Stage Of Endometriosis Research Articles

The appendix in endometriosis.

In the most severe stage of endometriosis, Stage IV, intestinal involvement is common. The true prevalence of endometriotic disease of the appendix in this population is not well described. A macroscopically normal looking appendix may harbour endometriosis. Our study aims to assess the role of routinely performing appendicectomy in Stage IV endometriosis surgery, and the histopathological prevalence of true appendiceal endometriosis in this population. This is a retrospective study of women undergoing surgery for Stage IV endometriosis between 2018 to 2022 in a tertiary public hospital in New South Wales, Australia. Patient demographics, age and post-operative complications were retrospectively retrieved from hospital medical records. Inclusion criteria were women with Stage IV endometriosis who underwent routine appendicectomy as part of their endometriosis surgery. Exclusion criteria were women who did not have Stage IV endometriosis, those who had cancer surgery or emergency surgery for endometriosis. The primary outcome of this study was to determine the incidence of appendiceal endometriosis. Secondary outcomes included post-operative complications and length of stay. Sixty-seven patients were included. The mean age was 36 years. All patients also underwent bowel resection for colorectal endometriosis. There were 35.8% who had confirmed appendiceal endometriosis on histopathology. Post-operative complications included port site infections, colitis, urinary tract infection and ureteric injury. There were no complications related to appendicectomy. Mean length of stay was 4.4 days. Laparoscopic appendicectomy can be safely performed at time of laparoscopic surgical excision of Stage IV endometriosis and should be routinely considered in a subset of Stage IV endometriosis patients with colorectal involvement undergoing surgery.

P-352 Evaluation of CD25 and CD69 activation markers expression on peripheral blood cells subpopulations in endometriosis patients

Abstract Study question We aim to determine the percentages of CD25-positive and CD69-positive lymphocytes in peripheral blood of endometriosis (EMS) patients. Summary answer Higher percentages of lymphocytes expressing CD69 and CD25 markers in EMS and their correlation with the severity of the disease, indicate persistent activation of lymphocytes What is known already Exposure to antigens causes activation markers to appear on the surface of lymphocytes. Among them, we can distinguish early and late activation markers. The earliest one is CD69, which is expressed upon activation by the TCR receptor. CD69 plays a role in the proliferation and survival of activated T lymphocytes. CD25 is a moderate late activation marker, considered the most important marker of cellular response activation. The significance of CD69 and CD25 expression by T cells in endometriosis has not yet been determined. Increased CD69 expression on various lymphocyte subsets in peritoneal fluid in EMS has been reported. Study design, size, duration Within this prospective study between January 2016 and August 2018 immune diagnostics of the number of CD25-positive and CD69-positive lymphocytes in peripheral blood of EMS patients (firstly diagnosed during laparoscopy and confirmed histopatologically) and non-EMS controls were performed using flow cytometry analysis. Total number of 74 subjects were included in the study. All patients signed written informed consent before their enrollment in the study. Participants/materials, setting, methods We enrolled 54 subjects with previously untreated endometriosis and 20 healthy age-matched controls. Peripheral blood was collected from control patients to assess the immunophenotype of lymphocytes and measure expression of activation markers Cd25 and CD69 on several subtypes B and T lymphocytes. Diagnosis and assessment of the stage of the EMS was established during laparoscopy using rASRM score. Differences were considered statistically significant with a p < 0.05. Main results and the role of chance Significantly higher expression of the CD25 and CD69 antigen was found in both CD3+ T, CD4+ T and CD8+ T cells as well as CD19+ B cells. In each of the studied groups, a significance level of p < 0.001 was obtained. There was a weak positive correlation between the percentage of CD4+CD25+ T cells and the stage of endometriosis (R = 0.357; p = 0.008) and negative correlations between the percentage of endometriosis and the percentage of CD3+CD69+ T cells (R = −0.554; p < 0.001), T CD4+CD69 + (R = −0.554, p < 0.001) and T CD8+CD69 + (R = −0.553, p < 0.001). The expression of activation markers, CD25 and CD69 antigens in patients suffering from endometriosis with accompanying clinical symptoms was also evaluated. n the group of patients with endometriosis accompanied by infertility or pelvic pain, no statistical differences in the expression of CD25 and CD69 antigens were observed. The only clinical condition coexisting with statistically different expression of activation markers is adhesion disease accompanying endometriosis - a statistically significantly lower percentages of T CD3+CD69 + (p = 0.002), T CD4+CD69 + (p = 0.002) and T CD8+CD69 + (p = 0.002). Limitations, reasons for caution Small sample size is an important limitation of this study. In addition, evaluating immunological analysis only in serum samples does not let us drive any conclusions on the local changes of endometriosis lesions. Wider implications of the findings Clinical interpretation of changed expression of CD69 and CD25 in EMS could be useful in evaluating mechanisms of cellular activation, peripheral tolerance and immune imbalance involved in pathogenesis of endometriosis. Further studies to understand mechanisms underlying correlation between stage of the disease and expression of CD69 should be considered. Trial registration number not applicable

