Correlation of Bladder Wall Endometriosis Histological Location, To Infertility Patients’ Clinical Characteristics and Severity of Peritoneal Endometriosis

Study question: What is the correlation of bladder wall endometriosis histological location, to the severity of peritoneal endometriosis in infertility patients? Summary answer: Secondary infertility, back pain, micturition problems, history of ectopic pregnancy and number of abortions can probably be considered as high-risk factors for bladder wall endometriosis for infertility patients. What is known already: Bladder and/or ureter endometriosis occur in 70–85% among patients with deep infiltrating endometriosis. The knowledge regarding the bladder wall involvement with endometriosis in association to peritoneal endometriosis and infertility patients’ clinical characteristics is limited. Study design, size, duration: Retrospective, longitudinal cohort, Sixty-six, primary and secondary infertility patients, collection of surgical and clinical data between 2010 to 2018. Participants/materials, setting, and methods: An experienced histopathologist on endometriosis was asked to review all the patients’ histopathological results. The histopathological reported findings were reviewed prior to the study to reassure the bladder wall depth of endometriosis involvement. The operation and tissue macroscopic description reports before processing were also reviewed. Attention was paid for possible discrepancies or missed important data that could influence the histopathological results. In cases where results were equivocal, the paraffin blocks were available for additional sections for reassuring the diagnosis. An extra effort was made to meticulously observe and identify the involvement of the bladder serosa, muscularis and mucosa with endometriotic cells and glands. Main results and the role of chance: Primary infertility was the indication for the current laparoscopic surgeries in 32 out of 66 (48.5%) patients and secondary infertility for the rest of the group. The highest incidence of bladder endometriosis (BE) was detected on the serosa of 12 patients and in the detrusor muscle (DM) of 11 cases. Bladder serosa endometriosis (BSE) was significantly more prominent among patients with history of ectopic pregnancy (p=0.004) and among patients with secondary infertility (p=0.029). Destrusor muscle endometriosis (DME) was significantly more frequent (p=0.012) in patients with increasing number of abortions. DME highest rates of 37.7% were observed among the severe spread of abdominal endometriosis as compared to 19% of the cases with bladder serosa endometriosis. No statistically significant difference found between serosa and detrusor muscle endometriosis involvement, when compared to severity and spread of endometriosis within the abdominal cavity. Back pain was most prominent with statistical significant difference (p=0.007) in 8 patients with BSE + DME as compared with other groups of patients (4 BSE, 3 DME and 3 BME+DME patients). Among 30 cases with an ovarian endometrioma detected by TVU, DME was diagnosed in 13 patients, in serosa of 10, and in serosa and DM of 6 patients. Statistical analysis was performed using Pearson chi-square, Fisher’s exact tests and the Kruskal-Wallis test by STATA version 15 SE (StataCorp. 2017). Limitations, reasons for caution: This is a cohort retrospective study. There is a possibility that other areas with endometriosis were also involved in the BW other than those diagnosed and treated. The mixture of patients with primary and secondary infertility could also affect the results, although statistical analysis did not show any significance in BWE, clinical symptoms and surgical findings. BE is rarely an isolated condition, and other forms of endometriosis are frequently concomitant Wider implications of the findings: Detrusor muscle endometriosis involvement was in 68% and bladder serosa in 32% of all cases with bladder endometriosis and infertility investigated. The severity of the peritoneal endometriosis can probably direct to meticulous intraoperative investigation for bladder endometriosis.

Peritoneal endometriosis and infertility

Peritoneal endometriosis and infertility in most of patients (in 80%) are pathogenetically conjugated. Both peritoneal endometriosis and infertility are based in ovarian failure. These women have a low endometrial receptivity for blastocysts implantation (retardation development of glands, vessels, and stroma; changes in the microrelief of the epithelium). Even at the beginning of the menstruation patients with peritoneal endometriosis and infertility have cells with a great adhesive and proliferative potential in the endometrium. This kind of cells have an ability for long autonomous existence. Ovarian failure in these women is a promotion factor for development of the retrograde menstruation. In these conditions the endometrial cells with adhesive potential are frequently bringing in the abdominal cavity. Active endometrium heterotopias support the ovarian failure and create conditions for uterine infertility (implantation disorders).

