J Minim Invasive Gynecol. 2013 Sep-Oct;20(5):595-603.

Ultrasound-guided aspiration and ethanol sclerotherapy (EST) for treatment of cyst recurrence in patients after previous endometriosis surgery: analysis of influencing factors using a decision tree.

Chang MY1Hsieh CLShiau CSHsieh TTChiang RDChan CH.

 

Abstract

STUDY OBJECTIVE:

To evaluate the efficiency of transvaginal aspiration accompanied by ethanol sclerotherapy for treating cyst recurrence in patients who have previously undergone surgery to treat endometriosis and to analyze various factors that influence success rates using a data mining system.

DESIGN:

Retrospective cohort study (Canadian Task Force classification II-3).

SETTING:

Teaching hospital affiliated with Chang Gung University, Taoyuan, Taiwan.

PATIENTS:

One hundred ninety-six patients with endometrioma recurrence.

INTERVENTION:

A total of 274 transvaginal aspirations followed by sclerotherapy with 95% ethanol. Treatment times varied from immediate removal (0-10 minutes) to in situ retention. Patients were followed up at 3, 6, and 12 months to detect complications, determine the size and persistence of cysts, obtain the pelvic pain score, and assess for pregnancy or the need for repeat surgical intervention. A decision tree was used to determine factors from the collected data that most influenced the success of treatment.

MEASUREMENTS AND MAIN RESULTS:

Cyst size was consistently reduced until 6 months after ethanol sclerotherapy. The mean (SD) cyst reduction rate was 37.2% (42.2%), and the pain score reduction rate was 20.5% (71.5%). The antral follicle count was simultaneously increased by 36.4%. Sixty-three patients (23%) required repeated surgery during the observation period and were treated with either repeat aspiration (13.5%) or major laparoscopic or open laparotomic interventions (8.4%). Eighteen of 101 infertile patients (17.8%) achieved pregnancy. The total recovery rate (pregnancy or no persistence of symptoms or cyst) was significantly higher in patients in the groups that received longer treatment (7-10 minutes and retention) than in the groups with shorter treatment (0-6 minute) (47.0% vs 28.7%; p < .005). The highest recovery rate was observed in patients with longer treatment time, smaller cysts (≤5.05 cm), lower CA 125 level (≤62.03 IU/mL), and fewer cysts (≤3 cm) (35 of 49 [71.4%]). In patients with larger cysts and cysts with clear contents, better success can be achieved with longer treatment. The use of postoperative ovarian suppression, traditional Chinese medicine, or no therapy for 6 months before the study was not significant among groups.

CONCLUSION:

Ultrasound-guided sclerotherapy with 95% ethanol retention is an effective alternative therapy for recurrent ovarian endometrioma, in particular in selected patient groups.

 

 

Fertil Steril. 2013 Dec;100(6):1650-9.e1-2.

Identification of multiple and distinct defects in prostaglandin biosynthetic pathways in eutopic and ectopic endometrium of women with endometriosis.

Rakhila H1Carli CDaris MLemyre MLeboeuf MAkoum A.

 

Abstract

OBJECTIVE:

To investigate prostaglandin (PG) biosynthesis and catabolism pathways in eutopic and ectopic endometrium of women with endometriosis.

DESIGN:

Retrospective study.

SETTING:

Human reproduction research laboratory.

PATIENT(S):

Forty-five women with endometriosis and 29 normal controls.

INTERVENTION(S):

Endometrial and endometriotic tissue samples were obtained during laparoscopic surgery.

MAIN OUTCOME MEASURE(S):

Cyclo-oxygenases (Coxs 1 and 2), PGE2 synthases (microsomal [m] PGES 1 and 2 and cytosolic [c] PGES), PGF2α synthases (aldoketoreductase [AKR]-1C3 and AKR-1B1), and the PG catabolic enzyme 15-hydroxyprostaglandin dehydrogenase messenger RNA expression by quantitative real-time polymerase chain reaction and protein localization by immunohistochemistry.

RESULT(S):

This study showed a marked increase in the key PG biosynthesis enzymes Cox-2, mPGES-1, mPGES-2, cPGES, and AKR-1C3 in ectopic endometrial tissue of women with endometriosis, particularly in the earliest and most active stages of the disease, without a noticeable change in the expression of the PG catabolic enzyme 15-hydroxyprostaglandin dehydrogenase. Meanwhile, the significant increase in rate-limiting Cox-2 expression upstream was correlated downstream by a significant stage- and cycle phase-dependent decrease in the terminal specific synthase mPGES-2, thereby revealing the presence of counter-regulatory mechanisms, which operate in the eutopic endometrium of women with endometrium but seem to be lacking in the ectopic implantation sites.

CONCLUSION(S):

This study reveals for the first time multiple defects in PG biosynthesis pathways, which differ between eutopic intrauterine and ectopic endometrial tissues and may, owing to the wide spectrum of PG properties, contribute to the initial steps of endometrial tissue growth and development and have an important role to play in the pathogenesis and symptoms of this disease.

 

 

Int J Mol Sci. 2013 Sep 12;14(9):18824-49.

ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas.

Samartzis EP1Noske ADedes KJFink DImesch P.

 

Abstract

Endometriosis is a common gynecological disease affecting 6%-10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review.

 

 

 

 

Reprod Sci. 2014 Mar;21(3):296-304.

Endometrial adult/progenitor stem cells: pathogenetic theory and new antiangiogenic approach for endometriosis therapy.

Pittatore G1Moggio ABenedetto CBussolati BRevelli A.

