Treatment after endometrioma recurrence: a narrative review.

INTRODUCTION: Ovarian endometrioma is a common subtype of endometriosis with a prevalence between 17 and 44%. The reported average recurrence of endometrioma after surgical management is 21.5% after 2 years and 40-50% after 5 years. The aim of this narrative review was to summarize the existing literature focusing on treatment options after endometrioma recurrence in order to provide an evidence-based approach for the clinical practice. EVIDENCE ACQUISITION: Three electronic databases (MEDLINE, EMBASE and Cochrane) were searched until September 2022 for eligible studies. EVIDENCE SYNTHESIS: The available studies showed that repeated surgery has a negative impact on ovarian function, without improving the fertility outcomes. Transvaginal aspiration as an alternative option for surgery has a high rate of recurrence, which varies from 8.20 to 43.5% depending on the technique used and on the study population. Pregnancy related outcomes were similar between transvaginal aspiration groups and no intervention groups in patients with endometrioma recurrence. Regarding medical treatments, only four studies were found, showing that progestins reduce the pain and the diameter of the ovarian cyst. CONCLUSIONS: Recurrent endometrioma is a challenging condition which could be encountered during the care of women with endometriosis. The decision about the treatment-strategy has to be individualized considering family planning status, age, ovarian reserve and transvaginal ultrasound findings. Well-designed randomized clinical trials are needed to export safer conclusions about the most appropriate treatment in each specific condition after endometrioma recurrence.

True Prevalence of Diaphragmatic Endometriosis and Its Association with Severe Endometriosis: A Call for Awareness and Investigation.

STUDY OBJECTIVE: To identify characteristics indicating preoperatively the presence of diaphragmatic endometriosis (DE). DESIGN: Comparison of characteristics of patients with diaphragmatic endometriosis (DE) with characteristics of patients with abdominal endometriosis without diaphragmatic involvement, in a prospective cohort study. SETTING: Tertiary referral center; endometriosis center. PATIENTS: A total of 1372 patients with histologically proven endometriosis. INTERVENTIONS: Surgery performed laparoscopically under general anesthesia. All patients with suspected endometriosis underwent a complete bilateral inspection of the diaphragm. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical pathologic characteristics were evaluated using basic descriptive statistics (comparison of the groups using the χ2 test and the Mann-Whitney t test). A logistic regression analysis was performed to evaluate the relationship (hazard ratio) between symptoms and the presence of DE. DE was diagnosed in 4.7% of the patients (65 of 1372). There was no significant difference between the 2 groups (patients with abdominal endometriosis with or without DE) with regard to typical endometriosis pain (dysmenorrhea, dyschezia, dysuria, and/or dyspareunia). However, in the DE group, diaphragmatic pain was present significantly more often preoperatively (27.7% vs 1.8%, p <.001). Four DE patients (6.1 %) were asymptomatic (with infertility the indication for surgery). In the DE group, 78.4 % had advanced stages of endometriosis (revised American Fertility Society III° or IV°); the left lower pelvis was affected in more patients (73.8%). In cases of ovarian endometriosis, patients with DE showed a significantly higher prevalence of left ovaries involvement (left 63% vs right 35.7%, p <.001). Patients with DE had a significantly higher rate of infertility (49.2% vs 28.7%, p <.05). CONCLUSION: Patients with shoulder pain, infertility, and/or endometriosis in the left pelvis have a significant higher risk of DE and therefore need specific preoperative counseling and if indicated surgical treatment.

Endometriosis is a risk factor for recurrent pelvic inflammatory disease after tubo-ovarian abscess surgery.

