Genes Chromosomes Cancer. 2010 Jul;49(7):630-4.HMGA1 and HMGA2 rearrangements in mass-forming endometriosis.Medeiros F, Araujo AR, Erickson-Johnson MR, Kashyap PC, Dal Cin P, Nucci M, Wang X, Bell DA, Oliveira AM.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.Endometriosis is a common gynecologic disorder characterized by ectopic endometrium associated ...
Mol Clin Oncol. 2017 May;6(5):758-764.
Comparison of lifestyle, hormonal and medical factors in women with sporadic and Lynch syndrome-associated endometrial cancer: A retrospective case-case study.
Data available on lifestyle-associated hormonal and medical factors among endometrial cancer (EC)-affected women who carry the Lynch Syndrome (LS) mutation is limited. The aim of the present retrospective case study was to compare the reproductive and medical history, as well as lifestyle-associated factors, among patients with LS and sporadic EC. The study population consisted of 50 verified germline mismatch repair (MMR) gene mutation carriers diagnosed with EC, and 110 sporadic EC patients. Data were collected using postal questionnaires. Apart from the mean age at the time of the EC diagnosis (LS, 48.7 years compared with sporadic patients, 55.2 years; P<0.0001), the characteristics of sporadic and LS EC patients were similar with regard to body mass index (BMI) at age 18, 40 or at the time of the survey, and smoking and alcohol consumption. LS women reported a significantly lower rate of spontaneous abortion (P=0.043) and also more frequent use of contraceptives (P=0.004). The prevalence of co-morbidities, including diabetes, atherosclerosis, hypercholesterolemia and hypertension, was similar between the LS and the sporadic groups. A trend for a higher prevalence of endometriosis among mutation carriers was detected (16.0 vs. 8.1%, P=0.137). As anticipated, the prevalence of gastrointestinal tract, urinary tract and ovarian cancer was higher among the LS women (P<0.0001, P=0.006 and P=0.056, respectively). Co-morbidity and lifestyle-associated factors appeared to be comparable among patients with LS and sporadic EC. The reported difference in the use of contraceptives warrants further investigation. Future studies are also required to address the possible association between LS and endometriosis.
Arch Esp Urol. 2017 May;70(4):480-486.
Laparoendoscopic single site (LESS) ureteral reimplantation.
To present in detail our surgical technique and to show our initial experience with ureteral reimplantation using the transumbilical LESS approach to treat patients with ureteral stenosis secondary to various diseases and surgical complications.
We performed 7 ureteral reimplantations from February 2012, using the multichannel Richard- Wolf (KeyPort) platform placed transumbilical by a small 2-2,5 cm transversal incision. We always use a 3.5 mm minilaparoscopy accessory trocar in the right iliac fossa, that is crucial to perform the laparoscopic suturing safely for the patient and in an optimal time. The etiology of ureteral lesions was: 1 endometriosis, 1 symptomatic ureterocele not responding to endoscopic treatment, 1 ureteral lesion after ureteroscopy for lithiasis, 1 ureteral lesion after radical prostatectomy and 3 gynecologic iatrogenic lesions (1 laparoscopically assisted vaginal hysterectomy, 2 radical hysterectomies with double anexectomy for cervix carcinoma). 5 ureteral reimplantations were left and 2 right sides. Before surgery, 5 patients had nephrostomy tubes inserted and the patient with endometriosis had a double J catheter. The patient with ureterocele did not require urinary diversion before the operation and endoscopic intraoperative catheterization was not feasible.
We present the operative and postoperative results of the patients undergoing surgery. They had a mean age of 49.3 [28-78] years. Mean intraoperative estimated blood loss was 132.1 [100-250] ml, with no transfusions required. Mean operative time was 127.4 [120-210] minutes, with no conversions to laparoscopic or open surgery required. Mean hospital stay was 2.1 [2-3] days and all patients had drainage removed at 48 hours. There were minor Clavien-Dindo complications in one patient presenting urinary tract infection 10 days after the operation. All patients had double J catheters that were removed with a mean of 34.3 [30-45] days. Mean time for bladder catheter removal was 7.8 [7-10] días. With a mean follow up of 32.6 [14-54] months no ureteral stenosis recurrence has been observed.
LESS ureteral reimplantation, in our initial experience, shows a low complication rate, similar to current laparoscopic series, offering less postoperative pain and abdominal wall aggression with great cosmetic results that are perceived by patients very positively, in addition to rapid recovery and return to normal daily life.
Obstet Gynecol Sci. 2017 May;60(3):283-288
Primiparous singleton women with endometriosis have an increased risk of preterm birth: Meta-analyses.
The objective of this study was to assess the association between women with endometriosis and risk of preterm birth.
Two reviewers independently determined all prospective cohort study, retrospective cohort study, large population based cohort study, retrospective secondary analysis, and double blinded, multicentric, observational and cohort study, placebo-controlled, randomized clinical trial published using PubMed, Medline, Korea Education and Research Information Service, and Scopus from March 1994 through February 2016 without language restrictions comparing obstetric outcomes women with endometriosis and women without endometriosis. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Six studies met inclusion criteria, including 50,472 women. Among 50,472 pregnancies, 39,659 had endometriosis and 10,813 had no endometriosis. Meta-analyses were estimated with odds ratios and 95% confidence intervals using random effect analysis according to heterogeneity of studies.
Data from six effect sizes from six studies involving 50,472 patients were enrolled. These meta-analyses showed women with endometriosis have an increased risk of preterm birth (odds ratio, 1.473; 95% confidence interval, 1.216 to 1.785).
These meta-analyses demonstrate women with endometriosis at pregnancy have an increased risk of preterm birth. Therefore, it is worthy for obstetrics to increase the careful inspection in women with endometriosis during pregnancy.
Case Rep Obstet Gynecol. 2017;2017
Endometriosis Nodule Causing Spontaneous Haemoperitoneum in Pregnancy: A Case Report and Literature Review.
Spontaneous haemoperitoneum in pregnancy (SHiP) due to endometriosis is a very rare condition and this is a case of a 41-year-old primigravida, who presented at 32 weeks with sudden onset of severe lower abdominal pain without any uterine activity. This was a dichorionic-diamniotic twin pregnancy, following in vitro fertilisation for subfertility secondary to severe endometriosis. On admission, pain score was eight, with ten being the maximum of the scale. The vital signs were stable. Abdominal palpation revealed generalised tenderness with no guarding or palpable contraction. There was no evidence of bleeding and the cervical os was closed on speculum examination. The cardiotocograph (CTG) was pathological and a plan was made to deliver the babies with emergency caesarean section. Intraoperatively, there was massive haemoperitoneum which was managed successfully with the involvement of multidisciplinary input from general surgeons and urologists with optimum maternal and fetal outcome.
Nat Commun. 2017 May 24;8:15539.
Meta-analysis identifies five novel loci associated with endometriosishighlighting key genes involved in hormone metabolism.
Sapkota Y1,2, Steinthorsdottir V3, Morris AP4,5, Fassbender A6,7, Rahmioglu N5, De Vivo I8,9, Buring JE8,10, Zhang F11, Edwards TL12, Jones S13, O D6,7, Peterse D6,7, Rexrode KM8,10, Ridker PM8,10, Schork AJ14,15, MacGregor S1, Martin NG1, Becker CM16, Adachi S17, Yoshihara K17, Enomoto T17, Takahashi A18, Kamatani Y18, Matsuda K19, Kubo M18, Thorleifsson G3, Geirsson RT20,21, Thorsteinsdottir U3,21, Wallace LM1,11; iPSYCH-SSI-Broad Group, Yang J11, Velez Edwards DR22, Nyegaard M23,24, Low SK18, Zondervan KT5,16, Missmer SA8,9, D’Hooghe T6,7,25, Montgomery GW1,11, Chasman DI8,10, Stefansson K3,21, Tung JY26, Nyholt DR1,27.
Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P<5 × 10-8), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts.
J Womens Health (Larchmt). 2017 Sep;26(9):941-950.
Beyond Body Mass Index: Using Anthropometric Measures and Body Composition Indicators to Assess Odds of an Endometriosis Diagnosis.
Body mass index (BMI) and endometriosis have been inversely associated. To address gaps in this research, we examined associations among body composition, endometriosis, and physical activity.
MATERIALS AND METHODS:
Women from 14 clinical sites in the Salt Lake City, Utah and San Francisco, California areas and scheduled for laparoscopy/laparotomy were recruited during 2007-2009. Participants (N = 473) underwent standardized anthropometric assessments to estimate body composition before surgery. Using a cross-sectional design, odds of an endometriosis diagnosis (adjusted odds ratio [aOR]; 95% confidence interval [CI]) were calculated for anthropometric and body composition measures (weight in kg; height in cm; mid upper arm, waist, hip, and chest circumferences in cm; subscapular, suprailiac, and triceps skinfold thicknesses in mm; arm muscle and fat areas in cm2; centripetal fat, chest-to-waist, chest-to-hip, waist-to-hip, and waist-to-height ratios; arm fat index; and BMI in kg/m2). Physical activity (metabolic equivalent of task-minutes/week) and sedentariness (average minutes sitting on a weekday) were assessed using the International Physical Activity Questionnaire-Short Form. Measures were modeled continuously and in quartiles based on sample estimates. Adjusted models were controlled for age (years, continuous), site (Utah/California), smoking history (never, former, or current smoker), and income (below, within 180%, and above of the poverty line). Findings were standardized by dividing variables by their respective standard deviations. We used adjusted models to examine whether odds of an endometriosis diagnosis were moderated by physical activity or sedentariness.
Inverse relationships were observed between endometriosis and standardized: weight (aOR = 0.71, 95% CI 0.57-0.88); subscapular skinfold thickness (aOR = 0.79, 95% CI 0.65-0.98); waist and hip circumferences (aOR = 0.79, 95% CI 0.64-0.98 and aOR = 0.76, 95% CI 0.61-0.94, respectively); total upper arm and upper arm muscle areas (aOR = 0.76, 95% CI 0.61-0.94 and aOR = 0.74, 95% CI 0.59-0.93, respectively); and BMI (aOR = 0.75, 95% CI 0.60-0.93), despite similar heights. Women in the highest versus lowest quartile had lower adjusted odds of an endometriosis diagnosis for: weight; mid-upper arm, hip, and waist circumferences; total upper arm and upper arm muscle areas; BMI; and centripetal fat ratio. There was no evidence of a main effect or moderation of physical activity or sedentariness.
In a surgical cohort, endometriosis was inversely associated with anthropometric measures and body composition indicators.
Eur Rev Med Pharmacol Sci. 2017 May;21(9):2027-2033.
Regulation of miR-33b on endometriosis and expression of related factors.
Endometriosis is a common benign disease in gynecology, and can cause chronic pelvic pain, dysmenorrhea and even infertility. Its pathogenesis mechanism has not been fully illustrated. miRNA (miR) participates in various biological activities including cell growth, proliferation, apoptosis, organ formation, inflammation and tumor. Its role in endometriosis has not been reported. MiR-33b is involved in cell metabolism, proliferation and invasion, but with its function and mechanism in endometriosis unknown.
PATIENTS AND METHODS:
Real-time PCR was used to test miR-33b expression in ectopic endometrial and normal tissues. In vitro cultured endometrial cells were transfected with miR-33b mimic or inhibitor, followed by Real-time PCR for miR-33b expression. MTT method detected endometrial cell proliferation. Caspase 3 activity was quantified by test kit. Real-time PCR and Western blot measured effect of miR-33b on vascular endothelial growth factor (VEGF) and matrix metalloprotein 9 (MMP-9).
MiR-33b was down-regulated in ectopic endometrial tissues (p < 0.05 compared to normal tissues). Transfection of miR-33b inhibitor facilitated endometrial proliferation, decreased Caspase 3 activity, increased VEGF and MMP-9 mRNA or protein expression (p < 0.05 compared to control group). MiR-33b mimic suppressed endometrial proliferation, elevated Caspase 3 activity, and decreased VEGF or MMP-9 expression (p < 0.05 compared to control group).
MiR-33b can mediate cell apoptosis, alter VEGF and MMP-9 expression and affect proliferation and apoptosis of uterus endometrial cells, thus participating endometriosis formation.
J Invest Surg. 2017 May 25:1-7.
A Novel Experimental Model of Colorectal Endometriosis.
Endometriosis is a disease that affects 6-10% of the female population, mainly women of reproductive age, and causes a variety of cyclic symptoms. Deep infiltrating endometriosis and in particular bowel involvement presents a challenge for modern surgery. To date, there are no experimental animal models in this field, demonstrating experimental induction of endometriosis directly attached to surface of the colon imitating human colorectal endometriosis; hence, the implementation of novel pharmaceutical and surgical strategies for the management of colorectal endometriosis is mainly limited to clinical studies.
AIM OF THE STUDY:
To investigate whether induction of colorectal endometriotic lesions in is feasible in rats.
MATERIALS AND METHODS:
Twenty, female, adult, non-pregnant Sprague Dawley rats sustained uterine horn resection, which was then placed around the rectum of the rat with the endometrial surface in direct contact with the bowel serosa and approximated in the serosal surface of the colon with two sutures.
Two weeks following, surgery rats were euthanized and the bowel was surgically explored. The presence of a cystic lump at the site of the surgical intervention was evaluated macroscopically and microscopically. Histopathology documented the presence of cystic endometriosis. The endometriotic focus was adherent to the bowel wall by large fibrous nodules with concomitant replacement of part of the outer longitudinal muscle layer.
The findings of our study support that the proposed experimental model of colorectal endometriosis is feasible, easily reproducible and may be implemented in future research in this field.
J Obstet Gynaecol Res. 2017 Jul;43(7):1180-1188
Differential expression of EWI-2 in endometriosis, its functional role and underlying molecular mechanisms.
We aimed to investigate EWI-2 expression in endometrium tissues collected from women with endometriosisat mRNA and protein levels, to evaluate its potential as a biomarker for endometriosis and to study its functional role via possible regulation of the PI3K/Akt signaling pathway.
Endometrium tissues were collected from patients with endometriosis and healthy individuals. EWI-2 mRNA expression was evaluated using quantitative real-time PCR (qRT-PCR) while EWI-2 protein levels were determined by western blotting. For functional studies, EWI-2 shRNA was transfected in endometrial epithelial cells and the in vitro migration and invasion assays were performed using the Transwell chambers.
EWI-2 was significantly downregulated in tissues obtained from patients with endometriosis compared with healthy individuals (P < 0.0001). EWI-2 expression in the secretory phase was lower than that in the proliferative phase (P < 0.0001). Receiver-operator curve analysis of EWI-2 expression showed that the area under the curve for endometriosis diagnosis was 0.8942 (P = 0.003), 0.9643 (P = 0.0001), 0.9912 (P < 0.0001), and 0.9150 (P < 0.0001), respectively, for healthy women compared with women with endometriosis in matched comparisons of data originated from the proliferative, early, middle, and late secretory phases. Over the menstrual cycle, the expression of EWI-2 was significantly decreased in the eutopic tissues compared to the ectopic tissues. Further cellular and molecular analyses showed that EWI-2 inhibited cell migration and invasion via the Akt signaling.