Near-Infrared Fluorescence Imaging for the Intraoperative Detection of Endometriosis: A Pilot Study

Introduction: Endometriosis surgery is associated with a high risk of reoperation due to an insufficient recognition of endometriotic lesions. Our aim was to explore the role of near-infrared fluorescence (NIRF) imaging for the visualization and identification of endometriotic lesions next to conventional white light (WL) laparoscopy. Materials and methods: Fifteen women scheduled for diagnostic laparoscopy in whom peritoneal endometriosis was suspected were included. Peritoneal exploration was performed in WL, followed by NIRF imaging after ICG administration. Biopsies of all the suspected lesions were taken for histological examination. Subjective evaluations of the equipment and NIRF imaging were also performed. Results: Only 61% (44) of the biopsied lesions contained endometriosis. The positive predictive value (PPV) for the lesions found in WL was 64%. The PPV for the lesions found under NIRF was 69% and the PPV for the lesions found in both modes was 61%. The mean satisfaction of surgeons regarding the surgical procedure and equipment using both imaging modalities was 6.5 (p > 0.05) on a 10 item Likert scale and the mean satisfaction with the quality of the NIRF imaging was 7.4 (p > 0.05). Conclusion: In this study, the additional value of NIRF imaging, although feasible, was found to be limited for the intraoperative detection of endometriotic lesions.

Ovarian Estrogen Synthesis Reduced by Peritoneal Endometriosis in Rat Autologous Transplantation Model

OBJECTIVE: To investigate the effects of peritoneal endometriosis on rat ovaries. METHODS: A rat model of peritoneal endometriosis was established by autologous transplantation. qPCR was performed to measure mRNA levels of steroid hormone and steroid synthesis-related genes in the ovaries of endometriosis rats. Immunohistochemistry was performed to characterize the distribution of FSHR in the ovaries of endometriosis rats. RNAseq was performed to find pathological changes in the ovaries of endometriosis rats. RESULTS: By qPCR, it was revealed that mRNA levels of steroid hormone synthesis-related genes were decreased in the ovaries of rats with endometriosis; With IHC, observed that FSHR expression was significantly decreased in the antral follicles of rats with endometriosis. RNAseq revealed that endometriosis affected transcription of the genes related to the microtubule structure and tight junctions of rat ovarian cells. CONCLUSION: Peritoneal endometriosis decreased the genic expression of ovarian steroid hormone synthetases and FSHR protein level in granulosa cells of antral follicles, and reduced the mRNA levels of the microtubule structure and tight junctions in rat ovarian cells, which contribute to the impairment of ovarian function.

The concomitant estrogen-dependent diseases and the ovarian reserve condition for patients with severe peritoneal endometriosis, included in the vitro fertilization programmes

Aim. Is specification of the nature and frequency of concomitant forms of genital endometriosis and other estrogen-dependent diseases (EDD) for the infertile women with severe peritoneal endometriosis (PE), as well as the assessment of the ovarian reserve condition for the patients of different ages. Materials and methods. The total 142 infertile women with severe peritoneal endometriosis (IIIIV stage of the external genital endometriosis according to the American Fertility Society classification) were examined at the age of 32.33.2 years (minmax = 2340 years). The clinical status assessment was conducted, using a standard set of diagnostic procedures, prescribed for the inclusion of patients in the IVF program. The ovarian reserve was estimated by the level of the anti-Mullerian Hormone level determined by the immunoenzyme method. Results. The concomitant 2-sided endometriotic ovarian cysts (96%), myoma (19.7%) and the adenomyosis (16.9%) were most common for the patients with severe peritoneal endometriosis. The severely reduced the anti-Mullerian Hormone rates (0.4 ng/ml) were much higher among patients 35 years old (24.6% compared to 10.6% for younger patients; p=0.028). Conclusion. The infertility for severe peritoneal endometriosis is supported by concomitant estrogen-dependent diseases, of which 2-sided endometriomas, adenomyosis and uterine myoma are of the most pathological. The low efficiency of IVF in the treatment of patients with severe peritoneal endometriosis and concomitant estrogen-dependent diseases is explained by the aggravation of the embryonic and endometrial factors for the infertility. The other reason that worsens the results of IVF for such patients is late reproductive age (35 years) that increases the observed reduction of the ovarian reserve.

