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Abdom Imaging. 2014 Jun;39(3):622-32

Deep pelvic endometriosis: don’t forget round ligaments. Review of anatomy, clinical characteristics, and MR imaging features.

Gui B1Valentini ALNinivaggi VMarino MIacobucci MBonomo L.



Deep infiltrating endometriosis is an important gynecologic disease that may develop during the reproductive years and is responsible for severe pelvic pain. Deep pelvic endometriosis can affect the retrocervical region, uterosacral ligament, rectum, rectovaginal septum, vagina, urinary tract, and other extraperitoneal pelvic sites. Surgery remains the best therapeutic treatment for affected patients and an accurate preoperative evaluation of the extension of endometriotic lesions is essential for a successful outcome. However, many atypical locations for deep pelvic endometriosis exist although still lesser known to both gynecologists and radiologists such as endometriosis of the round ligaments of the uterus (RLUs). In this article, we review embryology and anatomy of the RLUs as well clinical characteristics associated with these endometriotic locations. In addition, we describe magnetic resonance (MR) imaging protocol, normal MR imaging appearances of the RLUs and the most common abnormal findings of endometriotic involvement of these ligaments at MR imaging. Radiologists should always keep in mind the RLUs as a possible site of deep pelvic endometriosis localization and should not forget to carefully look for them on MR images.



PLoS One. 2014 Feb 18;9(2):e88354

The association between endometriosis and chronic endometritis.

Takebayashi A1Kimura F1Kishi Y2Ishida M3Takahashi A1Yamanaka A1Takahashi K4Suginami H2Murakami T1.



To evaluate the association between endometriosis and chronic endometritis.


Endometrial specimens were obtained from 71 patients, 34 with endometriosis (endometriosisgroup) and 37 without endometriosis (non-endometriosis group), who underwent hysterectomy, and the specimens were immunostained for the plasmacyte marker CD138. The rate of chronic endometritis was compared between the endometriosis group and the non-endometriosis group. Furthermore, the 71 patients were also divided into two groups, 28 with chronic endometritis (chronic endometritis group) and 43 without chronic endometritis (non-chronic endometritis group). Logistic regression analysis was performed with variables including age, body mass index (BMI), gravidity and parity, and diagnoses of leiomyoma, adenomyosis, and endometriosis on pathology to examine the independent effect of each variable on chronic endometritis. Patients suffering from cervical invasive carcinoma, endometrial carcinoma, and endometrial polyps or treated with gonadotropin-releasing hormone agonists, progestins, or oral contraceptives before surgery were excluded.


Chronic endometritis was identified in 52.94% of the endometriosis group and 27.02% of the non-endometriosis group (p<0.05). Logistic regression analysis revealed that endometriosis was associated with chronic endometritis.


This result suggests a strong association between endometriosis and chronic endometritis.



Diagn Pathol. 2014 Feb 21;9:39.

Dysplastic intestinal-type metaplasia of appendiceal endometriosis: a mimic of low grade appendiceal mucinous neoplasm.

Mitchell A1Dubé PSideris L.



We report an example of dysplastic intestinal-type metaplasia involving endometriosis of the appendix in a 45 year old woman. One other example of this phenomenon has been reported. As it occurs within the muscular wall of the appendix, confusion with low grade appendiceal mucinous neoplasm (LAMN) may occur. Evidence supporting the metaplastic nature of the intestinal epithelium is offered. As the initial pathological diagnosis was of invasive cancer with perforation of the appendix treatment consisted of peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).



BMC Cancer. 2014 Feb 22;14:120.

A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation.

Wiegand KCHennessy BTLeung SWang YJu ZMcGahren MKalloger SEFinlayson SStemke-Hale KLu YZhang FAnglesio MSGilks BMills GBHuntsman DGCarey MS1.



Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC.


Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33 CCC, 29 EC, and 65 high-grade serous ovarian carcinomas (HGSC)). Whole tumor lysates were prepared from frozen banked tumor samples and profiled by RPPA using 116 antibodies. ARID1A mutations were identified by exome sequencing, and PIK3CA mutations were characterized by MALDI-TOF mass spectrometry. SAM (Significance Analysis of Microarrays) was performed to determine differential protein expression by histological subtype and ARID1A mutation status. Multivariate logistic regression was used to assess the impact of ARID1A mutation status/BAF250a expression on AKT phosphorylation (pAKT). PIK3CA mutation type and PTEN expression were included in the model. BAF250a knockdown was performed in 3 clear cell lines using siRNA to ARID1A.


Marked differences in protein expression were observed that are driven by histotype. Compared to HGSC, SAM identified over 50 proteins that are differentially expressed in CCC and EC. These included PI3K/AKT pathway proteins, those regulating the cell cycle, apoptosis, transcription, and other signaling pathways including steroid hormone signaling. Multivariate models showed that tumors with loss of BAF250a expression showed significantly higher levels of AKT-Thr308 and AKT-Ser473 phosphorylation (p < 0.05). In 31 CCC cases, pAKT was similarly significantly increased in tumors with BAF250a loss on IHC. Knockdown of BAF250a by siRNA in three CCC cell lines wild type for ARID1A showed no increase in either pAKT-Thr308 or pAKT-S473 suggesting that pAKT in tumor tissues is indirectly regulated by BAF250a expression.


Proteomic assessment of CCC and EC demonstrates remarkable differences in protein expression that are dependent on histotype, thereby further characterizing these cancers. AKT phosphorylation is associated with ARID1A/BAF250a deficient tumors, however in ovarian cancers the mechanism remains to be elucidated.



Climacteric. 2014 Aug;17(4):410-6.

Guizhi fuling capsule, an ancient Chinese formula, attenuates endometriosisin rats via induction of apoptosis.

Hu C1Wang ZPang ZLu WCai XYang JWang DCao P.



The guizhi fuling (GZFL) capsule has been a traditional Chinese medicine for the treatment of gynecological inflammation for the past thousands of years. However, as a formula, its therapeutic mechanism has not been clearly elucidated. The aim of this study is to investigate the role of apoptosis during GZFL capsule therapy for the treatment of endometrial hyperplasia.


The rat model of endometriosis was established, and the rats were given different doses of GZFL capsule. Uterine histomorphometric analysis, real-time quantitative PCR (qPCR) and Western blotting were performed. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP biotin nick end labeling (TUNEL) method was performed to analyze the apoptosis induced by the GZFL capsule.


The TUNEL assay showed that different doses of GZFL capsule were able to induce apoptosis in rat endometriotic cells. qPCR and Western blot analysis showed that the GZFL capsule can inhibit the mRNA levels of the survivin gene. In addition, the GZFL capsule can inhibit the mRNA level of the mitochondrial apoptotic pathway-related apoptosis-inhibiting factor Bcl-2 but increases the mRNA level of apoptosis- promoting factor Bax.


These results indicate that the GZFL capsule can induce apoptosis of endometriotic cells and inhibit cell proliferation and metastasis of endometriotic cells through the mitochondrial apoptotic pathway.



Fertil Steril. 2014 Mar;101(3):608-14.

Relationship between ovarian cysts and infertility: what surgery and when?

Legendre G1Catala L2Morinière C2Lacoeuille C2Boussion F2Sentilhes L2Descamps P2.



The relationship between ovarian cysts and infertility is a subject of debate, mainly because it is difficult to determine the real impact of the cyst and its treatment on later fertility. For a long time it was hoped that surgical treatment could prevent potential complications (such as rupture or malignancy). For presumed benign ovarian tumors, fertility sparing should be the main concern. The goal of this survey of current knowledge on the subject is to thoroughly explore the potential relationship between cysts, their treatment, and infertility. Our study is based on a review of the literature dealing with the epidemiology of ovarian cysts and the effects of their surgical management in relation to infertility. Analysis of the epidemiologic data, drawn mainly from comparative studies and cohorts, shows that the role of cysts in infertility is controversial and that the effects of surgical treatment are often more harmful than the cyst itself to the ovarian reserve. Surgery does not seem to improve pregnancy rates. When a surgical option is nonetheless chosen, a conservative laparoscopic approach is more suitable. Besides excision, sclerotherapy and plasma vaporization are promising, offering a greater preservation of the ovarian parenchyma, especially in endometriomas. These techniques must be better defined. The context of the infertility is essential, and surgeons and specialists in reproductive medicine should decide management jointly.








