Ultrasound Obstet Gynecol. 2013 Apr;41(4):459-64. doi: 10.1002/uog.12292.

Tissue characterization using mean gray value analysis in deep infiltrating endometriosis.

Guerriero S1Pilloni MAlcazar JLSedda FAjossa SMais VMelis GBSaba L.

 

Abstract

OBJECTIVES:

To investigate differences in tissue characterization using three-dimensional sonographic mean gray value (MGV) between retrocervical and rectosigmoid deeply infiltrating endometriosis, and to assess intra- and interobserver concordance in MGV quantification.

METHODS:

In this retrospective study, stored ultrasound volumes from 50 premenopausal women (mean age, 32 years) with 57 histologically confirmed nodules of deep endometriosis were retrieved from our database for analysis. A single experienced operator had acquired all volumes. For each nodule, the MGV was evaluated using virtual organ computer-aided analysis (VOCAL) software with semiautomated sphere-sampling (1 cm3) from the central part of the nodule. In these patients the MGV was also quantified from the myometrium of the fundal part of the uterus. In addition, two observers calculated the MGV in a subset of 24 volumes in order to quantify inter- and intraobserver agreement using intraclass correlation coefficients (ICC).

RESULTS:

Mean MGV was significantly higher in rectosigmoid nodules (n = 34) than in nodules with a retrocervical location (n = 23) (23.863 vs. 17.705; P < 0.001). MGV of the myometrium was significantly higher in comparison with that of nodules in both locations (P < 0.001 for both). Intra- and interobserver measurement reproducibility was excellent (ICC > 0.95).

CONCLUSIONS:

Retrocervical and rectosigmoid endometriotic nodules display significantly different MGVs. Measurement of MGV is highly reproducible and its clinical value in the diagnosis and assessment of distribution of deep endometriosis should be assessed in future studies.

 

Indian J Urol. 2012 Apr;28(2):206-7. doi: 10.4103/0970-1591.98469.

Mullerianosis of the urinary bladder.

Kudva R1Hegde P.

Abstract

Mullerianosis of the urinary bladder is a rare and morphologically complex tumor-like lesion, composed of several types of mullerian lesions like endometriosis, endocervicosis, and endosalpingiosis. This disease occurs in women of reproductive age group. Implantative and metaplastic origins have been suggested in the pathogenesis.

 

Fertil Steril. 2012 Nov;98(5):1209-17. doi: 10.1016/j.fertnstert.2012.07.1103. Epub 2012 Aug 21.

Effect of antiangiogenic treatment on peritoneal endometriosis-associated nerve fibers.

Novella-Maestre E1Herraiz SVila-Vives JMCarda CRuiz-Sauri APellicer A.

 

Abstract

OBJECTIVE:

To investigate the effect of antiangiogenic treatment on experimental endometriotic lesion nerve fibers.

DESIGN:

Heterologous mouse model of endometriosis.

SETTING:

University Institute IVI, University Hospital La Fe.

ANIMAL(S):

Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4).

INTERVENTION(S):

Endometrium fragments stuck in the peritoneum of 5-week-old female nude mice treated with vehicle (n = 8) and antiangiogenic agent cabergoline (n = 8; Cb(2,) 0.05 mg/kg/day) for 14 days.

MAIN OUTCOME MEASURE(S):

Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (αSMA) for evaluating the number of immature blood vessels (IBV) and microvascular density (MVD); immunochemical analysis of protein-gene product 9.5 (PGP 9.5) to assess nerve fibers density (NFD), and blue toluidine staining to confirm presence of mast cells and macrophages in endometriotic lesions.

RESULT(S):

All the results were quantified by morphometric techniques. The IBV, NFD, and number of macrophages and mast cells were statistically significantly decreased in the Cb2-treated group when compared with controls.

CONCLUSION(S):

Antiangiogenic treatment statistically significantly diminishes new blood vessel formation after macrophage, mast cell, and nerve fiber reduction, providing a rationale to test antiangiogenic agents as a novel therapeutic approach to severe pelvic pain associated with human peritoneal endometriosis.

 

Neuroscience. 2012 Dec 6;225:269-82. doi: 10.1016/j.neuroscience.2012.08.033. Epub 2012 Aug 23.

Ectopic uterine tissue as a chronic pain generator.

Alvarez P1Chen XHendrich JIrwin JCGreen PGGiudice LCLevine JD.

 

Abstract

While chronic pain is a main symptom in endometriosis, the underlying mechanisms and effective therapy remain elusive. We developed an animal model enabling the exploration of ectopic endometrium as a source of endometriosis pain. Rats were surgically implanted with autologous uterus in the gastrocnemius muscle. Within two weeks, visual inspection revealed the presence of a reddish-brown fluid-filled cystic structure at the implant site. Histology demonstrated cystic glandular structures with stromal invasion of the muscle. Immunohistochemical studies of these lesions revealed the presence of markers for nociceptor nerve fibers and neuronal sprouting. Fourteen days after surgery rats exhibited persistent mechanical hyperalgesia at the site of the ectopic endometrial lesion. Intralesional, but not contralateral, injection of progesterone was dose-dependently antihyperalgesic. Systemic administration of leuprolide also produced antihyperalgesia. In vivo electrophysiological recordings from sensory neurons innervating the lesion revealed a significant increase in their response to sustained mechanical stimulation. These results are consistent with clinical and pathological findings observed in patients with endometriosis, compatible with the ectopic endometrium as a source of pain. This model of endometriosis allows mechanistic exploration at the lesion site facilitating our understanding of endometriosis pain.

 

Mol Hum Reprod. 2012 Dec;18(12):563-71. doi: 10.1093/molehr/gas037. Epub 2012 Aug 24. Review.

The molecular connections between the cannabinoid system and endometriosis.

Sanchez AM1Vigano PMugione APanina-Bordignon PCandiani M.

 

Abstract

The endocannabinoid system consists of an array of endogenously produced bioactive lipids that activate cannabinoid 1 (CB1) and 2 (CB2) receptors. Alterations of this system have been described in almost every category of disease. These changes can be protective or maladaptive, making the endocannabinoid network an attractive therapeutic target. Little is known about the potential role of endocannabinoids in endometriosisdevelopment although this is a topic worthy of further investigation since endocannabinoid modulators have recently been shown to affect specific mechanisms critical to endometriosis establishment and maintenance. A literature review was herein performed with the aim of defining the regulation and function of the endocannabinoid signaling in in vitro and animal models of endometriosis. The components of the endocannabinoid system, CB1 and CB2 receptors and the enzymes N-acylphosphatidylethanolamine-phospholipase D and fatty acid amide hydrolase are differentially regulated throughout the menstrual cycle in the endometrium and are expressed in deep endometriotic nodules and in sensory and sympathetic neurons innervating the lesions. Selective cannabinoid receptor agonists, such as WIN 55212-2, appear to have a favorable action in limiting cell proliferation and in controlling pain symptoms. Conversely, endometrial cell migration tends to be stimulated by receptor agonists. The phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 pathways seem to be involved in these processes. However, the underlying mechanisms of action are only just beginning to unfold. Given the complexity of the system, further studies are needed to clarify whether the endocannabinoid system might represent a promising target for endometriosis.

 

Curr Obstet Gynecol Rep. 2012 Sep;1(3):124-137. Epub 2012 Jun 15.

Insights into Assessing the Genetics of Endometriosis.

Rahmioglu NMissmer SAMontgomery GWZondervan KT.

Abstract

Endometriosis is a complex disease arising from the interplay between multiple genetic and environmental factors. The genetic variants potentially underlying the hereditary component of endometriosis have been widely investigated through hypothesis-driven candidate gene studies, an approach that generally has proven to be inherently difficult and problematic for a number of reasons. Recently, through major collaborative efforts in the endometriosis research field, hypothesis-free genome-wide approaches have started to provide new insights into potential pathways leading to development of endometriosis, as well as highlighting the phenotypic heterogeneity of the condition. This review summarizes the most recent studies investigating the genetic variation contributing to endometriosis, with a particular focus on genome-wide approaches, and discusses promising future directions of genetic research.

 

 

ANZ J Surg. 2012 Nov;82(11):844-7. doi: 10.1111/j.1445-2197.2012.06185.x. Epub 2012 Aug 24.

Pathologies of the appendix: a 10-year review of 4670 appendicectomy specimens.

Chandrasegaram MD1Rothwell LAAn EIMiller RJ.

 

Abstract

BACKGROUND:

Debate surrounds the management of the macroscopically normal appendix. Current literature recommends its removal given the high incidence of microscopic appendicitis, and other unusual pathologies in the normal-looking appendix. Negative appendicectomies are reported on the decline with increased use of diagnostic radiological adjuncts.

METHODS:

This study analysed pathologies of the appendix over 10 years in the Pathology Department in Canberra. A positive appendicectomy was defined as acute appendicitis, faecoliths, worms, endometriosis or appendiceal tumours. We reviewed the positive appendicectomy rate over this time period.

