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Am J Epidemiol. 2013 Mar 1;177(5):420-30. doi: 10.1093/aje/kws247. Epub 2013 Feb 3.

Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study.

Harris HR1Chavarro JEMalspeis SWillett WCMissmer SA.



The etiology of endometriosis is poorly understood, and few modifiable risk factors have been identified. Dairy foods and some nutrients can modulate inflammatory and immune factors, which are altered in women with endometriosis. We investigated whether intake of dairy foods, nutrients concentrated in dairy foods, and predicted plasma 25-hydroxyvitamin D (25(OH)D) levels were associated with incident laparoscopically confirmed endometriosis among 70,556 US women in Nurses’ Health Study II. Diet was assessed via food frequency questionnaire. A score for predicted 25(OH)D level was calculated for each participant. During 737,712 person-years of follow-up over a 14-year period (1991-2005), 1,385 cases of incident laparoscopically confirmed endometriosis were reported. Intakes of total and low-fat dairy foods were associated with a lower risk of endometriosis. Women consuming more than 3 servings of total dairy foods per day were 18% less likely to be diagnosed with endometriosis than those reporting 2 servings per day (rate ratio = 0.82, 95% confidence interval: 0.71, 0.95; P(trend) = 0.03). In addition, predicted plasma 25(OH)D level was inversely associated with endometriosis. Women in the highest quintile of predicted vitamin D level had a 24% lower risk of endometriosisthan women in the lowest quintile (rate ratio = 0.76, 95% confidence interval: 0.60, 0.97; P(trend) = 0.004). Our findings suggest that greater predicted plasma 25(OH)D levels and higher intake of dairy foods are associated with a decreased risk of endometriosis.



Gynecol Oncol. 2013 May;129(2):372-6. doi: 10.1016/j.ygyno.2013.01.027. Epub 2013 Feb 4.

In vitro fertilization is associated with an increased risk of borderline ovarian tumours.

Stewart LM1Holman CDFinn JCPreen DBHart R.



To compare the risk of borderline ovarian tumours in women having in vitro fertilization (IVF) with women diagnosed with infertility but not having IVF.


This was a whole-population cohort study of women aged 20-44 years seeking hospital infertility treatment or investigation in Western Australia in 1982-2002. Using Cox regression, we examined the effects of IVF treatment and potential confounders on the rate of borderline ovarian tumours. Potential confounders included parity, age, calendar year, socio-economic status, infertility diagnoses including pelvic inflammatory disorders and endometriosis and surgical procedures including hysterectomy and tubal ligation.


Women undergoing IVF had an increased rate of borderline ovarian tumours with a hazard ratio (HR) of 2.46 (95% confidence interval [CI] 1.20-5.04). Unlike invasive epithelial ovarian cancer, neither birth (HR 0.89; 95% CI 0.43-1.88) nor hysterectomy (1.02; 0.24-4.37) nor sterilization (1.48; 0.63-3.48) appeared protective and the rate was not increased in women with a diagnosis of endometriosis (HR 0.31; 95% CI 0.04-2.29).


Women undergoing IVF treatment are at increased risk of being diagnosed with borderline ovarian tumours. Risk factors for borderline ovarian tumours appear different from those for invasive ovarian cancer.



J Clin Endocrinol Metab. 2013 Mar;98(3):E455-62. doi: 10.1210/jc.2012-3387. Epub 2013 Feb 5.

Resveratrol potentiates effect of simvastatin on inhibition of mevalonate pathway in human endometrial stromal cells.

Villanueva JA1Sokalska ACress ABOrtega IBruner-Tran KLOsteen KGDuleba AJ.



Growth of endometriotic lesions in rodent model of endometriosis is inhibited by resveratrol, a natural polyphenol with antiproliferative and antiinflammatory properties, and simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) activity.


The objective of the investigation was to study the mechanism of action of resveratrol and its interactions with simvastatin, focusing on cholesterol biosynthesis and HMGCR gene expression and protein activity in primary cultures of human endometrial stromal (HES) cells.


HES cells were obtained from healthy volunteers. Biosynthesis of cholesterol was assessed by measuring the conversion of [(14)C]acetate to [(14)C]cholesterol. HMGCR mRNA transcripts were quantified by real-time PCR, protein expression by Western blot analysis, and enzyme activity by measuring the conversion of [3-(14)C]3-hydroxy-3-methyl-glutaryl-coenzyme A to [(14)C]mevalonic acid lactone in HES cell microsomes.


Resveratrol inhibited cholesterol biosynthesis, HMGCR mRNA, and enzyme activity. Simvastatin inhibited cholesterol biosynthesis and enzyme activity but increased HMGCR mRNA and protein expression. Resveratrol potentiated the inhibitory effects of simvastatin on cholesterol biosynthesis and HMGCR enzyme activity and abrogated the stimulatory effects of simvastatin on HMGCR mRNA transcripts and protein expression.


Resveratrol inhibits key steps of the mevalonate pathway by mechanisms that are partly complementary to and partly comparable with simvastatin via reducing both expression and activity of HMGCR. A combination of resveratrol and simvastatin may be of potential clinical relevance to development new treatments of human endometriosis.



Gynecol Obstet Invest. 2013;76(1):4-9. doi: 10.1159/000346457. Epub 2013 Feb 7.

Implementation of certified endometriosis centers: 5-year experience in German-speaking Europe.

Ebert AD1Ulrich UKeckstein JMüller MSchindler AESillem MTinneberg HRDe Wilde RLSchweppe KWEndometriosisResearch Foundation, and the European Endometriosis League.



The idea of quality improvement in the management of endometriosis has been brought to attention throughout Europe. This – first and foremost – includes the implementation of centers specialized in treating endometriosis. This leads to qualification of both physicians and other medical staff, enforcement of research efforts, and informing the patients, the public, politicians, healthcare providers, and industry. Given limited budgets, focusing on the existing national commitment may be the first step.



Neuro Endocrinol Lett. 2012;33(7):674-9. Review.

Management of infertility in women with endometriosis.

Grzechocinska B1Wielgos M.



Although there is confirmed an association between endometriosis and infertility, precise standards of managements have not yet been established. Ablation of endometriotic lesions plus adhesiolysis in minimal to mild endometriosis is more effective than diagnostic laparoscopy alone in improving fertility. Suppression of ovarian function and hormonal treatment alone are not effective in improving fertility. In women with stage I/II endometriosis associated infertility, expectant management or IUI after laparoscopy can be considered for younger patients. Women 35 years of age or older should be treated with IUI or IVF-ET. IVF pregnancy rate are lower in women with endometriosis than in those with tubal infertility. For women with stage III/IV endometriosiswho fail to conceive following conservative surgery IVF-ET is should be offered.



Dtsch Med Wochenschr. 2013 Feb;138(7):319-26; quiz 327-8. doi: 10.1055/s-0032-1327355. Epub 2013 Feb 7.

Autoimmune polyglandular syndromes.

Hansen MP1Kahaly GJ.



The autoimmune polyglandular syndrome (APS) is defined as the manifestation of at least two endocrine autoimmune diseases. In order to take the wide spectrum of components and the variations of the disease fully into account, APS is usually divided up into the rare juvenile type (APS I) and the more common adult type (APS II-IV). APS I is caused by a monogenetic mutation whereas APS II-IV has a multifactorial genesis with combination related subgroups. Early diagnosis, individual adjustment of therapy and screening of high risk patients in particular are regarded as clinically relevant. In addition to the patient’s history, the diagnosis of APS encompasses serologic measurement of organ-specific autoantibodies as well as a clinical examination and functional tests. However, the analysis of immunological modificating, zytokine-coding and tissue-specific genes could also be important within a screening. Although APS is a rather rare disease with an incidence of 1:100 000 (juvenile APS) and 1:20 000 (adult APS), the possibility of an autoimmune polyglandular syndrome should be timely considered. By this means, severe complications can be avoided to some extent and the patients’ physical as well as psychological quality of life can be ensured.