Fertil Steril. 2014 Mar;101(3):621-6.

Robot-assisted laparoscopy for infertility treatment: current views.

Carbonnel M1Goetgheluck J2Frati A2Even M2Ayoubi JM2.



To determine the interest of using robotic laparoscopic surgery in the management of female infertility, we reviewed our own activity and searched the Medline database for publications on robotic technology in infertility surgery, with the use of the following search words: robotic laparoscopy, tubal anastomosis, myomectomy, deep infiltrating endometriosis, and adnexal surgery. Robot-assisted laparoscopic surgery has seen rapid progression over the past few years. It has been mostly used for myomectomy, proximal tubal reanastomosis, and deep endometriosis surgery. Despite its increased range of indications, no randomized control studies are available. The place of robotic surgery in the management of infertility remains undetermined.



Med Hypotheses. 2014 Apr;82(4):493-501.

Clinical markers of endometriosis: have we been too quick to judge?

Toor K1Wessels JM1Agarwal SK2Leyland N1Foster WG3.



Numerous biochemical differences have been documented in women with endometriosis compared to controls; however, identification of a clinically useful marker of endometriosis remains elusive. We postulate that the diversity of clinical presentations, patient objectives, and complexity of the pathophysiology of endometriosis mandates rigorous attention to study design and standardization of procedures and questionnaires that has heretofore been overlooked in the pursuit of clinical markers of this enigmatic disease. We further propose that it is premature to conclude that clinical markers of endometriosis brought forward in the literature lack clinical value in the diagnosis of endometriosis. To address this hypothesis we reviewed the literature and assessed papers according to a modified version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria from which 55 high quality papers were reviewed. While pelvic inflammation and pain is a known significant component of endometriosis, control group definitions were widely divergent and included healthy women through to women with other inflammatory conditions. Although pain is a common presenting complaint in women with endometriosis, it was assessed in only 4 of 55 studies (7.3%) whereas infertility was documented in 34/55 studies (61.8%). Disease severity was assessed in 44 of 55 studies (80%) whilst the association between active vs. inactive disease was attempted in only 2 of the studies reviewed (3.6%). We conclude that experimental design criteria are inconsistently applied making comparisons across studies difficult. Thus, the clinical utility of previously described diagnostic markers of endometriosisremains uncertain.




Saudi Med J. 2014 Feb;35(2):115-22.

Catamenial pneumothorax. Is it time to approach differently?

Aljehani Y1.



Catamenial pneumothorax CP was considered a rare clinical entity that has gained tremendous interest recently. It is commonly overlooked, misdiagnosed, or under diagnosed. It is part of the thoracic endometriosissyndrome, which includes catamenial hemothorax, catamenial hemoptysis, and pulmonary endometriosis. These represent the spectrum of ectopic pelvic endometriosis. The presentation is variable leading to difficulty in developing a standardized approach to diagnosis and management. This review discusses the pathogenesis of these entities and the novel methods of investigation, management, and clinical protocols.



Biomed Res Int. 2014;2014:590950.

Hormonal contraceptive use and the prevalence of endometriotic lesions at different regions within the peritoneal cavity.

McKinnon BD1Bertschi D1Wanner J1Bersinger NA1Mueller MD1.



Endometriosis is an estrogen-dependent disease that can lead to chronic pain and subfertility. Endometriotic lesions found in different locations are heterogeneous and may represent a collection of related but distinct conditions. Whether there is a relationship between hormonal contraceptive (HC) use and endometriosis is still controversial. The purpose of this study was to determine whether HC use affected the prevalence of endometriotic lesions differently based on lesion location. Data was retrospectively collected from 161 patients presenting to the Berne University Women’s Hospital between 2008 and 2012 for laparoscopic investigation. Women with histologically proven endometriosis were included in the study and patients were grouped according to lesion location and HC use. The results of the study indicate that HC users are significantly less likely to have endometriotic lesions on the ovaries, although in contrast, no difference was observed in the incidence of lesions in the rectovaginal septum (RVS) or peritoneal region. In addition, women using HC who were diagnosed with endometriotic lesions on the peritoneum were significantly younger than women with lesions in other locations. In conclusion, women with endometriosis who are currently using HC are less likely to have ovarian endometriotic lesions than in alternate locations.







Hum Fertil (Camb). 2014 Mar;17(1):56-9.

Select and treat at laparoscopy and dye test improves the spontaneous pregnancy.

Younas K1Majoko FSheard KEdwards CBunkheila A.



Infertility affects 1 in 7 couples in the UK. Tubal patency tests are an important part of infertility investigations. We conducted this observational study to determine the interval between a laparoscopy and dye test and spontaneous conception in women with unexplained infertility and minimal to mild endometriosis and pelvic adhesions treated during the procedure. The clinical records of 432 women coded as having had a laparoscopy and dye test or laparoscopy and tubal patency test between April 2007 and March 2010 were retrieved from a computerised theatre database. Pregnancies were identified through a computerised maternity booking system. Spontaneous pregnancies were recorded in 162 women following surgery (37.5%). There was a significant difference in conception rates between women with unexplained infertility and those with minor abnormalities treated at the time of diagnosis (43% vs. 58%, p = 0.019). Eighty percent of women who conceived spontaneously achieved their pregnancy within 18 months of surgery. A high proportion of women with unexplained infertility or minor abnormalities treated at the time of a laparoscopy and dye test conceived spontaneously within 12 months.



J Reprod Med. 2013 Nov-Dec;58(11-12):469-76.

Endometriosis-associated ovarian malignancy: a retrospective analysis of presentation, treatment, and outcome.

Garrett LA1Growdon WB1Goodman A1Boruta DM1Schorge JO1del Carmen MG1.



To investigate the relationship of age and tumors associated with endometriosis and outcome of different histologies of epithelial ovarian cancer arising from endometriosis.


We identified cases of epithelial ovarian cancers with clear cell, endometrioid, or mixed clear cell and endometrioid histologies from January 2001 to March 2009. Tumors were classified as either “arising in” endometriosis, “associated with” endometriosis or “controls” (not associated with endometriosis). We collected information regarding patient demographics, past medical history, presentation at diagnosis, treatment, and outcome.


Of 140 patients identified, 42 (30.0%) had clear cell, 92 (65.7%) had endometrioid, and 6 (4.3%) had mixed. Of those, 28.6% of tumors were associated with endometriosis (n = 40), 37.1% were arising in endometriosis (n = 52), and 34.3% were controls (n = 48). Premenopausal women had tumors that were more likely arising from or associated with endometriosis as compared to tumors in postmenopausal women (p = 0.005). Premenopausal patients were also more likely to present with early stage disease as compared to postmenopausal women (80.4% vs. 63.6%, p = 0.04) and better overall survival (p < 0.008). Survival analyses of the entire cohort showed that improved survival was associated with stage (p < 0.001), grade (p < 0.001), endometrioid histology (p < 0.005), and with tumors associated with or arising in endometriosis (p < 0.04). Multivariate analysis controlling for menopausal status showed the presence of endometriosis was no longer associated with a survival advantage (p = 0.08).


The association with endometriosis does appear, at least in endometrioid tumors, to provide a survival benefit. Overall, menopausal status, stage, and grade are more powerful variables associated with improved survival.



Minerva Ginecol. 2014 Feb;66(1):69-76.

Post-traumatic amenorrhea: the role of diagnostic and operative hysteroscopy in the prevention, diagnosis, differential diagnosis and treatment.

Pulcinella R1Giannone LCandelori EGiannone EPatacchiola F.