RESULTS:

There were 4670 appendicectomy specimens in 2386 males (51.1%) and 2284 (49%) females. The incidence of acute appendicitis was 71.3% and the positive appendicectomy rate was 76.3%. There were significantly fewer negative appendicectomies in males (16.8%) compared with females (31.0%). There was no appreciable change in this trend over the study period. Of the positive appendicectomies, there were 129 (3.6%) faecoliths. Of these, only 39.5% had concomitant appendicitis. There were 44 (1.2%) specimens identified with worms. Of these, 40.9% had concomitant appendicitis. There were 14 cases of endometriosis of the appendix of which 36% had concomitant appendicitis. There were 58/3562 (1.6%) appendiceal tumours within the positive appendicectomy group the majority of which were carcinoid tumours (65.5%).

CONCLUSION:

There is a higher incidence of negative appendicectomies in women compared with men, which is similar to other published studies. Faecoliths and worms are a known cause of appendiceal colic and in our series were identified mostly in the absence of histological evidence of appendicitis.

 

 

 

Fertil Steril. 2012 Dec;98(6):1512-20.e3. doi: 10.1016/j.fertnstert.2012.07.1133. Epub 2012 Aug 25.

Adenosine triphosphate-binding cassette transporter G2 expression in endometriosis and in endometrium from patients with and without endometriosis.

Matsuzaki S1Darcha C.

 

Abstract

OBJECTIVE:

To investigate adenosine triphosphate (ATP)-binding cassette transporter G2 (ABCG2) expression in endometriosis and in samples of endometrium from patients with and without endometriosis.

DESIGN:

Prospective study.

SETTING:

University hospital.

PATIENT(S):

Patients with and without endometriosis.

INTERVENTION(S):

Endometrial and endometriotic tissues obtained throughout the menstrual cycle.

MAIN OUTCOME MEASURE(S):

Density of ABCG2(+) microvessels, density of CD31(+) microvessels.

RESULT(S):

No statistically significant differences in the density of ABCG2(+) microvessels were observed between endometrium of patients with and without endometriosis in the proliferative phase and early, middle, and late secretory phases. The density of ABCG2(+) microvessels was statistically significantly higher in the menstrual endometrium of patients with endometriosis compared with patients without endometriosis. The density of ABCG2(+) microvessels was reduced in the ectopic endometrium compared with matched eutopic endometrium except in cases of deep infiltrating endometriosis. The density of ABCG2(+) microvessels was statistically significantly higher in deep infiltrating endometriosis compared with ovarian endometriosis and red and black peritoneal lesions throughout the menstrual cycle.

CONCLUSION(S):

ABCG2 is strongly expressed in the endothelial cells of microvessels of eutopic endometrium, and the density of ABCG2(+) microvessels is reduced in ectopic endometrium except in cases of deep infiltrating endometriosis. ABCG2(+) microvessels may represent an integral part of the pathophysiology of deep infiltrating endometriosis.

 

 

 

Obstet Gynecol Surv. 2012 Jul;67(7):417-25. doi: 10.1097/OGX.0b013e31825cecb3. Review.

Systematic review of therapies for noncyclic chronic pelvic pain in women.

Yunker A1Sathe NAReynolds WSLikis FEAndrews J.

 

Abstract

We synthesized the literature (articles published between 1990 and May 2011) on the treatment of noncyclic and mixed cyclic/noncyclic chronic pelvic pain (CPP) in adult women. Two reviewers assessed studies against predetermined inclusion/exclusion criteria, extracted data regarding participant and intervention characteristics and outcomes, and assigned overall quality and strength of evidence ratings. Of 2081 studies, 21 addressed surgical or nonsurgical interventions. Definitions of CPP and participant characteristics varied across studies, and most studies were of poor quality, which precluded data synthesis. Although surgical and nonsurgical approaches both improved pain, neither was more effective when directly compared in 3 studies. Laparoscopic adhesiolysis or laparoscopic uterosacral nerve ablation did not further improve pain scores over diagnostic laparoscopy. The evidence to conclude that surgical intervention is either effective or ineffective or that one technique is superior to another is insufficient. Most studies on nonsurgical approaches evaluated hormonal therapies in endometriosis-associated CPP and were not placebo controlled. Few studies addressed nonhormonal or nonpharmacologic approaches. Harms reporting was limited. Overall, no nonsurgical treatment was more or less effective than another, except for the clear negative effect of raloxifene. In general, the literature addressing therapies for CPP in women is of poor quality and inconclusive. Improved characterizations of the targeted condition and interventions in CPP research, including a uniform definition and standardized evaluation, are necessary to inform treatment choices.

 

 

 

Med Glas (Zenica). 2012 Aug;9(2):268-72.

Is adenomyosis associated with the risk of endometrial cancer?

Gün I1Oner OBodur SOzdamar OAtay V.

 

Abstract

AIM:

To evaluate an association of adenomyosis with endometrial cancer and to determine the frequency of adenomyosis at hysterectomy specimens.

METHODS:

This study was carried out retrospectively on pathologic specimens of hysterectomies. A total of 472 women in the period 2007-2011 enrolled to the study. All pathologies seen in hysterectomy specimens were noted. The frequency of adenomyosis and the accompanying pathologies were determined. These women were categorized into two groups according to the presence of adenomyosis. The incidence of adenomyosis was analyzed together with the endometrial cancer.

RESULTS:

The incidence of adenomyosis was 20.8% at hysterectomy specimens. There was no statistically significant difference between the mean age of the two groups (p = 0.069). There were 98 cases with adenomyosis and the only pathologic finding was adenomyosis, in 28 (28.5%) cases. The most common accompanying pathologies with adenomyosis were uterine myomas in 51 (52%), uterine polyps in 16 (16.3%) and endometrial carcinomas in 11 (11.2%) cases. However, statistically significant association of the presence of adenomyosis with uterine myoma (p = 0.227) and endometrial polyps (p = 0.997) and endometrial carcinoma (p = 0.771) was not found.

CONCLUSION:

In hysterectomy specimens, no statistically significant difference was determined between the groups with and without adenomyosis in terms of co-occurrence with endometrial carcinoma.

 

 

 

Hum Reprod. 2012 Dec;27(12):3450-9. doi: 10.1093/humrep/des313. Epub 2012 Aug 27.

Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction.

Vercellini P1Somigliana EConsonni DFrattaruolo MPDe Giorgi OFedele L.

 

Abstract

STUDY QUESTION:

Does surgical or medical treatment for endometriosis-associated severe deep dyspareunia achieve better results in terms of patients’ satisfaction (main study outcome), variation of coital pain and frequency of intercourse?

SUMMARY ANSWER:

Surgery and progestin therapy were equally effective in the treatment of deep dyspareunia in women with rectovaginal endometriosis, whereas medical therapy performed significantly better than excisional treatment in those without deeply infiltrating lesions.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS:

Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. This study reports a direct comparison between the two treatment options in women with severe pain during intercourse.

DESIGN:

Patient preference, parallel cohort study with a 12-month follow-up. The effect of conservative surgery at laparoscopy was compared with treatment with a low-dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery.

PARTICIPANTS AND SETTING:

A total of 51 patients chose repeat surgery and 103 progestin treatment. Patient satisfaction was graded according to a five-category scale. Variations in pain during intercourse were measured by means of a 100-mm visual analogue scale.

MAIN RESULTS AND THE ROLE OF CHANCE:

In the surgery group, a marked and rapid short-term dyspareunia score reduction was observed, followed by partial recurrence of pain. The pain relief effect of the progestin was more gradual, but progressive throughout the study period. At a 12-month follow-up, the frequency of intercourse per month (mean ± SD) was 4.6 ± 1.8 in the surgery group and 5.3 ± 1.5 in the norethisterone acetate group (P = 0.02). A total of 22/51 (43%) women were satisfied in the surgery group compared with 61/103 (59%) in the progestin group [adjusted odds ratios (OR), 0.36; 95% confidence interval (CI), 0.16-0.82; P = 0.015]. Corresponding figures in women with and without rectovaginal endometriotic lesions were, respectively, 13/24 (54%) versus 18/35 (51%; adjusted OR, 0.77; 95% CI, 0.22-2.67; P = 0.68), and 9/27 (33%) versus 43/68 (63%; adjusted OR, 0.23; 95% CI, 0.07-0.76, P = 0.02). BIAS, CONFOUNDING, AND OTHER REASONS FOR CAUTION: Treatments were not randomly assigned, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions.

GENERALIZABILITY TO OTHER POPULATIONS:

Caucasian patients able to choose their treatment.

STUDY FUNDING/COMPETING INTEREST(S):

This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

 

 

 

Hum Reprod. 2012 Nov;27(11):3168-78. doi: 10.1093/humrep/des299. Epub 2012 Aug 27.

The ENDOCARE questionnaire guides European endometriosis clinics to improve the patient-centeredness of their care.

Dancet EA1Apers SKluivers KBKremer JASermeus WDevriendt CNelen WLD’Hooghe TM.

 

Abstract

STUDY QUESTION:

How patient-centered are two included specialized endometriosis clinics relative to each other and how can they improve the patient-centeredness of their care?

SUMMARY ANSWER:

The validated ENDOCARE questionnaire (ECQ) reliably concluded that the adjusted overall patient-centeredness did not differ between the clinics, that each clinic was significantly more patient-centered for 2 out of 10 dimensions of patient-centered endometriosis care and that clinics 1 and 2 had to improve 8 and 13 specific care aspects, respectively.

