower back pain (81%). The mean quality of life score was 45.9 ± 25.9. We observed no difference in quality of life scores between patients with and without endometriomas. Patients with endometriomas had lower mean scores for deep dyspareunia (0.8; 95% CI [0 to 1.5]; p = 0.049) and higher mean scores for superficial dyspareunia (1.4; 95% CI [0.2 to 2.6]; p = 0.028). Comorbid infertility (p = 0.049) was a factor that modified superficial dyspareunia intensity in patients with endometriomas. CONCLUSION: In patients with endometriosis, evidence was insufficient to conclude that the presence of endometriomas was not associated with a greater or lesser quality of life, but differences in specific symptoms of dyspareunia were identified.

What's now and what's next for surgical endometriosis management in the infertile patient?: An evidence based review for the general OB/GYN.

Endometriosis is a significant contributor to female infertility, and its complex nature and varied phenotypes lead to questions regarding the value of surgical management. In this manuscript, we summarize current evidence and recommendations regarding surgical treatment for infertility in peritoneal disease, endometriomas, adenomyosis, and deep endometriosis, and highlight recent evidence regarding perinatal outcomes in women with endometriosis. Our purpose is to provide a concise "user's guide" for decisions regarding surgical management of endometriosis in patients with infertility and generate awareness of recent perinatal outcome data. RéSUMé: L'endométriose est un facteur important d'infertilité féminine; sa nature complexe et ses différents phénotypes soulèvent des interrogations sur l'intérêt du traitement chirurgical. Dans ce manuscrit, nous résumons les données probantes et les recommandations actuelles sur le traitement chirurgical de l'infertilité en cas de maladie péritonéale, d'endométriomes, d'adénomyose et d'endométriose profonde, et mettons en lumière les récentes données probantes sur les résultats périnataux chez les femmes atteintes d'endométriose. Notre objectif est de fournir un « guide de l'utilisateur ¼ concis pour orienter les décisions concernant la prise en charge chirurgicale de l'endométriose chez les patientes atteintes d'infertilité et de faire connaître les données récentes sur les résultats périnataux.

What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs?

BACKGROUND: Endometriosis is commonly observed in infertile women and can be staged with regard to severity [e.g. according to the American Fertility Society (AFS) classification]. This condition can cause infertility through impaired oocyte quality, fertilization disorders, tubal lesions, adhesions, deep infiltration, and adenomyosis. Although women with endometriosis often turn to in vitro fertilization (IVF) programs, the literature data on IVF outcomes are sometimes contradictory (i.e. the same as in other etiologies of infertility, or worse). The objective of the present study was to assess and compare pregnancy rates in women with and without endometriosis and according to the endometriosis stage. METHODS: We retrospectively studied clinical and ongoing pregnancy rates in IVF and the cumulative pregnancy rates after frozen/thawed embryo transfers, in women without endometriosis (group A) or with endometriosis (group B). We further compared groups in which endometriosis was staged according to the revised AFS classification: stage 1/2 (group C), stage 3/4 (group D, without endometrioma), and endometrioma alone (group E). RESULTS: We documented 430 cycles in group A and 460 in group B (including 56 in group C, 88 in group D and 316 in group E). After fresh or frozen/thawed embryo transfers, the differences in ongoing pregnancy rates between groups A and B were not significant. However the cumulative rates per couple were significantly lower (p < 0.05) in group D. CONCLUSIONS: We recommend IVF for women with endometriosis because the pregnancy rates are similar to those observed for women with other types of infertility. This approach is in line with the international guidelines issued by assisted reproductive technology societies. These results again raise the question of whether surgical resection of deep infiltrating endometriosis (stage 3/4) should be recommended before admission to an IVF program. Trial registration This study was approved by an institutional review board (CPP Ouest VI, Brest, France): reference: B2020CE.43.

Comparison of ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants: An updated meta-analysis.