PURPOSE: To evaluate the clinical outcomes and prognosis of patients undergoing laparoscopic surgery for tubo-ovarian abscess (TOA) and identify risk factors for pelvic inflammatory disease (PID) recurrence. METHODS: We conducted a retrospective cohort analysis including 98 women who underwent laparoscopic surgery for TOA at the Department of Obstetrics and Gynecology at the Bern University Hospital from January 2011 to May 2021. The primary outcome studied was the recurrence of PID after TOA surgery. Clinical, laboratory, imaging, and surgical outcomes were examined as possible risk factors for PID recurrence. RESULTS: Out of the 98 patients included in the study, 21 (21.4%) presented at least one PID recurrence after surgery. In the univariate regression analysis, the presence of endometriosis, ovarian endometrioma, and the isolation of E. coli in the microbiology cultures correlated with PID recurrence. However, only endometriosis was identified as an independent risk factor in the multivariate analysis (OR (95% CI): 9.62 (1.931, 47.924), p < 0.01). With regard to the time of recurrence after surgery, two distinct recurrence clusters were observed. All patients with early recurrence (≤ 45 days after TOA surgery) were cured after 1 or 2 additional interventions, whereas 40% of the patients with late recurrence (> 45 days after TOA surgery) required 3 or more additional interventions until cured. CONCLUSION: Endometriosis is a significant risk factor for PID recurrence after TOA surgery. Optimized therapeutic strategies such as closer postsurgical follow-up as well as longer antibiotic and hormonal therapy should be assessed in further studies in this specific patient population.

Effects of vitamin D supplementation in endometriosis: a systematic review.

BACKGROUND: There is a growing body of human, animal and in vitro studies on vitamin D (vit D) substitution in endometriosis. The aim of this systematic review is to critically appraise and qualitatively synthesize the results of the available studies that examine the supplementation of vit D for endometriosis treatment. METHODS: A systematic search of the literature was conducted in four electronic databases (Medline, Cochrane, Scopus, Embase) and grey literature for original research articles on humans, animals and in vitro models published in any language. RESULTS: Four human studies, four animal studies and four in vitro studies were included. Quantitative synthesis of human studies showed no significant effect of vit D intake for dysmenorrhea (2 studies, 44 vit D vs 44 placebo, mean -0.71, 95% CI -1.94, 0.51) and non-cyclic pelvic pain (2 studies, 42 vit D vs 38 placebo, mean 0.34, 95% CI -0.02, 0.71). Regarding reproductive outcomes in women with endometriosis after in vitro fertilization, the only available study showed no differences between women taking vit D and women taking placebo. Three of the four included animal studies showed regression of endometriotic implants when treated with vit D. The in vitro studies demonstrated that vit D decreases invasion and proliferation of endometriotic lesions without affecting apoptosis. CONCLUSIONS: Although in vitro and animal studies suggest regression of the endometriotic implants and decrease of invasion and proliferation after vit D supplementation, this was not reflected in the results of the meta-analysis, which showed no benefit of vit D supplementation in patients with endometriosis and dysmenorrhea or non-cyclic pelvic pain as well as on the outcome of IVF treatment. However, given the heterogeneity and the diversity of the available studies, more research is required to shed light on the role of vit D supplementation in women with endometriosis.

Computer-Aided Histopathological Characterisation of Endometriosis Lesions.

Endometriosis is a common gynaecological condition characterised by the growth of endometrial tissue outside the uterus and is associated with pain and infertility. Currently, the gold standard for endometriosis diagnosis is laparoscopic excision and histological identification of endometrial epithelial and stromal cells. There is, however, currently no known association between the histological appearance, size, morphology, or subtype of endometriosis and disease prognosis. In this study, we used histopathological software to identify and quantify the number of endometrial epithelial and stromal cells within excised endometriotic lesions and assess the relationship between the cell contents and lesion subtypes. Prior to surgery for suspected endometriosis, patients provided menstrual and abdominal pain and dyspareunia scores. Endometriotic lesions removed during laparoscopic surgery were collected and prepared for immunohistochemistry from 26 patients. Endometrial epithelial and stromal cells were identified with Cytokeratin and CD10 antibodies, respectively. Whole slide sections were digitised and the QuPath software was trained to automatically detect and count epithelial and stromal cells across the whole section. Using this classifier, we identified a significantly larger number of strongly labelled CD10 stromal cells (p = 0.0477) in deeply infiltrating lesions (99,970 ± 2962) compared to superficial lesions (2456 ± 859). We found the ratio of epithelial to stromal cells was inverted in deeply infiltrating endometriosis lesions compared to superficial peritoneal and endometrioma lesions and we subsequently identified a correlation between total endometrial cells and abdominal pain (p = 0.0005) when counted via the automated software. Incorporating histological software into current standard diagnostic pipelines may improve endometriosis diagnosis and provide prognostic information in regards to severity and symptoms and eventually provide the potential to personalise adjuvant treatment decisions.

Altered differentiation of endometrial mesenchymal stromal fibroblasts is associated with endometriosis susceptibility.