WHAT IS KNOWN ALREADY:

Patient-centered endometriosis care is essential to high-quality care and is defined by 10 dimensions. The ECQ was developed, validated and proved to be reliable in a European setting of self-reported endometriosis patients but had not yet been used at a clinic level for quality management.

STUDY DESIGN, SIZE, DURATION:

A cross-sectional survey was disseminated in 2011 to all 514 women diagnosed with endometriosis during a laparoscopy indicated for pain and/or infertility during a retrospective 2-year period (2009-2010) in two university clinics from two different European countries.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

In total 337 patients completed the ECQ (216 and 121 per clinic). Respondents had a mean age of 34.3 years. Three in four reported a surgical diagnosis of moderate or severe endometriosis and the majority reported surgical treatment by a multidisciplinary team. The ECQ assessed the 10 dimensions of patient-centeredness, more specifically whether the health-care performance, as perceived by patients, measured up to what is important to patients in general.

MAIN RESULTS:

The ECQ was completed by 337 respondents (response rate = 65.6%). Reliability and validity of the ECQ for use on clinic level were confirmed. Clinics did not differ in overall mean importance scores; importance rankings of the ECQ dimensions were almost identical. The overall patient-centeredness scores (PCS), adjusted for education level, did not discriminate between the clinics. However, the adjusted PCS for the dimensions ‘clinic staff’ and ‘technical skills’ were significantly better in clinic 1, whereas the dimensions ‘physical comfort’ and ‘access to care’ were significantly better in clinic 2. There were 8 (clinic 1) and 13 (clinic 2) targets identified for joint and cross-clinic improvement.

LIMITATIONS, REASONS FOR CAUTION:

Response rates were relatively high. Recall bias was the most important limitation and research in more clinics is needed to define the statistical discriminative value of the ECQ.

WIDER IMPLICATIONS OF THE FINDINGS:

European endometriosis clinics can use the validated ECQ for reliable assessment of their ‘patient-centeredness’, for comparison with others and for setting specific targets to improve the patient-centeredness of their endometriosis care, to plan interventions, and to evaluate their effectiveness.

STUDY FUNDING/COMPETING INTEREST:

This work was funded by KU Leuven and European Network of Endometriosis (ENE), supported by the European Commission (Public Health Executive Agency). No competing interests are declared.

 

 

 

 

Hum Reprod. 2012 Nov;27(11):3179-86. doi: 10.1093/humrep/des304. Epub 2012 Aug 27.

Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2.

Ballester M1Gonin JRodenas ABernaudin JFRouzier RCoutant CDaraï E.

 

Abstract

STUDY QUESTION:

How is the expression of nectins and nectin-like molecules (Necls) detected by immunostaining altered by endometriosis?

SUMMARY ANSWER:

Our results suggest that Nectin-1, -3, -4 and Necl-2 may contribute to the pathogenesis of endometriosis. Immunostaining of nectins and Necls varies according to the anatomical location of endometriosis.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS:

Nectin and Necl molecules are immunoglobulin-like cell adhesion molecules involved in apoptosis, cell proliferation and in metastases. Previous studies have demonstrated the involvement of adhesion molecules in the development of endometriotic lesions but no data exist on immunostaining of nectins and Necls molecules in endometriosis.

DESIGN, PARTICIPANTS AND SETTING:

This retrospective study was conducted in a tertiary-care hospital (Tenon Hospital, Paris, France). Samples were collected from 55 women undergoing endometrial biopsy or surgery for endometriosis and 20 controls having hysterectomy or endometrial biopsy for other reasons; multiple samples were collected from 15 women. We studied the immunostaining of Nectin-1, -3, -4 and Necl-2 in secretory and proliferative endometrium from women with (n = 20) or without endometriosis (i.e. control group, n = 20), and in peritoneal (n = 20), ovarian (n = 20) and colorectal endometriosis (n = 20).

MAIN RESULTS:

Semi-quantitative immunostaining demonstrated that (1) Necl-2 staining was stronger in all types of endometriotic lesions than in the eutopic endometrium from patients with endometriosis (P < 0.0125) and in ovarian endometriotic cysts compared with other locations (P < 0.001); (2) Nectin-3 staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.03) and in all endometriotic lesions compared with the eutopic endometrium from patients with endometriosis (P < 0.0125); (3) Nectin-4, staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.04) and (4) Nectin-1 staining was significantly increased in colorectal endometriosis compared with other locations (P = 0.004).

BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION:

We did not assess the pattern of expression in endometriosis of all nectins and Necl molecules. Indeed, Necl-5 is implicated in many pathophysiological processes such as cell movement and proliferation with potential relevance to endometriosis. GENERALISABILITY TO OTHER POPULATIONS: At present, few data on implication of nectins and Necl molecules in endometriosis exist. Hence, our results should be confirmed by further quantitative studies at protein or RNA levels.

STUDY FUNDING/COMPETING INTEREST(S):

No funding source. All the authors declare no conflict of interest.

 

 

 

Int J Womens Health. 2012;4:383-93. doi: 10.2147/IJWH.S24948. Epub 2012 Jul 31.

Video-assisted laparoscopy for the detection and diagnosis of endometriosis: safety, reliability, and invasiveness.

Schipper E1Nezhat C.

 

Abstract

Endometriosis is a highly enigmatic disease with multiple presentations ranging from infertility to severe pain, often causing significant morbidity. Video-assisted laparoscopy (VALS) has now replaced laparotomy as the gold standard for the diagnosis and management of endometriosis. While imaging has a role in the evaluation of some patients, histologic examination is needed for a definitive diagnosis. Laboratory evaluation currently has a minor role in the diagnosis of endometriosis, although studies are underway investigating serum markers, genetic studies, and endometrial sampling. A high index of suspicion is essential to accurately diagnose this complex condition, and a multidisciplinary approach is often indicated. The following review discusses laparoscopic diagnosis of endometriosis from the pre-operative evaluation of patients suspected of having endometriosis to surgical technique for safe and adequate laparoscopic diagnosis of the condition and postsurgical care.

 

 

 

Ugeskr Laeger. 2012 Aug 27;174(35):1999-2000. Danish.

Endometriosis as a cause of pneumothorax.

Frost A1Bach P.

 

Abstract

A young woman, who had formerly been diagnosed with endometriosis, was admitted to hospital with five incidents of right-sided spontaneous pneumothorax. Despite two thoracoscopic operations the pneumothorax reoccurred. The third operation revealed histologically verified endometriotic tissue of the diaphragm causing diaphragmatic fenestrations. It was concluded that the patient suffered from catamenial pneumothorax, where transdiaphragmatic passage of air from the cervix through the peritoneum during the menstruation period is believed to cause pneumothorax.

 

 

Arch Gynecol Obstet. 2013 Jan;287(1):77-82. doi: 10.1007/s00404-012-2539-4. Epub 2012 Aug 29.

Comparative study between VEGF-A and CA-125 in diagnosis and follow-up of advanced endometriosis after conservative laparoscopic surgery.

Mohamed ML1El Behery MMMansour SA.

 

Abstract

OBJECTIVE:

To evaluate the role of serum level of VEGF-A in comparison to CA-125 in diagnosis and follow-up of patients with advanced endometriosis after conservative laparoscopic surgery.

METHODS:

A prospective randomized case-control study was performed on patients referred for laparoscopy complaining of unexplained primary infertility with or without chronic pelvic pain. Thirty patients with advanced endometriosis; stage III-IV were included (study group), another 30 women without endometriosis or any other medical conditions were settled as a control group. Pre-operative blood samples were collected from study and control cases. Post-operative blood samples were collected from 25 treated patients in the follicular phase of the third menstrual cycle; 5 cases were drop-outs. Serum level of cancer antigen-125 (CA-125) and vascular endothelial growth factor (VEGF-A) were assayed by using enzyme linked immunosorbent assay (ELISA) kit.

RESULTS:

There was a statistically significant difference in serum CA-125 and VEGF-A level in patients with advanced endometriosis before conservative laparoscopic surgery and those without endometriosis (p < 0.001) and after conservative laparoscopic surgery (p < 0.001). High sensitivity (93.3 %), specificity (96.7 %) and accuracy (95.0 %) of VEGF-A assay than in CA-125 distinguishing between patients with endometriosis from those without endometriosis; CA-125 has 70.0 %sensitivity, 90.0 % specificity and 85.0 % accuracy. Percentage of decrease of VEGF-A level after operation was higher than that of CA-125 (45.9 vs. 25.8 %) p < 0.001, respectively.

CONCLUSION:

The use of VEGF-A for diagnosis of advanced endometriosis at cut-off 680 pg/ml and for follow-up is better than CA-125.

 

Chin Med J (Engl). 2012 Aug;125(15):2688-93

Outcome of in vitro fertilization in endometriosis-associated infertility: a 5-year database cohort study.

Lin XN1Wei MLTong XMXu WHZhou FHuang QXWen GFZhang SY.

 

Abstract

BACKGROUND:

Endometriosis affects natural fertility through various approaches, and in vitro fertilization (IVF) is a good treatment. But the IVF result of endometriosis patients is still under debate. We investigated the effect of endometriosis on IVF by analyzing the data from a single reproductive center.

