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Pathologe. 2014 Jul;35(4):348-54.

Endometriosis-related ovarian tumors.

Schmidt D1Ulrich U.



Endometriosis is a frequent gynecological disease of unknown etiology and pathogenesis. It affects the gynecological organs and the peritoneum with varying frequency and can lead to severe symptoms, mainly pain and to infertility. Despite the fact that causal therapy is not feasible diagnostic and therapeutic procedures are necessary in many cases. In a small percentage of cases endometriosis is associated with neoplastic disease and in some cases it might develop into a neoplasm via the stage of atypical endometriosis, notably in the ovaries. Tumors which are most frequently associated with endometriosis are endometrioid carcinoma, clear cell carcinoma, and low grade serous carcinoma. According to some authors tumors associated with endometriosis have a better prognosis than those without. Other tumors are Mullerian adenosarcoma, endometrioid stromal sarcoma, and seromucinous borderline tumor. In addition to the morphological findings more recent molecular findings serve to demonstrate the origin of the different types of carcinoma from endometriosis. In both endometrioid and clear cell carcinoma, loss of heterozygosity (LOH) can be found in different gene loci. Mutations in CTNNB1 (beta catenin), PTEN, KRAS and ARID1a genes have been demonstrated in endometrioid carcinoma. Cases of clear cell carcinoma have been characterized by mutations of ARID1a gene, PIK3CA and less frequently PPP2R1A and KRAS.



Gynecol Endocrinol. 2014 Nov;30(11):798-803.

Patient satisfaction concerning assisted reproductive technology treatments in moderate to severe endometriosis.

van der Houwen LE1Schreurs AMSchats RLambalk CBHompes PGMijatovic V.



A prospective observational cohort study was performed to examine patient satisfaction after one Assisted Reproductive Technology (ART) treatment cycle in moderate to severe endometriosis patients. From May 2012 till September 2013, 25 patients with surgically proven endometriosis stage III-IV were included per group and received intrauterine insemination (IUI), in vitro fertilization (IVF) or IVF preceded by long-term pituitary down-regulation (IVF-ultralong). The median patient satisfaction scores were 8.3, 7.9 and 8.0 in patients receiving IUI (n = 22), IVF (n = 24) and IVF-ultralong (n = 23), respectively (p = 0.89). Both deterioration in pain and quality-of-life could not be identified as determinants of decreased patient satisfaction scores. Satisfaction was higher in women receiving their first ART treatment attempt (p = 0.002), after treatment accomplishment (p = 0.04) and after a positive pregnancy test (p = 0.04). A median satisfaction score concerning preceding long term pituitary down-regulation of 6.1 (IVF-ultralong n = 25, IUI n = 8) was reported. Only three patients would refrain from this preceding therapy in a next treatment attempt. We concluded that patient satisfaction scores were comparable between the three different ART treatments. Since patient satisfaction was in particular dependent on treatment outcomes, it is recommended to compare those three ART treatments in a randomized controlled trial investigating the efficacy, safety and cost-effectiveness.



BMC Complement Altern Med. 2014 Jul 5;14:222.

Post-laparoscopic oral contraceptive combined with Chinese herbal mixture in treatment of infertility and pain associated with minimal or mild endometriosis: a randomized controlled trial.

Zhu SLiu DHuang W1Wang QWang QZhou LFeng G.



Endometriosis affects fertility negatively. The study aims to evaluate whether laparoscopic surgery combined with oral contraceptive or herbs were more effective than laparoscopic alone in improving fecundity and pelvic pain in women with minimal/mild endometriosis.


A randomized controlled trial (RCT) was conducted in 156 infertile women with minimal/mild endometriosis. After laparoscopic surgery, patients were randomized to three groups: in Group A (n = 52) oral contraceptive (OC) was administered one pill a day, continuous for 63 days without intervals, in Group B (n = 52) OC was administered as above and then Dan’e mixture was added 30 g/day for the latter 30 days, and in control Group C (n = 52) patients tried to get pregnant after surgery without complementary treatment. The follow-up periods were 12 months in Group C and 14 months in complementary medical treatment Group A and B. The pregnant women were further followed up, and labor and pregnancy outcomes were assessed. Primary outcome was pregnancy rate (PR) and live birth rate (LBR). Secondary outcomes included changes of pelvic pain visual analog scale scores and side effects. Analyses were done as intention-to-treat.


The PR was 46.80% (73/156), and the LBR was 69.86% (51/73). Of the 73 pregnancies, 60 occurred within 12 months of follow-up and 7 of the remaining 13 patients underwent assisted reproductive technology for >1 year. No significant difference was observed in PR and LBR among the three groups. Patients given medical treatment (OCs or OCs plus herbal medicine) had significantly decreased pain scores compared with the laparoscopy alone group.


Combination of laparoscopy with OCs or OCs and herbal medicine does not have more advantages than laparoscopy alone in improving fertility of women with minimal/mild endometriosis.



Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:198-203

Visceral syndrome in endometriosis patients.

Hansen KE1Kesmodel US2Baldursson EB3Kold M4Forman A2.



Pain related to bowel and bladder function is seen more often in endometriosis. This study explored whether employed endometriosis patients experience multiple visceral symptoms more often than reference women without the disease.


In a cohort study, 610 patients with diagnosed endometriosis and 751 reference women completed an electronic survey based on the EHP-30 questionnaire. Percentages were reported for all data. Principal component analysis was used to find underlying structures of correlations among variables, and Cronbach’s alpha reliability analysis was used to demonstrate internal consistency of each scale. The level of statistical significance was set at p<0.025 in all the analyses.


Principal component analysis pointed at a specific visceral symptom-complex relating to the abdominal organs. This correlation was called “visceral syndrome” and consisted of the seven symptoms; “abdominal pain with no relation to menstruation”, “pain during urination”, “pain during defecation”, “constipation or diarrhea”, “irregular bleeding”, “nausea or vomiting” and “feeling tired/lack of energy”, with a Cronbach’s alpha value α=0.85. More women with endometriosis than reference women suffered between five and seven symptoms from the visceral syndrome (22.7% vs. 2.7%) and more women with endometriosis compared to women with pain from other conditions suffered between five and seven symptoms from the visceral syndrome (22.7% vs. 3.2%).


These data indicate that a significant number of endometriosis patients suffer from a specific symptom correlation, which is uncommon in women without the disease. These findings and previous data may suggest the occurrence of a visceral syndrome in endometriosis.


Immunol Invest. 2014;43(6):595-605.

A meta-analysis of the association between p53 codon 72 polymorphism and susceptibility to endometriosis.

Song GG1Lee YH.



The aim of this study was to determine whether the p53 codon 72 polymorphism is associated with susceptibility to endometriosis.


A meta-analysis was conducted on the associations between the p53 codon 72 polymorphism and endometriosis using 1) allele contrast, 2) a recessive model, 3) a dominant model, and 4) homozygote contrast.


Nine studies involving 1,803 patients and 2,006 controls were considered in the meta-analysis. Meta-analysis of the p53 polymorphism showed no association between endometriosis and the p53 C allele (odds ratio (OR) = 1.087, 95% confidence interval (CI) = 0.921-1.282, p = 0.323). Stratification by ethnicity indicated no association between the p53 C allele and endometriosis in Europeans and Latin Americans. However, a significant association was found between the p53 C allele and endometriosis in East Asians (OR = 1.405, 95% CI = 1.065-1.854, p = 0.016). Furthermore, association was found between the p53 polymorphism and endometriosis in East Asians using the dominant model (OR = 2.046, 95% CI = 1.123-3.730, p = 0.019).


This meta-analysis demonstrates that the p53 codon 72 polymorphism may be associated with susceptibility to endometriosis in East Asians, but not in Europeans and Latin Americans.



Fukuoka Igaku Zasshi. 2014 Mar;105(3):84-7.

Case of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome.

Horioka KKataoka KOoishi HTsunematsu ROkugawa KKobayashi HKato K.



We report the case of 23 year-old woman with OHVIRA syndrome (obstructed hemivagina and ipisilateral renal anomaly) discovered during management for right renal failure. Non-specific symptoms such as lower abdominal pain, dysmenorrhea, and genital bleeding sometimes occur with congenital uterine anomalies such as this. It is very difficult to diagnose OHVIRA syndrome accurately without ultrasound and magnetic resonance imaging, and patients can develop severe complications as a result of delays in diagnosis: endometriosis, pelvic adhesions, or infertility can occur through backflow of genital bleeding because of vaginal septum. In our patient we managed to avoid severe complications by surgically resecting the vaginal septum. She was treated within an appropriate time frame and without complications. Fortunately, after the surgery she managed to become pregnant in the left side of the uterus.