Comparison of pain intensity, smooth muscle cells density, and alpha-smooth muscle actin expression in ovarial and peritoneal endometriosis

HIGHLIGHT1. Pain intensity, smooth muscle cells density, and alpha-SMA expression can be used to analyze the role of smooth muscle in endometriosis.2. Compared to healthy individuals, those with endometriosis have higher pain intensity, smooth muscle cells density, and alpha-SMA expression. 3. Among endometriotic patients, those with peritoneal endometriosis have higher pain intensity, smooth muscle cells density, and alpha-SMA expression than those with ovarial endometriosis.3. The expression of alpha-SMA, smooth muscle density, and pain intensity were found to correlate significantly in endometriosis. ABSTRACTObjectives: to identify the role of smooth muscle through the analysis of smooth muscle cells density, expression of a-SMA, and the pain intensity.Materials and Methods: Study design is a cross sectional analytic observational. Study sample consists of women with ovarial endometrios and women with peritoneal endometriosis that undergo laparoscopy and laparotomy in RSUD Saiful Anwar Malang and RSIA Melati Malang from January until December 2019. There are 16 samples: 8 samples of ovarial endometriosis and 8 samples of peritoneal endometriosis. Smooth muscle cell density was analyzed by comparing the number of smooth muscle cells with the total area of endometriosis tissue in one microscopical field. a-SMA expression obtained by immunohistochemistry. Degree of pain obatined by filling the part 1 point 1-11 of EHP-30 queistionnaire the day after the procedure. Data was analyzed by Independent T-test and Pearson correlation.Results: Pain intensity, smooth muscle cells density, and a-SMA expression is higher in the endometriosis patient compared to healthy individual. Pain intensity, smooth muscle cells density, and a-SMA expression is lower in the ovarial endometriosis compared to peritoneal endometriosis.Conclusion: There are a significant correlation between the expression of a-SMA, smooth muscle density, and pain intensity in endometriosis.

ARGONOPLASMIC COAGULATION IN THE TREATMENT OF EXTERNAL GENITAL ENDOMETRIOSIS IN WOMEN

Aim: to evaluate the effectiveness of the argonoplasmic coagulation method in the treatment of external genital endometriosis (GE) in women. Materials and methods. An open, prospective, controlled, clinical and experimental study was conducted. 50 women with genital endometriosis aged 20 to 50 years and older were examined (the average age was 35±15 years). The following forms of GE were identified: peritoneal endometriosis - in 21 (42%) patients; extraperitoneal endometriosis - in 15 (30%); uterine body endometriosis - in 9 (18%); retrocervical endometriosis - in 5 (10%) patients. Clinical, laboratory (blood test, urinalysis, biochemical studies, hemostasiogram, bacteriological and microscopic studies of the cervical canal and vagina, cytological studies); instrumental and special research methods were used. By the method of enzyme immunoassay (ELISA), studies were conducted for the presence of infections: toxoplasmosis, herpes and cytomegalovirus, chlamydia, mycoplasma, ureaplasma infections, rubella. Results. For the treatment of external genital endometriosis, a combined treatment regimen was applied: argonoplasmic coagulation of endometrioid heteropathies using the FOTEK EA 141M apparatus, followed by the prescription of a course of hormone therapy including dienogest (visanna), which contributed to improving the general condition and quality of life, relieving clinical symptoms, reducing the frequency of relapses, improving the hormonal status of the women. With a mild form of external genital endometriosis, argonoplasmic coagulation of endometrioid heteropathies was carried out in the "spray" mode at a power of 37-42 W, at a depth of 0.1-1 mm with a time interval of exposure of 2-4 seconds. In the moderate-severe form of external genital endometriosis, argonoplasmic coagulation of endometrioid foci located at a depth of 1-2 mm was carried out in the "spray" mode at a given power of 42-50W, with a time interval of exposure to an argon torch of 3-5 seconds. In severe external genital endometriosis, argonoplasmic coagulation was performed in the "filgur" mode at a given power of 57-64 watts with a time interval of exposure of 4-7 seconds, at a distance of no more than 2.5-3.0 mm. Conclusions. The use of APC using the FOTEK EA 141M device ensures the effectiveness of treatment that enables to avoid the formation of rough scars, adverse reactions and / or complications, shortening of the time interval, absence of pain syndrome, microbial contamination, risk of massive bleeding. The use of dienogest group is effective in preventing relapses after surgical treatment of severe forms of genital endometriosis.

Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis

Endometriosis is a common non-malignant gynecological disease that significantly compromises fertility and quality of life of the majority of patients. The gold standard for diagnosis is visual inspection of the pelvic organs by surgical laparoscopy and there are no biomarkers that would allow non-invasive diagnosis. The pathogenesis of endometriosis is not completely understood, thus analysis of peritoneal fluid might contribute in this respect. Our prospective case–control study included 58 patients undergoing laparoscopy due to infertility, 32 patients with peritoneal endometriosis (cases) and 26 patients with unexplained primary infertility (controls). Discovery proteomics using antibody microarrays that covered 1360 proteins identified 16 proteins with different levels in cases versus the control patients. The validation using an ELISA approach confirmed significant differences in the levels of cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) and nonsignificant differences in angiotensinogen (AGT). A classification model based on a linear support vector machine revealed AUC of > 0.83, sensitivity of 0.81 and specificity of 1.00. Differentially expressed proteins represent candidates for diagnostic and prognostic biomarkers or drug targets. Our findings have brought new knowledge that will be helpful in the understanding of the pathophysiology of endometriosis and warrant further studies in blood samples.

Clinical and diagnostic aspects of deep infiltrative endometriosis (diagnosis, treatment, recurrence)

Aim. To analyze the recurrence of endometriosis after surgical treatment of patients with deep endometriosis. Materials and methods. The case histories of 90 patients aged 19 to 45 years were retrospectively analyzed. The study group consisted of 70 endometriosis patients: 20 with peritoneal endometriosis and 50 with deep infiltrative endometriosis (DIЕ). The comparison group included 20 women without endometriosis. There was an in-depth study of anamnestic data in the cohort of patients under study. The results of preoperative laboratory tests, including serum levels of the CA-125 and CA 19-9 oncomarkers, were processed. Results. Analysis of the obtained data showed that about half of the DIE patients (54%) in the main group had a history of surgical interventions for endometriosis. The number of operations was significantly higher in patients compared to the peritoneal endometriosis group (68% vs 20%, respectively; р=0.0012). Two subgroups were formed from the group of women with DIE: patients who had no history of previous surgical treatment for endometriosis and those hospitalized for repeated surgical treatment of endometriosis (patients with recurrent endometriosis). Patients with recurrent endometriosis had a significantly higher incidence of heavy menstruation, pregnancy terminations (abortions), and a high proportion of gastrointestinal diseases. Analysis of the hormonal therapy received in patients with DIE showed that every second patient with relapses (18/53%) after surgical treatment and every third patient without a prior history of surgery (5/31%) received hormonal therapy. Examination of the preoperative serum levels of CA-125 and CA 19-9 serum markers in patients with DIE showed an increase in their serum levels and a correlation with the frequency of endometriosis recurrence and the size of DIE foci. Conclusion. Despite the conservative and surgical treatment of DIE patients, the recurrence rate is still high. At present, there is no satisfactory therapy for all endometriosis patients. Therefore, the development of therapy for the conservative treatment of the disease remains an urgent task.