METHODS:

A retrospective, database-searched cohort study was performed. Relevant information was collected from the electronic records of women who underwent IVF/intracytoplasmic sperm injection between January 2006 and December 2010 in the Assisted Reproductive Unit of Sir Run Run Shaw Hospital. Patients with endometriosiswere enrolled the study group. The rest of the women formed the control group. The main outcome was the clinical pregnancy rate. Secondary outcomes were oocytes retrieved number, fertilization rate, high-quality embryo rate, number of high-quality embryo for embryo transplantation, and implantation embryo/high-quality embryo ratio (IE/HQE ratio). Comparisons were performed by the c(2)-test and independent t-test.

RESULTS:

The endometriosis group (n = 177) had a markedly lower oocytes retrieved number, fertilization rate, implantation rate, and clinical pregnancy rate (7.6 ± 5.1, 63.6%, 27.7%, and 45.2%, respectively) compared with the non-endometriosis group (n = 4267; 11.8 ± 7.3, 68.4%, 36.2%, and 55.2%, respectively). Stratified analysis showed that this difference was found in the subgroup younger than 35-years old, while only fertilization rate and implantation rate were different in the elder subgroup. The ratio of high-quality embryos transferred is lower in endometriosis group (53.7% vs. 71.8%, P < 0.05), but there is no difference in IE/HQE ratio between two groups. There is no significant difference in fertilization rate, implantation rate, and clinical pregnancy rate between mild and severe endometriosis patients.

CONCLUSIONS:

Endometriosis patients suffer a decreasing IVF pregnancy rates mainly caused by reducing oocytes number and fertilization rate, regardless of the severity of the disease. Appropriate intracytoplasmic sperm injection manipulation might improve the outcomes of IVF.

 

Zhonghua Fu Chan Ke Za Zhi. 2012 Jun;47(6):440-4. Chinese.

Influence of gonadotropin releasing hormone agonist on the expression of mRNA of nerve growth factor and its receptors in eutopic endometrial stromal cells.

Li XY1Leng JHLang JH.

 

Abstract

OBJECTIVE:

To investigate the influence of gonadotropin releasing hormone agonist (GnRH-a) on the expression mRNA of nerve growth factor (NGF) and its receptors (TrkA and P75NTR) in normal and eutopic endometrial stromal cells (ESC).

METHODS:

From January to April 2009, 3 patients with endometriosis undergoing surgery in Peking Union Medical College Hospital were obtained eutopic endometrium as study group matched with eutopic endometrium from 3 patients with teratoma as control group. ESC were incubated with different concentration of GnRH-a (0, 5×10⁻¹¹, 5×10⁻¹⁰, 5×10⁻⁹, 5×10⁻⁸, 5×10⁻⁷ g/ml). The expression of mRNA of NGF, TrkA and P75NTR were measured by real-time-PCR.

RESULTS:

At concentration of 0 g/ml, the levels of NGF, TrkA and P75NTR mRNA in ESC were 6.32, 8.55, 8.08 in study group, which were significantly higher than 0.94, 0.67, 1.08 in control group (P < 0.05). Treated by the following concentration of GnRH-a (5×10⁻¹¹, 5×10⁻¹⁰, 5×10⁻⁹, 5×10⁻⁸, 5×10⁻⁷ g/ml), the median expression of NGF, TrkA and P75NTR mRNA was 1.00, 0.96, 1.05; 1.09, 0.82, 1.27; 1.04, 0.52, 0.81;1.00, 0.55, 0.64; 0.78, 0.49, 1.02 in study group. Compared with the expressions of those untreated by GnRH-a in study group, they showed significantly lower trends (P < 0.05). In control group, the median expression of NGF, TrkA and P75NTR mRNA was 0.98, 0.37, 0.92; 0.70, 0.45, 1.15; 1.55, 0.80, 1.35; 1.09, 0.41, 1.35; 0.90, 0.82, 1.18. Compared with the expressions of those untreated by GnRH-a in control group, there were no statistically differences (P > 0.05). And treated by the same concentration of GnRH-a, the expressions of NGF, TrkA and P75NTR mRNA did not show statistically difference between the two groups (P > 0.05).

CONCLUSION:

The expression of NGF, TrkA and P75NTR mRNA were suppressed by GnRH-a.

 

 

Curr Obstet Gynecol Rep. 2012 Sep 1;1(3):116-123.

The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and Dysfunction: Potential Relevance to Humans.

Bruner-Tran KL1Resuehr D1Ding T1Lucas JA1Osteen KG1.

 

Abstract

In a murine model, we have linked early life toxicant exposure to reduced uterine sensitivity to progesterone, a phenotype we had previously associated with inflammation in endometriosis patients. Subsequent studies revealed that developmental toxicant exposure not only reduces fertility in male and female mice but also negatively impacts pregnancy leading to spontaneous preterm birth (PTB). An epigenetic alteration of the progesterone receptor gene correlated with reduced fertility and adverse pregnancy outcomes and persisted in multiple generations of mice in the absence of an additional toxicant exposure. Gene-environment interactions in women may explain why some patients “at risk” for PTB deliver at term while others without known risks deliver early. Our model provides a unique system to unravel the interactive influences of inflammation and reduced progesterone responsiveness on PTB and suggests that therapy needs to begin prior to pregnancy (and involve both partners) rather than once the inflammatory cascade has been initiated.

 

 

Iran J Reprod Med. 2012 Sep;10(5):453-8.

The rate of blastocysts production following vitrification with step-wise equilibration of immature mouse oocytes.

Mahmoudi R1Rajaei F2Ragardi Kashani I3Abbasi M3Amidi F3Sobhani A3Amiri I4.

 

Abstract

BACKGROUND:

Cryopreservation and in vitro maturation (IVM) of oocyte is becoming an important technique in infertility treatment and fertility preservation. Also it has been proposed to establish a genetic resource bank for endangered or commercially important animal species.

OBJECTIVE:

The aim of this study was to evaluate viability, maturation and fertilization rate of mouse immature oocytes after single and stepwise vitrification procedure.

MATERIALS AND METHODS:

Oocytes were obtained from 4 weeks old female mice 48h after intraperitoneal injection of 7.5 IU pregnant mare serum gonadotropin (PMSG). Collected oocytes before vitrification were exposed to cryoprotectant, which was composed of 30% (v/v) ethylene glycol, 18% (w/v) Ficoll-70, and 0.3 M sucrose, either by single step or in a step-wise way. After vitrification and storage in liquid nitrogen, the oocytes were warmed and washed two times in medium TCM199 and then subjected to IVM, fertilization and subsequent development to blastocysts.

RESULTS:

The oocytes survival rates after vitrifying-warming (88.96%), maturation rate (73.23%), the capacity of fertilization (57.80%) and embryonic development to blastocyst (16.41%) in the step-wise exposure were significantly higher (p<0.001) compared with corresponding rate in the single step procedure.

CONCLUSION:

The results suggest that vitrification with step-wise procedure has positive effects on maturation and developmental capacity of mice germinal vesicle oocytes in compare with single step vitrification procedure.

 

J Robot Surg. 2012 Sep;6(3):223-30. doi: 10.1007/s11701-011-0296-1. Epub 2011 Jul 28.

Experience with robot-assisted laparoscopic surgery of the lower ureteral segment in adults.

Musch M1Loewen H2Davoudi Y3Yanovskiy M2Hohenhorst JL2Vanberg M2Kroepfl D2.

 

Abstract

Open reconstructive surgery of the lower ureteral segments in adults requires wide exposure as the basic prerequisite for such complex procedures. Thus, open surgical reconstruction in this area is an invasive procedure for the patient. Nevertheless, during the last few years robot-assisted laparoscopic techniques have emerged and have also already been used successfully for minimally invasive complex reconstructive procedures in urology. We present the medical histories, descriptions of the surgical procedures, and the postoperative data for adult patients undergoing robot-assisted surgery of the lower ureteral segments. Between July 2009 and July 2010, three surgeons performed nine robot-assisted reconstructive operations of the lower ureteral segments including five segmental ureteral resections combined with the psoas hitch procedures in three cases and, in addition, a Boari flap in one of them, one ureteric stricture resection with end-to-end anastomosis, one extravesical ureteral reimplantation because of vesicorenal reflux, one bilateral intravesical ureteral reimplantation because of bilateral ureteral ectopia, and one ureterolysis with omental wrap in a patient with pelvic endometriosis. We observed no intraoperative complications. Postoperative complications occurred in six patients (Clavien Grad I n = 1, II n = 4, IVa n = 1). During a median follow up of five months all affected renal units remained asymptomatic and were free from hydronephrosis. Our data illustrate that robot-assisted surgery of the lower ureter is feasible and support the growing evidence from the literature that it can be successfully used for complex ureteric reconstruction.

 

 

Diagn Pathol. 2012 Sep 3;7:117. doi: 10.1186/1746-1596-7-117.

Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor.

Fang CL1Lin YHChen WY.

 

Abstract

Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained.

 

 

Fertil Steril. 2012 Sep;98(3):529-55. doi: 10.1016/j.fertnstert.2012.07.1120. Review.

Pharmacologic therapies in endometriosis: a systematic review.

Soares SR1Martínez-Varea AHidalgo-Mora JJPellicer A.