Cellular development is tightly regulated as mature cells with aberrant functions may initiate pathogenic processes. The endometrium is a highly regenerative tissue, shedding and regenerating each month. Endometrial stromal fibroblasts are regenerated each cycle from mesenchymal stem cells and play a pivotal role in endometriosis, a disease characterised by endometrial cells that grow outside the uterus. Why the cells of some women are more capable of developing into endometriosis lesions is not clear. Using isolated, purified and cultured endometrial cells of mesenchymal origin from 19 women with (n = 10) and without (n = 9) endometriosis we analysed the transcriptome of 33,758 individual cells and compared these to clinical characteristics and in vitro growth profiles. We show purified mesenchymal cell cultures include a mix of mesenchymal stem cells and two endometrial stromal fibroblast subtypes with distinct transcriptomic signatures indicative of varied progression through the differentiation processes. The fibroblast subgroup characterised by incomplete differentiation was predominantly (81%) derived from women with endometriosis and exhibited an altered in vitro growth profile. These results uncover an inherent difference in endometrial cells of women with endometriosis and highlight the relevance of cellular differentiation and its potential to contribute to disease susceptibility.

Preoperative application of the Enzian classification for endometriosis (The cEnzian Study): A prospective international multicenter study.

OBJECTIVE: To assess the diagnostic performance of preoperative application of the Enzian classification (cEnzian) using surgical findings as reference standard. DESIGN: A prospective international non-interventional study. SETTING: Twelve endometriosis centres in four European countries (Austria, Germany, Switzerland and Czech Republic). POPULATION: 1062 women with endometriosis surgery. METHODS: Extent of endometriosis was preoperatively classified using the cEnzian classification based on gynaecological examination and/or transvaginal ultrasound (TVS) and/or magnetic resonance imaging (MRI). After subsequent surgery, the surgeon classified the intraoperative findings using the Enzian classification. MAIN OUTCOME MEASURES: Sensitivity, specificity, PPV, NPV, LR+ , LR- and accuracy were calculated. Conditional frequencies of intraoperative Enzian codings and the corresponding 95% confidence intervals were computed for each preoperative coding and visualised in plots. RESULTS: Although overall consistency of cEnzian and Enzian was poor (35.14%, 95% confidence interval 32.26-38.03), high specificities and negative predictive values (NPVs) of the cEnzian compartments could be demonstrated. Looking at the individual parts of the Enzian classification, the poorest diagnostic performance was detected for compartment B and the highest PPVs were found for category 3 lesions (>3 cm), independent of the compartment. CONCLUSIONS: Using the Enzian classification in a non-invasive setting is a useful tool providing us with an 'at a glance' summary of the diagnostic workup regarding deep endometriosis with high specificities and NPVs. An attempt to merge the two new endometriosis classification systems (#Enzian and AAGL 2021) seems reasonable taking into consideration the respective advantages of each other.

Gestational diabetes is associated with SARS-CoV-2 infection during pregnancy: A case-control study.

AIM: Individuals with SARS-CoV-2 infection and (pre-existing) diabetes, including pregnant women, present with more severe morbidity, as compared to non-diabetic subjects. To date, evidence is limited concerning the role of gestational diabetes (GDM) in severity of SARS-CoV-2 infection during pregnancy, or vice versa. The aim of our study was to investigate the prevalence of GDM in a SARS-CoV-2 infected pregnant population and evaluate risk factors for and from severe infection in these patients. METHODS: A case-control study with prospective data collection for the case group and 1:2 matching with historical controls based on parity, BMI and ethnicity was conducted (n = 224). GDM screening was performed at 26 weeks' gestation. Multivariate binary logistic regression analysis was performed to assess risk factors for GDM and inpatient COVID-19 management. RESULTS: 34.6% of the patients in the case group suffered from GDM, vs. 16.1% in the control group (p = 0.002). 35.7% patients were diagnosed with GDM after, vs. 33.3% before SARS-CoV-2 infection (OR (95%CI) 1.11(0.40-3.08), p = 0.84), with no correlation between time point of infection and GDM diagnosis. SARS-CoV-2 (OR (95%CI) 2.79 (1.42, 5.47), p = 0.003) and BMI (OR (95%CI) 1.12 (1.05, 1.19), p = 0.001) were significant independent risk factors for GDM. CONCLUSION: Data suggests that GDM increases the risk of infection in SARS-CoV-2 infected pregnant women. Meanwhile, SARS-CoV-2 during pregnancy might increase the risk of developing GDM. Vaccination and caution in using protective measures should be recommended to pregnant women, particularly when suffering from GDM.