Reprod Sci. 2014 Sep;21(9):1093-107.

Mechanical signaling in reproductive tissues: mechanisms and importance.

Jorge S1Chang S2Barzilai JJ3Leppert P4Segars JH5.



The organs of the female reproductive system are among the most dynamic tissues in the human body, undergoing repeated cycles of growth and involution from puberty through menopause. To achieve such impressive plasticity, reproductive tissues must respond not only to soluble signals (hormones, growth factors, and cytokines) but also to physical cues (mechanical forces and osmotic stress) as well. Here, we review the mechanisms underlying the process of mechanotransduction-how signals are conveyed from the extracellular matrix that surrounds the cells of reproductive tissues to the downstream molecules and signaling pathways that coordinate the cellular adaptive response to external forces. Our objective was to examine how mechanical forces contribute significantly to physiological functions and pathogenesis in reproductive tissues. We highlight how widespread diseases of the reproductive tract, from preterm labor to tumors of the uterus and breast, result from an impairment in mechanical signaling.



Minerva Endocrinol. 2014 Sep;39(3):155-65.

Endometriosis and ovarian cancer: clinical and molecular aspects.

Pavlidou A1Vlahos NF.



Endometriosis is one of the most commonly encountered benign problems in gynecology. Even though endometriosis appears to predispose to ovarian cancer the progression from atypical epithelial proliferation (atypical endometriosis and metaplasia), to the formation of well-defined borderline tumors and finally to endometrioid ovarian cancer will take several years. To elaborate on the concept of endometriosis as a precursor of some types of ovarian cancer, we present an overview of the pathophysiological and genetic characteristics, common in those two conditions. Furthermore, we present the genetic mutations found in ovarian cancers and we outline the common genetic alterations of endometriosis and ovarian cancer, focusing on the PI3K/Akt/mTOR-signaling pathway.



Minerva Endocrinol. 2014 Sep;39(3):141-54.

Endometriosis: translation of molecular insights to management.

Langan KL1Farrell MEKeyser EASalyer BABurney RO.



Endometriosis is a debilitating gynecologic disorder causing pelvic pain and infertility and characterized by the implantation of endometrial tissue to extrauterine locations. Though aspects of the condition remain enigmatic, the molecular pathophysiology of endometriosis appears to be clarifying. Estrogen dependence of the disease is a sentinel endocrine feature and reduction of estrogen bioavailability is the therapeutic principle upon which traditional treatment and prevention approaches have been based. Endometriosis is a chronic inflammatory condition associated with lesional neoangiogenesis and attenuated progesterone action at the level of the endometrium. The elucidation of the molecular pathways mediating these observations has revealed new targets for directed medical and surgical treatment. This paper will review current approaches to the management of endometriosis in the context of the molecular pathophysiology.



Cochrane Database Syst Rev. 2014 Jul 9;(7)

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery.

Ahmad G1Mackie FLIles DAO’Flynn HDias SMetwally MWatson A.



Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by various conditions including pelvic inflammatory disease and endometriosis. Adhesions are associated with considerable co-morbidity, including pelvic pain, subfertility and small bowel obstruction. Patients may require further surgery-a fact that has financial implications.


To evaluate the role of fluid and pharmacological agents used as adjuvants in preventing formation of adhesions after gynaecological surgery.


The following databases were searched up to April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO. Studies involving hydroflotation, gel and such pharmacological agents as steroids, noxytioline, heparin, promethazine, N,O-carboxymethyl chitosan and gonadotrophin-releasing hormone agonists were evaluated.


Randomised controlled trials investigating the use of fluid and pharmacological agents to prevent adhesions after gynaecological surgery. Gels were defined as fluid agents.


Three review authors independently assessed trials for eligibility, extracted data and evaluated risk of bias. Results were expressed as odds ratios (ORs), mean differences (MDs) or standard mean differences (SMDs) as appropriate, with 95% confidence intervals (CIs).


Twenty-nine trials were included (3227 participants), and nine were excluded. One study examined pelvic pain and found no evidence of a difference between use of hydroflotation agents and no treatment. We found no evidence that any of the antiadhesion agents significantly affected the live birth rate. When gels were compared with no treatment or with hydroflotation agents at second-look laparoscopy (SLL), fewer participants who received a gel showed a worsening adhesion score when compared with those who received no treatment (OR 0.16, 95% CI 0.04 to 0.57, P value 0.005, two studies, 58 women, I(2) = 0%, moderate-quality evidence) and with those given hydroflotation agents (OR 0.28, 95% CI 0.12 to 0.66, P value 0.003, two studies, 342 women, I(2) = 0%, high-quality evidence). Participants who received steroids were less likely to have a worsening adhesion score (OR 0.27, 95% CI 0.12 to 0.58, P value 0.0008, two studies, 182 women, I(2) = 0%, low-quality evidence). Participants were less likely to have adhesions at SLL if they received a hydroflotation agent or gel than if they received no treatment (OR 0.34, 95% CI 0.22 to 0.55, P value < 0.00001, four studies, 566 participants, I(2) = 0%, high-quality evidence; OR 0.25, 95% CI 0.11 to 0.56, P value 0.0006, four studies, 134 women, I(2) = 0%, high-quality evidence, respectively). When gels were compared with hydroflotation agents, participants who received a gel were less likely to have adhesions at SLL than those who received a hydroflotation agent (OR 0.36, 95% CI 0.19 to 0.67, P value 0.001, two studies, 342 women, I(2) = 0%, high-quality evidence). No studies evaluated quality of life. In all studies apart from one, investigators stated that they were going to assess serious adverse outcomes associated with treatment agents, and no adverse effects were reported.Results suggest that for a woman with a 77% risk of developing adhesions without treatment, the risk of developing adhesions after use of a gel would be between 26% and 65%. For a woman with an 83% risk of worsening of adhesions after no treatment at initial surgery, the chance when a gel is used would be between 16% and 73%. Similarly, for hydroflotation fluids for a woman with an 84% chance of developing adhesions with no treatment, the risk of developing adhesions when hydroflotation fluid is used would be between 53% and 73%.Several of the included studies could not be included in a meta-analysis: The findings of these studies broadly agreed with the findings of the meta-analyses.The quality of the evidence, which was assessed using the GRADE approach, ranged from low to high. The main reasons for downgrading of evidence included imprecision (small sample sizes and wide confidence intervals) and poor reporting of study methods.


Gels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but no evidence indicates that they improve fertility outcomes or pelvic pain, and further research is required in this area. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society (mAFS) score. Statistical findings should be reported in full.



Hum Reprod. 2014 Oct 10;29(10):2171-5

‘Behind blue eyes’†: the association between eye colour and deep infiltrating endometriosis.

Vercellini P1Buggio L2Somigliana E3Dridi D2Marchese MA2Viganò P4.



Is the prevalence of blue eye colour higher in women with deep endometriosis?


Blue eye colour is more common in women with deep endometriosis when compared with both women with ovarian endometriomas and women without a history of endometriosis.


Recent and intriguing evidence suggests that women with deep endometriosismay have particular phenotypic characteristics including a higher prevalence of a light-colour iris. Available epidemiological evidence is however weak.


Case-control study performed in a large academic department specializing in the study and treatment of endometriosis. Individual iris colour was evaluated in daylight and categorized in three grades, namely blue-grey (blue), hazel-green (green) and brown. One observer assessed iris colour. In addition, the women themselves were invited to indicate the colour of their eyes according to the same classification system. Cases with discordant eye colour determinations between the observer and the woman were excluded from the final analysis.


Two hundred and twenty-three women with deep endometriosis (cases), 247 with ovarian endometriomas and 301 without a history of endometriosis were enrolled.


After exclusion of 52 discordant cases, the proportions of brown, blue and green eye colours were, respectively, 61, 30 and 9% in the deep endometriosis group, 74, 16 and 10% in the endometrioma group and 75, 15 and 10% in the non-endometriosis group. Women in the deep endometriosis group had a statistically significant excess of blue eyes and a reduced proportion of brown eyes compared with the two control groups (P = 0.002 and P < 0.001, respectively). The proportion of blue eyes was almost identical in the ovarian endometrioma group and the non-endometriosis group, and that of green eyes was substantially similar in all study groups. The OR (95% CI) of having blue eyes in women with deep endometriosis compared with women with ovarian endometriosis and with those without endometriosis was, respectively, 2.2 (1.4-3.6) and 2.5 (1.6-3.9).