 

Abstract

To assess the literature on preclinical and clinical efficacy and safety data of pharmacologic groups proposed in the treatment of endometriosis, we performed a systematic review of publications from March 2002 to January 2012 via PubMed search. Additional relevant articles were identified from citations within these publications. A high number of medications were tested in preclinical models of endometriosis due to their theoretic capacity of disrupting important pathophysiologic pathways of the disease, such as inflammatory response, angiogenesis and cell survival, proliferation, migration, adhesion, and invasion. Tumor necrosis factor α-blockers, nuclear factor κB inhibitors, antiangiogenic agents, statins, antioxidants, immunomodulators, flavonoids, histone deacetylase inhibitors, matrix metalloproteinase inhibitors, metformin, novel modulators of sex steroids expression, and apoptotic agents were all effective in in vitro/animal models. Most of these agents have not been tried in the clinical setting, mainly because of the high risk of adverse effects. However, some of them can be used in humans. Dopamine agonists and valproic acid have already been tested in pilot studies with good results. Etanercept, metformin, and statins are used in humans for other indications, and endostatin is now being tested in phase 2 oncologic trials. These drugs may constitute alternatives to conventional therapy with estrogen inhibitors and anti-inflammatory agents.

 

 

Fertil Steril. 2012 Sep;98(3):564-71. doi: 10.1016/j.fertnstert.2012.07.1061. Review.

Deep endometriosis: definition, diagnosis, and treatment.

Koninckx PR1Ussia AAdamyan LWattiez ADonnez J.

 

Abstract

Deep endometriosis, defined as adenomyosis externa, mostly presents as a single nodule, larger than 1 cm in diameter, in the vesicouterine fold or close to the lower 20 cm of the bowel. When diagnosed, most nodules are no longer progressive. In >95% of cases, deep endometriosis is associated with very severe pain (in >95%) and is probably a cofactor in infertility. Its prevalence is estimated to be 1% -2%. Deep endometriosis is suspected clinically and can be confirmed by ultrasonography or magnetic resonance imaging. Contrast enema is useful to evaluate the degree of sigmoid occlusion. Surgery requires expertise to identify smaller nodules in the bowel wall, and difficulty increases with the size of the nodules. Excision is feasible in over 90% of cases often requiring suture of the bowel muscularis or full-thickness defects. Segmental bowel resections are rarely needed except for sigmoid nodules. Deep endometriosis often involves the ureter causing hydronephrosis in some 5% of cases. The latter is associated with 18% ureteral lesions. Deep endometriosis surgery is associated with late complications such as late bowel and ureteral perforations, and recto-vaginal and uretero-vaginal fistulas. Although rare, these complications require expertise in follow-up and laparoscopic management. Pain relief after surgery is excellent and some 50% of women will conceive spontaneously, despite often severe adhesions after surgery. Recurrence of deep endometriosis is rare. In conclusion, defined as adenomyosis externa, deep endometriosis is a rarely a progressive and recurrent disease. The treatment of choice is surgical excision, while bowel resection should be avoided, except for the sigmoid.

 

 

 

Hum Reprod. 2012 Nov;27(11):3187-97. doi: 10.1093/humrep/des282. Epub 2012 Aug 30.

Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells.

Silveira CG1Abrão MSDias JA JrCoudry RASoares FADrigo SADomingues MARogatto SR.

 

Abstract

BACKGROUND:

Endometriosis is a multifactorial gynecological disease characterized by the presence of functional endometrium-like tissue in ectopic sites. Several studies have focused on elucidating the immunological, endocrine, environmental and genetic factors involved in endometriosis. However, its pathogenesis is still unclear.

METHODS:

High-resolution comparative genomic hybridization was applied to screen for genomic imbalances in laser microdissected stromal and epithelial cells from 20 endometriotic lesions and three samples of eutopic endometrium derived from eight patients. The expression of seven stemness-related markers (CD9, CD13, CD24, CD34, CD133, CD117/c-Kit and Oct-4) in endometrial tissue samples was evaluated by immunohistochemistry.

RESULTS:

Samples of eutopic endometrium showed normal genomic profiles. In ectopic tissues, an average of 68 genomic imbalances was detected per sample. DNA losses were more frequently detected and involved mainly 3p, 5q, 7p, 9p, 11q, 16q, 18q and 19q. Many of the genomic imbalances detected were common to endometriotic stroma and epithelia and also among different endometriotic sites from the same patient. These findings suggested a clonal origin of the endometriotic cells and the putative involvement of stem cells. Positive immunostaining for CD9, CD34, c-Kit and Oct-4 markers was detected in isolated epithelial and/or stromal cells in eutopic and ectopic endometrium in the majority of cases.

CONCLUSIONS:

The presence of shared genomic alterations in stromal and epithelial cells from different anatomical sites of the same patient and the expression of stemness-related markers suggested that endometriosis arises as a clonal proliferation with the putative involvement of stem cells.

 

 

Arch Gynecol Obstet. 2012 Dec;286(6):1563-9. doi: 10.1007/s00404-012-2538-5. Epub 2012 Sep 2. Review.

Controversies in the management of endometriomas in patients undergoing assisted reproduction.

Siristatidis C1Chrelias CSioulas VDStathopoulou VAMakris GMKoliopoulos GKassanos D.

 

Abstract

INTRODUCTION:

The presence of an endometrioma has been proposed to affect the ovarian function in a negative way. Our aim was to present the key evidence on multiple aspects of endometriomas’ management in subfertile couples scheduled for assisted reproduction technologies (ART).

MATERIALS AND METHODS:

A critical review of the existing literature was performed focusing on the need of endometrioma treatment prior to ART, the relevant options, the potentially participating surgeon’s characteristics and the socioeconomic perspective.

RESULTS:

To date, we have no definitive data to suggest whether the damage to the ovaries observed in women with endometriomas may be related to the mere presence of the cyst, the surgical procedure to remove it, the combination of the two, or factors currently unknown. Moreover, there is no conclusive evidence that, for subfertile couples, removal of endometriomas increases the chance of having a baby. The uncertainty regarding the best treatment strategy and factors such as the limited number of tertiary centers for laparoscopic surgery throughout the world seems to further complicate the decision.

CONCLUSIONS:

Until research addresses the current “grey areas”, the management of endometriomas in patients undergoing ART should be individualized and take into consideration numerous parameters.

 

 

Angiogenesis. 2013 Jan;16(1):59-69. doi: 10.1007/s10456-012-9299-4. Epub 2012 Sep 5.

Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice.

Wang CC1Xu HMan GCZhang TChu KOChu CYCheng JTLi GHe YXQin LLau TSKwong JChan TH.

 

Abstract

Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS(®) non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio(®) in vivo imaging and SCANCO(®) Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis.

 

 

Surg Endosc. 2013 Feb;27(2):625-32. doi: 10.1007/s00464-012-2505-z. Epub 2012 Sep 6.

Laparoscopic surgical treatment of diaphragmatic endometriosis: a 7-year single-institution retrospective review.

Ceccaroni M1Roviglione GGiampaolino PClarizia RBruni FRuffo GPatrelli TSDe Placido GMinelli L.

 

Abstract

BACKGROUND:

Diaphragmatic endometriosis is a rare condition that may cause invalidating epigastric or thoracic pain and catamenial pneumothorax. During the past decades, laparoscopy has been proposed as an optimal tool for diagnosis and surgical eradication of the disease.

METHODS:

We present a retrospective series of consecutive patients affected by diaphragmatic endometriosis, treated by laparoscopy at our institution, during a period of 7 years.

RESULTS:

Among 3,008 patients with pelvic endometriosis, 46 cases with intraoperative diagnosis of diaphragmatic endometriosis were identified. Operative findings showed multiple diaphragmatic lesions in 32 (69.5 %) patients and single lesions in 14 (30.4 %). Diaphragmatic implants were distributed on the right side in 40 (86.9 %) patients; in 5 patients (10.8 %) they were bilateral and 1 patient had a single lesion on the left hemidiaphragm. Most of the symptomatic patients were treated by complete excision of the nodules, whereas only three patients referring right upper-quadrant abdominal pain and right shoulder catamenial pain had superficial diaphragmatic endometriosis and were treated by diathermocoagulation.

CONCLUSION:

Diaphragmatic endometriosis should be included in the concept of complete eradication of endometriosis. This kind of surgery has been shown to be feasible and cost-effective; however, it should be managed in a referral center, by an expert laparoscopic gynecologist with knowledge of oncological surgical techniques, with the support of a general surgeon and a trained anesthesiologist.

 

 

Nanomedicine. 2013 Apr;9(3):439-48. doi: 10.1016/j.nano.2012.08.001. Epub 2012 Sep 5.

Mitigation of endometriosis using regenerative cerium oxide nanoparticles.

Chaudhury K1Babu K NSingh AKDas SKumar ASeal S.

 

Abstract

Cerium oxide nanoparticles (nanoceria) have recently received attention from the scientific community due to their unique free radicals (specially superoxide radical and hydrogen peroxide) scavenging property in biological system, both in vitro and in vivo. It is suggested that free radicals play an important role in the pathogenesis of endometriosis. In this study we have shown that nanoceria mitigate the endometrial lesions induced in mice model by decreasing oxidative stress and inhibiting angiogenesis. Moreover, nanoceria were also observed to protect endometriosis-related adverse effects on the oocytes, which is critical for successful pregnancy. Summarizing, nanoceria have shown promising efficacy against endometriosis related pathogenesis.