Endometriosis and Isthmocele: Common or Rare?

Higher cesarean section rates and better ultrasound diagnostics have led to a more frequent diagnosis of isthmocele, a cesarean scar defect. Sometimes, endometriosis is found in the isthmocele, but simultaneous extrauterine endometriosis and endometriosis in the isthmocele have not yet been reported. Additionally, the surgical technique to repair the isthmocele is the subject of ongoing controversy. The aim of this study is to analyze a possible correlation between uterine scar (isthmocele) endometriosis and extrauterine endometriosis and to investigate the outcome of laparoscopic isthmocele resection in the rendezvous technique. In this single-center retrospective study, we included 83 women of reproductive age with symptomatic isthmocele undergoing laparoscopic isthmocele repair in rendezvous technique from 2004 to 2020 at the University of Bern. We collected data on patient and surgical characteristics as well as on postoperative outcomes (symptoms, further pregnancy, and pregnancy outcomes) retrospectively. We analyzed and compared these data for patients with and without endometriosis. Endometriosis was diagnosed during surgery in 22 out of 83 operated patients (26.5%). Diagnosis of isthmocele endometriosis (n = 9, 11%) was significantly higher in patients with extrauterine endometriosis (n = 6, p = 0.004). While the duration of surgery was significantly longer for patients with endometriosis (p = 0.006), the groups did not differ with regard to blood loss or complications. In addition, both groups showed similar indications for isthmocele repair (infertility, abnormal uterine bleeding, or dysmenorrhea). Surgery significantly improved abnormal uterine bleeding (χ2 p < 0.001), dysmenorrhea (χ2, p = 0.03), and infertility (χ2, p < 0.001). Regardless of the presence of endometriosis, 25 of 40 (63%) infertile patients became pregnant after surgery. In one out of eight pregnancies, however, we observed scar complications during pregnancy such as uterine scar pregnancy (n = 3), uterine scar dehiscence (n = 3), and placenta previa (n = 1). Endometriosis is a non-negligible intraoperative finding in patients with symptomatic isthmocele. The laparoscopic approach in the rendezvous technique is safe and effective. Therefore, this method should be recommended, especially in women with secondary infertility, and preoperatively simultaneous endometriosis resection should be discussed with the patient. In follow-up, postoperative pregnancies have to be monitored with care.

Association of endocannabinoids with pain in endometriosis.

ABSTRACT: Endocannabinoid (eCB) levels fluctuate in inflammatory conditions and as such may take part in endometriosis-associated pain or even in endometriosis pathogenesis. In this case-control (23 cases and 19 controls) study, targeted lipids were measured in the serum and peritoneal fluid collected during laparoscopy. Endometriosis was confirmed histologically. Dysmenorrhea, abdominal pain, and dyspareunia were assessed using the Numeric Rating Scale for pain. Steroids, eCBs, and related lipids were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tumor necrosis factor alpha, IL-8, PAPP-A, PP14, RANTES, OPG, MIDKINE, MCP-1, VEGF, leptin, and defensins were quantified by ELISA. We found that eCB levels were significantly influenced by both noncyclic and cyclic abdominal pain. Specifically, women suffering from noncyclic abdominal pain were characterized by a higher 2-AG level in the peritoneal fluid throughout the menstrual cycle, whereas women suffering from dysmenorrhea had higher 2-AG levels and lower AEA levels during the proliferative phase alone. In addition, 2-AG positively correlated with prostaglandin E2 (PGE2), and the ratio AEA/2-AG positively correlated with defensins, suggesting a possible link between endocannabinoids system and inflammatory pain. The results of the current study indicate that the eCB system may play a role in endometriosis-associated pain, but additional studies are needed to investigate the causal relationship.

Effectiveness of Dietary Interventions in the Treatment of Endometriosis: a Systematic Review.