The aim of the study was to evaluate the clinical usefulness of the selective removal of residual intrauterine trophoblastic tissue by using a hysteroscopic procedure, especially in the prevention of the Intra-Uterine Adhesion’s Syndrome.


Seventy-six patients had an Asherman’s Syndrome: 5 cases after laparotomic myomectomy, 1 after caesarean section, 2 after hysteroscopic myomectomy, 10 after VIP, 1 with a severe vaginal endometriosis, 1 after conisation, 4 after a post-partum hemorrhage due to coagulopathy or uterine atony, 20 cases after D&C because of PPH due to placental retention, 26 after repetitive D&Cs because of AUB due to post abortion chorial residues’ retention, 6 cases after D&C for post menopausal AUB. Thirty-six patients presented AUB due to chorioplacental residues retention: 14 cases after a vaginal delivery or a caesarean section, 4 after VIP, 18 cases after repetitive D&Cs for incomplete or internal spontaneous abortion. Complete physical examination, transvaginal ultrasonography and operative hysteroscopy was offered as first treatment to all patients. Surgical treatment of IUA depends on the type (I-IV) and is based on the section of synechiae, liberation of the uterine cavity and tubal recesses, recovery of the residual endometrium to restore the physiology of the reproductive tract. Our technique to remove the chorioplacental residues is based on: correct use of loops and electric currents, enucleation by cold loops of the base of the placental implant, and to single out the level of miometrial infiltration.


After treatment we have noticed: two hysterectomies (for persistent AUB after myomectomy and for severe bleeding after dehiscence of a C. section), restoration of regular menstruations in 94.6% of patients (6 women in menopause), disappearance of pelvic pain and dysmenorrhea in all cases (100%), 8 pregnancies of the 9 women who were wanting child after hysteroscopic synechiolysis (88.9%).


According to the present study, the best way to prevent IUA is to make D&C for abortion, avoiding waiting longer than 24 hours, perform a D&C and then a diagnostic hysteroscopy after PPH in symptomatic women, reserve D&Cs only for a PPH, or an incomplete abortion, limit to only one D&C, always make a diagnostic hysteroscopy after D&C and uterine plugging for PPH.



DNA Cell Biol. 2014 May;33(5):328-35.

Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

Kowalczyńska LJ1Ferenc TWojciechowski MMordalska APogoda KMalinowski A.



To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.



Yonago Acta Med. 2013 Dec;56(4):81-4.

Dysmenorrhea and endometriosis in young women.

Harada T1.



Dysmenorrhea is defined as symptoms associated with menstruation, such as abdominal pain, cramping and lumbago, that interfere with daily activity. Primary dysmenorrhea refers to menstrual pain without underlying pathology, whereas secondary dysmenorrhea is menstrual pain associated with underlying pathology. Endometriosis, one of the main causes of secondary dysmenorrhea, induces dysmenorrhea, pelvic pain and infertility, resulting in marked reduction of quality of life during reproductive age. This review article is a comprehensive overview of dysmenorrhea and endometriosis in young women.



Case Rep Gastroenterol. 2014 Jan 25;8(1):51-5.

Gastrointestinal endometriosis causing subacute intestinal obstruction with gradual development of weight loss and misdiagnosed as irritable bowel syndrome.

Soumekh A1Nagler J1.



Both endometriosis and irritable bowel syndrome (IBS) are commonly found in young women and the diagnosis of either is challenging. Alarm symptoms can exclude the diagnosis of IBS, but their onset may be insidious and often no evidence of organic disease may be found. We present a patient with a 4-year history of presumed IBS, absent gynecological symptoms, negative gastrointestinal as well as gynecological testing who developed the only alarm symptom of weight loss and was eventually found to have endometriosis of the small intestine. This case illustrates the need for constant vigilance in patients with IBS.



J Ultrason. 2014 Mar;14(56):36-48

Sonography of tumors and tumor-like lesions that mimic carcinoma of the urinary bladder.

Smereczyński A1Szopiński T2Gołąbek T3Ostasz O1Bojko S1.



in EnglishPolish

One of the basic abdominal organs that is assessed during transabdominal ultrasound examination for urological reasons is the urinary bladder. The bladder must be filled with urine. This is a prerequisite for a reliable assessment and, at the same time, an acoustic window in examining adjacent structures and organs, for instance the prostate gland. In some cases, doubts occur with respect to the nature of lesions detected. The paper presents anatomic lesions, defects and pathologies which might be erroneously interpreted as tumors of the urinary bladder, i.e. transitional cell carcinoma of the urinary bladder. The following lesions are discussed: 1) anatomic defects (including urachus remnants, ligaments that stabilize the bladder or cyst in the opening of the ureter into the bladder – ureterocele); 2) tumor- like lesions in the lumen of the urinary bladder (such as blood clots, fungus balls, stones or foreign bodies); 3) bladder wall pathologies (i.e. cystitis or endometriosis), focal decidual transformation of stromal cells or inflammatory pseudotumor; 4) lesions impressing on the bladder from the outside (the mesentery of the sigmoid colon, the bowel, pathological lesions in organs adjacent to the urinary bladder, inflammatory infiltration, vasogenic compression of the bladder, pelvic lipomatosis, pathological lesions of the pubic symphysis); 5) postoperative lesions. All these lesions may mimic carcinoma of the urinary bladder in sonography. Bearing this fact in mind is significant in establishing a diagnosis. Due to the malignant character of carcinoma of the urinary bladder and the need for aggressive surgical treatment, a correct diagnosis of this disease is essential for patients, particularly because the lack of adequate treatment and delayed treatment considerably affect prognosis.



J Robot Surg. 2014 Mar;8(1):97-8.

Robot assisted laparoscopic documentation of endometriosis.

Martin DC1,2Detti L3,4Osborne S3.



The increased confirmation of endometriosis noted using robotically assisted laparoscopy may be the result of multiple factors, including the three-dimensional view provided with the robot, increased attention and awareness while using new technology, increased time spent considering histologic documentation in preparation for publication, or general improvement with experience.



Arch Pathol Lab Med. 2014 Mar;138(3):432-6.

Müllerianosis of the urinary bladder: a rare tumorlike lesion.

Branca G1Barresi V.



Müllerianosis was first described as a rare entity consisting of an admixture of cervical, tubaric, or endometrial epithelium within the lamina propria and muscularis propria of the urinary bladder. This lesion occurs mainly in the dome or posterior wall of the urinary bladder in women of fertile age. Its clinical presentation is characterized by hematuria, pelvic pain, and dysuria, nonspecific symptoms that are related to the responsiveness of müllerian glands to hormonal stimuli. The major interest of müllerianosis resides in its similarity, from clinical, cytologic, and histologic viewpoints, to more threatening conditions, such as neoplasias. The clinical context and the identification of periglandular endometrial stroma at histologic examination with conventional hematoxylin-eosin stain, as well as the immunohistochemical demonstration of estrogen and progesterone receptors in the glands, are of diagnostic utility in the differential diagnosis. Müllerianosis may be responsive to gonadotropin-releasing hormone agonists. Surgical resection may be justified in the case of clinical symptoms refractory to hormone therapy.



Aust N Z J Obstet Gynaecol. 2014 Apr;54(2):162-5.

Pelvic inflammatory disease in women with endometriosis is more severe than in those without.

Elizur SE1Lebovitz OWeintraub AYEisenberg VHSeidman DSGoldenberg MSoriano D.



To determine the incidence and severity of acute pelvic inflammatory disease (PID) or tubo-ovarian abscess (TOA) in hospitalised women with and without a history of endometriosis.


Retrospective analysis of hospital records retrieved for all women hospitalised with PID or TOA between January 2008 and December 2011 in a tertiary referral centre. Women were compared with regard to a history of endometriosis for demographic, clinical and fertility data.