AIM: The purpose of the study was to compare the ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants (HSs). METHODS: We performed a meta-analysis of studies in which post-cystectomy serum anti-Müllerian hormone (AMH) values were compared between bipolar coagulation and suture method or between bipolar coagulation and HSs. Through a literature search, we retrieved 14 articles which met inclusion criteria and were eligible for final analysis. The articles included 10 randomized trials, 3 prospective studies, and 1 retrospective study (n = 1435). The primary outcome was post-cystectomy serum AMH values. RESULTS: Both bipolar coagulation and suture methods showed significantly lower post-cystectomy AMH values at 3, 6, and 12 months. However, post-cystectomy serum AMH values at 12 months were significantly higher in the suture method group compared to the bipolar coagulation (weighted mean difference [WMD]: -1.10, 95% confidence interval [CI]: -1.83, -0.38, p = 0.003, I2 = 89, n = 3). The suture method also showed a lower decline rate at 3 months post-cystectomy compared to the bipolar coagulation group (WMD: -25.13%, 95% CI: -49.56 to -0.70, p = 0.04, I2 = 95%, n = 2). Overall, pregnancy rates were similar between the two groups. Between the bipolar coagulation and HSs group, serum AMH values at 3 months post-cystectomy were similar (WMD: -0.46, 95% CI: -1.04 to 0.13, p = 0.13, I2 = 0%, n = 3). However, the HSs group showed a less decline rate at 3 months post-cystectomy compared to the bipolar coagulation group (WMD: -17.02%, 95% CI: -22.81, -11.23, p < 0.00001, I2 = 0%, n = 3). CONCLUSIONS: Both the suture method and HSs may have potential benefits in the preservation of ovarian reserve over the bipolar coagulation method when cystectomy for ovarian endometrioma is performed.

Histological analysis of (antral) follicle density in ovarian cortex tissue attached to stripped endometriomas.

PURPOSE: When resecting endometriomas with the stripping technique, in the majority of cases, a thin line of adjacent ovarian cortex is attached to the endometrioma. In this study, we performed histological analysis to determine (antral) follicle density in the ovarian cortex tissue attached to stripped endometriomas and assessed patient- and surgical characteristics that could affect this. METHODS: Histological slides of previously removed endometriomas were assessed. Follicles in the attached ovarian tissue were classified according to maturation, and follicular density was determined. Immunofluorescent staining of antral follicles in a subset of endometriomas was also performed. RESULTS: In 90 out of 96 included endometriomas (93.7%), ovarian tissue attached to the cyst wall was observed. One thousand nine hundred forty-four follicles at different maturation stages were identified (3 follicles/mm3). Follicle density was negatively associated with age (p < 0.001). Antral follicles (< 7-mm diameter) were present in the ovarian tissue attached to 35 endometriomas (36.5%) derived from younger patients compared to endometriomas where none were detected (30 versus 35 years, p = 0.003). Antral follicle density was 1 follicle/mm3. Based on immunofluorescence, healthy antral follicles were identified in two out of four examined endometriomas. CONCLUSIONS: Ovarian tissue attached to stripped endometriomas holds potential as a non-invasive source for antral follicles. In theory, application of IVM could be an interesting alternative FP option in young patients with endometriomas who undergo cystectomy in order to transform the surgical collateral damage to a potential oocyte source. Our results encourage future research with fresh tissue to further assess the quality and potential of these follicles. TRIAL REGISTRATION: Clinical Trials.gov Identifier: B21.055 (METC LDD), date of registration 12-08-2021, retrospectively registered.

Potential damage to ovarian reserve from laparoscopic electrocoagulation in endometriomas and benign ovarian cysts: a systematic review and meta-analysis.

PURPOSE: Laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts is often conducted through hemostatic methods, with bipolar electrocoagulation as a common approach. This study evaluated the impact of electrocoagulation, primarily through bipolar energy, versus nonthermal hemostatic methods on ovarian reserve in patients undergoing laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts. METHODS: A systematic review with meta-analysis was conducted by searching the Cochrane Library, PubMed, EMBASE, and Web of Science databases. Randomized controlled trials (RCTs) comparing the impact of nonthermal hemostatic methods and electrocoagulation on the ovarian reserve during laparoscopic cystectomy were included. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (ROB 2.0) was utilized to assess the quality of the included studies. The meta-analysis included 13 RCTs involving 1043 patients. Postoperative serum anti-Müllerian hormone (AMH) levels and antral follicle counts (AFCs) were analyzed using Review Manager ver. 5.4. RESULTS: Compared with the bipolar group, patients with endometriomas in the nonthermal hemostatic group exhibited significantly higher postoperative AMH levels at 1, 3, 6, and 12 months. Conversely, no significant differences in AMH levels were observed in patients with benign ovarian cysts. Similarly, AFCs showed no significant differences, except for lower postoperative AFCs in patients with endometrioma in the electrocoagulation group. CONCLUSION: Nonthermal hemostatic methods are associated with more effective preservation of the ovarian reserve compared with bipolar electrocoagulation in laparoscopic cystectomy for ovarian endometriomas. However, no significant impact of bipolar electrocoagulation on the ovarian reserve was observed in patients with benign ovarian cysts. TRIAL REGISTRATION: Registered in PROSPERO on April 10, 2023; ID # CRD42023413158.