A patients' increasing interest in dietary modifications as a possible complementary or alternative treatment of endometriosis is observed. Unfortunately, the therapeutic potential of dietary interventions is unclear and to date no guidelines to assist physicians on this topic exist. The aim of this study, therefore, was to systematically review the existing studies on the effect of dietary interventions on endometriosis. An electronic-based search was performed in MEDLINE and COCHRANE. We included human and animal studies that evaluated a dietary intervention on endometriosis-associated symptoms or other health outcomes. Studies were identified and coded using standard criteria, and the risk of bias was assessed with established tools relevant to the study design. We identified nine human and 12 animal studies. Out of the nine human studies, two were randomized controlled trials, two controlled studies, four uncontrolled before-after studies, and one qualitative study. All of them assessed a different dietary intervention, which could be classified in one of the following principle models: supplementation with selected dietary components, exclusion of selected dietary components, and complete diet modification. Most of the studies reported a positive effect on endometriosis; they were however characterized by moderate or high-risk bias possibly due to the challenges of conducting dietary intervention trials. According to the available level of evidence, we suggest an evidence-based clinical approach for physicians to use during consultations with their patients. Further well-designed randomized controlled trials are needed to accurately determine the short-term and long-term effectiveness and safety of different dietary interventions.

Postoperative Pain Is Driven by Preoperative Pain, Not by Endometriosis.

(1) Background: The aim of this study was to evaluate the impact of endometriosis on postoperative pain following laparoscopic hysterectomy; (2) Methods: A total of 214 women who underwent a laparoscopic hysterectomy between January 2013 and October 2017 were divided into four subgroups as follows: (1) endometriosis with chronic pain before the surgery (n = 57); (2) pain-free endometriosis (n = 50); (3) pain before the surgery without endometriosis (n = 40); (4) absence of both preoperative pain and endometriosis (n = 67). Postoperative pain was compared by using Visual Analog Scale (VAS) scores and by tracking the use of painkillers during the day of surgery and the first two postoperative days; (3) Results: Women with chronic pain before the surgery reported higher VAS scores during the first postoperative days, while the use of analgesics was similar across the groups. There was no difference in the postoperative pain when comparing endometriosis patients to non-endometriosis patients; (4) Conclusions: Women with chronic pelvic pain demonstrated increased postoperative pain after laparoscopic hysterectomy, which was independent of the presence or severity of endometriosis. The increased VAS scores did not, however, translate into equally greater use of painkillers, possibly due to the standardised protocols of analgesia in the immediate postoperative period. These findings support the need for careful postsurgical pain management in patients with pain identified as an indication for hysterectomy, independent of the extent of the surgery or underlying diagnosis.

Leptin concentrations in endometriosis: A systematic review and meta-analysis.

INTRODUCTION: Endometriosis is an inflammatory condition, affecting mainly women of reproductive age. Leptin is a regulator of food intake and energy expenditure, posing pleiotropic actions, and regulating immunity and fertility. The aim of this study was to systematically review the literature regarding leptin concentrations in biological fluids and tissues of women with endometriosis, and to investigate and propose a possible role of leptin in the pathophysiology of endometriosis. MATERIALS AND METHODS: A systematic search of the literature was conducted in two electronic databases (MEDLINE, COCHRANE) and grey literature for original research articles on humans, published in any language. RESULTS: Twenty-nine studies with 1291 women with endometriosis and 1664 controls were included in the systematic review. Peritoneal fluid and follicular fluid leptin concentrations were higher in endometriosis compared with control group [mean difference (MD) 7.10, 95 % confidence interval (CI) 4.76 to 9.44 ng/mL, 18 studies), (MD 1.35, 95 % CI 0.54-2.17 ng/ml, 2 studies) respectively. No differences were evident in serum (MD 0.92, 95 % CI -0.84 to 2.68 ng/mL, 12 studies) or plasma (MD -0.95, 95 % CI -4.63 to 2.72 ng/mL, 3 studies) between the groups. No meta-analysis was conducted for ovarian tissue leptin (2 studies). CONCLUSIONS: This meta-analysis provided evidence for increased leptin concentrations in both peritoneal fluid and follicular fluid of women with endometriosis compared with control; these differences were not present in the serum or plasma. The above results support a potential pathophysiologic role for leptin in the local microenvironment while declines its use as a blood diagnostic marker. Furthermore, we propose a possible role of leptin in the pathophysiology of endometriosis.