Anticancer Res. 2013 Feb;33(2):615-7.

Primary vesical clear cell adenocarcinoma arising in endometriosis: a rare case of mullerian origin.

Lah K1Desai DHadway PPerry-Keene JCoughlin G.



Clear cell adenocarcinoma arising out of endometriosis of the urinary bladder is a rare entity. The published literature has a dearth of information about this entity and its histogenesis. In the present case review we present a 59-year-old patient who was treated with robotic anterior pelvic exenteration and ileal conduit. The initial biopsy of bladder tumour purported a high-grade urothelial carcinoma, however the final specimen revealed a clear cell adenocarcinoma arising in endometriosis without any urothelial cancer. Early case reports refer to these lesions as mesonephric or mesonephroid adenocarcinomas but the current WHO nomenclature classifies them under non-urothelial epithelial neoplasms as clear cell adenocarcinomas. Here, we review the literature and discuss their origins.



Climacteric. 2013 Dec;16(6):700-8. doi: 10.3109/13697137.2013.771331. Epub 2013 Mar 21.

Wenshen Xiaozheng Tang suppresses the growth of endometriosis with an antiangiogenic effect.

Zhang ZZ1Hu CPTang WWGui TQian RYXing YXCao PWan GP.



To evaluate the effect of Wenshen Xiaozhng Tang (WXT) on ectopic endometrial growth and on angiogenesis in endometrial implants in a rat model.


Sprague-Dawley rats with endometriotic implants were randomly treated with low-dose WXT, high-dose WXT, or vehicle (negative control) for 28 days. Cell proliferation and vascular density in the lesions were assessed by immunohistochemistry. The levels of VEGF in peritoneal fluid were determined by ELISA. The mRNA expression of HIF-1α and Flk-1 in the endometriotic lesions was evaluated by real-time PCR.


WXT treatment significantly decreased the lesion size and inhibited cell proliferation in the endometriotic lesions. Lowered vascular density and reduced mRNA expression of HIF-1α in the endometriotic lesions, associated with decreased concentration of VEGF in peritoneal fluid, were also observed in WXT-treated rats.


These results suggest that WXT could be effective to suppress the growth of endometriosis, partially through its antiangiogenic activity.



Colorectal Dis. 2013 May;15(5):e271-5. doi: 10.1111/codi.12167.

Late anastomotic leakage in colorectal surgery: a significant problem.

Morks AN1Ploeg RJSijbrand Hofker HWiggers THavenga K.



Reported incidence rates of colorectal anastomotic leakage (AL) vary between 2.5 and 20%. There is little information on late anastomotic leakage (LAL). The aim of this study was to determine the incidence of LAL after colorectal resection.


All patients undergoing colorectal resection with primary anastomosis between January 2004 and October 2009 at the University Medical Center Groningen were included. LAL was defined as anastomotic leakage diagnosed more than 30 days after surgery.


One hundred and forty-one patients were analysed. Indications for surgery included both benign and malignant conditions. The incidence of early anastomotic leakage (EAL) within 30 days after surgery was 13%. The LAL rate was 6%. Eighty-nine per cent of patients with EAL underwent relaparotomy compared with 44% for LAL (P = 0.02).


One-third of all anastomotic leakages were diagnosed more than 30 days after surgery. Of these, 44% underwent relaparotomy. Patients with leakage diagnosed within 30 days after surgery were more likely to undergo relaparotomy. LAL is a significant problem after colorectal surgery.



Actas Urol Esp. 2013 Apr;37(4):249-55. doi: 10.1016/j.acuro.2012.09.004. Epub 2013 Feb 9.

Ureterectomy in the treatment of urothelial carcinoma of the distal ureter.

García-Segui A1Gómez IGarcía-Tello ACáceres FAngulo JCGascón M.



Segmental ureterectomy with preservation of the kidney is a treatment option for the low grade urothelial carcinoma (LG-UC) in distal ureter that is not a candidate for endoscopic resection. Laparoscopic distal ureterectomy (LDU) with ureteral reimplantation is common in benign conditions (stenosis, iatrogenic lesion, endometriosis). However, it has been hardly described in malignant ureteral condition. The literature is reviewed in this regards and the surgical technique described.


The experience regarding two cases of LDU due to low grade urothelial carcinoma in distal ureter is presented. In both, previous bladder transurethral resection (RTU) was performed. The urinary cytology was negative and the imaging studies identified urinary obstruction and distal ureter filling defect. One of the patients had a background of T1G3 bladder cancer and suffered renal failure. In both, the ureter was ligated early. Segmental ureterectomy was performed using a combined endoscopic and laparoscopic procedure with ureteral desinsertion in one case. In the other, it was exclusively laparoscopic. Both were done with 4 trocars. Ureteral reimplantation was conducted with continuous hermetic suture and without tension. In one case with background of high grade bladder tumor, pelvic lymphadenectomy was also performed.


Operating time was 180 and 240 min, respectively, with estimated bleeding of 100 and 250 ml. Hospitalization time was 6 and 4 days. The only post-operatory complication was paralytic ileum (Clavien I) in the first case. With a 20 and 12 month follow-up, there is no evidence of recurrence or dilatation. In the patient with renal failure, creatinine clearance improved.


The LDU with ureteral reimplantation is a complex technique. However, it represents a feasible and effective alternative for the treatment of LG-UC in distal ureter, as long as the oncological and reconstructive principles are respected.



Ultrasound Obstet Gynecol. 2013 Jun;41(6):692-5. doi: 10.1002/uog.12431.

Uterine sliding sign: a simple sonographic predictor for presence of deep infiltrating endometriosis of the rectum.

Hudelist G1Fritzer NStaettner STammaa ATinelli ASparic RKeckstein J.



To evaluate whether the presence of uterorectal adhesions demonstrated by transvaginal sonography (TVS) could aid as a simple sonographic predictor for deep infiltrating endometriosis (DIE) of the rectum in patients with symptoms suggestive of endometriosis.


This was a prospective multicenter study of women scheduled for laparoscopy because of symptoms suggestive of endometriosis. Patients were assessed prospectively using TVS before laparoscopy and radical resection of disease followed by histological confirmation. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, accuracy and positive (LR+) and negative (LR-) likelihood ratios were calculated for the observation of a negative uterine ‘sliding sign’ on TVS in predicting the presence of DIE of the rectum.


In total, 117 patients underwent laparoscopy and resection. Thirty-four (29%) patients had DIE of the rectum. A negative sliding sign on TVS predicted DIE of rectum with a sensitivity of 85%, specificity of 96%, PPV of 91%, NPV of 94%, accuracy of 93.1%, LR + of 23.6 and LR- of 0.15.


Sonographic demonstration of uterorectal adhesions reflected by a negative uterine sliding sign is an easy and practical method for prediction of the presence of DIE involving the rectum. This could be a valuable ‘red flag’ sign for triaging patients to tertiary referral centers and specialized clinics for detailed investigation.



Ginecol Obstet Mex. 2012 Dec;80(12):753-60.

Symptomatic recurrence of endometriomas after ultrasound and laparoscopic surgery.

López Carpintero N1Paz Ramírez LHernández Gutiérrez Ade Santiago García JSan José Valentín B.



Endometriosis affects to 5-12% women. Laparoscopic surgery is the treatment of choice, but the high rate of recurrence is alarming.


Analyse the influence of various variables in the recurrence after ovarian endometrioma laparoscopic excision.