Evaluation of long-term efficacy and safety of dienogest in patients with chronic cyclic pelvic pain associated with endometriosis.

PURPOSE: To evaluate the efficacy and long-term safety (up to 108 months) of treatment with Dienogest in patients with endometriosis. METHODS: Patients with chronic pelvic pain endometriosis-related were enrolled in this observational study from June 2012 to July 2021. The patients enrolled took Dienogest 2 mg as a single daily administration. Group B of long-term therapy patients (over 15 months) were compared with group A of short-term therapy patients (0-15 months). The effects of the drug on pain variation were assessed using the VAS scale and endometriomas dimensions through ultrasonographic evaluation. Furthermore, has been valuated the appearance of side effects and the effect of the drug on bone metabolism by performing MOC every 24 months in group B. RESULTS: 157 patients were enrolled. The mean size of the major endometrioma progressively decreased from 33.2 mm (29.4-36.9) at T0 to 7 mm (0-15.8) after 108 months of treatment. We found a significant improvement in dysmenorrhea, dyspareunia, dyschezia and non-cyclic pelvic pain. As for the side effects, both groups complained menstrual alterations present in 22.9%. In 27.6% of group B, osteopenia was found. Group B had a higher percentage statistically significant of side effects such as headaches, weight gain and libido reduction compared to group A. 2 CONCLUSION: Long-term therapy with Dienogest has proven effective in controlling the symptoms of the disease and reducing the size of endometriomas, with an increase in the positive effects related to the duration of the intake and in the absence of serious adverse events. Study approved by the "Palermo 2" Ethics Committee on July 2, 2012 No. 16.

Immune Dysregulation in Endometriomas: Implications for Inflammation.

The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1ß, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.

Transvaginal ultrasound and magnetic resonance imaging in the diagnosis of endometrioma: a systematic review and meta-analysis of diagnostic test accuracy studies.

INTRODUCTION: The diagnosis of endometriomas in patients with endometriosis is of primary importance because it influences the management and prognosis of infertility and pain. Imaging techniques are evolving constantly. This study aimed to systematically assess the diagnostic accuracy of transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) in detecting endometrioma using the surgical visualisation of lesions with or without histopathological confirmation as reference standards in patients of reproductive age with suspected endometriosis. METHODS: PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov databases were searched from their inception to 12 October 2022, using a manual search for additional articles. Two authors independently performed title, abstract and full-text screening of the identified records, extracted study details and quantitative data and assessed the quality of the studies using the 'Quality Assessment of Diagnostic Accuracy Study 2' tool. Bivariate random-effects models were used to determine the pooled sensitivity and specificity, compare the two imaging modalities and evaluate the sources of heterogeneity. RESULTS: Sixteen prospective studies (10 assessing TVUS, 4 assessing MRI and 2 assessing both TVUS and MRI) were included, representing 1976 participants. Pooled TVUS and MRI sensitivities for endometrioma were 0.89 (95% confidence interval 'CI', 0.86-0.92) and 0.94 (95% CI, 0.74-0.99), respectively (indirect comparison p-value of 0.47). Pooled TVUS and MRI specificities for endometrioma were 0.95 (95% CI, 0.92-0.97) and 0.94 (95% CI, 0.89-0.97), respectively (indirect comparison p-value of 0.51). These studies had a high or unclear risk of bias. A direct comparison (all participants undergoing TVUS and MRI) of the modalities was available in only two studies. CONCLUSION: TVUS and MRI have high accuracy for diagnosing endometriomas; however, high-quality studies comparing the two modalities are lacking.