P-339 Activities and changes in the number of natural killer cells in endometriosis: systematic review and meta-analysis

Abstract Study question What are the differences in peripheral, uterine, and peritoneal NK (uNK, pNK, pfNK) cell counts/percentages, and activities in women with endometriosis compared controls Summary answer The mean percentage level of uNK, pNK, and peritoneal NK (pfNK) cells has no significant difference in women with endometriosis compared controls What is known already NK cells play an important role in the pathogenesis of endometriosis Study design, size, duration This systematic review and meta-analysis included 36 experimental studies (case control and cross sectional). Narrative review is also conducted on the NK cell activity, cytokine expression, regulations and receptors. Participants/materials, setting, methods Women suffering with endometriosis confirmed with laparoscopy and/or pathology was the cases whereas, women having different pelvic pathology such as myoma, ovarian cyst, healthy woman and verified not having endometriosis with laparoscopy and/or pathology was considered as controls for this study. Databases (PubMed, Web of Science, Scopus, Google scholar, and EMBASE through OVID) were used to search for the available studies. RevMan 5.4 and STATA 14 were used to analyze the data. Main results and the role of chance The mean percentage level of uNK, pNK, and peritoneal NK (pfNK) cells has no significant difference (standard mean difference SMD 0.13, 95%CI -0.35, 0.62; P = 0.59, I2 74%; total 393 women, 6 studies), (SMD 0.27, 95%CI -0.07, 0.61; P = 0.12, I2 80%; total 825 women, 11 studies), and (SMD 0.31, 95%CI -0.68, 01.29; P = 0.59, I2 94%; total 404 women,7 studies) in endometriosis patients compared with controls respectively. The pooled NK (uNK, pNK, pfNK) cell cytotoxicity/activity level is significantly higher in controls compared with women with endometriosis (MD 5.43, 95%CI 2.29, 8.57; P < 0.007, I2 50%; total 323 women, 7 studies). The NK cytotoxicity/activity level in early stages of endometriosis has no significant difference compared with advanced stages of endometriosis (MD 2.29, 95%CI –1.98-6.57; P = 0.29, I2 87%; total 263 women, 7 studies). There are variations in studies conducted in NK cell activities in endometriosis: broadly categorized as NK cell cytotoxicity, cytokine expression and NK cell regulation and receptors (Inhibition and activation). The cytotoxic activity of NK cells decreased in women with endometriosis and correlated with the severity of the disease, however the cytokine expression and inhibitor receptors are equivocal across studies. Limitations, reasons for caution We unable to conduct sub-group analysis to investigate the cytotoxic activity of NK cell in women with endometriosis and its stages in different samples such as pNK, uNK, and pfNK due to the lack of studies for the analysis. Wider implications of the findings This study revealed that the activity of NK cells in women with endometriosis is significantly lower than controls.Though the mean difference of NK cell count and percentage has no significant difference, the cytotoxicity activity of NK cell is higher in controls compared with women with endometriosis Trial registration number CRD42022384060

P-351 The impact of ovarian endometriosis on oocyte competence in IVF/ICSI cycles: A systematic review and meta-analysis