Retrospective study of 214 cases with laparoscopic treatment in 2005 and 2006 in the Hospital La Paz. A 5 years follow-up was made. Choosen recurrence criteria were pain and suggestive ultrasound finding. Variables studied were: age, pain (0-10), Ca 125 levels, myoma, adenomyosis, number, size and laterality of cyst, medical treatment before and after laparoscopic surgery, infertility, kind of surgery and characteristics, progression and treatment of recurrences.


30,8% (66/214) of patients presented pain recurrence, 28% (60/214) ultrasound recurrence. Patients with symptomatic recurrence had a bigger degree of dysmenorrhea and dyspareunia before surgery (6.8 +/- 2.5 and 1.3 +/- 2.5 against 3.8 +/- 3.4 and 0.2 +/- 1.0 in no recurrence ones (p = 0.0001; p = 0.0001). Previous dysmenorrheal and dyspareunia punctuation was also greater in ultrasound recurrences (5.9 +/- 3.3 and 1.2 +/- 2.5 against 4.3 +/- 3.4 and 0.2 +/- 1.1 of those with no recurrence) (p = 0.003; p = 0.002). Dysmenorrhea recurrence was greater in young (31.3 +/- 5.4 years old versus 34.3 +/- 7.8; p = 0.02), with cystectomy (35% versus 16,7% in adnexectomy; p = 0.02), adhesiolysis (46.4% versus 23.4%; p = 0.001) and with medical treatment after surgery (41.5% against 22.5%; p = 0.004). The mean time of no symptomatic recurrence was 44 months (CI 95%: 41-47) and the no ultrasound recurrence was 47 months (CI 95%: 45-50).


Dysmenorrhea and dyspareunia degree before surgery was the most clearly associated factor with recurrence.



Crit Rev Toxicol. 2013 Mar;43(3):200-19. doi: 10.3109/10408444.2013.766149. Epub 2013 Feb 13.

Reproductive and developmental effects of phthalate diesters in females.

Kay VR1Chambers CFoster WG.



Phthalate diesters, widely used in flexible plastics and consumer products, have become prevalent contaminants in the environment. Human exposure is ubiquitous and higher phthalate metabolite concentrations documented in patients using medications with phthalate-containing slow release capsules raises concerns for potential health effects. Furthermore, animal studies suggest that phthalate exposure can modulate circulating hormone concentrations and thus may be able to adversely affect reproductive physiology and the development of estrogen sensitive target tissues. Therefore, we conducted a systematic review of the epidemiological and experimental animal literature examining the relationship between phthalate exposure and adverse female reproductive health outcomes. The epidemiological literature is sparse for most outcomes studied and plagued by small sample size, methodological weaknesses, and thus fails to support a conclusion of an adverse effect of phthalate exposure. Despite a paucity of experimental animal studies for several phthalates, we conclude that there is sufficient evidence to suggest that phthalates are reproductive toxicants. However, we note that the concentrations needed to induce adverse health effects are high compared to the concentrations measured in contemporary human biomonitoring studies. We propose that the current patchwork of studies, potential for additive effects and evidence of adverse effects of phthalate exposure in subsequent generations and at lower concentrations than in the parental generation support the need for further study.




Acta Cytol. 2013;57(2):203-6. doi: 10.1159/000345898. Epub 2013 Feb 28.

Fine needle aspiration cytology: a tool to diagnose cervical and vaginal endometriosis in low-income places.

Oliveira-Filho M1Rao VSEleutério J JrMedeiros FC.



Regarded as infrequent, vaginal and cervical endometriosis is probably more common than is generally realized. The apparent rarity of the lesion may be ascribed to the limited awareness of its clinical appearance, combined with technical difficulty in obtaining suitable biopsy material for confirmation. Thus, clinical recognition and tissue confirmation become essential. This paper focuses on vaginal and cervical endometriosis, documenting the clinical, macroscopic, cytological and colposcopic findings in 4 cases seen at a single physical vaginal examination. Diagnosis in these patients was facilitated and improved by fine needle aspiration cytology and confirmed by histology. This technique, which is not used for the diagnosis of endometriosis, could be an option in low-income areas.




Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Jan;38(1):54-9. doi: 10.3969/j.issn.1672-7347.2013.01.010.

Effect of letrozole on endometrosis and apoptosis of ectopic endometrial cells in rats.

Xia X1Guo LSu JFang X.



To investigate the therapeutic mechanism of letrozole, the third-generation aromatase inhibitor, on endometriotic lesions in a rat model and its effect on the apoptosis of ectopic endometrial cells.


Endometriosis was induced by autotransplanting pieces of uterus onto the peritoneum in rats. The rats with successful ectopic implants were divided into 2 groups: A letrozole group (n=15) and a control group (n=15). The volume, appearance, and histopathology of ectopic implant were determined before and after the treatment. Expression of P450arom, COX-2, bcl-2, and bax in the ectopic implant was detected by immunohistochemistry and RT-PCR in the 2 groups.


The volume of ectopic implant in the letrozole group was significantly reduced compared with the control group (P<0.05). The protein and mRNA levels of P450arom and COX-2 in the ectopic implant were significantly decreased in the letrozole group compared with the control group (P<0.05). There was a positive correlation between the expression of P450arom and the expression of COX-2 (r=0.943, P<0.001; r=0.913, P<0.001). The protein and mRNA expression of bcl-2 was significantly decreased (P<0.05), and the bax protein and mRNA expression was significantly increased (P<0.05) in the ectopic implant with an increased bax/bcl-2 ratio in the letrozole group compared with the control group (P<0.05).


Letrozole can obviously reduce the size of ectopic implant through decreasing P450arom and COX-2 expression, suppressing the secretion of estrogen, inhibiting the proliferation, and inducing the apoptosis of ectopic implants.



J Neurosci. 2013 Feb 13;33(7):2849-59. doi: 10.1523/JNEUROSCI.3229-12.2013.

Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors.

Joseph EK1Green PGBogen OAlvarez PLevine JD.



Endothelin-1 (ET-1) is unique among a broad range of hyperalgesic agents in that it induces hyperalgesia in rats that is markedly enhanced by repeated mechanical stimulation at the site of administration. Antagonists to the ET-1 receptors, ET(A) and ET(B), attenuated both initial as well as stimulation-induced enhancement of hyperalgesia (SIEH) by endothelin. However, administering antisense oligodeoxynucleotide to attenuate ET(A) receptor expression on nociceptors attenuated ET-1 hyperalgesia but had no effect on SIEH, suggesting that this is mediated via a non-neuronal cell. Because vascular endothelial cells are both stretch sensitive and express ET(A) and ET(B) receptors, we tested the hypothesis that SIEH is dependent on endothelial cells by impairing vascular endothelial function with octoxynol-9 administration; this procedure eliminated SIEH without attenuating ET-1 hyperalgesia. A role for protein kinase Cε (PKCε), a second messenger implicated in the induction and maintenance of chronic pain, was explored. Intrathecal antisense for PKCε did not inhibit either ET-1 hyperalgesia or SIEH, suggesting no role for neuronal PKCε; however, administration of a PKCε inhibitor at the site of testing selectively attenuated SIEH. Compatible with endothelial cells releasing ATP in response to mechanical stimulation, P2X(2/3) receptor antagonists eliminated SIEH. The endothelium also appears to contribute to hyperalgesia in two ergonomic pain models (eccentric exercise and hindlimb vibration) and in a model of endometriosis. We propose that SIEH is produced by an effect of ET-1 on vascular endothelial cells, sensitizing its release of ATP in response to mechanical stimulation; ATP in turn acts at the nociceptor P2X(2/3) receptor.



Int J Clin Exp Pathol. 2013;6(3):431-44. Epub 2013 Feb 15.