 

Abstract

The cyclical arrival of endometrial cells into the abdominal cavity through retrograde flux at menstruation represents the etiopathogenetic basis of endometriosis. The endometrium has peculiar regenerative properties linked to the presence of adult stem cells similar to mesenchymal stem cells (MSCs). Once in the abdominal cavity, these MSCs could proliferate, invade, and differentiate into endometrial cells, finally generating ectopic implants. As only differentiated endometrial cells, and not endometrial MSCs, possess steroid hormone receptors, MSCs could be responsible for the high rate of persistence/recurrence of the disease after hypoestrogenism-inducing therapies. Even angiogenesis promoted by MSCs could play an important role, as survival and proliferation of endometriotic tissue depend on the formation of new blood vessels. Inhibition of angiogenesis represents, in fact, a new, promising therapeutic approach for the disease. Further, medications directly targeting endometriosis MSCs could be effective, alone or in association with hormonal treatments, in increasing the success of medical treatment.

 

 

J Clin Endocrinol Metab. 2013 Nov;98(11):4417-28

PCAF impairs endometrial receptivity and embryo implantation by down-regulating β3-integrin expression via HOXA10 acetylation.

Zhu LH1Sun LHHu YLJiang YLiu HYShen XYJin XYZhen XSun HXYan GJ.

 

Abstract

BACKGROUND:

Homeobox A10 (HOXA10), a key transcription factor, plays a critical role in endometrial receptivity by regulating the expression of downstream target genes, such as β3-integrin (ITGB3), but little is understood about the mechanisms of the posttranslational modification of HOXA10 during embryo implantation.

OBJECTIVE:

The aim of this study was to assess the effect of HOXA10 acetylation by p300/CREB-binding protein-associated factor (PCAF) in the embryo implantation process.

METHODS:

The association of HOXA10 with PCAF was detected by coimmunoprecipitation, Western blotting, and confocal immunofluorescent assays. A luciferase reporter assay, Western blotting, quantitative real-time PCR, and chromatin immunoprecipitation techniques were used to determine the effect of PCAF on HOXA10 protein stability and the HOXA10-mediated regulation of ITGB3 expression. HOXA10-PCAF association on embryo implantation was evaluated using a BeWo spheroid attachment assay. PCAF expression in the eutopic endometrium of women with endometriosis and fertile controls was measured by Western blotting technique.

RESULTS:

PCAF was identified as an HOXA10-interacting protein and inhibited HOXA10-mediated ITGB3 transcription via acetylating HOXA10 at K338 and K339. Overexpressing or knocking down PCAF in Ishikawa cells showed that PCAF not only down-regulated HOXA10-mediated ITGB3 protein expression but also diminished HOXA10-mediated embryo adhesiveness by acetylating HOXA10 (P < .05). Furthermore, we found aberrantly high PCAF expression in the eutopic endometrium of women with a diagnosis of endometriosiscompared with the fertile controls (P < .05).

CONCLUSIONS:

These observations demonstrate that 1) HOXA10 associates with and is acetylated by PCAF at lysines K338 and K339 in Ishikawa cells and 2) HOXA10-PCAF association impairs embryo implantation by inhibiting ITGB3 protein expression in endometrial epithelial cells.

 

 

PLoS One. 2013 Sep 10;8(9):e73085.

Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models.

Tomio K1Kawana KTaguchi AIsobe YIwamoto RYamashita AKojima SMori MNagamatsu TArimoto TOda KOsuga YTaketani YKang JXArai HArita MKozuma SFujii T.

 

Abstract

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.

 

 

Int J Clin Exp Pathol. 2013 Aug 15;6(9):1911-8.

The impact of endometriosis on IVF/ICSI outcomes.

Dong X1Liao XWang RZhang H.

 

Abstract

This retrospective cohort study was aimed to investigate the impact of endometriosis on the IVF/ICSI outcomes. A total of 1027 cycles of patients undergoing IVF/ICSI treatment in a reproductive medicine unit of academic hospital were enrolled. In the present study, 431 cycles of patients with endometriosis constituted the study group, including 152 cycles of patients with stage I-II endometriosis and 279 cycles of patients with stage III-IV endometriosis, while 596 cycles of patients with tubal factors infertility were considered as the control group. Ovarian stimulation parameters and IVF/ICSI outcomes were compared. Patients with stage I-II and stage III-IV endometriosis required higher dosage and longer duration of gonadotropins, but had lower day 3 high-quality embryos rate, when compared to patients with tubal infertility. In addition, the number of oocytes retrieved, the number of obtained embryos, the number of day 3 high-quality embryos, serum E2 level on the day of hCG, fertilization rate were lower in patients with stage III-IV endometriosis than those in tubal factors group. Except reduced implantation rate in stage III-IV endometriosis group, no differences were found in other pregnancy parameters. This study suggests that IVF/ICSI yielded similar pregnancy outcomes in patients with different stages of endometriosis and patients with tubal infertility. Therefore, IVF/ICSI can be considered as an effective approach for managing endometriosis-associated infertility.

 

 

 

Hum Reprod. 2013 Nov;28(11):2930-42.

Ranking and selection of MII oocytes in human ICSI cycles using gene expression levels from associated cumulus cells.

Ekart J1McNatty KHutton JPitman J.

 

Abstract

STUDY QUESTION:

Can the ranked expression levels of a cohort of cumulus cell (CC) genes be used to select MII oocytes with a potential for blastocyst development and live birth?

SUMMARY ANSWER:

A ranking method containing four (HAS2, FSHR, VCAN, PR) of the eight genes evaluated in this study for identifying good quality MII oocytes provides a significantly better outcome compared with random selection and is equally as good as using all oocytes for ICSI.

WHAT IS KNOWN ALREADY:

Recent evidence has identified a number of candidate genes in CC that have the potential to serve as markers of oocyte quality; however, a reliable method for selecting MII oocytes with blastocyst and live birth potential remains a challenge.

STUDY DESIGN, SIZE, DURATION:

A group of 25 patients (<38 years old) underwent rFSH-stimulated ICSI treatment with single embryo replacement (SET). A total of 270 cumulus cell-oocyte complexes (COCs) were recovered and assessed.