Abstract Study question Is oocyte competence affected in patients with ovarian endometriosis in IVF/ICSI cycles? Summary answer In IVF cycles ovarian endometrioma negatively impacts oocyte quality in terms of oocytes and mature (MII) oocytes retrieved but not the fertilization and blastulation rates. What is known already Is still controversial whether the presence of a non-surgically treated ovarian endometrioma alone may adversely affect the oocyte quality in IVF/ICSI treatments. As oocyte quality is well reflected by the ability to complete maturation and undergo successful fertilization, the best clinical markers of oocyte competence are represented by number of MII oocytes retrieved and fertilization rates. Even though women with endometriomas had fewer oocytes and MII oocytes retrieved than women without, no further differences in reproductive outcomes have been found. The most recent meta-analysis, however, has serious limitations, such as clinical heterogeneity of the studies and a small sample size. Study design, size, duration A systematic review and meta-analysis of studies evaluating clinical markers of oocyte competence in women with ovarian endometriosis were conducted. Electronic searches were performed in PubMed, Cochrane database, and ClinicalTrials.gov up to December 2022. Randomized controlled trials and observational studies were eligible for inclusion. The risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Participants/materials, setting, methods Studies reporting ART outcomes among women with endometrioma were included. The main outcomes were clinical markers of oocyte competence including the number of oocytes retrieved, MII oocytes retrieved, ovarian sensitivity index (OSI), fertilization and blastulation rates. Mean differences (MD) and odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random and fixed effects model. Main results and the role of chance Of 876 unique records identified, 30 studies met inclusion criteria, and 21 studies, totaling 5962 participants, were included in the meta-analysis. The results showed that significantly fewer oocytes retrieved (mean difference (MD) = -1.67; 95% confidence interval (CI), -2.46, -0.88; p = <0.0001; I2=92%; low quality) and MII oocytes (MD = -2.45; 95% CI, -3.23, -1.67; p = <0.0001; I2=86%; moderate quality) were observed in women with endometriomas compared with the control. However, the OSI (MD = -1.47; 95% CI, -3.74, 0.81; p = 0.21; I2=97%; very low quality), fertilization rate (Odds ratio (OR) = 1.04; 95% CI, 0.78, 1.39; p = 0.79; I2=93%; low quality) and blastulation rate (OR = 0.90; 95% CI, 0.66, 1.22; p = 0.51; I2=95%; low quality) were not significantly different between the groups. Limitations, reasons for caution Despite removing patients with previous surgeries and diverse stages of endometriosis, main outcomes showed significant heterogeneity. The unilaterality/bilaterality, size, and the general extent of endometriomas could cause this heterogeneity. The quality of evidence generated from our findings is low, mainly due to the factors mentioned above. Wider implications of the findings Our findings suggest that endometriomas do not hinder fertility chances, as fertilization and blastulation rates were not compromised. Due to the risk of ovarian damage, these results argue against endometrioma excision. Further clinical trials with adequately-powered sample sizes should focus on blastulation and euploidy rates to validate our findings. Trial registration number Not applicable

O-292 Does ovulation trigger enhance live birth in a natural cycle for frozen embryo transfer: A randomized controlled trial

Abstract Study question Does ovulation trigger enhance pregnancy rate in a natural cycle (NC) for frozen embryo transfer (FET)? Summary answer Pregnancy rates after a FET are similar in a natural cycle with detection of a spontaneous LH surge or with a triggered ovulation. What is known already Several studies have explored whether one approach might appear to be more beneficial in terms of pregnancy or live birth rates, but with inconsistent results. Thus, the best protocol to identify the time of ovulation in NC and to plan the FET is still undefined. Study design, size, duration This was a bicentric, two-arm, randomized, controlled and open-label trial, including 108 patients for 18 months. In the spontaneous-NC group, the LH surge was defined as a rise of the serum LH level at least three times above the basal LH serum value with a serum progesterone level three days after the LH surge above 3 ng/mL. Participants/materials, setting, methods Patients included were aged 18- to 39-year-old, had regular cycles and were planned for an autologous frozen day-5 blastocyst transfer in a NC. They did not have endometriosis stage AFSr 3 nor 4 nor adenomyosis. Fifty-four patients per group were included. In the modified-NC group, a spontaneous LH surge was observed in 16 women before the hCG-trigger could be administrated: they were re-allocated to the spontaneous-NC for the per-protocol (PP) analysis. Main results and the role of chance Patients characteristics were comparable in both groups. Pregnancy rates were similar in the spontaneous-NC and the modified-NC group in the intention-to-treat (ITT) (41.3 versus 37.8% respectively, p = 0.85) and in the PP analysis (39.3% versus 40% respectively, p = 0.9). Ongoing pregnancy, miscarriage and live birth rates were also similar. Significantly more visits were needed in the spontaneous-NC (3.4 ± 0.81 versus 2.59 ± 1.0, p < 0.0001 in the ITT analysis and 3.18 ± 0.93 versus 2.63 ± 1.03, p = 0.0064 in the PP analysis). Limitations, reasons for caution Due to group redistribution (spontaneous LH surge before hCG trigger), the number of subjects in the modified-NC group is low for the PP analysis. This may reduce the power of the trial which may fail to detect a small difference. Wider implications of the findings The results reinforce previous data that showed similar efficacy of the s-NC and the m-NC. This allows the patient to choose from several options depending on her preference. Trial registration number NCT03428165

P-640 No impact of Progestin Primed Ovarian Stimulation (PPOS) on euploid blastocyst rate per cohort of metaphase-II oocytes during PGT-A cycles: a case-control study