Our findings suggested that downregulation of EWI-2 may contribute to endometriosisphysiopathology and potentiate EWI-2 as a valuable diagnostic biomarker and therapeutic target for endometriosis.
Zhonghua Fu Chan Ke Za Zhi. 2017 May 25;52(5):307-313.
Efficacy and impact on quality of life of different drug treatments after partial resection of rectovaginal endometriosis.
Objective: To evaluate different postoperative medications as maintenance treatment for rectovaginal endometriosis (RVE) patients after conservative surgery. Methods: RVE patients who underwent transvaginal partial excision from January 2007 to September 2016 with regular outpatient follow-up were retrospectively screened. Those followed by a levonorgestrel-releasing intrauterine system (LNG-IUS) insertion or oral contraceptive drospirenone/ethinylestradiol (DRSP/EE) 3 mg/30 μg administration were enrolled. Variations in endometriosis-related pain, sexual function and quality of life were measured by visual analogue scale (VAS), female sexual function index (FSFI) and short form 36-item health survey (SF-36) respectively. Results: There were a total of 102 RVE patients with 48 (47.1%, 48/102) in LNG-IUS group and 54 (52.9%, 54/102) in DRSP/EE group included. A rapid and marked improvement was observed after 3 months postoperative medical treatment compared to preoperative in both groups (P<0.01). In dysmenorrhea, for LNG-IUS group (2.5±0.8) versus (7.6±1.3; P<0.01), for DRSP/EE group (2.7±0.6) versus (7.7±1.4; P<0.01); in FSFI, for LNG-IUS group (23.5±2.0) versus (21.0±2.7; P<0.01), for DRSP/EE group (23.4±1.2) versus (21.5±2.2; P<0.01); in SF-36, both groups had obvious improvements in physical component summary and mental component summary (P<0.01), for LNG-IUS group (74±13) versus (56±19), (75±13) versus (55±17), for DRSP/EE group (73±11) versus (59±15), (75±9) versus (54±14). These effects were maintained stably and progressively during postoperative medication at 6-, 12-, 24-month follow up. Conclusion: Transvaginal partial excision combined postoperative LNG-IUS or DRSP/EE treatment is a safe and viable technique to alleviate pain, improve sexual function and quality of life.
Zhonghua Fu Chan Ke Za Zhi. 2017 May 25;52(5):314-319
Risk factors of endometriosis associated ovarian carcinoma in women aged 45 years and older.
Obiective: To explore the risk factors of endometriosis-associated ovarian cancer (EAOC) in women with ovarian endometriosis aged 45 years and older in China. Methods: The medical records of total 1 038 women aged 45 years and older with a surgicopathological diagnosis of ovarian endometriosis treated at Peking Union Medical College Hospital from December 1994 to December 2014 were reviewed. Histology evaluation determined ovarian endometriosis with (n=30) or without (n=1 008) ovarian cancer. Results: (1) There were 30 (2.9%, 30/1 018) cases confirmed as having EAOC. Clear cell carcinoma (63.3%, 17/30) and endometrioid adenocarcinoma (23.3%, 7/30) were commonly observed subtypes and 70.0% of EAOC patients were at stage Ⅰ. (2) Compared women with ovarian endometriosis in the same age group, patients with EAOC were older (50.8 vs 48.5 years, P=0.002). There were more in postmenopausal status at diagnosis of EAOC (P<0.01). There were more found with a mass ≥8 cm (P<0.01). Women with EAOC had higher prevalence of coexisting endometrial disorders (P=0.003). No differences were found in preoperative CA(125) value and infertile or nulliparous women (P>0.05). Conclusions: For women with ovarian endometriosis aged 45 years and older, the subgroup of patients characterized by postmenopausal status and ovarian endometrioma (≥8 cm) have a higher risk of EAOC. Active intervention or intensive follow-up should be considered for this population group, especially for those concurrent with endometrial disorders.
Minerva Ginecol. 2017 Dec;69(6):587-596.
The current management of deep endometriosis. A systematic review.
Endometriosis is a chronic inflammatory disease that affects young women in reproductive age. It has mainly three different clinical presentations: superficial (peritoneal), ovarian (endometriomas) and deep endometriosis (DE). The last one is the most advanced form of the disease, frequently impairing fertility and harming women’s quality of life.
We conducted a systematic review on the surgical treatment of DE in the last ten years focusing on its benefits to improve quality of life (QoL) and for pain relief as well as related surgical complications.
Twenty-three studies were included for qualitative analysis. Overall, included studies showed a relevant improvement in QoL as well as in pain scores using specific questionnaires and the ten-point visual analogue scale (VAS) for pain.
Until further comparative studies regarding medical versus surgical treatment for DE are concluded, currently, surgery is the best option for patients with DE and severe pain (VAS>7).
J Obstet Gynaecol India. 2017 Jun;67(3):208-212.
Prevalence, Clinical and Laparoscopic Features of Endometriosis Among Infertile Women.
To study the prevalence, clinical and laparoscopic characteristics of endometriosis in infertile women.
This is a hospital-based prospective study.
Five hundred and two (502) patients underwent diagnostic laparoscopy for evaluation of cause for infertility. Staging of endometriosis was done according to the rAFS scoring system.
Out of 502 women, 276 (54.98 %) showed the presence of endometriosis, while 226 (45.01 %) did not have endometriosis. One hundred and eighty-three (66.3 %) women had stage I endometriosis, 49 (17.77 %) had stage II, 23 (8.33 %) had stage III and 21 (7.6 %) had stage IV endometriosis.
More than 50 % of patients in our study were asymptomatic; however, the presence of menorrhagia, dysmenorrhoea, dyspareunia and chronic pelvic pain are also clinically statistically significant. So, we would like to recommend the evaluation and treatment of a patient reporting in gynaecological OPD with the above-mentioned complaints with high suspicion of endometriosis.
J Obstet Gynaecol India. 2017 Jun;67(3):218-223.
Symptomatology and Surgical Perspective of Scar Endometriosis: A Case Series of 16 Women.
The prevalence of scar endometriosis is increasing with the increasing caesarean deliveries and laparoscopic procedures done for pelvic endometriosis. To analyse the symptomatology and surgical perspective of scar endometriosis.
MATERIALS AND METHODS:
Retrospective review of 16 women who underwent surgery for scar endometriosisin the period of 4 years in Amrita institute of medical sciences.
Mean age of the patients is 35.19 years. Mean interval from the index surgery to the presentation is 4.56 years. Mean size of the swelling is 2.84 cm. In 68.8% of the patients, caesarean section was the inciting surgery. 18.7% had port site endometriosis. Cyclical pain and swelling at the scar site was present in 93.8% of the women. 18.9% had concurrent pelvic endometriosis. All women had involvement of the subcutaneous tissue followed by 11 women with the involvement of rectus sheath. There was no recurrence of the lesion in the operated patients in the mean follow-up period of 11.91 months.
In all women presenting with cyclical scar site pain and swelling, scar endometriosis should be considered. It commonly follows caesarean section and laparoscopic surgeries done for endometriosis. Wide local excision with or without reconstruction is the method of choice for this condition. Role of tumescent solution during surgery and postoperative medical management to reduce recurrence needs further prospective studies.