FROM THE CLINICAL EDITOR:

Free radicals have been implemented in the pathogenesis of endometriosis. In a murine model the authors demonstrated successful treatment of endometriosis with nanoceria, and protection of endometriosis-related adverse effects on the oocytes, paving the way to potential clinical translational applications in the future.

 

 

Hum Reprod. 2012 Dec;27(12):3440-9. doi: 10.1093/humrep/des322. Epub 2012 Sep 7.

Are digestive symptoms in women presenting with pelvic endometriosisspecific to lesion localizations? A preliminary prospective study.

Roman H1Ness JSuciu NBridoux VGourcerol GLeroi AMTuech JJDucrotté PSavoye-Collet CSavoye G.

 

Abstract

STUDY QUESTION:

What are the types and frequency of digestive symptoms in patients with different localizations of pelvic endometriosis and which specific symptoms are related to rectal stenosis?

SUMMARY ANSWER:

There is a high prevalence of digestive complaints in women presenting with superficial pelvic endometriosis and deep endometriosis sparing the rectum.

WHAT IS KNOWN ALREADY:

Women presenting with pelvic endometriosis frequently report gastrointestinal complaints of increased intensity during menstruation, which are not necessarily linked to the infiltration of the disease into the rectal wall. Even though intrarectal protrusion of the nodule can have an impact on bowel movement, only a minority of women with rectal nodules seemed to be concerned by significant narrowing of the rectum.

STUDY DESIGN AND SIZE:

This three-arm cohort prospective study included 116 women and was carried out over 22 consecutive months.

PARTICIPANTS, SETTING AND METHODS:

Prospective recording of data was performed for women treated for Stage 1 endometriosis involving the Douglas pouch (n = 21), deep endometriosis without digestive infiltration (n = 42) and deep endometriosis infiltrating the rectum (n = 53). Patient characteristics, pelvic pain and data from preoperative standardized questionnaires The Gastrointestinal Quality of Life Index (GIQLI), the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS) and the MOS 36-Item Short-Form Health Survey (SF-36) were compared according to endometriosis localization.

MAIN RESULTS:

The values of total KESS and total GIQLI score were comparable for the three groups, as were a majority of the digestive complaints. Women presenting with rectal endometriosis were more likely to report an increase in intensity and length of dysmenorrhoea, while deep dyspareunia appeared to be more severe in women with superficial endometriosis. Women presenting with rectal endometriosis were more likely to present cyclic defecation pain (67.9%), cyclic constipation (54.7%) and a significantly longer stool evacuation time, although these complaints were also frequent in the other two groups (38.1 and 33.3% in women with Stage 1 endometriosis and 42.9 and 26.2% in women with deep endometriosis without digestive involvement, respectively). No independent clinical factor was found to be related to infiltration of the rectum by deep endometriosis. Among women with rectal endometriosis, only 26.4% presented with rectal stenosis. These women were significantly more likely to report constipation, defecation pain, appetite disorders, longer evacuation time and increased stool consistency without laxatives.

LIMITATIONS:

Patients treated for pelvic endometriosis in a tertiary referral centre may not be representative of the general endometriosis population presenting with those lesions. Statistically significant differences were revealed between the three groups; however, the results were based on a small number of subjects, which carries an inherent risk of type II error particularly when comparing variables with closed values.

WIDER IMPLICATIONS OF THE FINDINGS:

In women presenting with pelvic endometriosis, it seems likely that various digestive symptoms are the consequence of cyclic inflammatory phenomena leading to irritation of the digestive tract, rather than to actual infiltration of the disease itself into the rectum, with the exception of a limited number of cases where the disease leads to rectal stenosis.

STUDY FUNDING/COMPETING INTEREST:

The North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) is financed by the G4 Group (The University Hospitals of Rouen, Lille, Amiens and Caen). No financial support was specifically received for this study. The authors declare no conflict of interest.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Jan;166(1):76-80. doi: 10.1016/j.ejogrb.2012.08.023.

Antiproliferative and apoptotic effects of norethisterone on endometriotic stromal cells in vitro.

Minami T1Kosugi KSuganuma IYamanaka KKusuki IOyama TKitawaki J.

 

Abstract

OBJECTIVES:

Low-dose estrogen-progestin (LEP) agents are often used for relieving endometriosis-associated chronic pelvic pain, but a direct effect of LEP on endometriotic lesions remains to be demonstrated. The objective of this study is to investigate the antiproliferative and apoptotic effects of the synthetic progestin norethisterone (NET) against human endometriotic stromal cells (ESCs).

STUDY DESIGN:

Ovarian endometrioma specimens were obtained at laparoscopy from 19 patients with endometriosis, and ESCs were isolated. The antiproliferative effect of compounds against cultured ESCs was evaluated by measuring the inhibition of [(3)H]thymidine incorporation. The ability of compounds to induce apoptosis in the cultured cells was evaluated by the measurement of caspase 3/7 activity and by nuclear staining. The cytotoxicity of compounds was evaluated by measuring the leakage of lactate dehydrogenase (LDH) into the supernatant of the cell culture.

RESULTS:

NET and progesterone (P4) at concentrations of greater than 10nM significantly inhibited [(3)H]thymidine incorporation in a dose-dependent manner. Co-treatment with 17β-estradiol at 0.1 ng/mL did not affect the inhibition of [(3)H]thymidine incorporation by NET. At concentrations greater than 100 nM, NET significantly increased caspase 3/7 activity and the numbers of apoptotic cells, whereas P4 did not. Treatment of ESCs for 24h with NET or P4 at concentrations of up to 1000 nM did not cause LDH leakage.

CONCLUSIONS:

NET inhibits the proliferation of ESCs and induces their apoptosis. These results suggest a possible direct effect of NET on endometriotic lesions in patients with endometriosis.

 

 

Endocrinology. 2012 Nov;153(11):5566-74. doi: 10.1210/en.2012-1202. Epub 2012 Sep 11.

Migration of cells from experimental endometriosis to the uterine endometrium.

Santamaria X1Massasa EETaylor HS.

 

Abstract

Endometriosis is the estrogen-dependent growth of endometrial tissue outside the uterus. Endometriosis has an effect on the eutopic endometrium; however, the nature of the cellular or molecular signal from the lesion to the uterus is unknown. Here we demonstrate that cells migrate from endometriosis to eutopic endometrium. Experimental endometriosis was established by transplanting endometrial tissue from green fluorescent protein (GFP) mice to the peritoneal cavity of DS-Red mice. Immunofluorescence (IF) identified cells from the ectopic lesions in the uterus. The eutopic endometrial cells were sorted by fluorescence activated cell sorting, and the GFP(+)/DS-Red(-) population was characterized using microarray analysis. The results of cell sorting as well as the array results were confirmed by quantitative PCR and IF. GFP(+)/DS-red(-)/Cd45(-) cells were identified in the eutopic endometrium of mice with experimental endometriois (∼1.8%) and not in controls. Global gene expression profiling of these cells showed absence of leukocyte and increased expression of pan-epithelial markers in the uterine GFP(+) cells. Moreover, GFP(+) cells showed up-regulation of Wnt7A expression and 17 other genes associated with the Wingless pathway. Several genes that are associated with epithelial-to-mesenchymal transition were also highly differentially expressed in GFP(+) cells. IF confirmed the presence of the GFP(+)/CD45(-)/Wnt7a(+)/cytokeritin(+) cells in the endometrium of endometriotic animals, and not in controls. Cells from endometriotic lesions are capable of migrating to the eutopic endometrium. The ectopic expression of Wnt7A suggests a possible mechanism by which ectopic lesions affect the eutopic endometrium and interfere with embryo implantation and fertility.

 

J Clin Endocrinol Metab. 2012 Nov;97(11):4228-35. doi: 10.1210/jc.2012-1154. Epub 2012 Sep 11.

Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels.

Huhtinen K1Desai RStåhle MSalminen AHandelsman DJPerheentupa APoutanen M.

 

Abstract

CONTEXT:

Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described.

OBJECTIVE:

The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes.

PATIENTS:

Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study.

MAIN OUTCOME MEASURES:

We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes.

RESULTS:

Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, whereas in the secretory phase the E2 concentration was about half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was observed in the endometrium at the proliferative phase compared with the secretory phase. In the endometriosis lesions, E2 levels were predominating over those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17β) dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the E2 concentration in the endometrium, and HSD17B6 was strongly expressed, especially in the deep lesions.

CONCLUSIONS:

Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.

 

 

Front Pharmacol. 2012 Aug 30;3:158. doi: 10.3389/fphar.2012.00158. eCollection 2012.

Telemetric assessment of referred vaginal hyperalgesia and the effect of indomethacin in a rat model of endometriosis.

Dmitrieva N1Faircloth EKPyatok SSacher FPatchev V.