Abstract Study question Can progestins be used to prevent spontaneous LH surge during ovarian stimulation (OS) without affecting the euploid blastocyst rate (EBR) per metaphase-II (MII) oocytes? Summary answer Progestin Primed Ovarian Stimulation (PPOS) (conducted with norethisterone acetate) and conventional-OS with GnRH-antagonist show similar EBR per MII-oocytes What is known already PPOS is a novel OS protocol based exogenous progesterone to inhibit LH surge and spontaneous ovulation as an alternative to GnRH analogues. The rationale of its use is that multiple follicular waves arise during the ovarian cycle and no spontaneous ovulation occurs during the luteal phase. PPOS effectiveness and safety have been supported lately in the literature. A recent study reported similar number of euploid blastocysts after PPOS (conducted with medroxyprogesterone acetate) versus conventional-OS with GnRH-antagonist. Study design, size, duration Case-control study involving advanced-maternal-age women undergoing ICSI with PGT-A at two private IVF centers (May-2017 to February-2020). 80 PPOS women were matched with 160 control based on maternal-age and ovarian reserve markers. Patients with poor-ovarian-reserve (AFC<3), premature-ovarian-failure, III-IV stage endometriosis, ovarian cyst, severe-male-factor, PGT-SR or PGT-M were excluded. EBR per MII-oocytes was the primary outcome. All other embryological and clinical outcomes were reported. Participants/materials, setting, methods Both groups underwent recombinant-FSH OS with GnRH-agonist ovulation trigger; the only difference was that norethisterone acetate 10mg/day was administered orally to PPOS patients starting from the second day of the menstrual cycle until trigger. The control group, instead, underwent conventional antagonist protocol. The laboratory procedures were similar in both groups: ICSI, blastocyst culture, trophectoderm biopsy, comprehensive-chromosome-testing to report non-mosaic aneuploidies and vitrified-warmed euploid single-embryo-transfers (SETs). Main results and the role of chance The mean fertilization rate per MII-oocytes and blastulation rate per 2PN-zygotes were similar among PPOS and control (75.5%±21.8% versus 71.7±20.7%, p = 0.1; and 56.5%±27.7% versus 53.2%±27.5%, p = 0.4, respectively). No difference was reported for the EBR per MII-oocytes among PPOS and control (15.4%±19.8% versus 14.8%±18.2%, p = 0.9). No difference was reported among the biopsied blastocysts in terms of morphological quality and day of development. A total of 47 and 86 SETs were conducted in the two groups. There was no difference in the live-birth-rates (LBR) per SET in the two groups (N = 19/47, 40.4%, 95%CI 26.7-55.7 versus N = 35/86, 40.7%, 95%CI 30.4-51.8, p = 0.9), nor in the miscarriage rate per clinical pregnancy (N = 1/20, 5%, 95%CI 0.3-26.9 versus N = 3/36, 8.3%, 95%CI 2.2-25.6, p = 0.9). At last, the cumulative-LBR among concluded cycles (i.e., LB achieved or no transferable/all transferred euploid blastocysts) was also similar (N = 19/68, 27.9%, 95%CI 18.1-40.3 versus N = 31/132, 22.0%, 95%CI 15.4-30.2, p = 0.4). Limitations, reasons for caution The main limitation is the retrospective and non-randomized design. More data are required, especially for follicle recruitment, oocyte yield, gestational and perinatal outcomes. Wider implications of the findings Norethisterone acetate-based PPOS protocol has no impact on oocyte competence when compared to conventional GnRH-antagonist OS. These promising data support further investigation on PPOS, especially in view of its reduced cost, and putative increase in patient compliance and decrease in discomfort. Trial registration number none

Immunological factor development of external genital endometriosis

External genital endometriosis (EGE) is one of the common gynecological diseases of women of reproductive age with a relapsing, progressive course that worsens the quality of life of patients due to pain, emotional imbalance, fear of relapse and possible surgical intervention. Currently, endometriosis is recognized as one of the most common diseases associated with infertility. Thus, among fertile women with preserved childbearing function, the disease is generally diagnosed in approximately 6-7%, while among patients suffering from infertility, its frequency can reach 20-48%.However, the causes that determine reproductive dysfunction in patients with EGE are not well understood. Much attention is currently paid to the role of immunity in the formation of endometriosis. Patients with EGE show changes in both local immunity factors and immunological components of circulating blood.Purpose of the study: the study of factors of innate and adaptive immunity in patients of reproductive age with external genital endometriosis (EGE).The study included 71 patients with various stages of external genital endometriosis, the control group included 24 patients without endometriosis. Determination of the population composition of peripheral blood lymphocytes, the level of monocytes expressing TLR, activation markers, was carried out by laser flow cytometry — Immunotex (France), Caltag (USA), FITC (fluorescein isothiocynate) — labeled CD3, CD4, CD8, CD16, CD19, HLA-DR, CD282, CD284 and PE (phycoerythrin) - labeled with CD25, CD69, CD95, CD107a, CD14.External genital endometriosis is characterized by: at stages I-II of the disease - a violation of the early stages of the innate immune response (an increase in the number of monocytes expressing TLR-4, a violation of the activation and differentiation processes of immunocompetent cells, which is reflected in a decrease in the expression of CD16, CD8, CD16+HLA-DR+, CD16+CD107a+, CD8+CD107a+, at III-IV stages of the disease, there is a decrease in the level of CD16 and activation markers CD69, HLA-DR, CD107a on their surface, which is combined with a decrease in the expression of CD8, CD16, HLADR and CD107a on their surface. CD95+ and CD8+CD95+ were found at various stages of EGE.The results obtained allow us to understand the features of the functioning of innate and adaptive immunity at various stages of external genital endometriosis, and the studied immunological parameters can be used as diagnostic criteria for the formation of various stages of EGE. These data can serve as a theoretical basis for further identification of markers of EGE progression, as well as the mechanisms underlying immune inflammation.