We cannot exclude that some women without a previous diagnosis of endometriosis indeed had the disease. However, this would have led to a reduction of the observed difference in proportion of blue eyes, thus to a potential underestimation of the real strength of the association. Moreover, under-ascertainment is possible with regard to peritoneal disease, but unlikely with deep endometriotic lesions and ovarian endometriomas.


There are two possible explanations for our findings. Both may have intriguing implications for future research on endometriosis. Firstly, genes involved in the control of iris colour transmission may lie in a region with a strong pattern of linkage disequilibrium with genes involved in the invasiveness of endometriosis. Alternatively, blue eye colour could be considered an indicator of a photo-sensitive phenotype resulting in limited exposure to sunlight and UVB radiation. Limited sunlight exposure is associated with reduced circulating 25-hydroxyvitamin D3, an element that has recently been linked to endometriosis development.


ISRN Obstet Gynecol. 2014 Mar 26;2014:

Can platelet indices be new biomarkers for severe endometriosis?

Avcioğlu SN1Altinkaya SÖ1Küçük M2Demircan-Sezer S1Yüksel H1.



Objective. The aim of this study was to investigate whether platelet indices-mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) would be useful as noninvasive biomarkers for determining the severity of endometriosis. Methods. A retrospective review of the medical charts of 164 patients diagnosed with endometriosis and who were operated on between 2001 and 2013 was performed. The stage of endometriosis was determined according to revised American Society for Reproductive Medicine criteria. Results. In patients with advanced endometriosis (Stages 3-4), PLT, PCT levels were found to be significantly higher and MPV, PDW values to be significantly lower when compared to initial endometriosis (Stages 1-2). In addition, there was a significant positive correlation between PLT (r: 0.800, P: 0.001) and PCT (r: 0.727, P: 0.002) and the inflammatory marker white blood cell count (WBC). Conclusion. Our finding may not sufficient for employing platelet indices solely in this differential diagnosis, but our finding could provide a suggestion for clinical physicians so that attention is paid to the value of platelet indices and that these may be taken into account when making decisions about the initial or advanced stages of endometriosis.




Eur Radiol. 2014 Oct;24(10):2590-6.

Standard high-resolution pelvic MRI vs. low-resolution pelvic MRI in the evaluation of deep infiltrating endometriosis.

Scardapane A1Lorusso FScioscia MFerrante AStabile Ianora AAAngelelli G.



To compare the capabilities of standard pelvic MRI with low-resolution pelvic MRI using fast breath-hold sequences to evaluate deep infiltrating endometriosis (DIE).


Sixty-eight consecutive women with suspected DIE were studied with pelvic MRI. A double-acquisition protocol was carried out in each case. High-resolution (HR)-MRI consisted of axial, sagittal, and coronal TSE T2W images, axial TSE T1W, and axial THRIVE. Low-resolution (LR)-MRI was acquired using fast single shot (SSH) T2 and T1 images. Two radiologists with 10 and 2 years of experience reviewed HR and LR images in two separate sessions. The presence of endometriotic lesions of the uterosacral ligament (USL), rectovaginal septum (RVS), pouch of Douglas (POD), and rectal wall was noted. The accuracies of LR-MRI and HR-MRI were compared with the laparoscopic and histopathological findings.


Average acquisition times were 24 minutes for HR-MRI and 7 minutes for LR-MRI. The more experienced radiologist achieved higher accuracy with both HR-MRI and LR-MRI. The values of sensitivity, specificity, PPV, NPV, and accuracy did not significantly change between HR and LR images or interobserver agreement for all of the considered anatomic sites.


LR-MRI performs as well as HR-MRI and is a valuable tool for the detection of deep endometriosis extension.


  • High- and low-resolution MRI perform similarly in deep endometriosisevaluation • Low-resolution MRI significantly reduces the duration of the examination • Radiologist experience is fundamental for evaluating deep pelvic endometriosis.



Eur J Obstet Gynecol Reprod Biol. 2014 Sep;180:142-7

Serum anti-mullerian hormone in reproductive aged women with benign ovarian cysts.

Somigliana E1Marchese MA2Frattaruolo MP2Berlanda N3Fedele L2Vercellini P2.



There is consistent evidence demonstrating that laparoscopic removal of benign ovarian cysts significantly damages the ovarian reserve. In contrast, the pre-operative impact of these cysts on the ovarian reserve is yet controversial. To elucidate this aspect, we set up a cross-sectional study in reproductive age women with and without benign ovarian cysts.


Inclusion criteria were as follow: (1) Age 18-40 years, (2) regular menstrual cycles, (3) Indication to laparoscopic surgery. Eligible women donated a blood sample for anti-Mullerian hormone (AMH) testing. Women who were diagnosed at surgery with concomitant endometriotic and non-endometriotic ovarian cysts, deep infiltrating peritoneal endometriosis or malignancies were subsequently excluded.


Diagnoses of the included women were as follows: ovarian endometriomas (n=122), non-endometriotic ovarian cysts (n=50) and non-ovarian diagnoses (n=113). Serum AMH in the three groups did not significantly differ. The median (Interquartile range-IQR) was 1.8 (0.8-3.1), 2.0 (0.8-3.9) and 1.9 (0.9-3.3) ng/ml, respectively (p=0.60). The analyses were repeated grouping women into those with bilateral cysts (n=54), unilateral cysts (n=118) and intact gonads (n=113). Women with bilateral lesions were found to have significantly lower levels of serum AMH. The median (IQR) serum AMH in the three groups was 1.3 (0.5-2.5), 2.0 (1.1-3.6) and 1.9 (0.9-3.3) ng/ml, respectively (p=0.019). We failed to demonstrate any correlation between serum AMH and the dimension of the ovarian cysts.


Serum AMH is lower in women with bilateral ovarian cysts and this does not appear to be related to the histology or dimension of the lesions.



Domest Anim Endocrinol. 2014 Oct;49:49-59.

Pro- and anti-inflammatory mediators change leukotriene B4 and leukotriene C4 synthesis and secretion in an inflamed porcine endometrium.

Czarzasta J1Andronowska A1Jana B2.



We studied the effect of lipopolysaccharide (LPS), proinflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin [IL]-1β), and anti-inflammatory cytokines (IL-4 and IL-10) on leukotriene (LT) A4 hydrolase and LTC4 synthase (LTCS) protein expression in, and LTB4 and LTC4 secretion from, an inflamed porcine endometrium. On day 3 of the estrous cycle (day 0 of the study), 50 mL of either saline or Escherichia coli suspension (10(9) CFU/mL) was injected into each uterine horn of gilts (n = 12 per group). Endometrial explants, obtained 8 and 16 days later, were incubated for 24 h with LPS (10 or 100 ng/mL of medium), TNF-α, IL-1β, IL-4, and IL-10 (each cytokine: 1 or 10 ng/mL of medium). Although acute endometritis developed in all bacteria-inoculated gilts, a severe form of acute endometritis was diagnosed more often on day 8 of the study than on day 16. The amount of the LTA4 hydrolase (LTAH) protein in the inflamed endometrium on day 8 was greater after applying the lower dose of TNF-α (P < 0.001) and both doses of IL-1β (P < 0.001) and IL-4 (1 ng, P < 0.01 and 10 ng, P < 0.001) than in the saline-treated uteri. A similar situation was observed in the case of the inflamed tissue on day 16 in response to LPS (100 ng, P < 0.01), TNF-α (10 ng, P < 0.05), and IL-4 (1 ng, P < 0.001). The content of LTC4 synthase in the inflamed endometrium on day 8 was reduced by LPS (100 ng, P < 0.05), IL-1β (10 ng, P < 0.05), IL-4 (1 and 10 ng, P < 0.05), and IL-10 (1 ng, P < 0.01) but increased after the application of LPS (100 ng, P < 0.05) and TNF-α (1 and 10 ng, P < 0.001), IL-1β, and IL-4 (1 ng, P < 0.05 and 10 ng, P < 0.001) on day 16. On day 8, endometrial secretion of LTB4 from the saline-injected and E coli-injected organs was similar in response to all of the used mediators. On the other hand, the contents of LTB4 in the medium decreased after incubating the inflamed tissues from day 16 with TNF-α (1 ng, P < 0.05 and 10 ng, P < 0.01), IL-1β (1 ng, P < 0.01), and IL-10 (10 ng, P < 0.05) compared with the saline-treated ones. Secretion of LTC4 from the inflamed uteri on day 8 was elevated by the lower doses of TNF-α (P < 0.01) and IL-10 (P < 0.05), whereas on day 16, such an effect occurred in response to the higher doses of IL-4 (P < 0.01) and IL-10 (P < 0.05). The obtained results show that pro- and anti-inflammatory mediators participate in the synthesis/secretion of LTs from an inflamed porcine endometrium. Our data suggest that inflammatory mediators may indirectly affect the processes regulated by LTs by influencing LT production.