The diagnosis of endometriomas in patients with endometriosis impacts infertility and pain management. We performed a systematic review and meta-analysis to assess the accuracy of transvaginal ultrasound and magnetic resonance imaging for the diagnosis of endometrioma in patients of reproductive age with suspected endometriosis, and to compare the accuracy of the two imaging modalities. Five databases (PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov databases) were searched. Sixteen prospective studies were included, representing 1976 participants. We found high accuracy of transvaginal ultrasound and magnetic resonance imaging for diagnosing endometriomas. There was no statistically significant difference in diagnostic accuracy between the two modalities. However, high-quality studies comparing the two modalities in the same population are lacking.

Discrepancies in staging and perioperative classification of pelvic endometriosis according to #Enzian 2021.

AIM: The aim of this study is to compare the extent of ovarian endometriosis diagnosed at preoperative staging with subsequent perioperative findings. Definition of discrepancies observed according to the #Enzian 2021 classification. MATERIAL AND METHODS: The cohort includes 62 patients of reproductive age with preoperative findings of ovarian endometrioma. Patients were divided according to the #Enzian 2021 classification into subgroups (O1, O2 + O3) with unilateral and bilateral findings. The percentage concordance of preoperative and perioperative findings was evaluated. RESULTS: In the evaluation of ovarian involvement, the preoperative ultrasound diagnosis shows almost 100% agreement with the findings on the ovaries during surgery. Periadnexal adhesions were predicted preoperatively in only half of the cases. The difference in laterality was confirmed with T3 involvement in the O2 + O3 subgroup. In the bilateral involvement, the finding of the presence of grade 3 adhesions was doubled. An association of ovarian form of endometriosis (O2-O3) with deep infiltrating endometriosis of the small pelvis was observed in 50% of the cohort. CONCLUSION: The ovarian form of endometriosis is associated with the occurrence of other endometriosis lesions in the small pelvis. In this study, it was confirmed that preoperative staging underestimates the extent of endometriosis in the small pelvis. In the surgical management of ovarian endometriosis, extensive adhesive process should be expected.

Effect of Oral Contraceptive Use in Relation to Fertile Years on the Risk of Endometriosis in Women with Primary Infertility: A Ten-Year Single-Centre Retrospective Analysis.

Background and Objectives: Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. Materials and Methods: This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. Results: In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; p = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 [95% CI 0.87-1.29]). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 [95% CI 0.26-0.95]; p = 0.036) or superficial implants (aOR 0.88 [95% CI 0.58-0.95]; p = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. Conclusions: When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study's limitations.

[Surgical treatments for endometriosis]. / Les traitements chirurgicaux de l'endométriose.

Complete resection of scattered superficial lesions can be paradoxically more complex. If the endometriosis is ovarian, priority should be given to preserving the oocyte capital, and ovarian function should be assessed in patients of childbearing age who wish to become pregnant, prior to treatment by alcoholization of the cyst, abrasion of its contents by laser or plasma energy, or even cystectomy. Laparoscopic resection is recommended in cases of deep endometriosis. After a thorough clinical examination and precise imaging, deep lesions are treated by resection and shaving in the case of digestive or ureteral localizations, or even by discoid resection or digestive anastomosis resection with or without stoma, depending on fistula risk criteria. The aim is to reduce pain and functional consequences, while preserving ovarian function to improve pregnancy rates.

Endometriosis and IVF treatment outcomes: unpacking the process.

Advanced endometriosis is associated with a reduction of IVF success. Surgical damage to the ovarian reserve following the excision of endometriomas has been claimed as a critical factor in the explanation of this detrimental effect. However, it is generally inferred that other mechanisms might also hamper IVF success in affected women. They include diminished responsiveness to ovarian stimulation, altered steroidogenesis, a decline in oocyte quality, reduced fertilization and embryo development, and impaired implantation. To navigate these limitations, we scrutinized available literature for studies specifically designed to address distinct phases of the IVF process. Utmost consideration was given to intra-patient ovarian response comparisons in women with unilateral endometriomas and to studies applying a meticulous matching to control confounders. The following observations have been drawn: 1) endometriosis has a negligible impact on ovarian response. A slight reduction in stimulation response can only be observed for endometriomas larger than 4 cm. Follicular steroidogenesis is unaffected; 2) oocyte quality is not hampered. Fertilization rates are similar, and intracytoplasmic sperm injection (ICSI) is not justified. Embryonic development is uncompromised, with no increase in aneuploidy rate; 3) endometrial receptivity is either unaffected or only slightly impacted. In conclusion, our study suggests that, aside from the well-known negative effect on ovarian reserve from excisional endometrioma surgeries, endometriosis does not significantly affect IVF outcomes.