MATERIALS, SETTING, METHODS:

Expression levels of eight candidate genes (HAS2, FSHR, SLC2A4, ALCAM, SFRP2, VCAN, NRP1 and PR), corrected for RPL19, were measured in individual CC masses using multiplex QPCR. Expression levels of individual CC masses were assessed and ranked in relation to oocyte developmental indicators (blastocyst formation and live birth).

MAIN RESULTS AND THE ROLE OF CHANCE:

From the 25 women, 19 (76%) had achieved a successful live birth delivery following SET. In this population, the selection of MII oocytes according to relative ranking levels of a subset of CC-expressed genes provided a significantly higher chance of identifying a good quality oocyte compared with selecting MII oocytes randomly (blastocyst: 1× MII oocyte: 52 versus 23%, P = 0.008; 3× MII oocytes: 80 versus 52%, P = 0.002; live birth: 1× MII oocyte: 31 versus 15%, P<0.05, 3× MII oocytes: 60 versus 38%, P < 0.05) and a similar chance to that of using all oocytes available after recovery (blastocyst: 80% versus 96%, P = 0.085, live birth: 60% versus 76%, P = 0.206).

LIMITATIONS, REASONS FOR CAUTION:

The present method was validated only for young (<38 years) women, with male infertility, who had no signs of androgenicity, PCOS or endometriosis and were free of any chronic disease. This is a retrospective study that requires further validation in an unselected population.

WIDER IMPLICATIONS OF THE FINDINGS:

Results presented in this study could be used to assist the selection of oocytes with high blastocyst developmental potential in frozen oocyte cycles and for the selection of embryos with high developmental potential as early as 18 h after ICSI (2PN stage) in fresh human IVF cycles.

STUDY FUNDING/COMPETING INTEREST(S):

Funding was provided by Fertility Associates Ltd and the New Zealand Government. The authors declare there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

 

 

Recenti Prog Med. 2013 Jul-Aug;104(7-8):438-41.

Sigmoid endometriosis: a diagnostic dilemma on multidetector CT.

Telegrafo MLorusso VRubini GRella LPezzolla AStabile Ianora AAMoschetta M.

 

Abstract

Intestinal endometriosis represents a common condition that occurs particularly in women of reproductive age. The gastrointestinal tract is the third most common localization of endometriosis, after the ovaries and the peritoneum, and recto-sigmoid tract is involved in 70% of cases. Recto-sigmoid endometriosis has to be differentiated from other diseases of large bowel, especially in patients without a history of endometriosis. We report a case of sigmoid endometriosis which represented a diagnostic dilemma on multidetector computed tomography.

 

 

J Comput Assist Tomogr. 2013 Sep-Oct;37(5):809-14.

The usefulness of computed tomographic colonography for evaluation of deep infiltrating endometriosis: comparison with magnetic resonance imaging.

Jeong SY1Chung DJMyung Yeo DLim YTHahn STLee JM.

 

Abstract

OBJECTIVE:

We wanted to assess the diagnostic value and morphologic feature of deep infiltrating endometriosis (DIE), involving rectosigmoid colon, with computed tomography (CT) colonography in comparison with magnetic resonance (MR).

METHODS:

Fifty patients with DIE, who had undergone CT colonography and MR imaging (MRI) before surgery, were enrolled. Among these 50 patients who underwent laparoscopic surgery with DIE, 37 patients were diagnosed as rectosigmoid involvement of endometriosis (presence of rectal outer wall involvement, endometrial implantation in the rectouterine space, and complete obliteration of cul-de-sac with histologic confirmation). Image findings at CT colonography and MRI were reviewed by 2 radiologists to determine whether there are radiologic features that can help predict rectosigmoid endometriosis. Computed tomography images were analyzed for the luminal alteration of rectosigmoid colon, mural thickening, and mass formation in the rectosigmoid colon, whereas MR images were analyzed for the mass formation in the rectosigmoid colon, fat plane obliteration, between rectum and uterus or vagina, retroversion of uterus, retraction of uterus toward the colon, and detection of endometrial spot in rectovaginal or rectouterine space. Statistical analysis was performed with Pearson χ and receiver operating characteristic curve.

RESULTS:

With CT colonography, the luminal alteration of rectosigmoid colon was detected with sensitivity of 96.0% and specificity of 48.0% (P < 0.001) in the overall rectosigmoid endometriosis and with sensitivity of 84.0% and specificity of 80.0% (P = 0.005) in the case of DIE with cul-de-sac obliteration. With MR, the sensitivity and specificity for detection of endometriosis of rectosigmoid or rectouterine space were 94.4% and 37.5% (P = 0.013), respectively. Other variables had no statistical significance. The diagnostic accuracy of CT colonography is higher than that of MRI (area under the curve, 0.786 vs 0.691; P < 0.001), for the overall rectosigmoid endometriosis. In the evaluation of complete cul-de-sac obliteration, morphologic change of rectosigmoid colon is identified more accurately with CT colonography than that of MRI (area under the curve, 0.821 vs 0.686; P < 0.001).

CONCLUSIONS:

Both CT colonography and MRI are highly sensitive to the detection of rectosigmoid endometriosis, but lack specificity. However, the depiction rate of morphologic change in rectosigmoid colon is greater with CT colonography than that of MRI, in the case of cul-de-sac obliteration. The luminal alteration significantly correlates with morphologic change in rectosigmoid endometriosis.

 

 

Hum Reprod. 2013 Nov;28(11):2893-7.

Neonatal uterine bleeding as antecedent of pelvic endometriosis.

Brosens I1Brosens JBenagiano G.