Arch Gynecol Obstet. 2017 Aug;296(2):153-165.
Patient-completed or symptom-based screening tools for endometriosis: a scoping review.
The objective of this review was to evaluate existing patient-completed screening questionnaires and/or symptom-based predictive models with respect to their potential for use as screening tools for endometriosis in adult women. Validated instruments were of particular interest.
We conducted structured searches of PubMed and targeted searches of the gray literature to identify studies reporting on screening instruments used in endometriosis. Studies were screened according to inclusion and exclusion criteria that followed the PICOS (population, intervention, comparison, outcomes, study design) framework.
A total of 16 studies were identified, of which 10 described measures for endometriosis in general, 2 described measures for endometriosis at specific sites, and 4 described measures for deep-infiltrating endometriosis. Only 1 study evaluated a questionnaire that was solely patient-completed. Most measures required physician, imaging, or laboratory assessments in addition to patient-completed questionnaires, and several measures relied on complex scoring. Validation for use as a screening tool in adult women with potential endometriosis was lacking in all studies, as most studies focused on diagnosis versus screening.
This literature review did not identify any fully validated, symptom-based, patient-reported questionnaires for endometriosis screening in adult women.
Br J Pharmacol. 2017 Aug;174(16):2623-2635.
Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions.
BACKGROUND AND PURPOSE:
Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of COX-2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone.
Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were treated daily with an i.p. injection of telmisartan (10 mg·kg-1 ), parecoxib (5 mg·kg-1 ), a combination of telmisartan and parecoxib or vehicle. Therapeutic effects on lesion survival, growth, vascularization, innervation and protein expression were studied over 4 weeks by high-resolution ultrasound imaging as well as immunohistochemical and Western blot analyses.
Telmisartan-treated lesions exhibited a significantly reduced lesion volume when compared with vehicle-treated controls and parecoxib-treated lesions. This inhibitory effect of telmisartan was even more pronounced when it was used in combination with parecoxib. The combination therapy resulted in a reduced microvessel density as well as lower numbers of proliferating Ki67-positive cells and higher numbers of apoptotic cleaved caspase-3-positive stromal cells within the lesions. This was associated with a lower expression of COX-2, MMP-9 and p-Akt/Akt when compared with controls. The application of the two drugs further inhibited the ingrowth of nerve fibres into the lesions.
CONCLUSIONS AND IMPLICATIONS:
Combination therapy with telmisartan and a COX-2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis.
Acta Histochem. 2017 Jun;119(5):523-532.
Endocannabinoids modulate apoptosis in endometriosis and adenomyosis.
Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.
Prostaglandins Other Lipid Mediat. 2017 Jul;131:1-8.
Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells.
Colorectal cancer (CRC) is the most common cancer. A proper method to reduce mortality of CRC is chemoprevention to prevent initiation and promotion of intestinal tumorgenesis. One of the promising and developing chemopreventive agents is natural compounds found in plants. Frankincense, the resin extract from the Boswellia specious, has been used in traditional and modern medicine for treating various diseases with very minimal side effects. In the current study, we investigated the anti-cancer activity of methanolic extract of Boswellia serrata (B. serrata) on HT-29 human colon cancer cells.
HT-29 cells were treated with different concentrations of B. serrata and cell viability was assessed by MTT assay. mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1 (HIF-1) were examined by quantitative real-time PCR. Apoptosis was evaluated by the proportion of sub-G1 cells. Prostaglandin E2 (PGE2) level and caspase 3 activity were determined by ELISA assay. Tube formation potential and HT-29 cells migration were assessed using three-dimensional vessel formation assay and scratch test.
- serrata extract considerably decreased the expression of mPGES-1, VEGF, CXCR4, MMP-2, MMP-9 and HIF-1. The caspase 3 activity and percent of cells in sub-G1 phase were increased by B. serrata extract. Cell viability, PGE2 generation, in vitro tube formation and cell migration were decreased significantly in B. serrata-treated HT-29 compared to the control group.
Our findings suggest that B. serrata extract inhibits proliferation, angiogenesis and migration and induces apoptosis in HT-29 cells by inhibiting of mPGES-1 and decreasing the PGE2 level and its downstream targets.
Gynecol Obstet Fertil Senol. 2017 Jun;45(6):327-334.
Morbidity and functional long-term follow-up of patients with surgical treatment of urinary tract endometriosis.
To assess postoperative complications, improvement of pain symptoms and residual urinary functional symptoms after surgery for deep infiltrative endometriosis affecting ureter or bladder.
Retrospective study of complications (Clavien-Dindo classification), pain (visual analog scale [VAS]) and urinary functional symptoms (Urinary Symptom Profile questionnaire [USP]) of patients surgically treated between 2007 and 2015 in University Hospitals of Lyon.
Among 31 patients with endometriosis involving the bladder, 83.9% had a partial cystectomy and 16.1% an extra-mucosal resection. Among patients (n=20) with ureteral involvement, 85% had ureterectomy with ureterocystoneostomy and 15% had only ureterolysis. Grade III postoperative complications occurred in 6% and 0% of patients with bladder or ureteral surgery, respectively and no grade IV or V complications were reported. Mean bladder VAS dropped from 5.3±4.2 to 0.3±0.9 after a follow-up of 42 months (P<0.0001). In patients with ureteral involvement, mean flank VAS dropped from 3.6 to 0.9 after a follow-up of 33 months (P<0.0005). Mean postoperative USP score for dysuria and detrusor overactivity were 1.35/9 and 2.48/21 in case of bladder involvement, and 1.10/9 and 2.15/21 in case of ureteral involvement.
Multidisciplinary surgical management of deep infiltrative endometriosis affecting urinary tract was associated to a low risk of severe postoperative complications and to a long-term significant improvement of pain symptoms without significant residual functional urinary symptoms.
Microb Pathog. 2017 Aug;109:110-113.
Glycyrrhizin inhibits LPS-induced inflammatory mediator production in endometrial epithelial cells.
Endometriosis is a continuous inflammation of uterine endometrium that usually affects women of reproductive age. Glycyrrhizin, a triterpene isolated from the roots and rhizomes of licorice (Glycyrrhiza glabra), has been known to have anti-inflammatory effect. The purpose of this study was to investigate the anti-inflammatory effect of glycyrrhizin on LPS-stimulated mouse endometrial epithelial cells (MEEC). The levels of TNF-α, IL-1β, and PGE2 were measured by ELISA. The expression of COX-2, iNOS, TLR4, and NF-ĸB were detected by western blot analysis. The results showed that glycyrrhizin significantly suppressed LPS-induced TNF-α, IL-1β, NO, and PGE2 production. Also, LPS-induced iNOS and COX-2 expression were attenuated by glycyrrhizin. Furthermore, glycyrrhizin significantly attenuated TLR4 expression and NF-κB activation induced by LPS in MEEC. In conclusion, the present study demonstrated that glycyrrhizin inhibited LPS-induced inflammatory response by inhibiting TLR4 signaling pathway in MEEC. Glycyrrhizin may be used as a potential agent for the treatment of endometriosis.
Geburtshilfe Frauenheilkd. 2017 Apr;77(4):335-339.
Recurrent Interstitial Pregnancy: a Review of the Literature.