Predictive Factors for Voiding Dysfunction after Surgery for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To evaluate the prognostic value of pre- and perioperative factors for voiding dysfunction after surgery for deep infiltrating endometriosis (DIE). DESIGN: Single-center retrospective cohort study. SETTING: University hospital. PATIENTS: A total of 198 women with DIE in the posterior compartment who underwent surgery and a postoperative bladder scan. INTERVENTIONS: Surgical resection of the DIE nodule from the dorsal compartment. MEASUREMENTS AND MAIN RESULTS: After surgery, 41% of the patients initially experienced voiding dysfunction (defined as >100 mL postvoid residual urine volume at second bladder scan). The number decreased to 11% by the time of hospital discharge. Among those with a need for self-catheterization after discharge (n = 17), voiding dysfunction lasted for a median of 41 days before a return to normal bladder function, with a residual urine volume of <100 mL. The preoperative presence of DIE nodules in the ENZIAN compartment B was associated with postoperative voiding dysfunction (p = .001). The hazard ratio for elevated residual urine volume was highest when the disease stage was B3 (hazard ratio 6.43; CI, 2.3-18.2; p <.001), describing a nodule diameter of >3 cm in lateral distension. Receiver operating characteristic curve analyses showed that a first residual urine volume >220 mL has a good predictive value for the risk of intermittent self-catheterization (area under the receiver operating characteristic curve 0.893; p <.001). CONCLUSION: Postoperative voiding dysfunction is frequent; of note, in most cases the problem is temporary. When DIE with an ENZIAN classification B is noted intraoperatively and, most of all, when the diameter of the lesion is >3 cm, a higher risk of postoperative voiding dysfunction is to be expected.

Risk factors for non-response and discontinuation of Dienogest in endometriosis patients: A cohort study.

INTRODUCTION: Progestins are commonly prescribed first-line drugs for endometriosis. High rates of non-response and intolerance to these drugs have been previously reported. However, no study to date has investigated the characteristics and comorbidities of patients taking progestins in relation to treatment outcomes, so identifying which patients will respond to or tolerate the treatment is currently impossible. The purpose of this study, therefore, was to identify risk factors for non-response and discontinuation of Dienogest (DNG) in women with endometriosis. MATERIAL AND METHODS: This is a retrospective cohort study including women currently taking, or newly prescribed, DNG for endometriosis-associated pain presenting in the Endometriosis Clinic of the University Hospital of Bern between January 2017 and May 2018. Women with initiation of treatment directly after surgery for endometriosis were excluded. For all participants the symptoms and comorbidities were documented. Effectiveness, tolerability and discontinuation of DNG were the primary end points. Univariate and multivariate binary logistic regression models were carried out to identify risk factors for non-response, intolerance and discontinuation of DNG. RESULTS: A sufficient or excellent treatment response was reported by 85/125 (68%) participants. Genital bleeding during the DNG treatment was negatively (OR 0.185, 95% CI 0.056-0.610, P = .006) and rASRM endometriosis stages III and IV were positively (OR 3.876, 95% CI 1.202-12.498, P = .023) correlated with the DNG response. When accounting for exclusively pretreatment factors, primary dysmenorrhea (OR 0.236, 95% CI 0.090-0.615, P = .003) and suspicion of adenomyosis (OR 0.347, 95% CI 0.135-0.894, P = .028) were inversely correlated with DNG response, and the latter was also correlated with treatment discontinuation (OR 3.189, 95% CI 1.247-8.153, P = .015). CONCLUSIONS: Genital bleeding during the DNG treatment and low rASRM stages are independent risk factors for DNG non-response. Before treatment initiation, primary dysmenorrhea and suspicion of adenomyosis correlate with DNG non-response. The results could assist the clinician first to provide detailed information to women before treatment initiation, second to identify and possibly modify in-therapy factors correlated to treatment effectiveness and lastly to switch treatment on time if needed.

Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis.