J Obstet Gynaecol. 2015 Jan;35(1):64-8.

A higher anti-Müllerian hormone level is associated with an increased chance of pregnancy in patients undergoing controlled ovarian stimulation and intrauterine insemination.

Wang MH1Chen CHWang CWHsu MITzeng CR.



Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.




Ginekol Pol. 2014 May;85(5):386-9

Endometriosis in a post-laparoscopic scar–case report and literature review.

Chmaj-Wierzchowska KPieta BCzerniak TOpala T.



Endometriosis is an estrogen-dependent, chronic disease consisting in implantation and hyperplasia of the endometrium outside of the uterine cavity Endometriosis in post-laparoscopic scars applies to approx. 0.5-7% of the extraorganic locations of the disease. The purpose of the paper was to describe medical management and literature review for endometriosis in a post-laparoscopic scar. Two lesions located near the insertion site for the lower trocars were removed along with the border of healthy tissue. At the time of publication of this paper the patient did not report any complaints. In conclusion, each limited lesion in the subcutaneous tissue, with pain intensifying during menstruation, should suggest an initial diagnosis of scar endometriosis, regardless of patient age and type of surgery



Ultraschall Med. 2014 Dec;35(6):561-5.

Importance of transvaginal ultrasound applying elastography for identifying deep infiltrating endometriosis – a feasibility study.

Schiffmann ML1Schäfer SD1Schüring AN1Kiesel L1Sauerland C2Götte M1Schmitz R1.



To evaluate the presence of a lesion indicative of endometriosis with transvaginal elastography.


Transvaginal ultrasound and clinical examination were carried out in 48 women with clinical symptoms indicative of endometriosis. In 31 cases strain values were measured at two regions of interest (ROIs) in the Douglas’s cul-de-sac during a cycle of compression and decompression with a vaginal probe.


A significant difference was found for the ratio of the ROI measuring points in the Douglas’ cul-de-sacs of women with a palpable nodule in examination compared to women without a palpable nodule (p = 0.002).


The ratio of strain values between two ROIs in the Douglas’ s cul-de-sac is associated with the presence of an endometriotic lesion. In the future, these findings could allow for a more detailed pre-surgical evaluation and possibly serve as a novel diagnostic tool for predicting deep infiltrating endometriosis.



Adv Exp Med Biol. 2014;814:159-67.

The separation of sexual activity and reproduction in human social evolution.

Morin S1Keefe DNaftolin F.



In industrialized societies the progression of natural selection has been determined and in many cases superseded by social evolution. In the case of reproduction, there has been a decline and delay of childbearing without diminished sexual activity. While this has value for these societies, there are penalties associated with barren cycles. These include increases in endometriosis and breast and genital cancer. There also are associated issues regarding population movements that fill the “vacuums” left by underpopulation. These matters are of more than passing interest as we cope with unintended consequences of Man’s dominance over the environment and other life forms.



Reprod Sci. 2015 Apr;22(4):431-41.

Stress management affects outcomes in the pathophysiology of an endometriosis model.

Appleyard CB1Cruz ML2Hernández S2Thompson KJ2Bayona M3Flores I4.



We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim stress protocol. Corticosterone levels and fecal pellet numbers were measured as an indicator of stress. Uncontrollable stress increased the number and size of the endometriotic cysts. Rats receiving uncontrollable stress had higher anxiety than those exposed to controllable stress or no stress and higher corticosterone levels. Uncontrollable stressed rats had more colonic damage and uterine cell infiltration compared to no stress, while controllable stress rats showed less of an effect. Uncontrollable stress also increased both colonic and uterine motility. In summary, the level of stress controllability appears to modulate the behavior and pathophysiology of endometriosis and offers evidence for evaluating therapeutic interventions.


Orv Hetil. 2014 Jul 20;155(29):1152-7

Indications and methods of hysterectomy.

Németh G1.



Hysterectomy is one of the most frequently performed gynecological operations. The most common indications for hysterectomy are symptomatic uterine fibroids, endometriosis, and uterine and pelvic organ prolapse. The procedure can be performed by vaginally or abdominally and with laparoscopic assistance. Choosing the perfect method the gynecologist should take into consideration how the procedure can be performed most safely to fulfill the needs of the patient. In the last few years the number of the laparoscopic procedures has been increasing.



Eur J Obstet Gynecol Reprod Biol. 2014 Sep;180:16-23.

Effect of GnRH agonist therapy on the expression of human heat shock protein 70 in eutopic and ectopic endometria of women with endometriosis.

Imamura T1Khan KN2Fujishita A3Kitajima M1Hiraki K1Ishimaru T4Masuzaki H1.



Human heat shock protein 70 (HSP70) has been reported to enhance Toll-like receptor 4-mediated pelvic inflammation and growth of endometriotic cells. However, information on tissue expression of HSP70 before and after treatment with estrogen suppressing agent is scanty. Here, we investigated tissue expression HSP70 in the eutopic/ectopic endometria of gonadotropin-releasing hormone agonist (GnRHa)-treated and -non-treated women with endometriosis.


Biopsy specimens were collected from peritoneal lesions, cyst walls, and corresponding endometria of 20 women with peritoneal endometriosis, 35 women with ovarian endometrioma, and 15 control women during laparoscopy. Fifteen women with ovarian endometrioma were treated with GnRHa for a variable period of 4-6 months before laparoscopy. The immunoexpressions of HSP70 and CD68-positive macrophages (Mφ) in endometria, peritoneal lesions, and cyst walls were examined by immunohistochemistry. The immunoreactivity of HSP70 in tissues was analyzed by quantitative-histogram (Q-H) score.


Tissue expression of HSP70 was found to be the highest in the menstrual phase than in other phases of the menstrual cycle. A significantly higher immunoreactivity of HSP70 was found in the eutopic endometria of women with peritoneal and ovarian endometriosis than in controls and in opaque red lesions than in other peritoneal lesions. A significant correlation between Q-H scores of HSP70 and CD68-positive Mφ numbers was found in the endometria derived from women with peritoneal endometriosis (r=0.481) and in ovarian endometrioma (r=0.560) but not in control women. The Q-H scores of HSP70 expression were significantly lower in cyst walls, coexisting peritoneal lesions and corresponding endometria of women with ovarian endometrioma after GnRHa treatment comparing to similar tissues derived from women without GnRHa treatment.


These results suggest that as a marker of tissue stress reaction, immunoexpression of HSP70 was highly increased in pathological lesions and endometria of women with endometriosis and had a significant correlation with tissue inflammatory reaction. The higher tissue expression of HSP70 can be effectively suppressed after GnRHa treatment.



Eur J Obstet Gynecol Reprod Biol. 2014 Sep;180:28-34.

Gasless laparoendoscopic single-site surgery for management of adnexal masses during pregnancy.

Takeda A1Imoto S2Nakamura H2.



To evaluate the safety and feasibility of gasless transumbilical laparoendoscopic single-site (LESS) surgery with abdominal-wall lift method for the management of adnexal masses during pregnancy.


Retrospective study of 29 women each undergoing gasless LESS surgery and multiport laparoscopic surgery for the management of adnexal masses during pregnancy. The two groups were compared for their surgical and pregnancy outcome measures.


Conceptions occurred spontaneously in all women including 2 cases each of monochorionic-diamniotic twins in both groups. Three and 2 cases of bilateral adnexal masses were noted in the LESS surgery group and the multiport laparoscopic surgery group, respectively. Estimated gestational age at surgery was significantly older and tumor diameter was significantly larger in the LESS surgery group than in the multiport laparoscopic surgery group. However, significant differences between the two groups were not evident in other patient demographics. There were no significant differences in type of surgery between the two groups. In 28 masses that received LESS adnexal cystectomy, LESS-assisted extracorporeal cystectomy was achieved in 23 masses. Excised tissue weight in the LESS surgery group was significantly heavier than in the multiport laparoscopic surgery group. Significant differences were not observed in other operative parameters between the two groups. Significant differences in postoperative complications were not identified between the two groups. Benign pathologies were obtained in 61 masses from both groups, except for a case of clear cell carcinoma managed by LESS salpingo-oophorectomy. Significant differences in pathological diagnosis were not observed between the two groups. Delivery of 61 neonates occurred in 57 women except for the case of clear cell carcinoma in which termination of the pregnancy was chosen. In the LESS surgery group, threatened premature delivery requiring admission and preterm delivery was noted in 3 and 4 cases, respectively. However, significant differences in pregnancy outcomes were not identified between the two groups. The neonatal course was uneventful in all infants.