 

Abstract

Symptoms of endometriosis (ENDO), among others, include pelvic/abdominal and muscle pain. Non-steroidal anti-inflammatory agents are first-line treatment for this pain. Similar to women, rats with surgically induced ENDO, but not its surgical control, exhibit vaginal hyperalgesia, which in rats is evidenced by a decreased threshold for the visceromotor response (VMR) induced by vaginal distention. Here we assess the VMR in rats with implanted probes that telemetrically transmit EMG activity from the abdominal muscle. The feasibility and sensitivity of this technique for monitoring the VMR threshold across the estrous cycle and the influence of Indomethacin on ENDO-induced vaginal hyperalgesia were evaluated. VMR thresholds in response to vaginal distention with an infusion pump were measured in different estrous stages. Indomethacin (5 or 10 mg/kg i.p. or s.c.) was injected in proestrus rats and 40-60 min later the VMR threshold was measured. The VMR threshold varied across the estrous cycle only in ENDO rats, being lowest in proestrus. Indomethacin increased this threshold in proestrus ENDO rats. These results show that telemetric assessment of the VMR is a sensitive tool, suitable for long-term studies in conscious rats. The results with this technique also suggest that ENDO-associated vaginal hyperalgesia involves COX activity, the feature that also underlies inflammatory pains.

 

 

Exp Ther Med. 2012 Jan;3(1):18-24. Epub 2011 Oct 24

Modulation of estrogenic action in clear cell carcinoma of the ovary (Review).

Tanase Y1Yamada YShigetomi HKajihara HOonogi AYoshizawa YFurukawa NHaruta SYoshida SSado TOi HKobayashi H.

 

Abstract

Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC), are the common histology in ovarian cancer patients who have associated endometriosis. However, both tumor types have distinct clinicopathological characteristics and molecular phenotypes. EAC is predominantly positive for estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This study reviews the current understanding of the role of the ER information in the pathogenesis of CCC, as well as the English language literature for biochemical studies on ER expression and estrogenic action in CCC. The iron-mediated oxidative stress occurs due to repeated hemorrhage in endometriosis, then this compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be observed. There are a number of factors that interfere with ER expression and estrogen activity, which include DNA methylation of the promoter region, histone deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase activity. Loss of estrogen function may be a turning point in CCC progression and aggressiveness.

 

 

Exp Ther Med. 2012 Mar;3(3):410-414. Epub 2011 Dec 20.

Use of a murine endometriosis interna model for the characterization of compounds that effectively treat human endometriosis.

Otto C1Schkoldow JKrahl EFuchs IUlbrich HF.

 

Abstract

Endometriosis is a chronic, estrogen-dependent disease characterized by the presence of ectopic endometrium either in the pelvic cavity (endometriosis externa) or within the uterus (endometriosis interna, adenomyosis). Key symptoms are pelvic pain, dysmenorrhea and infertility. Established rodent animal models used for drug research in endometriosis have certain limitations. Since rodents do not menstruate, they cannot develop endometriosisexterna spontaneously, but they suffer from endometriosis interna. There is growing evidence that human endometriosis externa and interna represent two faces of the same disease. Both are estrogen-dependent and respond to similar treatment paradigms. Here, we addressed the question whether a murine endometriosis interna model may also be suitable for the characterization of drugs employed in human endometriosis. We examined the effects of danazol, Faslodex and cetrorelix in SHN mice that developed endometriosis interna after pituitary grafting. The GnRH antagonist cetrorelix and the estrogen receptor antagonist Faslodex, which negatively interfered with estrogen-mediated signaling, completely inhibited endometriosis interna, whereas danazol, an androgenic progestin, showed significant therapeutic activity in the majority of SHN mice. We conclude that this murine endometriosis interna model may be a valuable complement to established endometriosis externa models to support drug research in human endometriosis.

 

 

Oncol Lett. 2012 Sep;4(3):375-380. Epub 2012 Jun 22

Synchronous primary corpus and ovarian cancer: High incidence of endometriosis and thrombosis.

Yamanoi K1Mandai MSuzuki AMatsumura NBaba TYoshioka YKosaka KKonishi I.

 

Abstract

In an attempt to clarify the clinical characteristics of synchronous primary endometrial and ovarian cancer (SPC), we reviewed the clinicopathological features of 13 cases treated in the Department of Gynecology and Obstetrics at Kyoto University Hospital over the last 6 years and compared them with 186 cases of primary uterine corpus cancer (PCC) and 136 cases of primary ovarian cancer (POC). Comparisons were performed based on clinicopathological factors, including age, BMI, parity, complication of thrombosis and FIGO stage. For SPC patients, the mean age was 51.5 years; 6 (46%) were nulliparous, and 7 (53%) had complicated thrombosis. All had well-differentiated endometrial cancer and 12 (92%) had endometrioid cancer in the ovary. The mean age of the SPC patients was significantly lower than that of the PCC patients (51.5 vs. 58.9 years). Thrombosis occurred in the SPC patients at a significantly higher rate than in both the PCC and POC patients. When the incidence of endometriosis and the regularity of menstruation were compared between patients who developed SPC with those who develop PCC at a young age (under 45 years), the SPC patients exhibited a significantly higher rate of endometriosis (100 vs. 35%), whereas the PCC patients exhibited a higher rate of irregular menstruation (53 vs. 15%, p=0.05). As for thrombosis, the age and FIGO stage of thrombosis-positive patients were significantly higher than those of thrombosis-negative patients in PCC and POC, while in SPC patients there was no such difference. In conclusion, this study demonstrated the differences in clinical features between SPC and PCC, and also novel features of SPC, namely endometriosis and thrombosis, which are essential in the management of this disease.

 

 

 

Case Rep Pulmonol. 2012;2012:351305. doi: 10.1155/2012/351305. Epub 2012 Aug 30.

A rare case of hemoptysis: intrapulmonary cavitary lesion appearing as a thoracic endometriosis.

Celik A1Aydın EYazıcı UAgackıran YKaraoglanoglu N.

 

Abstract

Pulmonary endometriosis is a rarely seen disease of the lung. On computed tomography, a cavitary lesion of 15 × 26 in size was detected in the lung parenchyma of a 38-year-old female patient who was examined due to hemoptysis. The pathologic result of the surgically excised cavitary lesion was reported as pulmonary endometriosis.

 

Kathmandu Univ Med J (KUMJ). 2012 Jan-Mar;10(37):53-6.

Adenomyosis at hysterectomy: prevalence, patient characteristics, clinical profile and histopatholgical findings.

Shrestha A1Shrestha RSedhai LBPandit U.

 

Abstract

BACKGROUND:

Underlying adenomyosis is often the cause of treatment failure for patients undergoing medical therapy for abnormal uterine bleeding and or chronic pelvic pain. Given the limitation of ultrasonography in diagnosing adenomyosis and MRI being unaffordable to most of the patients belonging to developing countries like us, it often remains undiagnosed before a hysterectomy.

OBJECTIVE:

To find out the clinical profile associated with adenomyosis and to determine the prevalence of adenomyosis in hysterectomy specimens; frequency distribution, as well as to correlate clinical examination with histopathological examination.

METHODS:

A total of 60 women who had undergone hysterectomy with histopathologically proven adenomyosis between April 2009 and March 2010 were included . Data were collected on indication for the intervention, age, symptoms, clinical findings, hemoglobin, menopausal status, gross and histopathological findings.

RESULTS:

A total of 256 women were scheduled for hysterectomy. Adenomyosis was diagnosed in 60 of 256 cases (23.4%). Menorrhagia (91.2%), dysmenorrhoea (84.2%), lower abdominal pain (84.2%) beginning later in reproductive life (mean age- 45yrs) is the classic presentation. Adenomyosis was present in 10 of 61 patients (16.3%) with fibroids; 27 of 60 (45%) with abnormal uterine bleeding; 11 of 55 (20%) with prolapse; four of 35 (11.4%) with ovarian mass; five of 25 (20%) with chronic pelvic pain; three of four (75%) with endometriosis.

CONCLUSION:

Women undergoing hysterectomy with diagnosis of adenomyosis have a distinct symptomatology. The choice of therapy in adenomyosis is hysterectomy for those women who have completed family and had failed medical therapy .

 

 

Fertil Steril. 2012 Dec;98(6):1531-8. doi: 10.1016/j.fertnstert.2012.08.009. Epub 2012 Sep 10. Review.

Surgical excision of endometriomas and ovarian reserve: a systematic review on serum antimüllerian hormone level modifications.

Somigliana E1Berlanda NBenaglia LViganò PVercellini PFedele L.

 

Abstract

OBJECTIVE:

To evaluate serum antimüllerian hormone (AMH) level modification after surgical excision of ovarian endometriomas.

DESIGN:

Systematic review. MEDLINE search from January 1990 to April 2012 using the combination of medical terms endometriosis, endometrioma, endometriotic cyst, and AMH or antimüllerian hormone, MIF or müllerian inhibiting factor. Reference lists of selected studies were checked for additional potential contributions.

SETTING:

Not applicable.

PATIENT(S):

Women with ovarian endometriomas requiring surgery.

INTERVENTION(S):

Serum AMH level assessment.

MAIN OUTCOME MEASURE(S):

Serum AMH level modifications.

RESULT(S):

Eleven articles satisfied our selection criteria. Data pooling were deemed inopportune owing to the heterogeneity of the study designs and of the reported parameters. Nine of 11 studies documented a statistically significant reduction of serum AMH level after surgery. The two studies failing to document this decrease were published by the same study group and partly overlapped. The magnitude of the decline was more evident in women operated on for bilateral endometriomas.

CONCLUSION(S):

Evidence deriving from the evaluation of serum AMH level modifications after surgical excision of endometriomas supports a surgery-related damage to ovarian reserve.