 

Abstract

We elaborate on a new theory to explain pelvic endometriosis, including endometriosis in premenarcheal girls, based on the finding that the neonatal endometrium can display secretory activity immediately after birth and, in some cases, changes analogous to those seen at menstruation in adults. The neonatal uterus is therefore capable of shedding its endometrium. Indeed, occult vaginal bleeding occurs in a majority of neonates, although overt bleeding is estimated to occur in only 5% of neonates. This may be due to functional plugging of the endocervical canal in the neonate, which in turn would promote retrograde flux of endometrial cells contained in menstrual debris. Ectopic endometrial implantation in a newborn with hydrometrocolpos has been documented. These data, coupled with the observation of a significantly increased risk of endometriosis in adolescents with cervical outflow obstruction and patent Fallopian tubes, indicate that endometriosis, especially in children and young adolescents, may originate from retrograde uterine bleeding soon after birth.

 

 

J Reprod Med. 2013 Sep-Oct;58(9-10):411-6.

Measurement of serum and peritoneal levels of amyloid protein A and their importance in the diagnosis of pelvic endometriosis.

Ejzenberg D1Podgaec SDias JA Jrde Oliveira RMBaracat ECAbrão MS.

 

Abstract

OBJECTIVE:

To evaluate serum and peritoneal concentrations of amyloid protein A in women with endometriosisand to compare them with those of women without endometriosis.

STUDY DESIGN:

A prospective study evaluated 76 women suspected of having pelvic endometriosis. Fifty-seven women (group A) were confirmed by videolaparoscopy and had their serum and peritoneal amyloid A concentrations measured by ELISA. The average levels from group A were compared to those obtained in group B. Group B was composed of 13 women without endometriosis, submitted to elective laparoscopy for tubal ligation.

RESULTS:

Peritoneal amyloid A concentrations in group A (310.3 +/- 97.8 ng/mL) were higher than those of group B (53.4 +/- 58.2 ng/mL); p = 0.0. However, serum concentrations in groups A (14.01 +/- 32.3 ng/mL) and B (9.5 +/- 15.9 ng/mL) did not differ significantly; p = 0.35.

CONCLUSION:

The peritoneal amyloid A protein concentration in pelvic endometriosis was higher when compared to normal controls, corroborating the inflammatory nature of the disease. This finding suggests that the procedure of evaluating the peritoneal amyloid A concentration in endometriosis merits further investigation.

 

 

J Reprod Med. 2013 Sep-Oct;58(9-10):417-24.

Do women with deep infiltrating endometriosis have more tubal alterations? Objective evaluation of 473 patients.

Mabrouk M1Di Donato NMontanari GSavelli LFerrini GSeracchioli R.

 

Abstract

OBJECTIVE:

To evaluate whether deep infiltrating endometriosis (DIE) is associated with tubal alterations.

STUDY DESIGN:

This was a retrospective study. Our study included 335 women with ovarian endometriosis(Group A), 66 women with DIE (Group B), and 72 women presenting with both conditions (Group C). We evaluated tubal morphology and patency during laparoscopic excision of endometriosis. Tubal patency was assessed by tubal dye test. Tubal morphology was determined using the tubal morphology score (TMS), obtained by a total grade of 4 parameters: tubal caliber, course, surface and fimbrial morphology.

RESULTS:

There was no significant difference in the 3 groups regarding the presence of tubal occlusion (p = 0.23). Total TMS was not significantly different in the 3 groups (p = 0.13). A history of surgical treatment for endometriosis was associated with higher rate of tubal occlusion (p < 0.0005) and more severe morphological alterations (p < 0.0005). There was a positive correlation between number of previous surgical interventions and worse TMS (rho = 0.197, p < 0.0005).

CONCLUSION:

Alterations in tubal patency and morphology were not significantly different in patients with DIE as compared to women with ovarian endometriosis. History of surgical interventions for endometriosis was related with the presence of tubal alterations.

 

Eur J Obstet Gynecol Reprod Biol. 2013 Nov;171(1):107-15.

The analysis of the human plasma N-glycome in endometriosis patients.

Berkes E1Mužinić ARigo J JrTinneberg HROehmke F.

 

Abstract

OBJECTIVE:

Analysis of the plasma N-glycome in endometriosis patients compared with controls.

STUDY DESIGN:

In a case-control study, blood samples were collected from patients who underwent either diagnostic or operative laparoscopy between 2008 and 2011 in the Semmelweis University, Budapest, I. Department of Obstetrics and Gynaecology. From these patients, 92 with endometriosis (30 stage I-II and 62 stage III-IV, including altogether 18 deep infiltrating cases) and 62 controls were selected for glycan analysis. After release, plasma N-glycans were subjected to hydrophilic interaction high performance liquid chromatography, which resulted in 19 chromatographic glycan peaks (GP). The abundances of the GPs were compared between the study groups. For statistical analysis a non-parametric test, the Mann-Whitney-U test, was used.

RESULTS:

We found a statistically significant decrease of GP1 and increase of GP14, GP17 and GP18 in endometriosis patients. The latter peaks consist of glycans which play a role in inflammatory processes and malignancy. We also found significant differences in GP2, GP4, GP6, and GP9 between controls and the different endometriosis stage groups. The observed alterations in GP2, GP4 and GP6 may be related to altered glycosylation and remodelling of the glycan branches of the IgG molecule. The alterations of GP9 are presumably associated with changes of transferrin glycosylation. Furthermore we detected a highly significant decrease of GP1 in patients with deep infiltrating endometriosis compared with controls.

CONCLUSIONS:

This is the first analysis of the plasma N-glycome in endometriosis. The observed changes in GP14, GP17 and GP18 and in GP2, GP4, GP6 and GP9 provide new aspects to the pathophysiology of the disease and the alterations of the GP1 may serve as a new potential marker in the future.

 

 

Minerva Ginecol. 2013 Aug;65(4):453-63.

Administration of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: preliminary results.

Lo Monte G1Soave IMarci R.

 

Abstract

AIM:

Aim of the study was to evaluate the effectiveness of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis.