Interstitial pregnancies account for 2-4 % of all ectopic pregnancies. Despite its rarity, various treatment options exist. However, no gold standard has yet been defined and data regarding recurrence of interstitial pregnancies in subsequent pregnancies after different treatments are sparse. This makes it very difficult to provide adequate patient counselling for treatment options with regards to the treatment-related risk of recurrence. The present literature review demonstrates that recurrent interstitial pregnancy is a rare condition and more likely when additional anatomy-related risk factors for ectopic pregnancies are present, such as hydrosalpinges, blocked tubes, endometriosis, fibroids or prior tubal ectopic pregnancies. Therefore, at first appearance and in absence of additional anatomy-related risk factors, methotrexate intravenously, intramuscularly or into the amnion may be the first choice. In case of anatomical risk factors, cornual wedge resection seems to be first choice. In case of recurrence, cornual wedge resection is particularly justified in patients with anatomical alterations of the salpinges. The role of conservative surgical treatments in recurrence as cornuotomy, salpingectomy, endoloop ligation and resection and curettage under laparoscopic guidance remains unclear due to sparse data.
Int J Womens Health. 2017 May 16;9:323-330.
Anxiety and depression in patients with endometriosis: impact and management challenges.
Endometriosis is one of the most common gynecological diseases and affects ~10% of women in reproductive age. The most common clinical signs of endometriosis are menstrual irregularities, chronic pelvic pain (CPP), dysmenorrhea, dyspareunia and infertility. Symptoms of endometriosis often affect psychological and social functioning of patients. For this reason, endometriosis is considered as a disabling condition that may significantly compromise social relationships, sexuality and mental health. Considering this point, the aim of this narrative review is to elucidate the impact of anxiety and depression in the management of women with endometriosis. Psychological factors have an important role in determining the severity of symptoms, and women who suffer from endometriosis report high levels of anxiety, depression and other psychiatric disorders. In addition, endometriosis is one of the most important causes of CPP; women with endometriosis suffer from a wide range of pelvic pain such as dysmenorrhea, dyspareunia, nonmenstrual (chronic) pelvic pain, pain at ovulation, dyschezia and dysuria. Several studies have underlined the influence of CPP on quality of life and psychological well-being of women with endometriosis. Data suggest that the experience of pelvic pain is an important component of endometriosis and may significantly affect emotive functioning of affected women. It has been demonstrated that high levels of anxiety and depression can amplify the severity of pain. Further studies are needed to better understand the relationship between psychological factors and perception of pain. Treatment of endometriosismay be hormonal or surgical. Surgery is the primary treatment for more severe forms of endometriosis. There are few data in the literature about the influence of psychological factors and psychiatric comorbidities on the effectiveness of treatments. It is important to evaluate the presence of previous psychiatric diseases in order to select the most appropriate treatment for the patient.
Acta Obstet Gynecol Scand. 2017 Jun;96(6):715-726.
Uterine adenomyosis and infertility, review of reproductive outcome after in vitro fertilization and surgery.
This review includes an analysis of the clinical studies evaluating reproductive outcome and adenomyosis, and a review of studies on reproductive outcome and surgical treatment options for adenomyosis. Strict diagnostic criteria and classification of disease are needed for an image diagnosis of adenomyosis. Studies of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) populations and women with surgically treated deep endometriosis have suggested that adenomyosis has a negative impact on reproductive outcome, although there are substantial variations between studies. Few data are available on the relation between the extent of disease and impact on reproductive outcome, but a correlation appears to exist. Case series seem to confirm a positive effect of gonadotropin-releasing hormone analog treatment and surgery on reproductive outcome, but there are no controlled trials. Evidence is impaired by the poor quality of many studies, a lack of strict image diagnosis, and the absence of a classification of the extent of disease. Selection of the optimal evidence-based treatment options for adenomyosis in the fertility clinic is difficult because of a lack of evidence regarding the relation between fertility and the degree and composition of adenomyosis. Adenomyosis may reduce implantation so severely that surgical or other treatment options should be recommended, but the benefit of these treatment options needs to be verified. Referral of women with adenomyosis and recurrent miscarriage and repeated failure of assisted reproductive technology to centers with a special interest in adenomyosis research and treatment may be critical.
J Ultrasound Med. 2017 Nov;36(11):2271-2278.
Three-Dimensional Power Doppler Vascularization in Women With Ovarian Endometriomas and Relationship With Associated Painful Symptoms.
The objective of the study was to evaluate the correlation between endometrioma-associated pain and lesion vascularization as measured with 3-dimensional power Doppler transvaginal sonography.
Endometriomas were examined, and 4 indices were obtained: mean grayness, flow index, vascularization index, and vascularization-flow index. Dysmenorrhea, chronic pelvic pain, and dyspareunia were analyzed in terms of severity, presence/absence, and duration.
Twenty-nine women were selected. The univariable association of painful symptoms in terms of presence/absence and duration was low with the exception of mean grayness with the presence of chronic pelvic pain (β = -0.106; P = .047; 95% confidence interval, 0.810 to 0.998). The R2 value increased to 0.226 for dysmenorrhea (β = -0.475; P = .029) when analyzing the association between the vascularization index and the severity of painful symptoms. The visual analog scale scores for chronic pelvic pain and dyspareunia were higher (R2 = 0.300; β = -0.547 and -0.548, respectively; P = .028 and .053).
We observed an inverse association between the severity of pain and endometrioma vascularization. Further larger studies are required to confirm our findings.
Gynecol Endocrinol. 2017 Dec;33(12):928-932
Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients.
Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.
Reprod Sci. 2017 Dec;24(12):1566-1576.
What Is Known and Unknown About the Association Between Endometriosisand Sexual Functioning: A Systematic Review of the Literature.
It is well known that endometriosis is associated with an increase in the risk of deep dyspareunia, with potential negative effects on global female sexual functioning and couple relationship. The aims of this study were to review the literature on the impact of endometriosis on female sexual functioning and to suggest new avenues for future research and treatment strategies. An electronic database research was performed to identify all the studies on the relation between endometriosis and sexual functioning published in the period 2000 to 2016. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After the screening process, a total of 9 studies investigating the relation between endometriosis and female sexual functioning were considered. Overall, these studies indicated that around two thirds of women with endometriosis have some form of sexual dysfunction not limited to deep dyspareunia. These findings suggest that the global sexual impact of endometriosis requires further investigation, focusing not only on pain during intercourse but also on psychological and relational dimensions, including partner’s sexual functioning. Because sexual functioning is a complex, multidimensional phenomenon, the ideal treatment for endometriosis-related sexual dysfunctions should be conducted by a multidisciplinary team composed of gynecologists, sexologists, and psychologists/psychotherapists.
Reprod Sci. 2018 Feb;25(2):292-301
Saponin Extracts Induced Apoptosis of Endometrial Cells From Women With Endometriosis Through Modulation of miR-21-5p.
Among the several components in Korean red ginseng, the saponin components are known to have various pharmacologic activities. The objective of this study was to evaluate therapeutic effects of saponin extracts from Korean red ginseng on endometriosis and to identify microRNAs (miRNAs) associated with saponin treatment. This is an in vitro study which used human endometrial stromal cells (HESCs) obtained from patients who underwent laparoscopic surgery for endometriosis and other benign conditions. Human endometrial stromal cells were treated with saponin extracts, and microarray profiling was performed. Human endometrial stromal cells were then transfected with miRNAs identified in the profiling. After the saponin extract treatment, the expression of caspase 3 was significantly increased in HESCs. Microarray profiling revealed several miRNAs that were differentially expressed, and miR-21-5p was further validated. Expression of miR-21-5p was significantly upregulated in the endometrium of patients with endometriosis, compared with controls. Transfection of a miR-21-5p inhibitor significantly increased caspase 3 expression in HESCs. The apoptotic potential of saponin extracts and the miR-21-5p inhibitor were further validated in HESCs using flow cytometry analysis. In conclusions, treatment with saponin extracts significantly decreased the expression of miR-21-5p in HESCs from patients with endometriosis. Inhibition of miR-21-5p effectively increased the apoptotic potential of HESCs. These findings suggest that saponin extract treatment may have therapeutic potential for endometriosis via modulation of specific miRNAs.