QS ENDO Pilot - A Study by the Stiftung Endometrioseforschung (SEF) on the Quality of Care Provided to Patients with Endometriosis in Certified Endometriosis Centers in the DACH Region.

Introduction Endometriosis significantly reduces patients' quality of life and is additionally a burden on healthcare and social security systems. There are currently no quality indicators for the treatment of endometriosis. The care of patients with endometriosis must be considered inadequate. QS ENDO aims to record the quality of care available in the DACH region and to introduce quality indicators for the diagnosis and treatment of endometriosis as part of providing quality assurance in endometriosis care. The first phase, QS ENDO Real, recorded the reality of current care using a questionnaire. The second phase, QS ENDO Pilot, investigated the treatment of 435 patients who underwent surgical treatment within a defined one month period in certified endometriosis centers. Material and Methods An online tool was used to gather information about 9 points which covered both prior patient history and the process of clinical diagnosis. Surgery reports were reviewed to obtain information about the surgical approach, the investigated sites, findings of any histological examinations, the use of classification systems, and information about resection status. Results 85.3% of patients were asked all 4 questions about their prior medical history. All 5 diagnostic steps were carried out in 34.5% of patients. The 3 areas needed to describe potential sites of disease were recorded in 67.1% of patients. Samples for histological examination were taken in 84.1% of patients. The endometriosis stage was classified in 94.7% of surgeries. A combination of the rASRM and the ENZIAN classifications, which is needed for complex cases, was used in 46.1% of patients. Complete resection was achieved in 81.6% of surgical procedures. Conclusion For the first time, the quality of care in certified endometriosis centers has been recorded using QS ENDO Pilot. Despite the high certification standards, a substantial number of required indicators were omitted.

TGFBI as a candidate biomarker for non-invasive diagnosis of early-stage endometriosis.

Can cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) alone or in combination with cancer antigen 125 (CA-125) be considered as potential blood biomarkers of endometriosis? The results of this study indicate that COMP has no diagnostic value. TGFBI has potential as a non-invasive biomarker of the early stages of endometriosis, while TGFBI together with CA-125 has similar diagnostic characteristics as CA-125 alone for all stages of endometriosis. Endometriosis is a common, chronic gynecological disease that significantly affects patient quality of life by causing pain and infertility. The gold standard for diagnosis is visual inspection of pelvic organs by laparoscopy, therefore there is an urgent need for discovery of non-invasive biomarkers for endometriosis to reduce diagnostic delays and allow earlier treatment of patients. The potential biomarkers for endometriosis evaluated in this study (COMP and TGFBI) were previously identified by our proteomic analysis of peritoneal fluid samples. This is a case-control study divided into a discovery (n = 56 patients) and a validation phase (n = 237 patients). All patients were treated between 2008 and 2019 in a tertiary medical center. Patients were stratified based on the laparoscopic findings. The discovery phase included 32 endometriosis patients (cases) and 24 patients with confirmed absence of endometriosis (controls). The validation phase included 166 endometriosis and 71 control patients. Concentrations of COMP and TGFBI were measured by ELISA in plasma samples, whereas concentration of CA-125 was measured using a clinically validated assay for serum samples. Statistical and receiver operating characteristic (ROC) curve analyses were performed. The classification models were built using the linear support vector machine (SVM) method with the SVM built-in feature ranking method. The discovery phase revealed significantly increased concentration of TGFBI, but not COMP, in plasma samples of patients with endometriosis compared to controls. In this smaller cohort, univariate ROC analysis showed fair diagnostic potential of TGFBI, with an AUC value of 0.77, sensitivity of 58%, and specificity of 84%. The classification model built using linear SVM and combining TGFBI and CA-125 showed an AUC value of 0.91, sensitivity of 88% and specificity of 75% in distinguishing patients with endometriosis from controls. The validation phase results revealed similar diagnostic characteristics of the SVM model combining TGFBI and CA-125, with an AUC value of 0.83, sensitivity of 83% and specificity of 67% and CA-125 alone with AUC value of 0.83, sensitivity of 73% and specificity of 80%. TGFBI exhibited good diagnostic potential for early-stage endometriosis (revised American Society for Reproductive Medicine stage I-II), with an AUC value of 0.74, sensitivity of 61% and specificity of 83% compared to CA-125, which had an AUC value of 0.63, sensitivity of 60% and specificity of 67%. An SVM model combining TGFBI and CA-125 showed a high AUC value of 0.94 and sensitivity of 95% for diagnosing moderate-to-severe endometriosis. The diagnostic models were built and validated from a single endometriosis center, and thus further validation and technical verification in a multicenter study with a larger cohort is needed. Additional limitation was lack of histological confirmation of disease for some patients in the validation phase. This study revealed for the first time increased concentration of TGFBI in plasma samples of patients with endometriosis, particularly those with minimal-to-mild endometriosis, compared to controls. This is the first step in considering TGFBI as a potential non-invasive biomarker for the early stages of endometriosis. It also opens a path for new basic research to investigate the importance of TGFBI in the pathophysiology of endometriosis. Further studies are needed to confirm the diagnostic potential of a model based on TGFBI and CA-125 for the non-invasive diagnosis of endometriosis. The preparation of this manuscript was supported by grant J3-1755 from the Slovenian Research Agency to T.L.R and EU H2020-MSCA-RISE project TRENDO (grant 101008193). All authors declare that they have no conflicts of interest. NCT0459154.