26 (15%) of the 174 women hospitalised due to PID or TOA were excluded because of age older than 45 years, leaving 148 for analysis. The mean age was 35.7 ± 9.3 years and mean duration of hospitalisation was 5.9 ± 3.7 days. The women were divided into two groups: Group 1 with endometriosis(n = 21) and Group 2 without endometriosis (n = 127). Women in Group 1 as compared with Group 2 were significantly more likely to have undergone a fertility procedure prior to being admitted to the hospital with PID (9/27 (45%) vs 22/121 (17%), P < 0.001); particularly in vitro fertilisation (IVF) (7/ 27 (33%) vs 12/121 (9%), P < 0.006); Women in Group 1 more frequently experienced a severe and complicated course involving longer duration of hospitalisation (8.8 ± 4.7 vs 4.4 ± 2.3 days, P < 0.0001) and antibiotic treatment failure (10/27 (48%) vs 8/121 (6%), P < 0.0001).


Pelvic inflammatory disease in women with endometriosis is more severe and refractory to antibiotic treatment, often requiring surgical intervention. It is likely that endometriosis is a risk factor for the development of severe PID, particularly after IVF treatment.



J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):567-75.

Post-hysterectomy dyspareunia.

Siedhoff MT1Carey ET2Findley AD3Hobbs KA1Moulder JK1Steege JF4.



When appropriately performed, hysterectomy most often contributes substantially to quality of life. Postoperative morbidity is minimal, in particular after minimally invasive surgery. In a minority of women, pain during intercourse is one of the more long-lasting sequelae of the procedure. Complete evaluation and treatment of this complication requires a thorough understanding of the status and function of neighboring organ systems and structures (urinary system, gastrointestinal tract, and pelvic and hip muscle groups). Successful resolution of dyspareunia often may be facilitated with review of the patient’s previous degree of comfort during sex and the nature of her relationship with her partner. Repeat surgery is needed in a small minority of patients.




Eur J Obstet Gynecol Reprod Biol. 2014 Apr;175:87-91.

Is nerve-sparing surgery suitable for deeply infiltrating endometriosis?

Che X1Huang X2Zhang J2Xu H2Zhang X3.



To investigate the efficacy of nerve-sparing surgery for deeply infiltrating endometriosis (DIE) and the bladder and sexual dysfunction that follow this procedure.


A total of 108 women with DIE underwent conventional surgery (group A, n=63) and nerve-sparing surgery (group B, n=45). Three validated interview-based questionnaires – the visual analogue scale (VAS), the international prostate score symptom (IPSS), and the female sexual function index (FSFI) – were used to evaluate the efficacy and associated complications.


The VAS scores significantly decreased in both groups A and B after surgery, although two patients (4.4%) in group B had no improvement in their pain symptoms. The total FSFI and each domain scores significantly increased in the two groups after surgery except for satisfaction at the 24-month follow up in group A. Nine patients (15.9%) in group A required self-catheterization postoperatively. Based on the IPSS scores, a significant alteration in voiding symptoms in group A was observed at 6 months but not at 12 months or 24 months after surgery. In group B, however, no significant difference or self-catheterization requirement was observed after surgery.


Reduced bladder and sexual dysfunction, but with a risk of absence of pain relief, suggests that the pros and cons of nerve-sparing surgery for DIE should carefully be evaluated before operation.



Hum Reprod. 2014 May;29(5):1011-24.

Combined blockade of angiotensin II type 1 receptor and activation of peroxisome proliferator-activated receptor-γ by telmisartan effectively inhibits vascularization and growth of murine endometriosis-like lesions.

Nenicu A1Körbel CGu YMenger MDLaschke MW.



Is telmisartan effective in the treatment of endometriosis?


Combined blockade of angiotensin II type 1 receptor (AT1R) and activation of peroxisome proliferator-activated receptor (PPAR)-γ by telmisartan inhibits vascularization and growth of murine endometriosis-like lesions.


AT1R and PPAR-γ are involved in the regulation of inflammation, proliferation and angiogenesis. These processes are also crucial for the pathogenesis of endometriosis and both receptors are expressed in endometrial tissue. Telmisartan is a partial agonist of PPAR-γ, which additionally blocks AT1R.


This was a randomized study in the mouse dorsal skinfold chamber and peritoneal model of endometriosis. Endometriosis-like lesions were induced in dorsal skinfold chambers of 21 female C57BL/6 mice, and in the peritoneal cavity of 15 additional animals, which were daily treated with an i.p. injection of pioglitazone (10 mg/kg, n = 12), telmisartan (10 mg/kg, n = 12) or vehicle (5% dimethyl sulfoxide (DMSO), n = 12) throughout an observation period of 14 and 28 days, respectively.


The anti-angiogenic actions of pioglitazone, a full PPAR-γ agonist, and telmisartan were firstly assessed in vitro by an aortic ring assay. Endometriosis-like lesions were induced in the dorsal skinfold chamber or peritoneal cavity and the effects of telmisartan and pioglitazone on their vascularization, immune cell content and growth were studied by intravital fluorescence microscopy, high-resolution ultrasound imaging as well as histological, immunohistochemical and immunofluorescent analyses. Additional quantitative real-time polymerase chain reaction (qRT-PCR) arrays served for gene expression profiling of the lesions. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate vehicle-treated controls. Statistical significance was accepted for a value of P < 0.05.


Telmisartan inhibited vascular sprout formation of aortic rings more effectively than pioglitazone. Accordingly, endometriosis-like lesions in dorsal skinfold chambers of telmisartan-treated animals exhibited a markedly lower functional microvessel density and blood perfusion. High-resolution ultrasound analyses of peritoneal endometriosis-like lesions revealed that the compound inhibited the stromal tissue growth, resulting in a significantly reduced final lesion volume. In contrast, the development of cysts did not differ between the groups. Moreover, telmisartan induced an up-regulation of PPAR-γ and a down-regulation of AT1R proteins in endometriosis-like lesions, which was associated with a decreased density of CD31-positive microvessels, a reduced immune cell content and a lower number of Ki67-positive proliferating cells. qRT-PCR arrays further demonstrated an inhibitory action of telmisartan on the expression of several angiogenic and inflammatory genes.


Endometriosis-like lesions were induced by syngeneic tissue transplantation into recipient mice without the use of pathological endometriotic tissue of human nature. Therefore, the results obtained in this study may not fully relate to human patients with endometriosis.


This study demonstrates that telmisartan inhibits vascularization, immune cell content and growth of endometriosis-like lesions. Accordingly, the combined blockade of AT1R and activation of PPAR-γ represents a promising new concept in the development of novel compounds for the treatment of endometriosis.


There was no specific funding of this study. The authors have no conflicts of interest to declare.


ISRN Obstet Gynecol. 2014 Jan 20;2014:853902.

Posterior Deep Infiltrating Endometriotic Nodules: Operative Considerations according to Lesion Size, Location, and Geometry, during One’s Learning Curve.

Protopapas A1Giannoulis G1Chatzipapas I1Athanasiou S1Grigoriadis T1Haidopoulos D1Loutradis D1Antsaklis A1.



We conducted this prospective cohort study to standardize our laparoscopic technique of excision of posterior deep infiltrating endometriosis (DIE) nodules, according to their size, location, and geometry, including 36 patients who were grouped, according to principal pelvic expansion of the nodule, into groups with central (group 1) and lateral (group 2) lesions, and according to nodule size, into ≤2 cm (group A) and >2 cm (group B) lesions, respectively. In cases of group 1 the following operative steps were more frequently performed compared to those of group 2: suspension of the rectosigmoid, colpectomy, and placement of bowel wall reinforcement sutures. The opposite was true regarding suspension of the adnexa, systematic ureteric dissection, and removal of the diseased pelvic peritoneum. When grouping patients according to nodule size, almost all of the examined parameters were more frequently applied to patients of group B: adnexal suspension, suspension of the rectosigmoid, systematic ureteric dissection, division of uterine vein, colpectomy, and placement of bowel wall reinforcement sutures. Nodule size was the single most important determinant of duration of surgery. In conclusion, during the building-up of one’s learning curve of laparoscopic excision of posterior DIE nodules, technique standardization is very important to avoid complications.



Aust N Z J Obstet Gynaecol. 2014 Apr;54(2):156-61.