J Pediatr Adolesc Gynecol. 2017 Oct;30(5):568-570
Endometriosis in Adolescent and Young Girls: Report on a Series of 55 Cases.
The aim of this retrospective study was to evaluate endometriosis in adolescent and young girls and further to review the menstrual, reproductive characteristics, and risk factors.
DESIGN AND SETTING:
We reviewed the medical records of adolescent and young girls with endometriosis from 2 different countries. Data were collected and analyzed from charts of 900 patients with endometriosis.
PARTICIPANTS AND INTERVENTIONS:
Fifty-five female adolescents aged between 13 and 21 years (mean age 18.3 years) participated in our series. This study was conducted in the Obstetric and Gynecology Department of Venizeleio General Hospital of Crete and involved all patients diagnosed with endometriosis between 1996 and 2016.
MAIN OUTCOME MEASURES:
Statistical methods included χ2 and Mann-Whitney U test.
Of 900 patients with endometriosis we found 55 female adolescents (6.1%). The mean age was 18.3 ± 2.3 years, significantly younger compared with the advanced endometriosis patients (32.7 ± 7.2; P < .001). Regarding the menstrual reproductive and others characteristics, we observed several differences in adolescent young girls compared with the advanced age endometriosis group. The factors associated with an increased risk for young women include age at menarche, dysmenorrhea, history of asthma, and a positive family history of endometriosis. Additionally, we report on 16 of 55 (32%) adolescent women with endometriosis and congenital malformations (P < .01) and 5 patients who were diagnosed with dry eye syndrome.
There is an association between endometriosis in adolescent and young women and risk factors including early menarche, early onset of dysmenorrhea, history of asthma, previous surgical procedures, obstructive genital anomalies, and family history of endometriosis.
Hypertension. 2017 Jul;70(1):59-65.
Association Between Endometriosis and Hypercholesterolemia or Hypertension.
An altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years. Multivariable Cox proportional hazards models were applied. In 1989, there were 4244 women with laparoscopically confirmed endometriosis and 91 554 women without. After adjusting for demographic, anthropometric, family history, reproductive, dietary, and lifestyle risk factors prospectively, comparing women with laparoscopically confirmed endometriosis to women without, the relative risks were 1.25 (95% confidence interval, 1.21-1.30) for development of hypercholesterolemia and 1.14 (95% confidence interval, 1.09-1.18) for hypertension. Conversely, the relative risks of developing laparoscopically confirmed endometriosis were 1.22 (95% confidence interval, 1.15-1.31) comparing women with hypercholesterolemia to women without and 1.29 (95% confidence interval, 1.18-1.41) comparing women with hypertension to women without. The strength of associations of laparoscopically confirmed endometriosis with hypercholesterolemia or hypertension was strongest among women aged ≤40 and weakened as age increased (P values for interaction <0.001). We observed that ≈45% of the associations between endometriosis and hypercholesterolemia and hypertension could be accounted for by treatment factors after endometriosis diagnosis, including greater frequency of hysterectomy/oophorectomy and earlier age for this surgery. In this large cohort study, laparoscopically confirmed endometriosis was prospectively associated with increased risk of hypercholesterolemia and hypertension. Conversely, hypercholesterolemia and hypertension were prospectively associated with higher risk of laparoscopically confirmed endometriosis.
Intern Med. 2017;56(11):1405-1408.
Pulmonary Endometriosis which Probably Occurred through Hematogenous Metastasis after Artificial Abortion.
Pulmonary endometriosis (PEM) is a rare disease characterized by the proliferation of ectopic endometrial tissue in the lungs, which presents as catamenial hemoptysis. A 20-year-old-woman was admitted for repeated hemoptysis. Chest CT revealed a ground-glass opacity that appeared consistently with her menstrual cycle. Our detailed inquiry revealed a history of artificial abortion, which was followed by the use of oral contraceptives and catamenial hemoptysis after the discontinuation of these medications. Surgical removal was performed and histopathological examinations confirmed PEM. This clinical course suggested hematogenous metastasis. An inquiry regarding the patient’s history of uterine procedures and use of oral contraceptives was suggestive for the diagnosis of this disease.
Sci Rep. 2017 May 31;7(1):2546.
Endometriosis foci differentiation by rapid lipid profiling using tissue spray ionization and high resolution mass spectrometry.
Obtaining fast screening information on molecular composition of a tissue sample is of great importance for a disease biomarkers search and for online surgery control. In this study, high resolution mass spectrometry analysis of eutopic and ectopic endometrium tissues (90 samples) is done using direct tissue spray mass spectrometry in both positive and negative ion modes. The most abundant peaks in the both ion modes are those corresponding to lipids. Species of three lipid classes are observed, phosphatidylcholines (PC), sphingomyelins (SM) and phosphoethanolamines (PE). Direct tissue analysis gives mainly information on PC and SM lipids (29 species) in positive ion mode and PC, SM and PE lipids (50 species) in negative ion mode which gives complementary data for endometriosis foci differentiation. The biggest differences were found for phospholipids with polyunsaturated acyls and alkils. Although, tissue spray shows itself as appropriate tool for tissue investigation, caution should be paid to the interpretation of mass spectra because of their higher complexity with more possible adducts formation and multiple interferences must be taken into account. The present work extends the application of direct tissue analysis for the rapid differentiation between endometriotic tissues of different foci.
Aust N Z J Obstet Gynaecol. 2017 Aug;57(4):393-399.
The use of selective progestin receptor modulators (SPRMs) and more specifically ulipristal acetate in the practice of gynaecology.
This review discusses the development of selective progestin receptor modulators (SPRMs) for use in women’s health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.
J Biosci. 2017 Jun;42(2):251-263.
Estrogen is essential but not sufficient to induce endometriosis.
Endometriosis is a common gynaecological disorder of unknown aetiology. Among the several factors, estrogen has been implicated as a causative factor in endometriosis. In the present study using mouse model, we assessed the role of estrogen in the initial implantation and growth of endometrium in ectopic locations. Uterine tissues from green fluorescent protein (GFP) mice were transplanted in to the peritoneum of wild type mice in presence and absence of estrogen. As compared to untreated controls, the implantation of uterine tissue at ectopic locations was higher when estrogen was administered to both host and donor animals. However, this effect was not sustained as lesions regressed within 14 days of treatment. Irrespective of the treatment, peritoneal adipose was the most preferred site of lesion establishment. The lesions did not have typical features of the endometriosis (presence of glands and stroma) even after estrogen treatment and the ectopic tissue underwent regression by apoptosis irrespective of treatment. Since estrogen promotes implantation of endometrial tissue to ectopic locations but failure of these ectopic lesions to grow and sustain even in high estrogenic environment we propose that estrogen is necessary but not sufficient to sustain endometriosis.
Med Hypotheses. 2017 Jun;103:10-20.
Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis.