Pregnancy after laparoscopic surgery for endometriosis: How long should we wait? A retrospective study involving a long-term follow up at a university endometriosis center.

To find the factors that influence the time until pregnancy after laparoscopic intervention and to evaluate the proper time to start assisted reproductive therapy (ART). This is a retrospective analysis that includes a prospective evaluation of patients with infertility and with a diagnosis of endometriosis. A subgroup of patients who desired to be pregnant after laparoscopic intervention (102 patients) was followed up for 36-197 months after the surgery. In this study, 71 (69.9%) and 60 (58.8%) of the patients achieved pregnancy and live birth, respectively. In the group of patients who became pregnant, the duration of infertility was significantly lower (2.7 ± 2.1 years vs. 4.7 ± 3.2 years). The median time until pregnancy after laparoscopic intervention was 8 months (the average was 10 months). After 38 months, no pregnancy occurred. In the group of patients with endometriosis and infertility, the first 12 months were the optimal time for pregnancy. For women with revised American Society for Reproductive Medicine classification of endometriosis (rASRM) stages I and II, spontaneous pregnancy can probably be delayed for up to 24 months, but in patients with rASRM stages III and IV, ART may be considered after 12 months. The gynecologist must be careful about the timing of further interventions after the operation.

Pelvic pain comorbidities associated with quality of life after endometriosis surgery

After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (β=3.19), pelvic floor myalgia (β=2.44), and Patient Health Questionnaire 9 depression score (β=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.

Performance de l’échographie UBESS (Ultrasound Based Endometriosis Staging System) dans la prédiction d’une atteinte rectale et du type de geste opératoire chez les patientes atteintes d’endométriose digestive

ObjectivePreoperative assessment of rectal damage in digestive endometriosis requires rectal endoscopic ultra-sonography an invasive exam that is not well received by the patients. A standardized approach using an Ultrasound-Based Endometriosis Staging System (UBESS)could be an interesting tool in this indication. This article aims to evaluate the performance of UBESS in the prediction of rectal involvement and the type of surgical procedure. Materials and MethodsThis monocentric retrospective study was conducted on patients with rectal endometriosis who underwent a curative surgical procedure, evaluated by UBESS ultrasound between January 2016 and December 2019 at the Poissy referral centre. The main analysis of the study was to assess the adequacy of the UBESS ultrasound stage, the presence of rectal involvement during surgery and the surgical technique required.The secondary objective was to determine the correlation between UBESS stages and RCOG levels of surgical difficulty. ResultsA total of one hundred and twenty-two patients were included and one hundred were analysed. Of these, thirty-nine had rectal involvement. There was a statistically significant association between the UBESS stage and the presence of a digestive lesion(P<0.0001). The ultrasound's parameters of thickness(P=0.0007), width(P=0.0082) and volume(P=0.0013) of the digestive lesion were significantly correlated with the extent of the surgical procedure. The correlation between the UBESS and RCOG classifications was very weak. ConclusionUBESS is a powerful diagnostic tool for digestive damage allowing to give clear information to patients before surgery and optimizing the management plan of the surgery.