 

 

Acta Histochem. 2013 May;115(4):301-7. doi: 10.1016/j.acthis.2012.08.006. Epub 2012 Sep 10

Pigment epithelial-derived factor expression in endometriotic lesions in a rat model of endometriosis.

Fu G1Che XSun YHuang XXu HZhou CZhang X.

 

Abstract

Angiogenesis is a prerequisite for endometriotic lesion formation and development. Pigment epithelium-derived factor (PEDF) is a potential inhibitor of angiogenesis. The objective of this study was to detect PEDF immunolocalization in endometriotic lesions and the correlation with vascular endothelial growth factor (VEGF) and microvascular density (MVD) in a rat model of endometriosis. A subcutaneous endometriosis rat model was established by using auto-transplantation. Expression of PEDF, VEGF and MVD labeled by von Willebrand factor (v-WF) in endometriotic lesions and endometrial tissues was evaluated using immunohistochemical staining. We detected lower PEDF immunostaining and higher VEGF and MVD immunostaining in active lesions in a rat model of endometriosis than that in endometriosis endometrium or control endometrium (P<0.05), but no differences between endometriosis and control endometrium were found (P>0.05). In lesions, PEDF expression was negatively correlated with VEGF expression, MVD or sizes of cysts (P<0.01). On the contrary, both VEGF expression and MVD were positively correlated with lesion sizes (P<0.05). In addition, VEGF expression was positively correlated with MVD (P<0.01). Our results suggest that PEDF might be involved in the pathogenesis of endometriosis and may lead to novel treatment for this disease.

 

 

Int J Gynecol Cancer. 2012 Oct;22(8):1310-5.

Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma.

Ayhan A1Mao TLSeckin TWu CHGuan BOgawa HFutagami MMizukami HYokoyama YKurman RJShih IeM.

 

Abstract

OBJECTIVES:

ARID1A is a recently identified tumor suppressor participating in chromatin remodeling. Somatic inactivating mutations of ARID1A and loss of its expression occur frequently in ovarian clear cell and endometrioid carcinomas and in uterine endometrioid carcinomas. Because endometriotic epithelium is thought to be the cell of origin of most ovarian clear cell and endometrioid carcinomas, we undertook an analysis of ARID1A expression of these tumors arising within an endometriotic cyst (endometrioma).

MATERIALS AND METHODS:

Our immunohistochemical study set consisted of 47 endometriotic cysts containing clear cell carcinoma in 24 cases, well-differentiated ovarian endometrioid carcinoma in 20 cases, and mixed clear cell and endometrioid carcinoma in 3 cases.

RESULTS:

ARID1A loss was observed in 31 (66%) of 47 carcinomas; and therefore, these cases were informative for determining the temporal sequence of loss of ARID1A expression in tumor progression. In 16 of the 47 cases, ARID1A immunoreactivity was retained in both the endometriotic cyst and the carcinoma; and thus, these cases were not informative. All of the 31 informative cases showed loss of ARID1A immunoreactivity in the carcinoma and in the endometriotic cyst epithelium in direct continuity with the carcinoma but not in the cyst epithelium that was not adjacent to the tumor.

CONCLUSIONS:

Loss of ARID1A function as shown by loss of expression, presumably due to mutations, is an early molecular event in the development of most ovarian clear cell and endometrioid carcinomas arising in endometriomas.

 

 

Int J Clin Exp Pathol. 2012;5(7):642-50. Epub 2012 Sep 5.

Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma.

Xiao W1Awadallah AXin W.

 

Abstract

Ovarian endometriosis has been associated with increased risk for ovarian clear cell carcinoma (CCC). Atypical endometriosis shares common molecular alterations with CCC and therefore, has been proposed as a precursor lesion of CCC, although it is unclear if benign endometriosis is pre-neoplastic. In this study, we examined some molecular alterations in ovarian benign endometriosis, atypical endometriosis, and CCC in comparison to papillary serous carcinoma (PSC). These included BAF250a (encoded by ARID1A), a recently identified major tumor suppressor in ovarian CCC, as well as hepatocyte nuclear factor (HNF)-1b, estrogen receptor (ER), progesterone receptor (PR), and P53. We confirmed that CCC but not PSC had loss of BAF250a expression, HNF-1b up-regulation, loss of ER expression and P53 expression. We further showed that both atypical endometriosis and adjacent CCC had loss of BAF250a expression (38.5% vs. 57.7%), HNF-1b up-regulation (53.8% vs. 92.3%), and loss of ER (84.6% vs. 92.3%) and PR (76.9% vs. 84.6%) expression. Importantly, about 20% of benign ovarian endometriosis had loss of BAF250a expression, 33% with HNF-1b up-regulation, 23% loss of ER expression and 50% loss of PR expression, respectively. The concurrent rate of loss of BAF250a expression, HNF-1b up-regulation, and loss of ER expression was not observed in any benign endometriosis, and was increased to 23.1% in atypical endometriosis, and was further increased to 42.3% in CCC. Therefore, the molecular alterations accumulate in a stepwise manner along the transformation process from benign endometriosis through atypical endometriosis to CCC. These data suggest that a portion of benign ovarian endometriosis has already undergone genetic alterations that lead to aberrant protein expression, possibly conferring a higher risk for malignant transformation.

 

 

 

Bratisl Lek Listy. 2012;113(9):544-7.

Does ovarian endometrioma affect the number of oocytes retrieved for in vitro fertilization?

Kiran H1Arikan DCKaplanoglu MBisak UCetin MT.

 

Abstract

OBJECTIVE:

To investigate the effects of ovarian endometrioma on the number of oocytes retrieved for in vitro fertilization (IVF).

BACKGROUND:

The presence of endometrioma may be the most important predictor of a poor reproductive outcome. Literature data suggest that ovarian endometriomas might affect the response to ovarian stimulation and oocyte retrieval.

METHODS:

The present retrospective study evaluates 2,023 women who applied to our center with an infertility complaint. Twenty-nine women with endometriomas (group 1) who were treated with IVF were included in the study. They were compared with 51 women with unexplained infertility (group 2) regarding the number of retrieved oocytes after egg retrieval and number of metaphase II oocytes. The diagnosis of endometrioma was made via ultrasound examination with the identification of low-density cystic masses in the ovaries. The patients underwent a controlled ovarian hyperstimulation (COH) with either the long agonist mini-dose protocol or the multi-dose antagonist protocol.

RESULTS:

The incidence of endometrioma in infertile women was found to be 1.4 %. The women’s ages ranged between 24 and 45 years, and the duration of their infertility ranged between 12 and 216 months. The endometrioma was bilateral in 24 % of the cases. The mean endometrioma diameter was 26.2±7.3 mm for the right ovary and 23.2±6.1 mm for the left ovary. The average number of retrieved oocytes after egg retrieval in groups 1 and 2 was 12.4±8.3 and 12.2±8.6, respectively. The average number of metaphase II oocytes in groups 1 and 2 was 8.6±6.1 and 9.4±7.3, respectively. The number of retrieved oocytes after egg retrieval and the number of metaphase II oocytes in both endometrioma group and unexplained infertile group were similar (p >0.05).

CONCLUSION:

Endometrioma did not reduce the number of retrieved oocytes in a COH cycle for IVF treatment. However it should be noted that the ovarian response is affected by the size of endometriomas, bilaterality, previous surgeries, recurrence, and the patient’s age

 

 

Fertil Steril. 2012 Dec;98(6):1521-30.e2. doi: 10.1016/j.fertnstert.2012.08.003. Epub 2012 Sep 12.

Sorafenib inhibits growth, migration, and angiogenic potential of ectopic endometrial mesenchymal stem cells derived from patients with endometriosis.

Moggio A1Pittatore GCassoni PMarchino GLRevelli ABussolati B.

 

Abstract

OBJECTIVE:

To characterize the proliferation, migration, and angiogenic properties of mesenchymal stem cells (MSC) from ectopic and eutopic endometrial tissue and to investigate the effect of the tyrosine kinase inhibitor sorafenib.

DESIGN:

In vitro studies.

SETTING:

University hospital and research center.

PATIENT(S):

Patients receiving surgical treatment of endometriosis (n = 4) and control patients without endometriosis (n = 2) undergoing surgery for benign gynecologic diseases.

INTERVENTION(S):

Mesenchymal stem cell lines were isolated from ectopic and eutopic endometrial tissue, and sorafenib was administered to them.

MAIN OUTCOME MEASURE(S):

Proliferation, migration, invasion of endometrial MSC, and expression of ezrin, vascular endothelial growth factor, and hypoxia-inducible factor-1α (HIF-1α) were measured.

RESULT(S):

Ectopic endometrial MSC from patients with endometriosis showed a higher proliferation, migration, and angiogenic ability than eutopic MSC from the same patient or control MSC from patients without endometriosis. Sorafenib reduced the proliferation, motility, ezrin phosphorylation, vascular endothelial growth factor release, and HIF-1α expression of ectopic MSC.

CONCLUSION(S):

The increased proliferative, migratory, and angiogenic phenotype of ectopic MSC may be reverted by treatment with sorafenib. Targeting of the MSC population involved in sustaining the ectopic lesions might be useful in eradicating endometriotic implants.

 

 

 

 

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