Gasless LESS surgery for adnexal masses during pregnancy is a safe and feasible alternative to multiport laparoscopic surgery, with the avoidance of potential negative effects of carbon dioxide gas insufflation on mother and fetus.



Taiwan J Obstet Gynecol. 2014 Jun;53(2):220-3.

Suitable timing of surgical intervention for ruptured ovarian endometrioma.

Huang YH1Hsieh CL2Shiau CS2Lo LM2Liou JD2Chang MY3.



Patients with a rare rupture of endometriomas may require surgery. In this retrospective study, we assessed the outcomes of surgical interventions for ruptured ovarian endometriomas.


Forty-three patients who underwent surgical intervention for ruptured ovarian endometriomas were studied. Depending on the latency to surgery and endometrioma recurrence, patients were divided into two groups, and then compared with respect to patient profiles, intraoperative findings, and outcomes.


Thirty-one of the 43 patients had a known ovarian endometrioma with an average diameter of 6.04 cm. Seventeen (39.5%) patients had a recurrent ovarian tumor during the postoperative follow up. Patients who underwent surgery within 72 hours or after 72 hours showed no difference in baseline characteristics and most clinical outcomes, except for the choice of surgery (p = 0.003) and future fertility (p = 0.005).


Comprehensive and early surgical intervention after endometrioma rupture can assist in excluding ovarian malignancy and can reduce the effects of cyst fluids, prevent adhesions, and preserve fertility.



Taiwan J Obstet Gynecol. 2014 Jun;53(2):224-6.

Stages of endometriosis: does it affect in vitro fertilization outcome.

Pop-Trajkovic S1Popović J2Antić V2Radović D2Stefanović M2Vukomanović P2.



Women with endometriosis often need in vitro fertilization (IVF) to conceive. There are conflicting data on the results of IVF in patients with endometriosis. The present study was undertaken to investigate whether or not the stage of endometriosis affects the IVF outcome in order to give the best patient counseling


We compared IVF outcome measures between 40 patients with surgically confirmed minimal and mild endometriosis (American Society for Reproductive Medicine Stage I/II) and 38 patients with moderate and severe endometriosis (Stage III/IV). Each group was also compared with a control group of 157 patients with tubal factor infertility. Outcome measures included number of follicles, number of oocytes, mean number of ampoules of gonadotropins, cumulative pregnancy, and live birth rates


Higher cancelation rates, higher total gonadotropin requirements, and lower oocyte yield were found in women with endometriosis Stage III and IV compared with both the Stage I/II and control groups. The fertilization rate was higher in Stage III/IV endometriosis compared to Stage I/II. Clinical pregnancy and live birth rates were comparable between patients with endometriosis Stage I/II and control group, whereas they were significantly lower in patients with endometriosis Stage III/IV compared to other two groups.


The American Society for Reproductive Medicine classification of endometriosis is useful in predicting IVF outcome. Advanced endometriosis means a worse prognosis for IVF treatment compared to milder stages or tubal factor infertility. The decreased fertilization rate in Stage I/II endometriosis might be a cause of subfertility in these women, as a result of a hostile environment caused by the disease.


J Cancer Res Ther. 2014 Apr-Jun;10(2):324-9.

Resveratrol successfully treats experimental endometriosis through modulation of oxidative stress and lipid peroxidation.

Yavuz S1Aydin NECelik OYilmaz EOzerol ETanbek K.



The purpose of this study was to investigate the potential therapeutic efficiency of resveratrol in the treatment of experimental endometriosis in rats.


Experimental study was carried out in a University hospital.


Endometriosis was surgically induced in 24 female rats. Four weeks after this procedure, the viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups: (1) Control group (n = 8); (2) low dose (10 mg/kg) resveratrol group (n = 8); (3) high dose (100 mg/kg) resveratrol group (n = 8). At the end of the 7-day treatment, blood samples were taken and laparotomy was performed. The endometrial implants were processed for biochemical, histological and immunohistochemical studies.


The Kruskal-Wallis H test and one-way ANOVA test were used.


Resveratrol-treated rats showed significantly reduced endometriotic implant volumes (P = 0.004). After treatment, a significant and dose-dependent increase in activities of superoxide dismutase and glutathione peroxidase in serum and tissue of the rats in Group 2 and Group 3 was detected. Similarly, serum and tissue malonyl dialdehyde levels and tissue catalase levels were significantly higher in Group 3 than that of control animals. Histological scores and proliferating cell nuclear antigen expression levels were also significantly reduced in Group 2 and Group 3 than that of control group.


In a rat endometriosis model, resveratrol showed potential ameliorative effects on endometriotic implants probably due to its potent antioxidative properties.



Int J Dev Biol. 2014;58(2-4):95-106

Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus.

Wetendorf M1DeMayo FJ.



Infertility and reproductive-associated disease are global problems in the world today affecting millions of women. A successful pregnancy requires a healthy uterus ready to receive and support an implanting embryo. As an endocrine organ, the uterus is dependent on the secretions of the ovarian hormones estrogen and progesterone which signal via their cognate receptors, the estrogen and progesterone receptors. The progesterone receptor not only functions using classical nuclear receptor signaling, but also participates in non-genomic signaling at the cellular membrane. The complexity of progesterone signaling is further enhanced by the existence of multiple isoforms and post-translational regulation via kinases and transcription coregulators. This dynamic means of regulation of the progesterone receptor is evidenced in its necessary role in a successful pregnancy. Within early pregnancy, the progesterone receptor elicits activation of its target genes in a spatiotemporal manner in order to allow for successful embryo attachment and uterine decidualization. Additionally, appropriate progesterone signaling is important for the prevention of uterine disease such as endometrial cancer, endometriosis, and leiomyoma. The utilization of progesterone receptor modulators in the treatment of these devastating uterine diseases is promising. This review presents a general overview of progesterone receptor structure, function, and regulation and highlights its important role in the establishment of pregnancy and as a therapeutic target in uterine disease.



Mol Hum Reprod. 2014 Oct;20(10):1002-8.

A peptide inhibitor of synuclein-γ reduces neovascularization of human endometriotic lesions.

Edwards AK1Ramesh S1Singh V2Tayade C2.



Endometriosis is a chronic painful gynecological condition characterized by adherence and growth of endometrium outside of the uterine cavity. Neovascularization is essential to the developing endometriosislesion to support its growth. Synuclein-γ (SNCG), a protein implicated in cellular proliferation, is associated with a broad range of malignancies as well as endometriosis. We hypothesized that SNCG plays an important role in the neovascularization and growth of endometriosis and blocking of SNCG will interfere with survival of endometriotic lesions in a mouse model. We developed SP012, a novel 12 amino acid peptide inhibitor of SNCG. SP012 inhibited three-dimensional endothelial cell tube formation in a dose-dependent manner. Using intravital microscopy, SP012 was shown to be successfully delivered to human endometriotic lesions in a xenograft mouse model in vivo. Alymphoid (BALB/c-Rag2-/-Il2rγ-/- lacking T, B and NK cells) mice were surgically induced with human endometriotic lesions and treated with SP012 or phosphate-buffered saline control. SP012 treated endometriotic lesions had decreased growth, development and vascularization at the time of necroscopy. Endometriotic lesions treated with SP012 also had fewer isolectin (+) microvessels. These results, using a mouse model, indicate that SNCG plays a role in the neovascularization and subsequent growth of human endometriotic lesions. Targeting SNCG function using peptide inhibitor might provide a potential therapeutic option for the treatment of endometriosis in the future.



J Clin Endocrinol Metab. 2014 Sep;99(9):E1738-43.

Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis.

Greaves E1Grieve KHorne AWSaunders PT.



Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens.


The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons.


The study was performed using human tissue analysis and cell culture.


The study was conducted at a university research institute.


Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18).


mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens.


TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P < .001, P < .01). TRPV1, SCN9A, and TAC1 were elevated in endometriosis lesions (P < .05). P2RX3 mRNA was increased in the peritoneum of women with CPP, with and without endometriosis (P < .05). Incubation of sensory neurons with 17β-estradiol increased TRPV1 mRNA (P < .01). The estrogen receptor-β-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile increased concentrations of TRPV1, P2RX3, SCN9A, and TAC1 mRNAs.