The importance of the genital tract microflora in the endometriosis development

Endometriosis is a common pathology among women of reproductive age. In the pathogenesis of its development a great importance is paid to the process of regulation of estrogens and other sex hormones, the implementation of the immune response at the general and local levels, the inflammatory response, and genetic background. In recent years, the role of the microbiota in different parts of the genital tract of the female organism has been studied not only from the standard approach of inflammatory diseases research of the reproductive organs and pathological vaginal discharge, but its contribution into the development of other gynecological diseases, in particular endometriosis, is presented.The article is devoted to a review of scientific publications about researches devoted to the significance of the genital tract microflora in the pathophysiology of endometriosis. The article presents the concepts of states of eubiosis and dysbiosis, describes the features of the microflora of the lower (vagina, cervix) and upper parts (uterus, fallopian tubes) of the genital tract in healthy women. The data on the importance of Lactobacillus in maintaining an optimal state of acidity in the vaginal environment are presented. The difference in the composition of the microbiota of the vagina, cervical mucus, uterine cavity and peritoneal fluid in women with and without endometriosis is revealed. The pathogenetic mechanisms of the role of the microbiota in the processes of endometriosis pathogenesis, namely, the regulation of the immune response and inflammation processes in this pathology, are described. It has been shown that in women with endometriosis there are differences in the microflora composition of the vagina, cervix, uterine cavity, peritoneal fluid, manifested by a decreased concentration of Lactobacillus and the presence of a variety of other microorganisms in relation to healthy women. The data about the role of gut microflora in patients with this pathology are also presented. The results of research about the diagnosis of various stages of endometriosis by studying the composition of the genital tract microbiota are described.

Diagnosis and treatment of early-stage endometriosis by Transvaginal Hydro laparoscopy.

Transvaginal Hydro Laparoscopy (THL) is known as a minimal invasive procedure allowing endoscopic exploration of the female pelvis. To evaluate the possibilities of the THL as a tool for early diagnosis and treatment of minimal endometriosis. A retrospective study of a consecutive series of 2288 patients referred for fertility problems to a tertiary centre for reproductive medicine was undertaken. Mean duration of infertility was 23.6 months (SD ±11-48), mean age of patients was 31.25 (SD± 3.8y). With normal findings at clinical and ultrasound examination patients underwent, as part of their fertility exploration, a THL. Evaluation of feasibility, identified pathology and pregnancy rate. Endometriosis was diagnosed in 365 patients (16%); the localisation was higher on the left side (n=237) than on the right side (n=169). Small endometriomas, with diameters between 0.5 and 2 cm, were present in 24.3% (right side in 31, left side 48 and bilateral 10). These early lesions were characterised by the presence of active endometrial like cells and a pronounced neo-angiogenesis. Destruction of the endometriotic lesions with bipolar energy resulted in an in vivo pregnancy rate (spontaneous/IUI) of 43.8% (CPR after 8 months: spontaneous 57.7%; IUI/AID 29.7%). THL allowed in a minimally invasive way an accurate diagnosis of the early stages of peritoneal and ovarian endometriosis with the possibility of offering treatment with minimal damage. This is the largest series reporting the usefulness of THL for the diagnosis and treatment of peritoneal and ovarian endometriosis in patients without obviously visible preoperative pelvic pathology.

Oxidative Stress as a Potential Underlying Cause of Minimal and Mild Endometriosis-Related Infertility

Oxidative stress (OS) plays an important role in a variety of physiological and pathological processes of the female reproductive system. In recent years the relationship between OS and endometriosis has been of particular interest, and a theory has been suggested that OS may be a cause of endometriosis development. While the link between endometriosis and infertility is well established, minimal or mild stages of endometriosis are not considered to cause infertility. Increasing evidence of OS as a leading agent in the development of endometriosis has brought up a theory of minimal/mild endometriosis itself being one of the manifestations of high OS rather than a separate disease which directly causes infertility. Moreover, further development of the disease is thought to contribute to an increased production of reactive oxygen species (ROS) thus leading to the progression of endometriosis itself as well as to other pathological processes in the female reproductive system. Therefore, in case of minimal or mild endometriosis, the less invasive treatment could be offered in order to stop the ongoing cycle of endometriosis-reinforced excess ROS production and to reduce their harmful effects. In this article the existing connection between OS, endometriosis, and infertility is explored.