The theory of retrograde menstruation as aetiopathogenesis of endometriosis formulated by John Sampson in 1927 shows clear shortcomings: this does not explain why retrograde menstruation is a physiological process that affects 90% of women, while endometriosis occurs in only 10% of cases; it also does not explain the endometriotic foci distant from the pelvis, nor explains the cases of endometriosis in male patients. The immunological alterations of the peritoneal fluid explains the effects of disease, such as the inhibition of the physiological processes of cytolysis, but does not explain the cause. There is evidence to support the hypothesis that ectopic müllerian remnants of the endometrium, endocervix and endosalpinx are items from the genital ridge leaked during organogenesis. It is known that tissues derived from coelomatic epithelial and mesenchymal cells have the potential to metaplastically differentiate into epithelium and stroma. In addition, the phenotype of the ectopic endometrial cells is significantly different from those ectopic. There is scientific evidence that, during organogenesis, the genes of the Homeobox and Wingless family play a fundamental role in the differentiation of the ducts of Muller and development of the anatomical structure of the urogenital tract. We present here a hypothesis that deregulation of genes and the Wnt signaling pathway Wnt/β-catenin leads to aberrations and deregulation within the mesoderm, thus, may cause aberrant placement of stem cells. In addition, immune cells, adhesion molecules, extracellular matrix metalloproteinase and pro-inflammatory cytokines activate/alter peritoneal microenvironment, creating the conditions for differentiation, adhesion, proliferation and survival of ectopic endometrial cells.
Arch Gynecol Obstet. 2017 Aug;296(2):263-268.
Inpatient hospitalizations in women with and without assisted reproductive technology live birth.
The aim of this study is to evaluate frequency of hospitalization before, during, and after assisted reproductive technology (ART) treatment by cycle outcome.
Six thousand and one hundred thirty women residing in Massachusetts undergoing 17,135 cycles of ART reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SARTCORS) from 2004 to 2011 were linked to hospital discharges and vital records. Women were grouped according to ART treatment cycle outcome as: no pregnancy (n = 1840), one or more pregnancies but no live birth (n = 968), or one or more singleton live births (n = 3322). Hospital delivery discharges during 1998-2011 were categorized as occurring before, during, or after the ART treatment. The most prevalent ICD-9 codes for non-delivery hospital discharges were compared. Groups were compared using chi square test using SAS 9.3 software.
The proportion of any hospitalization was 57.0, 58.3, and 91.3% for women with no pregnancy, no live birth, and ART singleton live birth, respectively; the proportion of non-delivery hospitalizations was 30.4, 31.0, and 28.3%, respectively. The non-ART delivery proportion after ART treatment did not differ by group (33.4, 36.2, and 36.9%, respectively, p = 0.17). Most frequent non-delivery diagnoses (including fibroids, obesity, ectopic pregnancy, depression, and endometriosis) also did not differ by group. A secondary analysis limited to only women with no delivery discharges before the first ART cycle showed similar results.
All groups had live birth deliveries during the study period, suggesting an important contribution of non-ART treatment or treatment-independent conception to overall delivery and live births. Hospitalizations not associated with delivery suggested similarity in morbidity for all ART patients regardless of success with ART treatment.
J Clin Endocrinol Metab. 2017 Sep 1;102(9):3206-3217.
Exacerbation of endometriosis due to regulatory T cell dysfunction.
Endometriosis is a chronic inflammatory disease associated with altered immune response to endometrial cells facilitating the implantation and proliferation of ectopic endometrial tissues. Although regulatory T (Treg) cells play a key role in T cell-mediated immune response and development of immune disorders, their significance in endometriosis remains to be elucidated. Recently, CD4+CD45RA- forkhead box protein 3 (Foxp3)hi T cells, activated Treg cells, have been identified as a functionally true suppressive population of Treg cells.
To investigate the role of Treg cells in endometriosis.
Three Treg cell fractions (resting Treg cells, activated Treg cells, and non-Treg cells) were examined using flow cytometry in the endometrioma, endometrium, peritoneal fluid, and peripheral blood obtained from women with (n = 27) and without (n = 28) endometriosis. A mouse model of endometriosis was made in Foxp3tm3Ayr/J (Foxp3DTR) C57BL/6 Treg cell-depleted mice (n = 28).
In women with endometrioma, the proportion of activated Treg cells in the endometrioma and the endometrium, but not in the peritoneal fluid or peripheral blood, was significantly decreased compared with that in women without endometriosis. In Foxp3DTR/ diphtheria toxin (DT) mice, the number and weight of endometriotic lesions, inflammatory cytokine levels and angiogenetic factors were significantly increased compared with those in control mice.
Treg cell deficiency exaggerates local inflammation and angiogenesis and simultaneously facilitates the attachment and growth of endometrial implants. The findings provide a novel insight into dysregulated immune response for the pathogenesis and development.
Best Pract Res Clin Obstet Gynaecol. 2017 Oct;44:3-14.
Genetic basis of eugonadal and hypogonadal female reproductive disorders.
This review discusses the current state of our understanding regarding the genetic basis of the most important reproductive disorders in women. For clarity, these disorders have been divided into eugonadal and hypogonadal types. Hypogonadal disorders have been further subdivided according to serum gonadotropin levels. Our review focuses on historical and recent data regarding the genetics of the hypothalamic-pituitary-gonadal axis dysfunction, as well as the development and etiology of eugonadal disorders including leiomyomata, endometriosis, spontaneous ovarian hyperstimulation syndrome, polycystic ovarian syndrome, mullerian aplasia, and steroid hormone resistance syndromes. We discuss the known genes most commonly involved in hypergonadotropic hypogonadism (Turner syndrome and premature ovarian failure) and hypogonadotrophic hypogonadism (Kallmann syndrome and normosmic types). In addition, we summarize the current clinical testing approaches and their utility in practical application.
J Minim Invasive Gynecol. 2017 Nov – Dec;24(7):1234-1238
Utero-abdominal wall fistula after cesarean section in patient with prior colorectal resection for endometriosis: case report and systematic review.
Utero-Abdominal Wall Fistula (UAWF) is a very rare complication of cesarean section. We report an unusual case of a UAWF occurring in a 37-year-old woman, 4 years after a cesarean section and previously radical surgery for deep infiltrating endometriosis (DIE) with bowel resection. The patient presented with persistent purulent discharge of the Pfannenstiel scar and had noted that the discharge was blood-stained during menstruation. Magnetic resonance imaging confirmed the diagnosis of UAWF. Surgery was performed by laparotomy and was complicated by a postoperative rectovaginal fistula (RVF) which was successfully treated by the placement of a biological mesh via the vagina route. The postoperative course was favorable at 6 months with disappearance of painful symptoms and good quality of the colorectal anastomosis. A systematic review was conducted and 18 case reports were found from 1939 to 2016. This case report highlights the risk of post-delivery complications in women with DIE and colorectal involvement especially after cesarean section. Persistent abdominal discharge in this context should suggest a diagnosis of UAWF despite its low incidence. Finally, the vaginal route for RVF might be considered as an option for patients with prior multiple laparotomies.
Arch Gynecol Obstet. 2017 Aug;296(2):269-276.
Promotor analysis of ESR1 in endometrial cancer cell lines, endometrial and endometriotic tissue.
The nuclear hormone receptor estrogen receptor α (ERα) is pivotal for numerous processes in the cell. As a transcription factor, it regulates eukaryotic gene expression and affects cellular proliferation and differentiation in target tissues. Moreover, ERα is known for its influence on various gynecological diseases and carcinogenesis. Since its expression is often altered in diseased tissues and this alteration was found to be caused by hypermethylation of the ESR1 promotor region in cancer, including breast and colorectal cancer, the aim of this study is to elucidate if the expression of ERα is also regulated epigenetically in endometriosis and endometrial cancer.