Estrogen-dependent expression of TRPV1 in sensory neurons may explain why ovarian suppression can reduce endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

Ginekol Pol. 2014 Jun;85(6):446-50.

Ovarian reserve assessment in women with different stages of pelvic endometriosis.

Posadzka EJach RPityński KNocuń A.



Endometriosis is defined as the appearance of ectopic endometrial cells outside the uterine cavity. Ectopic cells demonstrate functional similarity to eutopic cells, but structural and molecular differences are significant and manifest themselves in gene expression of the metalloproteinase genes, integrin or the Bcl-2 gene. Pelvic pain remains to be the main symptom of the disease. Endometriosis may cause dysfunction of the reproductive system and lead to infertility. Pathogenesis of infertility in endometriosis is based on its influence on the hormonal, biochemical and immunological changes in the eutopic endometrium, as well as structural damages of the ovaries and the fallopian tubes.


The aim of the study was to assess the ovarian reserve in patients with endometriosis.


A total of 39 patients (aged 22-34 years) with different stages of endometrial changes were recruited for the study. The number of antral follicles was rated by vaginal ultrasonography and the level of FSH was measured between days 1-3 of the menstrual cycle. The stage of the disease was established after laparoscopy with the rASRM scale.


No statistically significant correlation between the number of follicles (AFC), the level of FSH and the stage of endometriosis was found.


Evaluation of the number of antral follicles and measurements of the FSH level do not allow to predict the ovarian reserve in women with endometriosis.



Arch Gynecol Obstet. 2014 Dec;290(6):1275-7.

Gastric endometriosis associated with transverse colon endometriosis: a case report of a very rare event.

Anaf V1Buggenhout AFranchimont DNöel JC.



Gastric endometriosis is a very rare event. It enters in the differential diagnosis of cyclical or chronic epigastric pain, especially in the context of endometriotic patients. The diagnosis of a gastric submucosal mass requires further investigations to rule out the presence of malignancy or associated adenocarcinoma. Because of it can be associated with transverse colon endometriosis and/or diaphragmatic endometriosis, careful examination of the upper abdomen at laparoscopy should be emphasized. We report here a very rare case of gastric endometriosis associated with transverse colon endometriosis.



Environ Sci Pollut Res Int. 2014 Dec;21(24):13964-73.

Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes.

Huang PC1Li WFLiao PCSun CWTsai EMWang SL.



Evidence has shown that polymorphisms of various genes known to be involved in estrogen biosynthesis and function are associated with estrogen-dependent diseases (EDDs). These genes include CYP17A1, estrogen receptor 1 (ESR1), and 2 (ESR2). Phthalates are considered estrogenic endocrine disruptors, and recent research has suggested that they may act as a risk factor for EDDs. However, extremely few studies have assessed the effects of gene-environment interaction on these diseases. We recruited 44 patients with endometriosis or adenomyosis, 36 patients with leiomyoma, and 69 healthy controls from a medical center in Taiwan between 2005 and 2007. Urine samples were collected and analyzed for seven phthalate metabolites using liquid chromatography tandem mass spectrometry. Peripheral lymphocytes were used for DNA extraction to determine the genotype of CYP17A1, ESR1, and ESR2. Compared to controls, patients with leiomyoma had significantly higher levels of total urinary mono-ethylhexyl phthalate (ΣMEHP) (52.1 vs. 29.6 μg/g creatinine, p = 0.040), mono-n-butyl phthalate (MnBP) (75.4 vs. 51.3 μg/g creatinine, p = 0.019), and monoethyl phthalate (MEP) (103.7 vs. 59.3 μg/g creatinine, p = 0.031). In contrast, patients with endometriosis or adenomyosis showed a marginally increased level of urinary MEHP only. Subjects who were homozygous for both the ESR1 C allele (rs2234693) and CYP17A1 C allele (rs743572) showed a significantly increased risk for leiomyoma (OR = 19.8; 95 % CI, 1.70; 231.5; p = 0.017) relative to subjects with other genotypes of ESR1 and CYP17A1. These results were obtained after adjusting for age, cigarette smoking, MEHP level, GSTM1 genotype and other covariates. Our results suggested that both CYP17A1 and ESR1 polymorphisms may modulate the effects of phthalate exposure on the development of leiomyoma.



Gynecol Endocrinol. 2014 Nov;30(11):808-12.

Increased levels of oxidative and carbonyl stress markers in normal ovarian cortex surrounding endometriotic cysts.

Di Emidio G1D’Alfonso ALeocata PParisse VDi Fonso AArtini PGPatacchiola FTatone CCarta G.



Many evidence support the view that endometriotic cyst may exert detrimental effect on the surrounding ovarian microenvironment so representing a risk to functionality of adjacent follicles. Patients with benign ovarian cyst (endometriotic, follicular and dermoid cysts) subjected to laparoscopic cystectomy were enrolled in the present retrospective study in order to analyze whether endometriotic tissue could negatively affect the surrounding normal ovarian cortex more severely than other ovarian cysts. To this end we carried out immunohistochemistry analysis and comparative determination of the transcription factor FOXO3A, oxidized DNA adduct 8-OHdG (8-hydroxy-2′-deoxyguanosine) and damaged proteins known as AGEs (Advanced Glycation End products) as markers of ovarian stress response and molecular damage. Our results show that all the markers analyzed were present in normal ovarian tissue surrounding benign cysts. We observed higher levels of FOXO3A (15.90 ± 0.28), 8-OHdG (13.33 ± 2.07) and AGEs (12.58 ± 4.34) staining in normal ovarian cortex surrounding endometriotic cysts in comparison with follicular cysts (9.04 ± 0.29, 2.67 ± 2.67, 11.31 ± 2.95, respectively) and dermoid cysts (2.02 ± 0.18, 4.33 ± 2.58 and 10.56 ± 4.03, respectively). These results provide evidence that ovarian endometrioma is responsible for more severe alterations to cellular biomolecules than follicular and dermoid cysts.




Reprod Sci. 2015 Apr;22(4):442-51

Endometrial CXCL13 expression is cycle regulated in humans and aberrantly expressed in humans and Rhesus macaques with endometriosis.

Franasiak JM1Burns KA2Slayden O3Yuan L4Fritz MA4Korach KS5Lessey BA6Young SL7.



C-X-C ligand 13 (CXCL13), a regulator of mucosal immunity, is secreted by human endometrial epithelium and may be involved in embryo implantation. However, cyclic expression of human endometrial CXCL13 in health and disease is not well studied. This study examines cycle stage-specific endometrial CXCL13 expression in normal humans when compared to those with biopsy-confirmed, stage 1 to 4 endometriosis using real-time reverse transcriptase, real-time polymerase chain reaction and immunohistochemistry. Eutopic endometrial CXCL13 expression was also compared between normal, control Rhesus macaques, and macaques with advanced endometriosis. In healthy women, CXLC13 messenger RNA expression was minimal in the proliferative phase and maximal in the secretory phase. However, in the presence of endometriosis, proliferative-phase endometrial expression markedly increased in both humans and rhesus subjects (P < .05). The cross-species and cross-stage concordance suggests a pathophysiologic role for CXCL13 in endometriosisand its use as a biomarker for disease.



Hippokratia. 2013 Oct;17(4):376-7.

Non traumatic liver herniation due to persistent cough mimicking a pulmonary mass.

Pataka A1Paspala A1Sourla E1Bagalas V1Argyropoulou P1.



Non traumatic liver herniation through a diaphragmatic defect is rare.


A 44 year old woman presented with lower lobe opacity at the right lung. Chest Computed tomography (CT) demonstrated a round tumor adjacent to the right diaphragm. Percutaneous needle biopsy revealed liver tissue. A small liver herniation through a diaphragmatic defect was detected in saggital and coronal CT views but no traumatic rupture of the diaphragm or endometriosis were documented.


The patient suffered from gastroesophageal reflux disease and increased transdiaphragmatic pressure from paroxysmal cough due to aspirations may have provoked the diaphragmatic rupture.



Int J Clin Exp Pathol. 2014 May 15;7(6):2743-57.

Indoleamine 2,3-dioxygenase-1 (IDO1) in human endometrial stromal cells induces macrophage tolerance through interleukin-33 in the progression of endometriosis.

Mei J1Xie XX2Li MQ1Wei CY1Jin LP1Li DJ1Zhu XY3.