Prediction Models of Endometriosis Stage Generated From Potential Hematological Biomarkers

Objective: The aim of the study assess efficacy of hematological biomarkers for predicting the stage of endometriosis.&#x0D; Materials and methods: Patients underwent surgery and diagnosed with endometriosis confirmed by pathology report between January 2015-December 2020 were included. Individuals were divided into two groups as stage 1-2-3 and stage 4 patients.&#x0D; Results: 91 patients with stage 1-2-3 and 105 with stage 4 endometriosis were identified. There was no significant relationship between endometriosis score and complete blood count parameters. However, endometriosis score revealed a significant correlation with serum CA125 level and the combined markers including CA125. The logarithm of the CA 125 was used to predict the endometriosis score. In order to quantify the relationship, a univariate linear model was performed to predict the endometriosis score with log (CA 125). It demonstrated for every increase in the level of log (CA 125), endometriosis score increased by 8.57 (β=8.57. R2=0.115. p&lt;0.001). The p values of alternative parameters analyzed to predict the stage of endometriosis. p-values were 0.263 for neutrophile/lymphocyte; 0.457 for platelet/lymphocyte; 0.790 for red cell distribution width/lymphocyte and 0.842 for mean platelet volume/lymphocyte ratios.&#x0D; Conclusion: CA 125 alone was found substaintally efficient in predicting endometriosis stage preoperatively.

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

To identify characteristics indicating preoperatively the presence of diaphragmatic endometriosis (DE). Comparison of characteristics of patients with DE with characteristics of patients with abdominal endometriosis without diaphragmatic involvement, in a prospective cohort study. Tertiary referral center; endometriosis center. 1372 patients with histologically proven endometriosis. Surgery performed laparoscopically under general anesthesia. All patients with suspected endometriosis underwent a complete bilateral inspection of the diaphragm. Demographic and clinical pathologic characteristics were evaluated using basic descriptive statistics (comparison of the groups using the chi-square 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 (65/1372). There was no significant difference between the two 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 pre-operatively (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 (rAFS 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). 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.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Predictive Value of Serum YKL-40, Interleukin-37, and Cancer Antigen 125 Panel in Noninvasive Staging of Endometriosis

Abstract Background: The diagnosis of advanced endometriosis remains challenging with considerable limitations in the diagnosis of retroperitoneal and deep infiltrating lesions. Thus, a well-defined panel of inexpensive, noninvasive inflammatory biomarkers could be a crucial tool for appropriate staging for women with suspected endometriosis. The aim of this work is to explore the potential use of serum YKL-40, interleukin-37 (IL-37), and cancer antigen 125 (CA125) for noninvasive staging of endometriosis patients for proper intervention and most optimal management of the condition. Methods: This study was conducted on 90 women, who had undergone laparoscopic or laparotomy surgery due to suspected pelvic endometriosis. Blood samples for serum YKL-40, IL-37, and CA125 levels assay were taken from all participants at admission for laparoscopy or laparotomy. After histopathological confirmation of the diagnosis, the selected cases were immunostained for YKL-40, IL-37, and CA125. Results: YKL-40, IL-37, and CA125 serum levels were significantly elevated in patients with endometriosis than healthy controls. Moreover, the association between the serum level and immunoexpression and grading of endometriosis. A triple combination panel of serum YKL-40, IL-37, and CA125 was found to have the best sensitivity and specificity (96.67% and 100.0%, respectively) compared to any single serum marker alone or double combination panel in predicting the severity of endometriosis. Conclusions: A triple combination panel of serum YKL-40, IL-37, and CA125 could be used in the future for predicting endometriosis stage, providing a practical reference for making better-informed decisions on the best treatment plan.

Comparison of Dydrogesterone and GnRH-a Effects After Laparoscopic Surgery in Patients with Stage III and IV Endometriosis.

To compare the spontaneous pregnancy rates between dydrogesterone and Gonadotropin-releasing hormone agonist (GnRH-a) treatments in patients with endometriosis stage III and IV after laparoscopy. The clinical data of patients with endometriosis stage III and IV administered laparoscopic surgery in our hospital from January 2018 to March 2020 were retrospectively analyzed. Totally 151 cases were divided into two groups according to postoperative medication, including the study (70 cases) and control (81 cases) groups treated with dydrogesterone and GnRH-a, respectively. The spontaneous pregnancy and subsequent pregnancy outcomes were assessed within 12 months. Totally 49 patients had spontaneous pregnancy. Among them, there were 31 cases in the dydrogesterone group (spontaneous pregnancy rate of 44.3%, 31/70), including 25 live birth cases (35.7%, 25/70), 4 miscarriage cases, and 2 ectopic pregnancy cases. The time to conception was 1-10 months (median value of 5 months). Totally 18 cases in the GnRH-a group had spontaneous pregnancy (22.2%, 18/81), including 16 live birth cases (19.8%, 16/81). 81) and 2 miscarriage cases; the time to conception was 3-11 months (median value of 6 months). There were significant differences in spontaneous pregnancy rate and cumulative spontaneous pregnancy rate between the two groups (P = 0.005 and 0.003, respectively). Dydrogesterone after laparoscopic surgery in patients with endometriosis stage III and IV improved the natural pregnancy rate.