METHODS:

Twenty-four patients with suspected endometriosis affected by severe pelvic pain were enrolled. All patients received two tablets a day of PEA 400 mg and 40 mg polydatin for 90 days consecutively. A Visual Analogic Scale was used for the assessment of the severity of global pain, dysmenorrhea, dyspareunia, dysuria and dischezia. A second questionnaire was submitted to patients to assess the quality of life. The compilation of a diary lead us to evaluate the monthly assumption of any painkillers. Patients were evaluated at the begin of the treatment and then monthly until the end of the study (90 days). The statistical analysis was performed by using the ANOVA for the analysis of variance.

RESULTS:

Statistically significant results were found in relation to pelvic pain, dysmenorrhea and dyspareunia compared to the initial evaluation of patients. Results related to dysuria and dischezia were not statistically significant (P>0.05). The decrease in pelvic pain leads to an improvement of the quality of life of patients. A decreased assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) was also observed.

CONCLUSION:

PEA could be considered an effective supplement to conventional analgesic therapies in the management of pelvic pain related to endometriosis.

 

 

Rev Med Liege. 2013 Jul-Aug;68(7-8):378-81.

Clinical case of the month. Rare case of ureteral endometriosis nine years after hysterectomy.

Bawin I1Troisfontaines ENisolle M.

 

Abstract

Ureteral endometriosis is a rare entity, especially when it occurs in the postmenopausal period. In certain circumstances, this severe disease can cause obstruction, leading to ureterohydronephrosis and, finally, to a progressive and often silent loss of renal function. The symptomatology is variable and non specific, making preoperative diagnosis difficult. The treatment is mainly surgical. Its aim is the relief of obstruction to preserve the renal function. We report the case of a 39 year old patient, hysterectomised for endometriosis nine years earlier, who developed a recurrence demonstrated by ureteral endometriosis and revealed by ureterohydronephrosis. Robot-assisted laparoscopic ureterolysis allowed a complete resection of the lesion and resolved the obstruction. No recurrence of ureterohydronephrosis was found at the fifth and ninth postoperative month ultrasonographic controls.

 

 

Int Braz J Urol. 2013 Jul-Aug;39(4):593-6.

Endoscopic management of ureteral calculus in a patient with ureterosigmoidostomy diversion.

Abreu LA1Lara CDionísio MAPelosi ADFigueiredo FA.

 

Abstract

Lithiasis after urinary diversion is an uncommon condition that poses therapeutic challenges. The authors report the case of a patient submitted to cystectomy and ureterosigmoidostomy 35 years ago due to bladder endometriosis. The patient presented with a ureteral stone and was treated by retrograde endoscopic extraction.

 

 

Fertil Steril. 2013 Dec;100(6):1735-9.

Association of blood type and patient characteristics with ovarian reserve.

Timberlake KS1Foley KLHurst BSMatthews MLUsadi RSMarshburn PB.

 

Abstract

OBJECTIVE:

To assess whether blood type was associated with diminished ovarian reserve (DOR) (day-3 follicle-stimulating hormone level >10 IU/L), controlling for history of tobacco smoking, body mass index (BMI), history of endometriosis, ovarian surgery, previous pregnancy, and maternal age.

DESIGN:

Cross-sectional study.

SETTING:

Academic medical center, Division of Reproductive Endocrinology and Infertility.

PATIENT(S):

Women undergoing in vitro fertilization (IVF) from 2006-2011 (n = 305).

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Presence of DOR in relation to a patient’s blood type.

RESULT(S):

Other investigators have reported an increased risk for DOR in patients with blood type O and a protective effect on ovarian reserve for blood type A. We observed no association between a woman’s blood type and DOR. We found an increased risk for DOR in patients aged 35 and older. Obesity (BMI ≥ 30 vs. BMI <25) was associated with lower odds of DOR.

CONCLUSION(S):

In comparison with blood type A, blood type O is not associated with an increase in DOR. We found no clinical implications for using blood type as a risk factor for DOR.

 

 

Reprod Biomed Online. 2013 Nov;27(5):515-29.

Tissue and circulating microRNA influence reproductive function in endometrial disease.

Hull ML1Nisenblat V.

 

Abstract

microRNA (miRNA) have emerged as important epigenetic modulators of gene expression in diverse pathological and physiological processes. In the endometrium, miRNA appear to have a role in the dynamic changes associated with the menstrual cycle, in implantation and in the pathophysiology associated with reproductive disorders such as recurrent miscarriage and endometriosis. This review explores the role of miRNA in endometrial physiology and endometrial disorders of reproduction and also raises the prospect that circulating miRNA may modulate endometrial function or reflect disordered endometrial activity. The clinical potential to use miRNA in diagnostic tests of endometrial function or in the treatment of endometrial disorders will also be discussed.

 

 

Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Jul;44(4):677-80.

Efficiency of postoperative ovulation induction on infertile women with minimal-mild endometriosis.

Gong J1Chen LZhang D.

 

Abstract

OBJECTIVE:

To investigate the efficacy of timely ovulation induction on Infertility women with minimal-mild endometriosis (EMS) after laparoscopy combined with hysteroscopy.

METHODS:

A randomized controlled trial was performed on 132 infertility women diagnosed with minimal-mild EMS according to r-AFS by laparoscopy. They were divided into two groups after operations. The experimental group (n = 68) was administrated timely ovulation induction with clomiphene citrate tablets at the first menstrual cycle post-operation and given conceive guidance. The control group (n = 64) was treated with expectant treatment only. All the patients were followed up for 18 months after the surgery. Pregnancy rates and pregnancy outcomes within 1 year post-operation were compared between the two groups.