A randomised controlled trial of intra-uterine insemination versus in vitro fertilisation in patients with idiopathic or mild male infertility.

Elzeiny H1Garrett CToledo MStern KMcBain JBaker HW.



The cause of infertility is unexplained or poorly explained in 30-40% of couples undergoing standard investigations, and treatment ranges from expectant management to IUI and IVF.


The aim of this study was to compare the clinical pregnancy rates and costs of intra-uterine insemination (IUI) and in vitro fertilisation (IVF) in women where the same ovarian stimulation led to the development of two or three mature follicles.


A randomised controlled clinical trial compared the efficacy of IUI and IVF in a tertiary fertility centre (ISRCTN28780587). Primary outcome measures were fetal heart positive pregnancy rate and cost per live birth. The selection criteria were age: females 18-42 years and males 18-60 years, infertility for one year or more, no IVF or IUI for 12 months prior to the trial, and no coital, tubal or ovulatory disorders, oligospermia, untreated endometriosis or contraindication for multiple pregnancy. All women (n = 102) had the same dose FSH stimulation protocol. Those who developed two or three preovulatory follicles were randomised 3:1 to IUI (n = 33) or IVF (n = 10). IUI or IVF was performed 36 h after hCG administration with single or double embryo transfer on day two.


Clinical pregnancy rates (40% vs 12%, P = 0.04) and live birth rate (40% vs 6%, P = 0.01) were higher for IVF than IUI. The cost per live birth was AU$8735 for IVF compared with $42,487 for IUI.


This study provides evidence that IVF is more successful and cost-effective than IUI using the same doses of FSH. Further confirmatory studies are required.



Reprod Biomed Online. 2014 Apr;28(4):515-21.

The development of endometriosis in a murine model is dependent on the presence of dendritic cells.

Pencovich N1Luk J2Hantisteanu S3Hornstein MD4Fainaru O5.



Endometriosis is a common condition associated with pelvic pain and infertility. This study group has previously shown that supplementation of dendritic cells led to enhancement of endometriosis lesion growth and angiogenesis. This study determined whether endometriosis is dependent on the presence of endogenous dendritic cells. Surgical induction of endometriosis was performed in CD11c⁺ DTR/GFP transgenic (Tg) female mice in which dendritic cells were ablated upon injection of diphtheria toxin (DT). Mice were allocated into four groups (n=5 each): group I, wild-type mice treated with vehicle; group II, wild-type mice treated with DT; group III, Tg mice treated with DT; and group IV, Tg mice treated with vehicle. After 10 days, mice were killed and endometriosis lesions were analysed by flow cytometry. DT treatment led to ablation of dendritic cells in spleens and endometriosis lesions in Tg mice while no ablation was observed in controls. Corresponding to dendritic cell ablation, endometriosis lesions in group III were ∼5-fold smaller than in the control groups (ANOVA P<0.0001). This study suggests that endometriosis development is dependent on the presence of endogenous dendritic cells. Therapies designed to inhibit dendritic cell infiltration as possible treatments for endometriosis warrant further study.



J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):978-9.

Combined cystoscopic and laparoscopic approach in deep endometriosis of the bladder.

Roman H1Arambage K2Pasquier G3Resch B2Huet E4.



To report the combined cystoscopic and laparoscopic approach in deep endometriosiswith full-thickness infiltration of the bladder.


Video (Canadian Task Force classification III).


University hospital.


A 34-year-old nulliparous woman with a large (35-mm) endometriosis nodule infiltrating the bladder and deep endometriosis of the rectum and sigmoid colon.


The urologic surgeon performed cystoscopy, identified the limits of mucosal involvement, and incised the muscular layer up to fat tissues surrounding the bladder. The gynecologic surgeon identified and followed the circular incision, and completed full-thickness resection of the bladder wall. Surgical technique reports in anonymous patients are exempt from ethical approval by the institutional review board.


The patient’s functional outcome was uneventful. Laparoscopic resection of large endometriotic nodules of the bladder per se may lead to inadvertent removal of healthy bladder muscle. Thus it increases the risk of postoperative complications and symptoms due to small bladder volume. Conversely, if resection of the nodule is performed only cystoscopically, it probably would not be completely removed. We routinely combine the 2 approaches because this enables complete resection of the endometriotic nodule. It not only averts the risk of excessive removal of healthy bladder muscle but also leaves no disease behind.


On the basis of our experience, we propose the combined cystoscopic and laparoscopic approach in managing large endometriotic nodules with full-thickness infiltration of the bladder.



Ann Thorac Cardiovasc Surg. 2014;20 Suppl:686-8.

Pulmonary sequestration presenting elevated CA19-9 and CA125 with ovarian cysts.

Komatsu H1Mizuguchi SIzumi NInoue HOka HSuehiro SNishiyama N.



A 41-year-old woman was evaluated because of elevated serum levels of the tumor markers CA19-9 and CA125. Whole-body examination revealed an intralobar pulmonary sequestration in the right lower lobe and bilateral cystic ovarian tumors (right: 20 mm, left: 60 mm in diameter, respectively). The left ovarian cyst was resected and diagnosed as an endometrioma. The right ovarian cyst was preserved because of its small size. However, the tumor marker levels remained elevated postoperatively. S10 segmentectomy of the right lung was subsequently performed. Immunohistochemical examination of the sequestrated lung demonstrated positive staining for CA19-9 in the bronchial and alveolar epithelia and mucus. After the pulmonary resection, the CA19-9 and CA125 levels decreased to their normal ranges.



Reproduction. 2014 Jun;147(6):847-53.

The role of SRC1 and SRC2 in steroid-induced SDF1 expression in normal and ectopic endometrium.

Shi X1Xu W1Dai HH1Sun Y1Wang XL2.



To compare the expression patterns of steroid receptor coactivators (SRCs) and steroid-induced stromal cell-derived factor 1 (CXCL12 (SDF1)) in normal and ectopic endometrium and to explore the roles of NCOA1 (SRC1) and NCOA2 (SRC2) in the steroid-induced CXCL12 expression in normal and ectopic endometrial stromal cells (ESCs). The NCOA1, NCOA2, NCOA3 (SRC3), and CXCL12 (SDF1)α mRNA levels in normal and ectopic endometrium were analyzed by quantitative real-time PCR. Steroid-induced CXCL12 expression was detected by the ELISA method and the chemotactic activity of conditioned supernatant to monocyte was assessed by the Boyden chamber method before and after the silencing of NCOA1 or NCOA2 with siRNA in normal and ectopic ESCs. The expression of NCOA1 and CXCL12 in ectopic endometrium was significantly greater than that in normal endometrium in the secretory phase. Progesterone (P4) was able to significantly inhibit estradiol (E2)-stimulated CXCL12 expression in normal and ectopic ESCs. The inhibitory rate of P4 in ectopic ESCs at 72 and 96 h was significantly lower than that in normal ESCs. Silencing of NCOA1 but not NCOA2 significantly reduced the E2-induced CXCL12 expression in normal and ectopic ESCs. The ability of P4 to inhibit E2-induced CXCL12 expression and monocyte chemotaxis in normal and ectopic ESCs was significantly attenuated when NCOA2 was silenced. NCOA1 plays a necessary role in E2-induced CXCL12 expression and NCOA2 is required for P4 to inhibit the E2-induced CXCL12 production in normal and ectopic endometrium.



PLoS One. 2014 Feb 24;9(2):e89742.

Lipoxin A prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E production and estrogen signaling.

Kumar R1Clerc AC2Gori I2Russell R2Pellegrini C2Govender L3Wyss JC3Golshayan D3Canny GO2.



Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄), an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂) levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating transforming growth factor (TGF)-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.



Expert Opin Pharmacother. 2014 Apr;15(6):767-73.

A comparison of progestogens or oral contraceptives and gonadotropin-releasing hormone agonists for the treatment of endometriosis: a systematic review.

Jeng CJ1Chuang LShen J.