Using real-time methylation-specific PCR (rt-MSP), we examined endometrial and endometriotic tissues as well as five endometrial cancer cell lines and compared the methylation status with the actual expression of ERα.
The results of our study indicate that, though its expression is altered in endometrial and endometriotic tissue, ERα is not regulated by methylation of the promotor region in endometriosis. In contrast, three of the five endometrial cancer cell lines are methylated in the promotor region of ESR1.
Thus, further investigation of the connection between ERα and endometrial cancer will be the next step.
Fertil Steril. 2017 Jul;108(1):117-124.
Sclerotherapy in the management of ovarian endometrioma: systematic review and meta-analysis.
To evaluate the efficacy of sclerotherapy for ovarian endometrioma on the risk of recurrence, clinical symptoms, and reproductive function.
Systematic review and meta-analysis.
Patients who underwent sclerotherapy of ovarian endometrioma.
An electronic-based search with the use of Pubmed, Embase, Ovid Medline, Google Scholar, Clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials.
MAIN OUTCOME MEASURE(S):
Recurrence rate, symptoms relief, fertility outcome, and adverse events.
Eighteen studies were included in our review. The overall recurrence rates of endometrioma after sclerotherapy ranged from 0 to 62.5%. The risk of recurrence was significantly higher in women who were treated by means of ethanol washing than by means of ethanol retention. The number of oocytes retrieved was higher after endometrioma sclerotherapy compared with laparoscopic cystectomy, but clinical pregnancy rates were similar. There was no difference in the number of oocytes retrieved and the clinical pregnancy rates between the sclerotherapy-treated group with and the untreated group.
Sclerotherapy for ovarian endometrioma may be considered in symptomatic women who plan to conceive.
Biomed Rep. 2017 Jun;6(6):654-662.
Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: A preliminary study.
The etiology and pathophysiology of endometriosis remain unclear. The aim of the current study was to identify a candidate pathogenic gene, as well as potential biomarkers of endometriosis using messenger RNA (mRNA) sequencing (mRNA-seq). Twenty-three eutopic endometria from women with endometriosis and 20 endometria from control subjects were investigated. Eight eutopic endometria and five normal endometria were selected for mRNA-seq. Differentially expressed genes (DEGs) were identified and functional analysis was conducted. Validation of certain DEGs was performed in the remaining cases and control subjects by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 72 DEGs (66 upregulated and 6 downregulated) were identified in samples from women with endometriosis and compared with the control subjects. High DEGs included those involved in various functions, such as extracellular matrix (ECM) remodeling, angiogenesis, cell proliferation and differentiation. Enriched by these DEGs, 100 Gene Ontology terms were identified as significantly important, particularly ‘ECM’ and ‘endogenous stimulus’. Validation using RT-qPCR indicated that matrix metallopeptidase 11, dual specificity phosphatase 1, Fos proto-oncogeneand serpin family E member 1 were significantly upregulated and adenosine deaminase 2 was significantly downregulated in the eutopic endometrium of patients with endometriosis. The identified DEGs may be involved in the pathogenesis of endometriosis and may be potential biomarkers in the eutopic endometrium. The current study provides a comprehensive, but preliminary insight for elucidating the mechanisms of endometriosis, which require further in-depth studies for confirmation.
Gynecol Endocrinol. 2017 Nov;33(11):822-829.
Non-contraceptive benefits of intrauterine levonorgestrel administration: why not?
Levonorgestrel intrauterine systems (LNG-IUS) represent a modern therapy for an array of preexisting gynecological conditions, though they were first marketed in Finland in 1990. However, there are countries in which their use is extremely limited by social and cultural factors. This manuscript describes the possible reasons for this misuse, taking in consideration the clinical noncontraceptive benefits of intrauterine levonorgestrel in routinary practice. Medical diseases in which LNG-IUS represent a treatment include abnormal uterine bleeding, iron-deficiency anemia, endometrial hyperplasia, uterine fibroids, adenomyosis, endometriosis, and coagulopathies. The advantage of reducing the need for more radical treatments such as surgery or hysterectomy is well demonstrated, with remarkable benefits for patients. However, in many countries, surgery is still used as a first-line treatment and there is a need to define who could benefit from a less invasive option. It seems clear that such a reduced use of LNG-IUS depends on factors that imply both patients and practitioners, and that the role of counseling is becoming a key component in the decision-making process to reach the ultimate goal of compliance.
Iran J Vet Res. 2017 Winter;18(1):63-66.
A case of spontaneous abortion related to ovarian endometriosis in a Golden Retriever dog.
This report describes a case of spontaneous abortion in a 4-year-old Golden Retriever dog with ovarian endometriosis. Clinical findings indicated that there was not any senstivity in the abdomen and the viability parameters were within the reference values. On vaginal examination, serosanguineous discharge was determined. Ultrasonographic examination revealed that no fetus was observed in cornu uteri and an hypoechoic cystic structure, measuring 3.2 × 3.4 cm was found behind the left kidney. Ovarian cyst was suspected, and then ovariohysterectomy was performed. On laparotomy, the presence of a cystic structure was confirmed in the left ovary similar to ultrasonographic findings. Cyst was smooth, flat, hemorrhagic and thick-walled structure. Histopathologic examination of the ovarian stroma revealed covered luteinizing cells and midline hemorrhagic cyst. However, the internal surface of the cyst wall was covered by an endometrial lining. Interestingly, the endometriotic tissue had a maximal penetration into the cyst wall. It was thought that the ovarian endometriosis caused a failure in the luteinizing hormone action which is responsible for luteal function and spontaneous abortion was observed in this case. Although ovarian endometriosis is quite usual in human, this case could be the first report to describe ovarian endometriosis in a dog, and thus it has been reported to cause spontaneous abortion.
Arch Gynecol Obstet. 2017 Jul;296(1):115-122.
Endometrial thickness influences neonatal birth weight in pregnancies with obstetric complications achieved after fresh IVF-ICSI cycles.
Pregnancy-associated complications, duration of gestation and parity are well-known predictors of neonatal birth weight. Assisted reproductive technology (ART) affects neonatal birth weight as well. Endometrial thickness as measured on the day of HCG triggering may therefore impact on the neonatal birth weight.
The data of 764 singleton deliveries achieved after fresh transfer between November 1997 and 2014 were collected retrospectively with the intention to analyze the relationship of maternal and neonatal characteristics with endometrial thickness and the possible predictive value of endometrial thickness on neonatal birth weight.
Higher maternal age (p < 0.001), diminished ovarian reserve (p < 0.001), endometriosis (p = 0.008) and hypogonadotropic hypogonadism (p < 0.001) predicted thin endometrium. Neonatal birth weight (p = 0.004), longer duration of pregnancy (p = 0.008), parity (p = 0.026) and higher maternal BMI (p = 0.003) were correlated significantly with the degree of endometrial proliferation. Endometrial thickness strongly predicted neonatal birth weight (p = 0.004). After adjusting regression analysis for maternal age and BMI, parity, neonatal gender and pregnancy duration, endometrial thickness remained predictive for neonatal birth weight in pregnancies with obstetric complications (p = 0.017). In uneventful pregnancies duration and parity are determinants of neonatal birth weight.
Our findings suggest that endometrial thickness is an additional ART-related factor influencing neonatal birth weight. This finding should be confirmed in large cohort studies.