RESULTS:

During the follow up period, there were 6 cases lost. At 3 months after surgery, pregnancy rates (PR) in the experimental group and the control group were 37.88%, 21.67% respectively; the PR at 4-6 months were 29.27%, 19.15% in the two groups respectively. The less-than-6-months PR in the experimental group (56.06%) was significantly higher than that of the control group (36.67%) (P < 0.05), and also higher than the PR of 7-12 months post-operation in the same group (P < 0.05). Significant difference was found for the abortion rate between the ovulation induction group (12.19%) and the control group (26.92%) (P < 0.05).

CONCLUSION:

Timely ovulation induction after laparoscopic surgery combined with hysteroscopy could significantly increase pregnancy rate and reduce abortion rate in infertility patients with minimal-mild endometriosis.

 

 

 

Clin Sci (Lond). 2014 Jan;126(2):123-38.

Genetic, epigenetic and stem cell alterations in endometriosis: new insights and potential therapeutic perspectives.

Forte A1Cipollaro MGalderisi U.

 

Abstract

Human endometrium is a highly dynamic tissue, undergoing periodic growth and regression at each menstrual cycle. Endometriosis is a frequent chronic pathological status characterized by endometrial tissue with an ectopic localization, causing pelvic pain and infertility and a variable clinical presentation. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation in approximately 1.0% of affected women, with the involvement of multiple pathways of development. Increasing evidence supports a key contribution of different stem/progenitor cell populations not only in the cyclic regeneration of eutopic endometrium, but also in the pathogenesis of at least some types of endometriosis. Evidence has arisen from experiments in animal models of disease through different kinds of assays (including clonogenicity, the label-retaining cell approach, the analysis of undifferentiation markers), as well as from descriptive studies on ectopic and eutopic tissue samples harvested from affected women. Changes in stem cell populations in endometriotic lesions are associated with genetic and epigenetic alterations, including imbalance of miRNA expression, histone and DNA modifications and chromosomal aberrations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem/progenitor cells in eutopic endometrium and the aetiology of endometriosis, together with a report of the most recently identified genetic and epigenetic alterations in endometriosis. We also describe the potential advantages of single cell molecular profiling in endometrium and in endometriotic lesions. All these data can have clinical implications and provide a basis for new potential therapeutic applications.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Dec;171(2):319-24.

Effect of carbon dioxide pneumoperitoneal pressure on the ultrastructure of implanted endometriotic lesions in a rat model.

Chen X1Liu HFeng LLiu Y.

 

Abstract

OBJECTIVE:

To evaluate the effect of carbon dioxide (CO2) pneumoperitonal pressure on the ultrastructure of implanted endometriotic lesions in a rat model.

STUDY DESIGN:

An endometriotic model was established in Sprague-Dawley rats with peritoneal implantation of their own endometrial tissue to form ectopic endometrial tissue. Thirty rats were divided at random into three groups: control group, 10 mmHg CO2 pneumoperitoneum group and 20 mmHg CO2 pneumoperitoneum group. CO2 inflation lasted for 1 h in both pneumoperitoneum groups. Selected endometriotic lesions were examined by electron microscopy 1 week after CO2 pneumoperitoneum to determine changes in the ultrastructure of cell organelles of glandular and stromal cells.

RESULTS:

In the control group, stromal cells had an orderly arrangement, and the structure of the microvilli was normal. The 10 mmHg and 20 mmHg CO2 pneumoperitoneum groups had increased chromatin margination of glandular epithelial cells, reduced or absent mitochondrial cristae and mitochondrial swelling. Further ultrastructural damage included reduced or absent microvilli, widened or collapsed cell junctions, and stromal cells with a disorderly arrangement. Ultrastructural damage of glandular epithelial cells was more severe in the 20 mmHg group compared with the 10 mmHg group.

CONCLUSION:

CO2 pneumoperitoneum leads to significant ultrastructural damage of endometriotic lesions. Higher CO2 pneumoperitoneal pressure resulted in more damage than lower CO2 pneumoperitoneal pressure.

 

Endocrinology. 2013 Dec;154(12):4803-13.

PPARγ activation inhibits growth and survival of human endometriotic cells by suppressing estrogen biosynthesis and PGE2 signaling.

Lebovic DI1Kavoussi SKLee JBanu SKArosh JA.

 

Abstract

Endometriosis is a chronic inflammatory disease of reproductive age women leading to chronic pelvic pain and infertility. Current antiestrogen therapies are temporizing measures, and endometriosis often recurs. Potential nonestrogenic or nonsteroidal targets are needed for treating endometriosis. Peroxisome proliferator-activated receptor (PPAR)γ, a nuclear receptor, is activated by thiazolidinediones (TZDs). In experimental endometriosis, TZDs inhibit growth of endometriosis. Clinical data suggest potential use of TZDs for treating pain and fertility concurrently in endometriosis patients. Study objectives were to 1) determine the effects of PPARγ action on growth and survival of human endometriotic epithelial and stromal cells and 2) identify the underlying molecular links between PPARγ activation and cell cycle regulation, apoptosis, estrogen biosynthesis, and prostaglandin E2 biosynthesis and signaling in human endometriotic epithelial and stromal cells. Results indicate that activation of PPARγ by TZD ciglitazone 1) inhibits growth of endometriotic epithelial cells 12Z up to 35% and growth of endometriotic stromal cells 22B up to 70% through altered cell cycle regulation and intrinsic apoptosis, 2) decreases expression of PGE2 receptors (EP)2 and EP4 mRNAs in 12Z and 22B cells, and 3) inhibits expression and function of P450 aromatase mRNA and protein and estrone production in 12Z and 22B cells through EP2 and EP4 in a stromal-epithelial cell-specific manner. Collectively, these results indicate that PGE2 receptors EP2 and EP4 mediate actions of PPARγ by incorporating multiple cell signaling pathways. Activation of PPARγ combined with inhibition of EP2 and EP4 may emerge as novel nonsteroidal therapeutic targets for endometriosis-associated pain and infertility, if clinically proven safe and efficacious.