This systematic review examined the use of progestogens or oral contraceptives and gonadotropin-releasing hormone (GnRH) agonists for the treatment of endometriosis.


Inclusion criteria were: i) randomized controlled trials (RCTs); ii) comparison of progestogens with GnRH agonists for treatment of endometriosis; and iii) endometriosisdiagnosed by laparoscopy or laparotomy.


Pelvic pain, bone mineral density, serum estradiol level, and side effects.


Of 128 articles identified, there were four RCTs comparing the use of progestogens and GnRH agonists. In three studies a progestogen (gestrinone, lynestrenol, or dienogest) was compared with leuprolide. In one study, ethinyl estradiol/norethindrone was compared with leuprolide/norethindrone. A meta-analysis was not possible as the studies varied markedly in their protocols, inclusion criteria, and the drugs and doses administered. Leuprolide was as effective as gestrinone, dienogest, and continuous oral contraceptives (OCs) for the relief of endometriosis-related pain, whereas it was superior to lynestrenol. Leuprolide was associated with a significant reduction in bone mineral density and estradiol levels and a higher incidence of hot flushes, headaches, mood changes, and vaginal dryness, whereas progestogens were associated with higher incidences of weight gain and acne.


These results suggest that progestogens or OCs may be used as first-line therapy for endometriosis.



J Mol Med (Berl). 2014 Jun;92(6):595-602.

The peritoneum–an important factor for pathogenesis and pain generation in endometriosis.

Barcena de Arellano ML1Mechsner S.



Endometriosis (EM) is an oestrogen-dependent disease affecting 10-15 % of women during reproductive age. It is characterised by the presence of endometrial glands, stromal- and smooth muscle-like cells outside of the uterine cavity. Fifty to sixty per cent of women and teenage girls with pelvic pain suffer from EM. EM causes disability and compromises the quality of life in women and young girls significantly. Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments.


Colorectal Dis. 2014 Jul;16(7):O253-6.

New disc excision procedure for low and mid rectal endometriosis nodules using combined transanal and laparoscopic approach.

Roman H1Tuech JJ.



Colorectal resection in women with endometriosis involving the low and mid rectum may result in a poorer outcome than conservative procedures. In this technical note we present a new technique for transanal full thickness disc excision of endometriosis nodules involving the rectum.


The procedure is performed by combined laparoscopic and transanal routes. The former involves paring the area of the rectum infiltrated by the nodule, which is then made amenable to endoluminal removal using the Contour Transtar stapler to carry out a large disc excision.


The technique can remove a specimen as large as 80 mm in diameter and can be applied to patients with infiltrating rectal endometrial nodules up to 10 cm from the anal margin and 50-60% of the rectal circumference. The procedure is probably less likely to lead to rectal stenosis and denervation than colorectal resection.


This technique of transanal rectal disc excision using the Contour stapler is suitable in patients with infiltrating deep endometriosis nodules of the lower and mid rectum. It avoids a low rectal resection with its potential complications and unfavourable function.



Reprod Sci. 2014 Oct;21(10):1228-36.

Dendritic cells attenuate the early establishment of endometriosis-like lesions in a murine model.

Stanic AK1Kim M2Styer AK3Rueda BR4.



Complex interplay of innate and adaptive immune cells has been implicated in the establishment, maintenance, and progression of endometriosis. Defining the identity, activation state, and functional role of immune cells during lesion establishment will provide invaluable insight into the underlying mechanisms of disease. This study utilized a transgenic mouse model with conditional dendritic cell (DC) depletion (diphtheria toxin-treated B6.FVB-Itgax-hDTR-EGFP(tg)) and multiparametric flow cytometry to examine immune cell composition and activation state and to assess the functional role of DCs in endometriosis-like lesions. T cells and DCs were increased in lesions compared to native uteri and control splenocytes and demonstrated an activated phenotype (P < .05). Lesions in DC-depleted hosts demonstrated greater size (P < .001) and reduced expression of T-cell activation marker CD69 compared to controls (P < .05). Collectively, these results suggest that activated DCs within lesions activate T cells and result in the impairment of early lesion establishment.


Cochrane Database Syst Rev. 2014 Mar 5;(3):CD008797.

Non-surgical interventions for the management of chronic pelvic pain.

Cheong YC1Smotra GWilliams AC.



Chronic pelvic pain is a common and debilitating condition; its aetiology is multifactorial, involving social, psychological and biological factors. The management of chronic pelvic pain is challenging, as despite interventions involving surgery, many women remain in pain without a firm gynaecological diagnosis.


To assess the effectiveness and safety of non-surgical interventions for women with chronic pelvic pain.


We searched the Menstrual Disorders and Subfertility Group Specialised Register. We also searched (from inception to 5 February 2014) AMED, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We handsearched sources such as citation lists, trial registers and conference proceedings.


Randomised controlled trials (RCTs) on non-surgical management of chronic pelvic pain were eligible for inclusion. We included studies of women with a diagnosis of pelvic congestion syndrome or adhesions but excluded those with pain known to be caused by endometriosis, primary dysmenorrhoea (period pain), active chronic pelvic inflammatory disease or irritable bowel syndrome. We considered studies of any non-surgical intervention, including lifestyle, physical, medical and psychological treatments.


Study selection, quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using the Peto odds ratio (Peto OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). The primary outcome measure was pain relief, and secondary outcome measures were psychological outcomes, quality of life, requirement for analgesia and adverse effects. The quality of the evidence was assessed by using GRADE methods.


Twenty-one RCTs were identified that involved non-surgical management of chronic pelvic pain: 13 trials were included in the review, and eight were excluded. The studies included a total of 750 women-406 women in the intervention groups and 344 in the control groups. Included studies had high attrition rates, and investigators often did not blind adequately or did not clearly describe randomisation procedures. Medical treatment versus placebo Progestogen (medroxyprogesterone acetate (MPA)) was more effective than placebo at the end of treatment in terms of the number of women achieving a greater than 50% reduction in visual analogue scale (VAS) pain score immediately after treatment (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I(2) = 22%, moderate-quality evidence). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I(2) = 0%, moderate-quality evidence). Women treated with progestogen reported more adverse effects (e.g. weight gain, bloatedness) than those given placebo (high-quality evidence). The estimated effect of lofexidine on pain outcomes when compared with placebo was compatible with benefit and harm (Peto OR 0.42, 95% CI 0.11 to 1.61, one study, 39 women, low-quality evidence). Women in the lofexidine group reported more adverse effects (including drowsiness and dry mouth) than women given placebo (moderate-quality evidence). Head-to-head comparisons of medical treatments Head-to-head comparisons showed that women taking goserelin had greater improvement in pelvic pain score (MD 3, 95% CI 2.08 to 3.92, one study, n = 47, moderate-quality evidence) at one year than those taking progestogen. Women taking gabapentin had a lower VAS pain score than those taking amytriptyline (MD -1.50, 95% CI -2.06 to -0.94, n = 40, low-quality evidence). Study authors reported that no statistically significant difference was observed in the rate of adverse effects among women taking gabapentin compared with women given amytriptyline. The study comparing goserelin versus progestogen did not report on adverse effects. Psychological treatment Women who underwent reassurance ultrasound scans and received counselling were more likely to report improved pain than those treated with a standard ‘wait and see’ policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90, low-quality evidence). Significantly more women who had writing therapy as a disclosure reported improvement in pain than those in the non-disclosure group (Peto OR 4.47, 95% CI 1.41 to 14.13, n = 48, very low-quality evidence). No difference between groups in pain outcomes was noted when other psychological therapies were compared with standard care or placebo (quality of evidence ranged from very low to low). Studies did not report on adverse effects. Complementary therapy Distension of painful pelvic structures was more effective for pain when compared with counselling (MD 35.8, 95% CI 23.08 to 48.52 on a zero to 100 scale, one study, n = 48, moderate-quality evidence). No difference in pain levels was observed when magnetic therapy was compared with use of a control magnet (very low-quality evidence). Studies did not report on adverse effects.The results of studies examining psychological and complementary therapies could not be combined to yield meaningful results.