Indoleamine 2,3-dioxygenase-1 (IDO1) enhances survival and invasiveness of endometrial stromal cells via the activation of JNK signaling pathway.

Mei J1Li MQDing DLi DJJin LPHu WGZhu XY.



Evidence for an immunosuppressive function of indoleamine 2,3-dioxygenase (IDO) has been accumulating. However, the unusual distribution of IDO1 in gynecologic cancer cells suggests that modulating immunity may not its only function. To clarify the physiological importance of IDO1 in endometriosis, a tumor-like benign disease, we have investigated the potential mechanism by which IDO1 modulated endometrial stromal cells (ESCs) proliferation and invasion. ESCs were obtained from 16 control women (normal) and 14 patients with ovarian endometrioma, then the normal ESCs were treated with plasmid pEGFP-N1-IDO1 or SD11-IDO1 short hairpin RNA (shRNA) alone, or in combination with c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and subjected to cell viability, proliferation, apoptosis assay and Matrigel invasion assay. IDO1 mRNA expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (real-time PCR), and protein levels of IDO1, survivin, protein 53 (p53), matrix metalloproteinase (MMP)-2, MMP-9, tissue-inhibitor of metalloproteinase-1 (TIMP-1) and cyclooxygenase-2 (COX-2) in IDO1-overexpressing and IDO1-deficiency ESCs were analyzed by in-cell Western. We found that IDO1 expression was higher in endometriosis-derived eutopic and ectopic ESCs, compared with endometriosis-free normal ESCs. As a result, IDO1-overexpression in ESCs was markedly linked to reduction of apoptosis and p53 expression, and upregulation of survival, proliferation, invasion, as well as expression of MMP-9, COX-2 expression, rather than expression of survivin, MMP-2 and TIMP-1. Reversely, JNK blockage could abrogate these alterations of ESCs in IDO1-overexpressing milieu, suggesting that JNK signaling pathway was indispensable for ESCs survival, proliferation and invasion enhanced by IDO1, which may contribute to the pathophysiology of endometriosis.




Fertil Steril. 2013 Mar 15;99(4):1135-45. doi: 10.1016/j.fertnstert.2013.01.097. Epub 2013 Feb 13.

Biomarkers of endometriosis.

Fassbender A1Vodolazkaia ASaunders PLebovic DWaelkens EDe Moor BD’Hooghe T.



A noninvasive test for endometriosis would be useful for the early detection of endometriosis in symptomatic women who have pelvic pain and/or subfertility with normal ultrasound results. This would include nearly all cases of minimal-to-mild endometriosis, some cases of moderate-to-severe endometriosis without a clearly visible ovarian endometrioma, and cases with pelvic adhesions and/or other pelvic pathology that might benefit from surgery to improve pelvic pain and/or subfertility. This overview discusses the diagnostic performance of noninvasive or semi-invasive tests for endometriosis, including panels of known peripheral blood biomarkers, protein/peptide markers discovered by proteomics, miRNA, and endometrial nerve fiber density. Tests with high sensitivity and acceptable specificity have been developed; some have been validated in independent populations and are therefore promising. To make real progress, international agreement on biobank development is needed for standard operating procedures for the collection, treatment, storage, and analysis of tissue samples and for detailed clinical phenotyping of these samples. Furthermore, it is necessary to validate the diagnostic accuracy of any promising test prospectively in an independent symptomatic patient population with subfertility and/or pain without clear ultrasound evidence of endometriosis and with a clinical indication for surgery, divided into cases with laparoscopically and histologically confirmed endometriosis and controls with laparoscopically confirmed absence of endometriosis.



Ageing Res Rev. 2013 Mar;12(2):595-604. doi: 10.1016/j.arr.2013.01.008. Epub 2013 Feb 13.

Mesothelial cell: a multifaceted model of aging.

Książek K1.



Human peritoneal mesothelial cells (HPMCs) dominate within the peritoneal cavity and thus play a central role in a variety of intraperitoneal processes, including the transport of water and solutes, inflammation, host response, angiogenesis, and extracellular matrix remodeling. In addition, they contribute to the development of abdominal adhesions, peritonitis, endometriosis, cancer cell metastases, and peritoneal dialysis complications. For less than a decade the primary cultures of omental HPMCs have also been used as an experimental tool in studies on cellular aging. This paper provides the first comprehensive overview of the current state of art on molecular mechanisms underlying HPMC senescence in vitro. Special attention is paid to the causes of the very fast dynamics of HPMC senescence, and in particular to the role of non-telomeric DNA damage, the autocrine activity of TGF-β1, and the causative effects of oxidative stress. In addition, some clinical manifestations of HPMC senescence will be discussed, including its interplay with organismal aging, peritoneal dialysis, and cancer progression.




Eur J Obstet Gynecol Reprod Biol. 2013 Jun;168(2):209-13. doi: 10.1016/j.ejogrb.2013.01.009. Epub 2013 Feb 14.

The adjuvant use of N-palmitoylethanolamine and transpolydatin in the treatment of endometriotic pain.

Giugliano E1Cagnazzo ESoave ILo Monte GWenger JMMarci R.



To test the adjuvant use of the combination of N-palmitoylethanolamine and transpolydatin in the medical treatment of endometriotic pain.


We enrolled 47 patients admitted to the Outpatient Endometriosis Care Unit of Ferrara University from January 2011 to December 2011. They were divided into two groups according to the endometriosis site (group A: recto-vaginal septum; group B: ovary). One tablet, containing 400 mg of micronized N-palmitoylethanolamine plus 40 mg transpolydatin, was administered twice daily on a full stomach for 90 days. Each patient was requested to grade the severity of dysmenorrhea, chronic pelvic pain, dyspareunia and dyschezia using a 0-10 cm visual analogic scale prior to beginning treatment (T0), after 30 days (T1), 60 days (T2) and 90 days (T3). The continuous and categorical variables were compared, respectively, using Student’s t-test and the chi-square test. Analysis of variance for repeated measures was used to verify the reduction of endometriotic pain.


The intensity of endometriotic pain decreased significantly for both groups (p<0.0001). The efficacy of drug treatment was significant after 30 days. Pain intensity decreased equally in the two groups except for dysmenorrhea, which was reduced more rapidly in group B.


The combination of N-palmitoylethanolamine and transpolydatin reduced pain related to endometriosis irrespective of lesion site. It had a marked effect on chronic pelvic pain determined by deep endometriosis and on dysmenorrhea correlated to ovarian endometriosis.




Fertil Steril. 2013 May;99(6):1714-9. doi: 10.1016/j.fertnstert.2013.01.110. Epub 2013 Feb 15.

In vitro fertilization outcome in women with unoperated bilateral endometriomas.

Benaglia L1Bermejo ASomigliana EFaulisi SRagni GFedele LGarcia-Velasco JA.




To evaluate IVF outcome in women with unoperated bilateral endometriomas.


Multicenter retrospective cohort study.


Two infertility units.


Thirty-nine women with bilateral endometriomas matched with 78 unexposed control subjects.


Analysis of data from patients who underwent in vitro fertilization (IVF)-intracytoplasmic sperm injection.


Ovarian responsiveness and oocyte quality.


Responsiveness to ovarian hyperstimulation was significantly reduced in women with bilateral endometriomas. The total numbers of developing follicles in case and control subjects were 9.6 ± 3.3 and 14.1 ± 6.8, respectively. The numbers of oocytes retrieved were 7.1 ± 3.2 and 9.8 ± 5.5, respectively. Conversely, oocyte retrieval was not hampered by the presence of the ovarian endometriomas. The rates (interquartile range) of oocytes retrieved per total number of developing follicles in case and control subjects were 77% (57%-88%) and 71% (63%-79%), respectively. Moreover, the quality of the retrieved oocytes did not differ. The fertilization rates (IQR) were 67% (56%-100%) and 70% (57%-100%), respectively. The rates (IQR) of top quality embryos per oocyte used were 33% (25%-50%) and 33% (20%-43%), respectively. The implantation rates were 22% and 23%, respectively. The clinical pregnancy rate and the delivery rate also did not differ.