 

 

Int J Mol Med. 2013 Dec;32(6):1394-400.

Vitamin D binding protein plays an important role in the progression of endometriosis.

Hwang JH1Wang TLee KSJoo JKLee HG.

 

Abstract

Endometriosis, characterized by the growth of the endometrial gland and stroma outside the uterine cavity, is a gynecological disorder affecting 6‑10% of women of reproductive age. However, the pathogenesis of endometriosis and the molecular mechanisms involved in the progression of this disease remain to be clarified. Therefore, in this study two-dimensional gel electrophoresis (2‑DE) combined with mass spectrometry (MS) were applied to explore endometrial proteins with a role in the progression of endometriosis. Expression of global proteins in ectopic endometrial tissue (n=13; endometriosis group) was compared with that of the normal endometrial tissue (n=6; control group). Sixteen differently expressed proteins, including Vitamin D binding protein (DBP), with various functions were primarily identified in the ectopic endometrial tissue. DBP was confirmed to be significantly increased in the ectopic endometrial tissue compared with that in the normal endometrial tissue (P<0.05). Results of the present study therefore showed that DBP may play an important role in the progression of endometriosis.

 

 

J Clin Endocrinol Metab. 2013 Dec;98(12):E1871-9.

Increased AKT or MEK1/2 activity influences progesterone receptor levels and localization in endometriosis.

Eaton JL1Unno KCaraveo MLu ZKim JJ.

 

Abstract

CONTEXT:

Endometriosis is characterized by progesterone resistance and hyperactivity of the AKT and MAPK pathways. Kinases can cause posttranslational modifications of the progesterone receptor (PR) to influence cellular localization and protein stability.

OBJECTIVE:

The objective of this study was to determine whether the increased AKT or MAPK kinase-1/2 (MEK1/2) activity observed in endometriotic stromal cells (OSIS) from ovarian endometriomas influences levels of PR protein. In turn, the effects of inhibiting AKT or MEK1/2 in the presence of the progestin R5020 on cell viability were investigated.

RESULTS:

Inhibiting AKT with MK-2206 or MEK1/2 with U0126 for 24 hours in the absence of R5020 increased total and nuclear PRA and PRB protein levels in OSIS but not in eutopic endometrial stromal cells from disease-free patients from disease-free patients. MK-2206 and R5020 decreased OSIS viability and increased apoptosis. Trends toward decreased volumes of sc grafted endometriosis tissues were demonstrated with MK-2206 and progesterone.

CONCLUSIONS:

Inhibition of AKT or MEK1/2 increased total and nuclear PR protein in OSIS. MK-2206 and R5020 decreased OSIS viability and increased apoptosis. The AKT and MAPK pathways may be potential molecular targets for the treatment of endometriosis.

 

Menopause. 2014 May;21(5):442-9.

Incidence, time trends, laterality, indications, and pathological findings of unilateral oophorectomy before menopause.

Laughlin-Tommaso SK1Stewart EAGrossardt BRRocca LGRocca WA.

 

Abstract

OBJECTIVE:

Unilateral oophorectomy (UO) is a common surgical practice, yet it remains understudied. We investigated trends in incidence rates, indications, and pathological differences in the right and left ovaries in women younger than 50 years.

METHODS:

The Rochester Epidemiology Project medical records linkage system was used to identify all women in Olmsted County, MN, who underwent UO between 1950 and 2007 (n = 1,838). We studied the incidence rates, indications, and pathologies of UO by laterality, and investigated trends across time.

RESULTS:

Pooling all oophorectomies across a 58-year period, we found that the incidence of UO was higher than the incidence of bilateral oophorectomy through the age of 39 years; however, bilateral oophorectomy surpassed UO thereafter. The incidence of UO increased from 1950 to 1974 but decreased thereafter and was surpassed by the rate of bilateral oophorectomy after 1979. Before 1985, left ovaries were removed more frequently than right ovaries with or without a medical indication for UO. Ovaries removed with a medical indication showed pathological differences between the right ovary and the left ovary, with endometriosis being more common in the left ovary. Ovaries removed without a medical indication did not differ in pathology by side.

CONCLUSIONS:

There have been major changes in incidence rates of UO across six decades. Medically indicated UO has been more common on the left side due, in part, to the higher prevalence of endometriosis. However, UO without a medical indication has also been more common on the left side because of surgical preferences and traditions. The long-term consequences of right or left UO on timing of menopause, morbidity, and mortality need further study.

 

 

Reprod Biol Endocrinol. 2013 Sep 26;11:94.

Expression of the gamma 2 chain of laminin-332 in eutopic and ectopic endometrium of patients with endometriosis.

Locci R1Nisolle MAngioni SFoidart JMMunaut C.

 

Abstract

BACKGROUND:

Endometrial cells, which are shed by retrograde menstruation, may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to investigate the expression of the laminin gamma 2 chain (LAMC2) in the tissues of women with and without endometriosis.

METHODS:

Endometrial biopsy specimens were collected from healthy volunteers and from endometriosispatients. Biopsy specimens from the corresponding endometriotic lesions were also collected. The expression of laminin gamma 2 chain was evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).

RESULTS:

Endometrial tissue from women with or without endometriosis showed constitutive expression of LAMC2 mRNA throughout the menstrual cycle. A higher mRNA level was observed in ectopic endometrium (Ec) from women with endometriosis compared with eutopic endometrium (Eu) from women with endometriosis. Immunohistochemistry revealed a varied pattern of laminin gamma 2 chain expression, with increased epithelial expression in eutopic endometrium from women with endometriosis compared with those without endometriosis.

CONCLUSIONS:

The altered expression of laminin gamma 2 chain in eutopic endometrium from women with endometriosis may provide new opportunities for diagnosis and treatment.

 

Abdom Imaging. 2014 Feb;39(1):92-107

Imaging female infertility.