Evidence of moderate quality supports progestogen as an option for chronic pelvic pain, with efficacy reported during treatment. In practice, this option may be most acceptable among women unconcerned about progestogenic adverse effects (e.g. weight gain, bloatedness-the most common adverse effects). Although some evidence suggests possible benefit of goserelin when compared with progestogen, gabapentin as compared with amytriptyline, ultrasound versus ‘wait and see’ and writing therapy versus non-disclosure, the quality of evidence is generally low, and evidence is drawn from single studies.Given the prevalence and healthcare costs associated with chronic pelvic pain in women, RCTs of other medical, lifestyle and psychological interventions are urgently required.



J Reprod Med. 2014 Jan-Feb;59(1-2):13-6.

In vitro effect of danazol on endometrioma cells in culture.

Ollivierre BA1Cuenca V1Kaufman L1Badawy SZ1.



To evaluate the effect of danazol on endometrioma cells in culture, in relation to cell proliferation.


Danazol has been shown to be effective in treating endometriosis, leading to remission. The mode of action is through suppression of gonadotropins. A direct effect on endometriosis implants has been suggested. This study was conducted on endometrioma cell lines using various concentrations of danazol in ethanol solution.


Danazol showed a decrease in proliferation ofendometrioma cells in culture. This was also associated with an increase in apoptosis and necrosis ofcultured cells.


This study demonstrates the direct effect of danazol on endometrioma cells in culture.



World J Surg Oncol. 2014 Mar 5;12:51.

Clear cell carcinoma arising from abdominal wall endometriosis: a unique case with bladder and lymph node metastasis.

Liu H1Leng JLang JCui Q.



The malignant transformation of abdominal wall endometriosis is a rare event and poorly understood. Less than 30 cases have been reported in the literature. Most of the reported cases have a solitary tumor in the abdominal scar. A few cases have metastasis. Here we report a case of clear cell carcinoma in abdominal wall endometriosis with bladder and lymph system metastasis. The patient had a history of abdominal wall endometriosis and recently developed symptoms of urgent urination and inguinal mass. Physical examination and a computed tomography (CT) scan detected lymph node metastasis. CT and cystoscopy confirmed bladder involvement. The patient underwent extensive surgery and chemotherapy. Pathological analysis made a diagnosis of clear cell carcinoma with bladder and lymph node metastasis. The patient was followed up and died of the disease. Symptoms of bladder invasion and lymph node spread could be a sign of malignant transformation. Local invasion and lymph node spread are two important forms of tumor metastasis. Extensive lymph nodes metastasis might be related with poor prognosis.



Histol Histopathol. 2014 Sep;29(9):1153-60.

Increased endometrial expression of CC-chemokine receptor-1 in women with adenomyosis.

Xu H1Yang Y1Zhou C1Huang X1Lin J1Zhang X2.



Abnormal endometrial expression of CC-chemokine receptor-1 (CCR1) may play a role in the pathogenesis of endometriosis. Adenomyosis, also called endometriosis interna, occurs when the endometrium invades the myometrium. The objective of this study was to determine CCR1 expression in endometrium in women with adenomyosis as compared to women without adenomyosis. We evaluated endometrial mRNA and protein expression in women with and without adenomyosis using quantitative polymerase chain reaction (PCR), immunohistochemical staining and western blot analysis, respectively. We detected CCR1-immunoreactive expression in endometrium in all women with and without adenomyosis. CCR1-immunoreactive staining in endometrial cells was significantly higher in women with adenomyosis (4.89±1.06) compared to those without adenomyosis (2.21±1.16, P<0.001). Women with adenomyosis had higher levels of CCR1 mRNA in endometrium compared to women without adenomyosis (P<0.05). CCR1 protein levels in endometrium were significantly higher in women with adenomyosis (1.66±0.79) compared to women without adenomyosis (0.56±0.13, P<0.001), and positively correlated with the severity of dysmenorrhea (r=0.87, P<0.001). These results suggest that increased CC-chemokine receptor expression may play a role in the pathogenesis of adenomyosis.



Reproduction. 2014 Jun;147(6):R199-207.

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis.

Pirdel L1Pirdel M2.



This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis.



Womens Health (Lond). 2014 Mar;10(2):161-6.

Surgery versus pharmacological treatment for endometriosis.

Avraham S1Seidman DS.



The two major consequences of endometriosis are pain and infertility. Despite numerous studies and proposed guidelines, some aspects of the treatment for these complications are still under debate or lack convincing evidence that favors one approach over the other. Future studies will hopefully present new evidence in regard to the optimal treatment for each indication and suggest innovative pharmacotherapy following improved understanding of the pathophysiology of endometriosis. Until then, individualization of the treatment according to the specific indication, taking into consideration the benefits versus the risks for the patient and the tolerability profile, remains the most appropriate approach.



Fertil Steril. 2014 Apr;101(4):988-93.e1.

Ovarian endometriomas and oocyte quality: insights from in vitro fertilization cycles.

Filippi F1Benaglia L2Paffoni A2Restelli L2Vercellini P3Somigliana E2Fedele L3.



To evaluate whether the presence of endometriomas affects ovarian function.


Prospective cohort study.


Infertility unit of an academic setting.


Twenty-nine women undergoing an IVF cycle.


Prospective evaluation of women with unoperated unilateral endometriomas undergoing IVF. The affected and contralateral intact gonads were compared in terms of responsiveness and oocyte quality.


Oocyte developmental competence.


Ovarian responsiveness and oocyte quality did not significantly differ between the affected and intact gonads. The number of codominant follicles, the number of oocytes retrieved, and the number of suitable oocytes in affected and intact gonads were 3.7 ± 2.4 and 4.1 ± 1.7, 4.2 ± 3.1 and 4.7 ± 2.5, and 3.1 ± 2.6 and 3.5 ± 2.3, respectively. The number of viable embryos and the number of high-quality embryos were 1.8 ± 2.1 and 1.8 ± 1.4 and 1.0 ± 1.7 and 0.8 ± 0.7, respectively. The fertilization rate in the affected and intact gonads was 64% and 64%, respectively. The cleavage rate was 58% and 51%, respectively. The rate of high-quality embryos was 31% and 21%, respectively.


In women undergoing IVF, the presence of ovarian endometriomas does not affect oocyte developmental competence.



Gynecol Obstet Invest. 2014;77(3):180-5.

Reproductive performance after surgery for endometriosis: predictive value of the revised American Fertility Society classification and the endometriosis fertility index.

Zeng C1Xu JNZhou YZhou YFZhu SNXue Q.



To determine whether the revised American Fertility Society (rAFS) classification and endometriosis fertility index (EFI) predict pregnancy rates (PRs) in patients with surgically confirmed endometriosis attempting natural conception.


We retrospectively assessed 194 women with endometriosis who underwent laparoscopic surgery; 161 women completed the follow-up. Pregnancy outcomes, rAFS stages and EFI scores were documented. Cumulative PRs were compared using Kaplan-Meier survival analysis.


The cumulative PR 36 months after surgery was 46.6% (stage I, 53.6%; stage II, 36.0%; stage III, 51.7%, and stage IV, 41.7%; log-rank test, χ(2) = 4.143, p = 0.246). In the 1st year, PRs significantly differed between patients with rAFS stage IV and those with stages I-III (Pearson’s χ(2) test, χ(2) = 6.024, p = 0.014). Significant differences in cumulative PRs were observed among EFI scores (group 1, EFI score 0-3, 8.3%; group 2, EFI score 4-7 41.2%, and group 3, EFI score 8-10 60.9%; log-rank test, χ(2) = 16.254, p < 0.001).


EFI scores, but not rAFS stage, predict PRs in patients with endometriosis-associated infertility. EFI scores may be used to guide postoperative treatment.



PLoS Genet. 2014 Mar 6;10(3):e1004158.

Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis.