Although the presence of bilateral endometriomas at the time of IVF affects responsiveness to hyperstimulation, the quality of the oocytes retrieved and the chances of pregnancy are not affected.




Reprod Biomed Online. 2013 Apr;26(4):345-52. doi: 10.1016/j.rbmo.2012.12.012. Epub 2013 Jan 16.

Elevated blood plasma antioxidant status is favourable for achieving IVF/ICSI pregnancy.

Velthut A1Zilmer MZilmer KKaart TKarro HSalumets A.



The aim of the study was to determine the roles of intrafollicular and systemic oxidative stress and antioxidant response in ovarian stimulation and intracytoplasmic sperm injection (ICSI) outcomes. For this purpose, 102 ICSI patients undergoing controlled ovarian stimulation were enrolled and samples were collected on the day of follicle puncture. Total peroxide (TPX) concentrations and total antioxidant response (TAR) were measured in follicular fluid and blood plasma, and an oxidative stress index (OSI) was calculated based on these two parameters. Urinary concentrations of 8-iso-prostaglandin F2a (F2IsoP) were measured. Elevated intrafollicular oxidative stress was positively correlated with ovarian stimulation outcome: less FSH per retrieved oocyte was used, more oocytes were collected and higher serum oestradiol concentrations were measured in patients with higher follicular OSI. However, high urinary F2IsoP related to lower embryo quality and F2IsoP was also elevated in smoking patients. Patients with endometriosis had lower follicular antioxidant status. Most importantly, higher systemic blood TAR was significantly favourable for achieving clinical pregnancy (P=0.03). In conclusion, the findings suggest clear associations between oxidative stress, antioxidant status and several aspects of ovarian stimulation and IVF/ICSI outcome, including pregnancy rate. Several oxygen-dependent biochemical reactions produce reactive oxygen species as by-products that may eventually lead to oxidative stress, which is detrimental to cells and tissues. Total antioxidant status, on the other hand, comprises several agents that balance the excess of these reactive oxygen species and reduce potential damage to the body. The aim of the current work was to study this balance in 102 patients participating in an ICSI programme and to examine the degree to which total peroxide content and antioxidant status influence infertility and pregnancy outcome. During the study, several tests were performed to characterize oxidative stress levels in ovarian follicular fluid, blood plasma and urine. We found a significantly higher oxidative stress environment in the ovary when compared with blood plasma. This suggests a prominent role of oxidative stress in the ovaries of these patients. The elevated oxidative stress levels were correlated to a higher number of oocytes that could be obtained via the procedure and to a lower amount of FSH needed to mature the oocytes, suggesting that oxidative stress, to some degree, is favourable for hormone stimulation outcome. A high level of lipid peroxidation products in the urine, another marker of oxidative stress, was observed in smokers and this marker was elevated in patients with embryos that had lower developmental potential. A higher overall antioxidant status in blood plasma was advantageous for achieving pregnancy.






Free Radic Biol Med. 2013 Jul;60:63-72. doi: 10.1016/j.freeradbiomed.2013.01.034. Epub 2013 Feb 14.

17β-Estradiol and steady-state concentrations of H2O2: antiapoptotic effect in endometrial cells from patients with endometriosis.

Andrade SS1Azevedo Ade CMonasterio ICParedes-Gamero EJGonçalves GABonetti TCAlbertoni GSchor EBarreto JALuiza Oliva MJuliano LGirão MJda Silva ID.



Increased levels of hydrogen peroxide (H2O2) can initiate protective responses to limit or repair oxidative damage. However, H2O2 signals also fine-tune responses to growth factors and cytokines controlling cell division, differentiation, and proliferation. Because 17β-estradiol (E2) also plays important roles in these processes, and is considered a major risk factor in the development and progression of endometriosis, this study evaluated whether E2 has an antiapoptotic effect on oxidative stress in endometrial cells in combination with steady-state H2O2 levels ([H2O2]ss). Endometrial stromal cells were prepared from the eutopic endometrium of 18 women with and without endometriosis to produce primary cells. These cells were stimulated with E2 for 20h, exposed to [H2O2]ss, and examined for cell viability, proliferation, and apoptosis. The endometrial cells from women with endometriosis maintained the steady state for 120min at high H2O2 concentrations. When they were pretreated with E2 and exposed to [H2O2]ss, a decrease in apoptosis level was observed compared to the control cells (p<0.01). The endometrial cells from patients with endometriosis subjected to both E2 and [H2O2]ss showed increased ERK phosphorylation. These findings suggested that H2O2 is a signaling molecule that downregulates apoptosis in endometrial cells, supporting the fact that endometriosis, albeit a benign disease, shares some features with cancer such as decreased catalase levels. These results link the E2 effects on [H2O2]ss to resistance to apoptosis and progression of endometriosis.




Ann Ital Chir. 2013 Jan 31;84(ePub). pii: S2239253X13020872.

Ileo-colic endometriosis: a rare localization of a frequent disease. Case report.

Portale TRBranca AScilletta RPesce APuleo S.


Endometriosis is a common entity affecting females of reproductive age. Clinical manifestations are not specific, making the preoperative diagnosis difficult to establish. Intestinal endometriosis is common, but ethiology is unknown. The complications of intestinal endometriosis include intestinal obstruction, perforation, hemorrhagic ascites, protein-losing enteropathy, anasarca, and intussusception. We report a case of a young woman, 26 years old, that for 3 years had a conditioned life by monthly sub-occlusion due to a small-bowel obstruction for an ileocaecal endometriosis. A high index of suspicion is required to have a diagnosis of this rare localization of endometriosis.




Mymensingh Med J. 2013 Jan;22(1):218-21. Review.

Aetiology and pathogenesis of endometriosis – a review.

Begum T1Chowdhury SR.



Endometriosis is a complex gynaecological disorder that affects nearly 1 in 7 women of reproductive age. Ectopic dissemination of endometrial cell and their subsequent implantation are the mechanisms involved in the development of endometriosis. Endometriosis is a common multifactorial disease caused by an interaction between multiple gene loci and environment. Causes of stress on immune functioning or may be genetically determined. Environmental factors can be responsible for immunosuppressive activities in patient with endometriosis. In addition, toxin modulates steroid receptors expression resulting in altered tissue specific responses to hormones. Chronic immunosuppression in combination with hormonal regulation may have facilitated the aberrant growth of endometrial tissue within the peritoneum. However, the mechanism appears to require endometrium and retrograde menstruation in most cases of the disease.




Int J Dev Biol. 2012;56(10-12):969-74. doi: 10.1387/ijdb.120172fn.

Gliomatosis peritonei as a natural experiment in tissue differentiation.

Nogales FF1Preda ODulcey I.