Fertility preservation for women with ovarian endometriosis: results from a retrospective cohort study.

RESEARCH QUESTION: What is the outcome of fertility-preservation treatments in women with endometrioma, especially those with endometrioma larger than 4 cm? DESIGN: Retrospective cohort study. Women with definitive diagnosis of ovarian endometriosis (by histology or ultrasound), who underwent fertility-preservation treatment in two IVF units between 2016 and 2021, were included. As some women cryopreserved oocytes and other embryos, the primary outcome was the number of metaphase II (MII) oocytes retrieved. RESULTS: Seventy-one women with ovarian endometriosis (OMA) underwent 138 fertility-preservation cycles. The median age of patients was 31 years. Forty out of 71 (56%) women underwent at least one surgery for OMA before fertility-preservation treatment. Multivariate analysis of each patient's first cycle was used. Women who underwent OMA surgery before fertility-preservation treatment had a 51.7% reduction (95% CI 26.1 to 68.5, P = 0.001) in the number of MII oocytes compared with women with OMA who did not undergo surgery. Among a subgroup who did not undergo surgery, those with an endometrioma larger than 4 cm had similar anti-Müllerian hormone concentration (2.6 ng/ml versus 2.1 ng/ml), number of oocytes retrieved (9 versus 9) and number of MII oocytes (7.6 versus seven 7) compared with women with an endometrioma of 4 cm or less. CONCLUSIONS: Discussing fertility-preservation treatment options with patients with OMA is recommended, especially if surgery is planned.

Adnexal masses during pregnancy: diagnosis, treatment, and prognosis.

Adnexal masses are identified in pregnant patients at a rate of 2 to 20 in 1000, approximately 2 to 20 times more frequently than in the age-matched general population. The most common types of adnexal masses in pregnancy requiring surgical management are dermoid cysts (32%), endometriomas (15%), functional cysts (12%), serous cystadenomas (11%), and mucinous cystadenomas (8%). Approximately 2% of adnexal masses in pregnancy are malignant. Although most adnexal masses in pregnancy can be safely observed and approximately 70% spontaneously resolve, a minority of cases warrant surgical intervention because of symptoms, risk of torsion, or suspicion of malignancy. Ultrasound is the mainstay of evaluation of adnexal masses in pregnancy because of accuracy, safety, and availability. Several ultrasound mass scoring systems, including the Sassone, Lerner, International Ovarian Tumor Analysis Simple Rules, and International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adneXa scoring systems have been validated specifically in pregnant populations. Decisions regarding expectant vs surgical management of adnexal masses in pregnancy must balance the risks of torsion or malignancy with the likelihood of spontaneous resolution and the risks of surgery. Laparoscopic surgery is preferred over open surgery when possible because of consistently demonstrated shorter hospital length of stay and less postoperative pain and some data demonstrating shorter operative time, lower blood loss, and lower risks of fetal loss, preterm birth, and low birthweight. The best practices for laparoscopic surgery during pregnancy include left lateral decubitus positioning after the first trimester of pregnancy, port placement with respect to uterine size and pathology location, insufflation pressure of less than 12 to 15 mm Hg, intraoperative maternal capnography, pre- and postoperative fetal heart rate and contraction monitoring, and appropriate mechanical and chemical thromboprophylaxes. Although planning surgery for the second trimester of pregnancy generally affords time for mass resolution while optimizing visualization with regards to uterine size and pathology location, necessary surgery should not be delayed because of gestational age. When performed at a facility with appropriate obstetrical, anesthetic, and neonatal support, adnexal surgery in pregnancy generally results in excellent outcomes for pregnant patients and fetuses.