Dyson MT1Roqueiro D2Monsivais D1Ercan CM1Pavone ME1Brooks DC1Kakinuma T1Ono M1Jafari N1Dai Y2Bulun SE1.



Endometriosis is a gynecological disease defined by the extrauterine growth of endometrial-like cells that cause chronic pain and infertility. The disease is limited to primates that exhibit spontaneous decidualization, and diseased cells are characterized by significant defects in the steroid-dependent genetic pathways that typify this process. Altered DNA methylation may underlie these defects, but few regions with differential methylation have been implicated in the disease. We mapped genome-wide differences in DNA methylation between healthy human endometrial and endometriotic stromal cells and correlated this with gene expression using an interaction analysis strategy. We identified 42,248 differentially methylated CpGs in endometriosiscompared to healthy cells. These extensive differences were not unidirectional, but were focused intragenically and at sites distal to classic CpG islands where methylation status was typically negatively correlated with gene expression. Significant differences in methylation were mapped to 403 genes, which included a disproportionally large number of transcription factors. Furthermore, many of these genes are implicated in the pathology of endometriosis and decidualization. Our results tremendously improve the scope and resolution of differential methylation affecting the HOX gene clusters, nuclear receptor genes, and intriguingly the GATA family of transcription factors. Functional analysis of the GATA family revealed that GATA2 regulates key genes necessary for the hormone-driven differentiation of healthy stromal cells, but is hypermethylated and repressed in endometriotic cells. GATA6, which is hypomethylated and abundant in endometriotic cells, potently blocked hormone sensitivity, repressed GATA2, and induced markers of endometriosis when expressed in healthy endometrial cells. The unique epigenetic fingerprint in endometriosis suggests DNA methylation is an integral component of the disease, and identifies a novel role for the GATA family as key regulators of uterine physiology-aberrant DNA methylation in endometriotic cells correlates with a shift in GATA isoform expression that facilitates progesterone resistance and disease progression.



Reprod Sci. 2014 Nov;21(11):1362-9.

Resveratrol and endometrium: a closer look at an active ingredient of red wine using in vivo and in vitro models.

Amaya SC1Savaris RF2Filipovic CJ1Wise JD3Hestermann E3Young SL4Lessey BA5.



Resveratrol is a natural phytoestrogen with antiproliferative properties present in red wine, grapes, and berries. Published reports on the effects of resveratrol in human endometrial function are limited. The objective of this study was to investigate the expression of estrogen receptor α (ESR1), Ki-67 (a proliferative marker), aryl hydrocarbon receptor (AhR), and members of the cytochrome P450 superfamily of enzymes (CYP1A1 and CYP1B1) in an in vitro and vivo assay. Alkaline phosphatase assay of estrogenicity was used to compare estrogen activity of different concentrations of resveratrol to estradiol (E2) and diethylstilbestrol (DES), using Ishikawa cell culture. Immunohistochemical expression of ESR1 and Ki67, and reverse transcriptase polymerase chain reaction of AhR, CYP1A1, and CYP1B1 were analyzed from xenograft implants of human endometrial tissue in ovariectomized immunodeficient RAG-2-γ(c) mice, after 30 days of treatment with subcutaneous pellets of E2, E2 plus progesterone (P4), or E2 plus resveratrol (6, 30, or 60 mg) for 30 days. Compared to E2, resveratrol acted as an agonist and antagonist of estrogen in low and high concentrations, respectively, when combined with E2. Xenografts of human endometrial tissues in RAG-2 mice exhibited reduced expression of ESR1 and proliferative activity (Ki67) with 60 mg of resveratrol. This study suggests that resveratrol, at high doses, has the potential benefit to reduce proliferation of human endometrium through ESR1.




Reprod Sci. 2014 Oct;21(10):1256-65.

Synergistic effects of E2MATE and norethindrone acetate on steroid sulfatase inhibition: a randomized phase I proof-of-principle clinical study in women of reproductive age.

Pohl O1Bestel E1Gotteland JP2.



The combination of a progestin such as norethindrone acetate (NETA) reducing the ovarian estrogen production with a steroid sulfatase (STS) inhibitor (STS-I) decreasing the local estrogen production could result in a new treatment option for endometriosis. The study reported was a randomized, double-blind, and placebo-controlled study to investigate the pharmacodynamics, pharmacokinetics, and safety of the STS-I PGL2001 (E2MATE) and NETA. A total of 24 healthy women of reproductive age were treated with weekly doses of PGL2001 or daily doses of NETA or a combination of both compounds for 4 weeks. Four weeks of treatment with PGL2001 or PGL2001 + NETA reduced the STS activity in the endometrium by 91% (±3%) and 96% (±4%), respectively, and comparable values were observed 1 month after the treatment was stopped. The combined treatment of PGL2001 + NETA led to significantly higher STS inhibition at both times (P < .01 and P < .05, respectively). This study showed that administration of PGL2001 alone at 4 mg/week or combined with NETA to healthy women of reproductive age led to STS inhibition and changes in functional STS biomarkers in the endometrium, resulting in synergistic effects of PGL2001 and NETA on STS activity.



J Biophotonics. 2014 Apr;7(3-4):254-65.

Measuring similarity and improving stability in biomarker identification methods applied to Fourier-transform infrared (FTIR) spectroscopy.

Trevisan J1Park JAngelov PPAhmadzai AAGajjar KScott ADCarmichael PLMartin FL.



FTIR spectroscopy is a powerful diagnostic tool that can also derive biochemical signatures of a wide range of cellular materials, such as cytology, histology, live cells, and biofluids. However, while classification is a well-established subject, biomarker identification lacks standards and validation of its methods. Validation of biomarker identification methods is difficult because, unlike classification, there is usually no reference biomarker against which to test the biomarkers extracted by a method. In this paper, we propose a framework to assess and improve the stability of biomarkers derived by a method, and to compare biomarkers derived by different method set-ups and between different methods by means of a proposed “biomarkers similarity index”.



Acta Obstet Gynecol Scand. 2014 Jan;93(1):38-44.

Postoperative levonorgestrel-releasing intrauterine system versus oral contraceptives after gonadotropin-releasing hormone agonist treatment for preventing endometrioma recurrence.

Cho SJung JALee YKim HYSeo SKChoi YSLee JSLee BS.



Although the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in reducing the recurrence of endometriosis-associated pain, its efficacy in preventing endometrioma recurrence is questionable. We compared the efficacy of postoperative use of LNG-IUS with oral contraceptives (OC) for preventing endometrioma recurrence.


A retrospective cohort study.


Medical university hospital.


Ninety-nine women with endometriomas.


A chart review was performed of women of reproductive age who had undergone laparoscopic surgery for endometrioma followed by three cycles of gonadotropin-releasing hormone agonist (leuprolide acetate) treatment. Women were categorized into two groups: a group that had postoperative LNG-IUS placement (n = 42) and a group that received postoperative, cyclic, low-dose, monophasic, OCs (n = 57). Main outcome measures. Endometrioma recurrence was analyzed according to several clinical variables and postoperative treatment modalities.


During the follow-up period (median 17 months), recurrent endometriomas were detected in eight women (8.1%). Patients with LNG-IUS had a recurrence rate of 4.8% (2/42), whereas women receiving OC had a recurrence rate of 10.5% (6/57). Cumulative recurrence-free survival assessment revealed that mean disease-free survival times for both groups were similar, but that for LNG-IUS was slightly longer than that for OC, with statistical significance (34.4 ± 1.0 months, 95% confidence interval 32.3–36.5, vs. 33.4 ± 1.3 months, 95% confidence interval 30.8–36.0, p = 0.045). Univariate analysis revealed a hazard ratio of 0.178 (95% confidence interval 0.029–1.075) (p = 0.060) for postoperative LNG-IUS use and endometrioma recurrence. However, for the multivariate regression analysis, only postoperative serum CA 125 levels were significantly associated with endometrioma recurrence (hazard ratio 1.012, p = 0.010).


Postoperative LNG-IUS use seemed to be comparable to the use of cyclic OC in preventing endometrioma recurrence.


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