Gliomatosis peritonei (GP) is an unusual condition in which nodules of mature astroglia, often miliary and microscopic in size, are widespread in the peritoneum and abdominal lymph nodes. Its behaviour is benign and it is usually found in association with ovarian teratoma and rarely with teratomas of other organs. Implants grow rapidly and can remain unchanged for life. Astroglia is the main component, but other neural lineage elements and many other tissues can be found. Cells are mature but not terminal, since they express SOX2. Secondary associated lesions include: a) degenerative astrocytic changes, b) granulomatous and follicular chronic inflammatory changes, c) association with hormonally related changes, such as decidual peritoneal metaplasia and endometriosis and d) endothelial and adventitial vascular hyperplasia leading to haemoperitoneum.Two pathogenetic mechanisms are considered: direct seeding of immature neural cells from a primary tumour with subsequent differentiation and metaplasia from peritoneal stem cells. The former proposal is supported by clinicopathologic data such as ample cellular heterogeneity, coexistence of mature astroglia with neural blastema, as well as the shed keratin and hairs from the ovarian neoplasm. However, metaplasia is sustained by a heterozygosity pattern of GP nodules, identical to the normal tissue and different from the coexistent ovarian teratoma. GP would constitute a response to growth factors from teratoma or macrophages. While an implantative origin from ovarian teratoma remains in most cases a more probable mechanism, metaplasia from peritoneal stem cells would explain cases of GP which present a monomorphic astrocytic cell population.




Int J Surg. 2013;11(3):233-7. doi: 10.1016/j.ijsu.2013.02.003. Epub 2013 Feb 15.

The ‘evil twin syndrome’ in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis.

Tirlapur SA1Kuhrt KChaliha CBall EMeads CKhan KS.



Chronic pelvic pain (CPP), a common gynaecological presentation, may be due to bladder pain syndrome (BPS) or the co-existence of BPS and endometriosis, known as the ‘evil twins syndrome’.


To estimate the prevalence of BPS and the co-existence of BPS and endometriosis in women with CPP.


We searched until March 2012: The Cochrane Library, DARE (1997-2012), EMBASE (1980-2012), Medline (1950-2012), PSYCHINFO (1806-2012), Web of knowledge (1900-2012), LILACS (1982-2012) and SIGLE (1990-2012) with no language restrictions. We manually searched through bibliographies and conference proceedings of the International Continence Society.


Observational studies of women suffering from CPP, who were not pregnant or suffering from cancer, who underwent a laparoscopy and cystoscopy to investigate their symptoms. Study selection, data extraction and quality assessment was performed independently by two reviewers. Statistical analysis was performed to estimate prevalence and confidence intervals (CI).


Nine studies were included with 1016 patients with CPP. Study quality and diagnostic assessment varied. The mean prevalence of BPS was 61% (range 11-97%, CI 58-64%, I(2) = 98%). The mean prevalence of endometriosis was 70% (range 28-93%, CI 67-73%, I(2) = 93%) and co-existing BPS and endometriosis was 48% (range 16-78%, CI 44-51%, I(2) = 96%).


Almost two thirds of women presenting with CPP have BPS. Large variations in prevalence may be due to variable study selection and quality. Clinicians need to actively investigate patients for BPS, a condition that appears to co-exist with endometriosis.



Reprod Biomed Online. 2013 Apr;26(4):323-36. doi: 10.1016/j.rbmo.2012.12.011. Epub 2013 Jan 21.

Diet and endometriosis risk: a literature review.

Parazzini F1Viganò PCandiani MFedele L.



A connection between dietary factors and endometriosis onset has become a topic of interest mostly due to the observation that physiological and pathological processes of the disease can be influenced by diet. This paper systematically reviews prior publications dealing with this aspect in order to identify potentially modifiable risk factors. Comprehensive searches in the electronic databases MEDLINE, EMBASE and Science Citation Index Expanded were conducted to identify published studies evaluating the association between food intake (nutrients and food groups) and endometriosis. Eleven studies were identified: 10 case-control and one cohort study. Information on diet was collected using food frequency questionnaires in seven studies, while in one study the questionnaire focused on caffeine and alcohol intake. Women with endometriosis seem to consume fewer vegetables and omega-3 polyunsaturated fatty acids and more red meat, coffee and trans fats but these findings could not be consistently replicated. Most data have also been discussed herein in light of the available experimental and animal model results. At present, evidence supporting a significant association between diet and endometriosis is equivocal. Further studies are needed to clarify the role of diet on endometriosis risk and progression.





Reprod Sci. 2013 May;20(5):514-23. doi: 10.1177/1933719113477479. Epub 2013 Feb 20.

Elevated peritoneal fluid TNF-α incites ovarian early growth response factor 1 expression and downstream protease mediators: a correlation with ovulatory dysfunction in endometriosis.

Birt JA1Nabli HStilley JAWindham EAFrazier SRSharpe-Timms KL.



Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis.



Reprod Sci. 2013 May;20(5):483-99. doi: 10.1177/1933719113477495. Epub 2013 Feb 20.

Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis In Montpellier, France.

Rogers PA1D’Hooghe TMFazleabas AGiudice LCMontgomery GWPetraglia FTaylor RN.



Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.(1) A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.




Reprod Sci. 2013 Sep;20(9):1116-24. doi: 10.1177/1933719113477487. Epub 2013 Feb 20.

Analysis of follicular fluid retinoids in women undergoing in vitro fertilization: retinoic acid influences embryo quality and is reduced in women with endometriosis.

Pauli SA1Session DRShang WEasley KWieser FTaylor RNPierzchalski KNapoli JLKane MASidell N.



Retinol (ROL) and its biologically active metabolite, all-trans retinoic acid (ATRA), are essential for a number of reproductive processes. However, there is a paucity of information regarding their roles in ovarian folliculogenesis, oocyte maturation, and early embryogenesis. The objectives of this study were to quantify and compare peripheral plasma (PP) and follicular fluid (FF) retinoid levels, including ATRA in women undergoing in vitro fertilization (IVF) and to investigate the relationship between retinoid levels and embryo quality. Retinoid levels were evaluated in PP and FF from 79 women undergoing IVF at the time of oocyte retrieval and corresponding embryo quality assessed on a daily basis after retrieval for 3 days until uterine transfer. Analysis compared the retinoid levels with day 3 embryo grades and between endometriosis versus control patients. Results demonstrated distinctive levels of retinoid metabolites and isomers in FF versus PP. There was a significantly larger percentage of high-quality grade I embryos derived from the largest versus smallest follicles. An increase in follicle size also correlated with a >50% increase in FF ROL and ATRA concentrations. Independent of follicle size, FF yielding grade I versus nongrade I embryos showed higher mean levels of ATRA but not ROL. In a nested case-control analysis, control participants had 50% higher mean levels of ATRA in their FF and PP than women with endometriosis. These findings strongly support the proposition that ATRA plays a fundamental role in oocyte development and quality, and that reduced ATRA synthesis may contribute to decreased fecundity of participants with endometriosis.




Hum Reprod. 2013 May;28(5):1339-47. doi: 10.1093/humrep/det031. Epub 2013 Feb 20

Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis.

Rudzitis-Auth J1Menger MDLaschke MW.



Does the phytochemical compound resveratrol inhibit vascularization of endometriotic lesions?


Resveratrol suppresses the development of new microvessels in endometriotic lesions by inhibiting endothelial cell proliferation.


Establishment and progression of endometriosis is crucially dependent on angiogenesis. Resveratrol is a pleiotropic agent, which dose-dependently suppresses the development of new blood vessels.


This was a randomized study in a mouse model of endometriosis. Twenty female BALB/c mice with surgically induced endometriosis were treated with resveratrol (40 mg/kg/day, n = 10) or vehicle (n = 10) for 4 weeks.


Peritoneal and mesenteric endometriotic lesions were surgically induced by uterine tissue transplantation into the abdominal cavity of BALB/c mice. The animals were daily treated with resveratrol (40 mg/kg) or vehicle by oral gavage. Lesion growth, vascularization, apoptosis and cell proliferation were subsequently analyzed by means of high-resolution ultrasound imaging, caliper measurements, histology and immunohistochemistry throughout an observation period of 4 weeks.