This study aimed to investigate the association of adenomyosis with fertility, pregnancy and neonatal outcomes. An electronic search was conducted using the MEDLINE, PubMed and Cochrane databases up to April 2020. Seventeen observational studies were included. Adenomyosis was significantly associated with a lower clinical pregnancy rate (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.51-0.94) and higher miscarriage rate (OR 2.17; 95% CI 1.25-3.79) after treatment with assisted reproductive technology (ART). The lower clinical pregnancy rate was more significant in the subgroup of patients with short down-regulation protocols. Similar associations were recorded after age adjustment. Adenomyosis was also significantly associated with an increased risk of pre-eclampsia, preterm delivery, Caesarean section, fetal malpresentation, small for gestational age infancy and post-partum haemorrhage, which was confirmed after correction for age and mode of conception. In conclusion, adenomyosis is associated with negative effects on fertility after ART. The potentially protective role of the ultra-long down-regulation protocols needs further evaluation in randomized controlled studies. Adenomyosis is also associated (independently of the mode of conception) with adverse pregnancy and neonatal outcomes. Proper counselling prior to ART and close monitoring of pregnancy in patients with adenomyosis should be recommended.

Peritoneal fluid biomarkers in patients with endometriosis: a cross-sectional study.

OBJECTIVES: Elevated concentrations of numerous molecules have been reported in the peritoneal cavity of women with endometriosis. Until now, no factor proved sufficiently specific to endometriosis. We aimed to investigate several biomarkers in endometriosis and report their association with the menstrual cycle in a large sample size study. METHODS: Patients of reproductive age undergoing laparoscopic procedures for benign pathology in the Department of Obstetrics and Gynaecology, University of Bern between 2007 and 2018 were included. Exclusion criteria were the use of hormonal treatment in the three months prior to surgery, patients suffering from other inflammatory diseases, pregnancy, malignancy and surgery performed in an emergency. The concentrations of 13 different biomarkers in the peritoneal fluid (PF) were compared between patients with and without endometriosis both in the proliferative and the secretory cycle phase. RESULTS: Out of 1,256 patients in the database, 521 met the inclusion and exclusion criteria. Glycodelin (PP14) and Midkine concentrations were significantly higher in patients with endometriosis compared to controls irrespective of the cycle phase in which the PF was collected. Interleukin-8 (IL-8), regulated on activation normal T cell expressed and secreted (RANTES) and osteoprotegerin (OPG) concentrations were higher in patients with endometriosis only in the proliferative cycle phase. Monocyte chemoattractant protein 1, CCL2 (MCP-1) and Defensin concentrations were higher in patients with endometriosis only in the secretory cycle phase. CONCLUSIONS: Certain pathophysiological processes may take place only in the one cycle phase leading to a temporary increase of specific PF biomarkers. Correlation with clinical outcomes is mandatory to establish their potential as prognostic or therapeutic tools in endometriosis.

Recurrence Patterns after Surgery in Patients with Different Endometriosis Subtypes: A Long-Term Hospital-Based Cohort Study.

Recurrence of endometriosis after surgery constitutes a serious challenge. Whether there is an evolution of lesion subtypes with each recurrence and whether certain lesions subtypes tend to recur faster than others is not adequately addressed. Medical records of all patients who underwent surgery for endometriosis between 1997 and 2018 in the Department of Gynecology and Obstetrics, University of Bern, were reviewed. Inclusion criteria was surgically confirmed endometriosis recurrence, defined as a subsequent surgery for endometriosis after a previous complete surgical excision of endometriosis lesions. Three subtypes of endometriosis were defined: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). Time to recurrence and variation in endometriosis subtype between the first and recurrent surgeries were the primary outcome measures. Out of the 322 patients with recurrent surgery that were identified, for 234 of them, the endometriosis subtype at first surgery was confirmed and classified (SUP = 56, OMA = 124, DIE = 54). No statistically significant difference was found for time to recurrence between lesion subtypes. SUP compared to the other groups had a higher possibility of presenting with SUP at recurrence (Odds Ratio (OR): 3.65, 95% confidence interval (CI): 1.74-7.51) and OMA compared to the other groups had a higher possibility of presenting with OMA at recurrence (OR: 3.72, 95% CI: 2.04-6.74). Nevertheless, a large number of SUP patients subsequently presented with OMA (10/56: 17.9%) or DIE (27/56: 48.2%) lesions at recurrence. Similarly, a large number of OMA patients subsequently presented with DIE (49/124: 39.5%) lesions at recurrence. In conclusion, although SUP and OMA patients compared to the others are more likely to present with the same subtype at recurrence, increasing lesion subtype severity occurs in a substantial proportion of patients. Time to recurrence is independent from the lesion subtype at first surgery.