In the peritoneal fluid, macrophages and their secretory cytokines are essential for endometriosis, but the factors that favor their involvement in the endometriosis-associated inflammatory response are still elusive. Given the anomalous expression of indoleamine 2,3-dioxygenase-1 (IDO1) in endometrial stromal cells (ESCs) and its potentially important roles in immune modulation, we aimed to determine the effects of IDO1 in ESCs on macrophages and the mechanism of those effects. Normal ESCs and ectopic ESCs transfected with the SD11-IDO1 shRNA (short hairpin RNA) or vector-only plasmid SD11 were subsequently co-cultured with peripheral blood (PB)-derived monocytes (PBMC)-driven macrophages directly and indirectly. Cytokine production was determined by analyzing the supernatant of the co-culture unit by enzyme-linked immunosorbent assay (ELISA). The phenotypes and the phagocytic ability of the macrophages were determined by flow cytometry. Compared to normal ESCs, the PBMC-driven macrophages co-cultured with ectopic ESCs displayed lower phagocytic ability. Additionally, macrophages co-cultured with ectopic ESCs exhibited higher levels of CD163 and CD209 and lower levels of HLA-DR and CD11c. Moreover, both the intracellular expression and extracellular secretion of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) were significantly increased, while that of IL-12p70 was decreased in macrophages after being co-cultured with ectopic ESCs. However, there was no significant difference in macrophage phagocytic ability, immunophenotype or cytokine secretion between the direct and indirect co-culture units. Reversely, SD11-IDO1 shRNA transfection of ectopic ESCs could abrogate the decreased phagocytic ability and alternative activation of macrophages in ectopic ESC-macrophage co-culture unit, suggesting that higher IDO1 in ectopic ESCs was indispensable for the induction of macrophage tolerance. Furthermore, the decrease in phagocytic macrophages and alternatively activated macrophages induced by IDO1 in ectopic ESCs was reversed by the addition of an IL-33 inhibitor, that is, soluble ST2 (sST2). Therefore, through the activation of IL-33, the increased expression of IDO1 in ectopic ESCs contributed to the truncated phagocytic ability of macrophages in endometriosis.





Sex Dev. 2014;8(5):281-96.

Molecular genetics of Müllerian duct formation, regression and differentiation.

Mullen RD1Behringer RR.



The Müllerian duct (MD) forms the female reproductive tract (FRT) consisting of the oviducts, uterus, cervix, and upper vagina. FRT function is vital to fertility, providing the site of fertilization, embryo implantation and fetal development. Developmental defects in the formation and diseases of the FRT, including cancer and endometriosis, are prevalent in humans and can result in infertility and death. Furthermore, because the MDs are initially formed regardless of genotypic sex, mesenchymal to epithelial signaling is required in males to mediate MD regression and prevents the development of MD-derived organs. In males, defects in MD regression result in the retention of FRT organs and have been described in several human syndromes. Although to date not reported in humans, ectopic activation of MD regression signaling components in females can result in aplasia of the FRT. Clearly, MD development is important to human health; however, the molecular mechanisms remain largely undetermined. Molecular genetics studies of human diseases and mouse models have provided new insights into molecular signaling during MD development, regression and differentiation. This review will provide an overview of MD development and important genes and signaling mechanisms involved.



Hum Reprod. 2014 Oct 10;29(10):2176-89.

An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression.

Kang YJ1Jeung IC2Park A3Park YJ3Jung H3Kim TD3Lee HG4Choi I3Yoon SR5.



Is the decreased natural killer (NK) cell cytolytic activity in the peritoneal fluid (PF) of endometriosis patients due to primary cytokine activity?


An increased level of interleukin-6 (IL-6) in the PF of patients with endometriosissuppresses NK cell cytolytic activity by down-regulating cytolytic granule components, such as granzyme B and perforin, through the modulation of Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) expression.


Endometriosis is known to be related to a defect in NK cell cytolytic activity. Additionally, the levels of inflammatory cytokines are elevated in the PF of women with endometriosis.


The effects of PF on the differentiation and functional activity of NK cells were investigated in patients with or without endometriosis, and cytokines that reduce NK cell cytolytic activity in endometriosis patients were examined. The study included women who underwent laparoscopic examination for the diagnosis of endometriosis from August 2012 to July 2013 (33 women with, and 15 women without, endometriosis).


Women of reproductive age (20-40 years old) who underwent laparoscopic examination for endometriosis were included. Cytokines present in the PF were identified by enzyme-linked immunosorbent assay. The cytolytic activity of NK cells in the PF was also analyzed using a calcein-acetoxy methyl ester (AM) release assay.


PF from patients with endometriosis suppressed the differentiation and cytotoxicity of NK cells compared with PF from controls (P < 0.05). Increased levels of IL-6 were also found in the PF of patients with endometriosis (P < 0.01), and IL-6 levels were negatively correlated with the cytolytic activity of NK cells (rs = -0.558, P = 0.03). Furthermore, IL-6 reduced the cytolytic activity of NK cells, concomitantly with the down-regulation of granzyme B and perforin (P < 0.05), by modulating SHP-2. Importantly, the addition of anti-IL-6 to the PF of endometriosis patients restored the activity of NK cells (P < 0.01), suggesting that IL-6 plays a crucial role in the reduction of NK cell activity in the PF of patients with endometriosis.


PF contains various inflammatory cytokines in addition to IL-6 and so it is possible that other cytokines may affect the differentiation and activity of NK cells.


Our results imply that the suppression of IL-6 using an anti-IL-6 antibody or soluble IL-6 receptor could rescue the impairment of NK cell activity in patients with endometriosis.


This work was supported by the KRIBB Creative Research Program (KCS3051312); the STP project (DTM0111221) of the Ministry of Knowledge & Economy and the Basic Science Research Program (RBM0271312) of the National Research Foundation of Korea (NRF) from the Ministry of Education, Science & Technology. There are no conflicts of interest.



BMJ Case Rep. 2014 Jul 17;2014.

Decidualised fallopian tube endometriotic implant causing spontaneous haemoperitoneum in a twin pregnancy.

Aggarwal I1Tan P2Mathur M2.



Spontaneous haemoperitoneum in pregnancy (SHiP) is a rare but serious condition associated with an adverse pregnancy outcome. We present a case of previable twin pregnancy presenting with SHiP secondary to endometriosis, necessitating an emergency laparotomy and hysterotomy as a life-saving measure to achieve haemostasis. At laparotomy there was massive haemoperitoneum with active bleeding from the left fallopian tube and a left salpingectomy was performed. Histological examination showed haemorrhagic foci of endometriosis on the fallopian tube exhibiting florid stromal decidual change. We wish to raise awareness of this uncommon but potentially life-threatening condition requiring early recognition and prompt recourse to surgical intervention to minimise the morbidity and mortality.



Tuberk Toraks. 2014;62(2):151-3.

Catamenial hemoptysis: a case report.

Okur A1Metin Bİntepe YSSerin Hİ.



Herein we present a 25-year-old female patient who was admitted with recurrent hemoptysis in menstrual period. At the thorax computed tomography taken during menstruation of patient, diffuse ground glass density and acinar nodules at superior segment of lower lobe at left lung were detected. There was no this findings at the thorax tomography taken in non-menstruation period. Therefore, patient was considered catamenial hemoptysis with clinical and radiological findings. Pulmonary endometriosis is rarely seen disease of the lung, so we are presenting it in the light of the literature knowledge.



Curr Probl Diagn Radiol. 2014 Nov-Dec;43(6):374-85.

Multimodality imaging of the postpartum or posttermination uterus: evaluation using ultrasound, computed tomography, and magnetic resonance imaging.

Laifer-Narin SL1Kwak E2Kim H2Hecht EM2Newhouse JH2.



Postpartum and posttermination complications are common causes of morbidity and mortality in women of reproductive age. These complications can be broadly categorized into vascular, infectious, surgical, and neoplastic etiologies, or are due to ectopic implantation of placental or endometrial tissue. Causes of postpartum vascular complications include retained products of conception, arteriovenous malformation, and pseudoaneurysm. Infectious entities include endometritis, abscess, wound cellulitis, and pelvic septic thrombophlebitis. Postsurgical complications include uterine scar dehiscence, bladder flap hematoma, and subfascial hematoma. Neoplastic complications include the spectrum of gestational trophoblastic neoplasms. Ectopic tissue implantation complications include abnormal placentation and uterine scar endometriosis. Imaging is essential for diagnosis, and radiologists must be familiar with and aware of these entities so that accurate treatment and management can be obtained. In this review, we illustrate the imaging findings of common postpartum and posttermination complications on ultrasound, computed tomography, and magnetic resonance imaging.



Fertil Steril. 2014 Sep;102(3):790-4

Endometriosis in association with Herlyn-Werner-Wunderlich syndrome.