Resveratrol inhibited angiogenesis in peritoneal and mesenteric endometriotic lesions, as indicated by a significantly reduced microvessel density when compared with controls. Additional immunohistochemical analyses revealed that this was caused by a decreased proliferating activity of CD31-positive endothelial cells in the newly developing microvasculature of the lesions. In line with these findings, lesions in resveratrol-treated mice exhibited a reduced growth rate and a smaller final size than controls. This was associated with lower numbers of proliferating cell nuclear antigen- and Ki67-positive stromal and glandular cells. Apoptotic cells were not detectable in either group. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate controls. Statistical significance was accepted for a value of P < 0.05.


Endometriotic lesions were surgically induced by uterine tissue transplantation without the use of pathological endometriotic tissue of human origin. Therefore, the results obtained in this mouse model may not fully correlate to human patients with endometriosis.


Resveratrol is a potent inhibitor of vascularization in endometriotic lesions. This, most probably, causes the suppression of lesion growth. Accordingly, resveratrol represents a promising candidate therapy for future phytochemical treatment of endometriosis.


This work was supported by a grant of the ‘Freunde des Universitätsklinikums des Saarlandes’. The authors have no conflicts of interest to declare.



Ginecol Obstet Mex. 2012 Nov;80(11):705-11

Treatment of patients with endometriosis and infertility.

Mateo Sánez HA1Mateo Sánez EHernández ALSalazar Ricarte EL.



The Word Endometriosis Society estimates that 176 millions of women in the world have experienced endometriosis symptoms way before their quality of life has been compromised. Despite the advances, endometriosis continues to be a challenge for doctors nowadays.


The purpose of this article is to make an attempt to unify the foundations and theories worldwide accepted on endometriosis infertility treatment.


Infertility management caused by endometriosis remains daring. Laparoscopic cystectomy for ovarian endometriomas larger than 4 cm of diameter improves fertility compared with drainage and coagulation. Those with mild disease (I and II) after surgical reconstruction can undergo ovarian stimulation with artificial insemination. At the identification of endometriosis it must be treated surgically, except in those patients that because of special circumstances (elderly, compromised pelvis, azoospermia, etc.) is advisable to appeal in vitro fertilization with embryos transference, like in advanced stages cases (III and IV).



Arch Gynecol Obstet. 2013 Jun;287(6):1225-33. doi: 10.1007/s00404-013-2767-2. Epub 2013 Feb 22.

Possible effects of endometriosis-related immune events on reproductive function.

Kokcu A1.



To examine possible effects of endometriosis-related immune events on reproductive function.


The synthesis and review of the relevant current literature in English language.


The endometriosis-related immune events may have a negative impact on almost all components of the reproductive function including fallopian tube function, oocyte quality, sperm function, fertilization, embryo quality, endometrial receptivity, implantation and placentation.


An important portion of the cases of infertility or miscarriage seen in women with endometriosismay be due to some immunological alterations associated with endometriosis.




J Med Primatol. 2013 Jun;42(3):112-9. doi: 10.1111/jmp.12042. Epub 2013 Feb 21.

Medical treatment improves social behavior in a primate endometriosis model (Callithrix jacchus).

Arnold C1Einspanier A.



As endometriosis is known to be very painful in humans, therapeutic studies should consider pain-related aspects in experimental animals too. In a previous study, we found that common marmosets suffering from endometriosis show remarkable deviations in social behavior and cognitive tasks.


Female marmosets with endometriosis undergoing medical treatment were tested vs. two control groups (healthy and endometriosis monkeys without treatment) concerning behavioral aspects, cognitive skills, and mobility.


The treated monkeys performed significant more social and self-grooming, comfort behavior and were more active than the untreated endometriosis monkeys. The treated marmosets even returned to equal levels as their healthy conspecifics. Cognitive and mobility tests revealed no significant differences.


A beneficial effect of the applied endometriosis medication on behavioral impairments could be obtained. Including such measurements in therapeutic research contributes to aspects of animal welfare and pain-relieving potential of the tested compound.





J Reprod Immunol. 2013 Mar;97(1):85-94. doi: 10.1016/j.jri.2012.10.012.

Animal models for anti-angiogenic therapy in endometriosis.

Edwards AK1Nakamura DSVirani SWessels JMTayade C.



Endometriosis is a gynecological disease characterized by the growth of endometrium outside of the uterine cavity. It is often associated with dysmenorrhea, dyspareunia, pelvic pain and infertility. One of the key requirements for endometriotic lesions to survive is development of a blood supply to support their growth. Indeed, dense vascularization is characteristic feature of endometriotic lesions. This has led to the idea that suppression of blood vessel growth (anti-angiogenic therapy) may be a successful therapeutic approach for endometriosis. Potential effectiveness of anti-angiogenic therapies has been assessed in some animal models but there are no reports of human clinical trials. Without understanding the specific mechanism by which endometriosis lesions establish a new blood supply, short-term animal experiments will have limited value for translation into human medicine. Further, it is crucial to use appropriate animal models to assess efficacy of anti-angiogenic compounds. Syngeneic and autologous rodent models, where endometrial fragments are auto-transplanted into the peritoneal cavity are commonly used in anti-angiogenic therapy studies. Another approach is xenograft models where human endometrium is engrafted into immunodeficient mice. Here we review the animal models and experimental techniques used to evaluate anti-angiogenic therapies for endometriosis. We also review our own work on the role of stromal cell derived factor-1 in the recruitment of endothelial progenitor cells in endometriotic lesion angiogenesis, and the effects of the anti-angiogenic peptide ABT-898, a thrombospondin-1 mimetic, on endometriotic lesion growth and vascular development.



J Reprod Immunol. 2013 Mar;97(1):95-103. doi: 10.1016/j.jri.2012.10.013.

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis: potential implications for macrophages and follicle maturation.

Heublein S1Vrekoussis TKuhn CFriese KMakrigiannakis AMayr DLenhard MJeschke U.



Endometriosis is an estrogen dependent chronic inflammation and thus a condition of stress. Though the G-protein coupled estrogen receptor (GPER) has been shown to be up-regulated in ovarian endometriosis, insights involved in inducing this receptor expression are largely elusive. Therefore, this study investigated whether stress-related factors (ACTH, prednisolone) or inflammatory factors (IL-1β, TNFα, and PGE(2)) factors may affect GPER. To further link GPER to endometriosis pathophysiology it was tracked in macrophages and follicles of endometriotic ovaries. This study found GPER expression to be modulated by stress-related hormones as well as inflammation and to be up-regulated in endometriosis-associated macrophages. At the same time, follicles of ovaries affected by endometriosis presented significantly reduced GPER positivity when compared to controls, suggesting a possible way by which endometriosis may affect folliculogenesis. The multiple roles of GPER as presented herein make it a promising future candidate for targeted molecular endometriosis treatment.




Arab J Gastroenterol. 2012 Dec;13(4):186-7. doi: 10.1016/j.ajg.2012.07.001. Epub 2012 Oct 10.

An infrequent cause of colonic stenosis.

Greco S1Signorelli SIndriolo AFagiuoli SRavelli P.



We present the case of a young woman with intestinal endometriosis, in which colonic stenosis unusually represents the clinical onset; diagnostic workup allows to highlight the role of gastrointestinal ultrasounds that suggest the nature of the stenosis.




Cochrane Database Syst Rev. 2013 Jan 31;(1):CD005072. doi: 10.1002/14651858.CD005072.pub3.

Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

Abou-Setta AM1Houston BAl-Inany HGFarquhar C.