Tong J1Zhu L2Chen N1Lang J1.



To describe the clinical characteristics of patients with Herlyn-Werner-Wunderlich syndrome (HWWS) and explore the relationship between an obstructive genital abnormality and pelvic endometriosis.


Case series.


University hospital.


A total of 94 women with Herlyn-Werner-Wunderlich syndrome (HWWS).


Retrospectively reviewed charts of patients diagnosed with HWWS and follow-up contact.


Data for each patient regarding demographics, presenting symptoms, concomitant complications, and anatomic variations were obtained from operation notes and clinical records.


The occurrence of pelvic endometriosis was 19.15% (18/94) in patients with HWWS. All ovarian endometrial cysts (100%) occurred ipsilateral to the vaginal septum. Pelvic endometriosis was significantly more frequent in patients with complete hemivaginal obstructions (10/27, 37.0%) than those with incomplete obstructions (8/67, 11.9%).


One-fifth of patients with HWWS were susceptible to pelvic endometriosis, and all of the ovarian endometriotic cysts were ipsilateral to the vaginal septum. Pelvic endometriosis in adolescents appeared to be related to the obstructed genital abnormality. Vaginal septum resection should be the first step in treatment and surgery has an important role in the treatment of endometriosis and pelvic adhesion.

Biomed Res Int. 2014;2014:786830.

Are mood and anxiety disorders and alexithymia associated with endometriosis? A preliminary study.

Cavaggioni G1Lia C1Resta S2Antonielli T2Benedetti Panici P2Megiorni F3Porpora MG2.



The aim of this preliminary study was to determine whether psychiatric disorders, psychopathological symptoms, and alexithymia are associated with endometriosis in an Italian population.


A preliminary study comprising 37 Italian patients with surgically confirmed endometriosis and 43 controls, without clinical and ultrasound signs of endometriosis, was carried out. Both patients and controls were evaluated for the presence/absence of psychiatric disorders, psychopathological symptoms, alexithymia, and pain symptoms (nonmenstrual pelvic pain, dysmenorrhea, and dyspareunia).


Statistically significant differences were found between cases and controls for prevalence of mood and anxiety disorders, malfunctioning on obsessive-compulsive subscale (P < 0.01) and depression subscale (P < 0.05) of the Symptom Checklist-90-Revisited (SCL-90-R), and higher alexithymia levels (P < 0.01). Patients with endometriosis-associated pain showed greater prevalence of psychiatric disorders compared to pain-free patients but that difference was not significant. Significant correlation was found between malfunctioning in some SCL-90-R dimensions and pelvic pain, dysmenorrhea, and dyspareunia scores at the visual analog score (VAS).


Some psychopathological aspects, such as psychoemotional distress and alexithymia, are more frequent in women with endometriosis and might amplify pain symptoms in these patients.



Nat Commun. 2014 Jul 22;5:

Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

Sugihara K1Kobayashi Y2Suzuki A3Tamura N2Motamedchaboki K2Huang CT2Akama TO2Pecotte J4Frost P4Bauer C4Jimenez JB Jr4Nakayama J5Aoki D3Fukuda MN2.



Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosisoccurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.



Arch Gynecol Obstet. 2015 Jan;291(1):223-30.

Leiomyomas beyond the uterus; benign metastasizing leiomyomatosis with paraaortic metastasizing endometriosis and intravenous leiomyomatosis: a case series and review of the literature.

Mahmoud MS1Desai KNezhat FR.



Uterine leiomyomas affect 20-30 % of women 35 years and older. Extrauterine leiomyomas are rare and present a greater diagnostic challenge. Those unusual growth patterns occur more often in women of reproductive age with a history of hysterectomy or surgery for uterine leiomyomas. They have been reported in the literature in case reports and small case series and include benign metastasizing leiomyoma (BML), disseminated peritoneal leiomyomatosis, intravenous leiomyomatosis (IVL), parasitic leiomyomas, and retroperitoneal growth. In this case series we present a case of BML with a first report of concomitant endometriosis metastasis to paraaortic lymphnodes, and a case of IVL. The findings and surgical management of those cases, as well as a review of the literature pertinent to those entities, are also presented.


Arch Gynecol Obstet. 2015 Jan;291(1):85-91

Detection of the pan neuronal marker PGP9.5 by immuno-histochemistry and quantitative PCR in eutopic endometrium from women with and without endometriosis.

Zevallos HB1McKinnon BTokushige NMueller MDFraser ISBersinger NA.



To assess endometrial gene as well as protein expression of neuroendocrine and supposedly endometriosis-associated product PGP9.5 and pain symptoms in women with endometriosis and controls undergoing laparoscopy, using molecular biological and immuno-histochemical approaches in the same patients.


Biopsy of eutopic endometrium from 29 patients by sharp curettage, and preparation of paraffin blocks. Determination of PGP9.5 gene expression and protein abundance using qPCR and immuno-histochemistry.


qPCR; The PGP9.5 mRNA expression level between women with (N = 16) and without (N = 13) endometriosis was not different, regardless of pain symptoms or menstrual cycle phase. PGP9.5 expression was higher in women who reported pain compared to those who did not; however, this association was not statistically significant. The expression of PGP9.5 mRNA was higher in women with endometriosis and pain during the proliferative than in the secretory phase (P = 0.03). Furthermore, in the first half of the cycle, the abundance of the PGP9.5 transcript was also significantly higher in endometriosis patients compared to those without (P = 0.03). Immuno-histochemistry; Thirteen of the 16 endometriosis patients showed positive PGP9.5 immuno-reactivity in the endometrium, whereas no such signal was observed in women without endometriosis. The absolute number of nerve fibres per mm(2) in women with endometriosis was similar, regardless of the pain symptoms.


PGP9.5 mRNA expression is increased in the proliferative phase of endometriotic women with pain. The presence of nerve fibres was demonstrated by a PGP9.5 protein signal in immuno-histochemistry and restricted to patients with endometriosis. Based on these results, however, there did not appear to be a direct association between the gene expression and protein abundance in women with and without endometriosis or those that experienced pain.


J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):982-3.

Laparoscopic dissection and anatomy of sacral nerve roots and pelvic splanchnic nerves.

Zanatta A1Rosin MM2Machado RL2Cava L2Possover M3.



To demonstrate the technique of laparoscopic dissection for identification of sacral nerve roots and pelvic splanchnic nerves.


Case report (Canadian Task Force classification III).


Private practice hospital in São Paulo, Brazil.


A 31-year-old woman with suspected iatrogenic and/or compression of sacral nerve roots. She reported debilitating pelvic, gluteal, and perineal unilateral left-sided pain (score 8 on a pain scale of 0-10), and had primary infertility with 1 previous failed attempt at in vitro fertilization. Surgical history included laparoscopic excision of endometriosis 10 months before the procedure and left oophoroplasty during adolescence because of a benign neoplasm.


Standard 4-puncture laparoscopy was performed. The peritoneum of the left pelvic sidewall was resected to preclude eventual residual endometriosis. This also enabled identification of uterine vessels including the deep uterine vein, which is the limit between the pars vascularis superiorly and the pars nervosa inferiorly in the uterine broad ligament. Surgery was using the laparoscopic neuro-navigation (LANN) technique, previously described by one of us (M. P.). For identification of the sacral roots, dissection was begun medial to the ureter and lateral to the uterosacral ligament. The Okabayashi pararectal space was entered as deep as possible via blunt dissection in avascular spaces. Hemostasis was performed using 5-mm bipolar forceps, and harmonic energy was not used. The hypogastric fascia was entered from medial to lateral, and the piriformis muscle was identified. The sacral nerve root S1 was identified lying over it. Dissection then proceeded caudally, and sacral roots S2 and S3 were sequentially identified. Small and delicate fibers forming the pelvic splanchnic nerves were isolated emerging from sacral roots S2 and S3. Other nerve fibers were identified caudally, probably representing pelvic splanchnic nerves emerging from S4.


The surgical operative time was 70 minutes, and bleeding was minimal. No suspected compression or iatrogenic injury was identified. The patient was discharged on the day after the procedure. At 8-month follow-up, she had partial resolution of pain (score 5, pain scale 0-10), and another failed attempt at in vitro fertilization was attributed to unsatisfactory quality of the embryos. There were no symptoms or dysfunctions attributable to manipulation of the nerves.


Laparoscopy is a useful tool for identification of sacral roots and pelvic splanchnic nerves in suspected diseases. Its application in the field of neuropelveology can be expanded with proper knowledge and training.


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