Various options exist for treating endometriosis, including surgical, medical, such as ovarian suppression, or a combination of these strategies. Surgical treatment of endometriosis aims to remove visible areas of endometriosis. The aim of medical therapy is to inhibit growth of endometriotic implants by induction of a hypo-estrogenic state. Treatment with a hormone-releasing intrauterine device, using levonorgestrel (LNG-IUD), has also been suggested.


To determine whether postoperative LNG-IUD insertion in women with endometriosis improves pain and reduces recurrence of symptoms compared with no postoperative treatment, postoperative insertion of a placebo, or postoperative therapy.


The following databases were searched from inception to June 2012: Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, CINAHL, and the World Health Organization (WHO) International Clinical Trials Registry Platform. EMBASE was searched from 2010 to June 2012. The citation lists of relevant publications, review articles, abstracts of scientific meetings, and included studies were also searched.


Trials were included if they compared women undergoing surgical treatment for endometriosis with uterine preservation and then randomised within three months to LNG-IUD insertion versus no postoperative treatment, placebo (inert IUD), or other treatment. Diagnostic laparoscopy alone was not considered suitable treatment.


Two review authors independently selected studies for inclusion and extracted data to allow for an intention-to-treat analysis. For dichotomous data, the risk ratio (RR) and 95% confidence interval (CI) were calculated using the Mantel-Haenszel random-effects method. For continuous data, the mean difference (MD) and 95% CI were calculated using the inverse variance random-effects method.


Three randomised controlled trials were included. In two trials, there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUD group compared with expectant management (RR 0.22, 95% CI 0.08 to 0.60, 95 women, I(2) = 0%, moderate strength of evidence). The proportion of women who were satisfied with their treatment was also higher in the LNG-IUD group but did not reach statistical significance (RR 1.21, 95% CI 0.80 to 1.82, 95 women, I(2) = 0%). The number of women reporting a change in menstruation was significantly higher in the LNG-IUD group (RR 37.80, 95% CI 5.40 to 264.60, 95 women, I(2) = 0%) but the number of women not completing the allocated treatment did not differ between groups (RR 0.66, 95% CI 0.08 to 5.25, I(2) = 43%).In one trial, women receiving LNG-IUD noted lower pain scores compared with women receiving gonadotrophin-releasing hormone agonists (MD -0.16, 95% CI -2.02 to 1.70, 40 women) but this did not reach statistical significance.


There is limited but consistent evidence showing that postoperative LNG-IUD use reduces the recurrence of painful periods in women with endometriosis. Further well-designed RCTs are needed to confirm these findings.



Hum Reprod. 2013 May;28(5):1221-30. doi: 10.1093/humrep/det041. Epub 2013 Feb 26.

Surgical versus low-dose progestin treatment for endometriosis-associated severe deep dyspareunia II: effect on sexual functioning, psychological status and health-related quality of life.

Vercellini P1Frattaruolo MPSomigliana EJones GLConsonni DAlberico DFedele L.



Does surgical and low-dose progestin treatment differentially affect endometriosis-associated severe deep dyspareunia in terms of sexual functioning, psychological status and health-related quality of life?


Surgery and progestin treatment achieved essentially similar benefits at 12-month follow-up, but with different temporal trends.


Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results.


Patient preference, parallel cohort study with 12-month follow-up. The effect of conservative surgery at laparoscopy versus 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 was compared.


A total of 51 patients chose repeat surgery and 103 progestin treatment. Variations in sexual function, psychological well-being and quality of life were measured by means of the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS) and the Endometriosis Health Profile-30 (EHP-30).


Four women in the surgery group and 21 women in the progestin group withdrew from the study for various reasons. Total FSFI scores, anxiety and depression scores and EHP-30 scores improved immediately after surgery, but worsened with time, whereas the effect during progestin use increased more gradually, but progressively, without overall significant between-group differences at 12-month follow-up. A tendency was observed towards a slightly better total FSFI score after surgery at the end of the study period.


Treatments were not randomly allocated, 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.


Both surgery and medical treatment with progestins are valuable options for improving the detrimental impact of endometriosis-associated dyspareunia on sexual functioning and quality of life. Women should be aware of the pros and cons of both options to decide which one best suits their needs.


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.




Diagn Cytopathol. 2014 Jul;42(7):615-8. doi: 10.1002/dc.22961. Epub 2013 Feb 27.

Spontaneous cutaneous endometriosis in the mons pubis region: a case report diagnosed by fine-needle aspiration biopsy.

Zhai J1.



Most cutaneous endometriosis develops at the site of an abdominal surgical scar. Spontaneous cutaneous endometriosis is extremely rare. We report a case of spontaneous cutaneous endometriosis in the mons pubis region. A 41-year-old woman presented with a mass in the right mons pubis, causing cyclic pain associated with menses. Fine-needle aspiration (FNA) biopsy was performed. The smears contained three cellular components: honeycombed sheets of glandular epithelial cells, fragments of ovoid-to-spindle shaped stromal cells, and background inflammatory cells, including hemosiderin-laden macrophages, histiocytes, and neutrophils. Biphasic clusters of glandular epithelial cells and stromal cells were identified. FNA cytology is a safe and useful adjunctive tool for diagnosing cutaneous endometriosis.




Clin Exp Obstet Gynecol. 2012;39(4):452-3.

Diagnostic laparoscopy findings in unexplained infertility cases.

Göçmen A1Atak T.



Evaluation of diagnostic laparoscopy findings in 600 unexplained infertility cases.


A total of 600 diagnostic laparoscopies performed between 1995 and 2008 were investigated. Laparoscopies were performed in the proliferative phase of the cycle, General anesthesia was performed in all cases.


Normal genital findings were determined in 47.50% of primary infertile cases and in 47% of secondary infertile cases. Pelvic adhesion was the most frequent finding encountered and it was seen at a rate of 20% in the primary infertility group and 18% in the secondary infertility group. Endometriosis was determined to have a rate of 15% in the primary infertility group and 11.5% in the secondary infertility group.


Laparoscopy has an important place in the diagnosis and planning in the treatment of infertility. Planning the convenient treatment for patients will prevent both economic loss and time loss.



Clin Exp Obstet Gynecol. 2012;39(4):474-8.

Three-dimensional ultrasound and three-dimensional power Doppler improve the preoperative evaluation of complex benign ovarian lesions.

Vrachnis N1Sifakis SSamoli EKappou DPavlakis KIliodromiti ZBotsis D.



To evaluate the diagnostic accuracy of three-dimensional ultrasound (3D-US) and three-dimensional power-Doppler (3DPD-US) as adjuncts to conventional B-mode-US in evaluation of complex benign ovarian lesions.


Transvaginal B-mode-US, 3D-US and 3DPD-US were performed in 29 patients with unilateral ovarian lesion. Patients were classified as low or high risk for malignancy according to a standardized scoring system composed of ten morphological and vascular parameters. Preoperative scores were matched to the histological results and the diagnostic performance of the scoring system was calculated.


Seven out of the 16 cases of endometriomas (44%) were graded as low risk masses according to B-mode-US, while the addition of 3D-US and 3DPD-US increased the accuracy to 56% and 94%, respectively. All dermoid cysts were classified as high risk cases by B-mode-US, but 3D-US and 3DPD-US correctly classified 14% and 57% of cases, respectively. The use of B-mode-US, 3D-US and 3DPD-US correctly classified all four cystadenomas. Only the use of 3DPD-US correctly classified one out of two hemorrhagic corpus luteum cases, whereas the other imaging modalities characterized these lesions as high risk. The overall diagnostic accuracy increased from 38%, 48%, ana 83% with the application of B-mode-US alone, or combined with 3D-US and 3DPD-US, respectively.


Conventional ultrasound supplemented with 3D-US and 3DPD-US and the evaluation of findings according to a specific scoring system can facilitate the preoperative classification of complex benign ovarian lesions.


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