Sadow CA1Sahni VA.

 

Abstract

The purpose of this pictorial review is to discuss causes of female infertility, in particular, those etiologies in which imaging plays a key role in detection. Included are disorders of cervical, ovarian, fallopian tube, and uterine origin. We also discuss the role of various imaging modalities including hysterosalpingography, pelvic ultrasonography, hysterosonography, and pelvic MR imaging in elucidating the cause of female infertility. Radiologists need to know the conditions to be aware of when these patients are sent for diagnostic imaging, as well as how to direct further management, if necessary, should an abnormality be detected.

 

 

Am J Epidemiol. 2013 Aug 15;178(4):665-6.

Managing female sexual dysfunction.

Buster JE1.

 

Abstract

Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article’s most important note: how to initiate the conversation.

 

 

J Minim Invasive Gynecol. 2014 Mar-Apr;21(2):285-90.

Fast-track surgery in intestinal deep infiltrating endometriosis.

Kondo W1Ribeiro R2Zomer MT3.

 

Abstract

STUDY OBJECTIVE:

To evaluate the length of hospital stay (LOS) and the readmission rate in patients undergoing laparoscopic surgery to treat intestinal deep infiltrating endometriosis (DIE) with application of the concepts of fast-track surgery.

DESIGN:

Retrospective study of women undergoing laparoscopic treatment of intestinal DIE (Canadian Task Force classification II-3).

SETTING:

Tertiary referral private hospital.

INTERVENTIONS:

We evaluated 161 women who underwent laparoscopic surgery between January 2010 and April 2013 for complete treatment of intestinal DIE, via either conservative surgery (rectal shaving, mucosal skinning, or anterior disk resection) or radical surgery (segmental bowel resection). After surgery, all specimens were sent for pathologic examination to confirm the presence of endometriosis.

MEASUREMENTS AND MAIN RESULTS:

Patients were divided into 2 groups according to type of surgery (conservative [n = 102] or radical [n = 59]), and LOS and readmission rate were measured in both groups. Median LOS was shorter in the conservative group compared with the segmental bowel resection group (19 vs 28 hours; p < .001). Ninety-two patients (90.2%) in the conservative surgery group were discharged to home on the first postoperative day, compared with only 38 patients (64.4%) in the segmental bowel resection group. Overall, the readmission rate was low (3.1%): 6.8% in the segmental bowel resection group and 1% in the conservative group (p = .04; odds ratio, 7.34; 95% confidence interval, 0.8-67.3); however, the need for repeat operation was similar in both groups (3.4% vs 1%; p = .28; odds ratio, 3.54; 95% confidence interval, 0.31-39.95).

CONCLUSION:

Implementation of fast-track concepts in the laparoscopic treatment of intestinal DIE resulted in a short LOS and low readmission rate in both the segmental bowel resection and conservative surgery groups.

 

 

J Minim Invasive Gynecol. 2014 Mar-Apr;21(2):266-71.

Effect of vasopressin injection technique in laparoscopic excision of bilateral ovarian endometriomas on ovarian reserve: prospective randomized study.

Qiong-Zhen R1Ge Y2Deng Y3Qian ZH4Zhu WP4.

 

Abstract

STUDY OBJECTIVE:

To evaluate the effects of vasopressin injection technique in laparoscopic cystectomy on ovarian reserve in patients with bilateral endometriomas.

DESIGN:

Randomized prospective study (Canadian Task Force classification I).

SETTING:

University hospital.

PATIENTS:

Eighty-six women with bilateral endometriomas.

INTERVENTIONS:

Laparoscopic cystectomy of bilateral endometriomas was performed using different techniques including laparoscopic cystectomy by stripping without injection (control group), laparoscopic cystectomy by stripping with injection of saline solution (saline group), and laparoscopic cystectomy by stripping with vasopressin injection technique (VIT group).

MEASUREMENTS AND MAIN RESULTS:

The number of coagulation events on the ovarian cortex for hemostasis was counted in different groups, and the thickness of ovarian tissues removed was measured. The basal follicle-stimulating hormone (FSH) level was determined before surgery and at 3-, 6-, and 12-month follow-up after laparoscopic cystectomy in the different groups. In the saline group, fewer coagulation events were required to achieve hemostasis, less ovarian tissues were removed, and lower preoperative FSH levels were detected than in the control group (p < .01). In the VIT group, even fewer coagulation events (p < .01) and lower preoperative FSH levels (p < .01) were detected than in the saline group. There was no significant difference in the thickness of ovarian tissues removed in the 2 groups (p > .05). Basal FSH levels were significantly different before and after surgery in the control and saline groups (p < .01) but not in the VIT group (p > .05).

CONCLUSION:

Vasopressin injection is an ideal procedure to reduce damage from usual laparoscopic cystectomy of bilateral ovarian endometriomas to protect ovarian reserve.

 

 

BMJ Case Rep. 2013 Sep 30;2013.

Uterine duplicity without communication between both hemiuteri and cervicovaginal atresia: importance of a thorough diagnosis before treatment.

Martínez-Escoriza JC1Palacios-Marqués AOliva-García ABBallester-Galiana H.

 

Abstract

The study described diagnostic and therapeutic processes for an exceptional congenital female genital anomaly involving a 15-year-old girl with progressive dysmenorrhoea and intense abdominal pain, and analyses pathogenesis of embryological anomalies associated with uterine duplicity (UD). Diagnostic methodology is analysed; treatment is described; and recommendations are provided. For the study of anomalies such as UD, we recommend the use of an ultrasound, vaginoscopy, MRI and laparoscopy imaging. Keeping in mind that hemihysterectomy should only be performed in cases with endometriosis or other unusual circumstances, surgical treatment should be avoided. A complete study based on gynaecological examination and ultrasound should be performed in adolescents with severe and progressive dysmenorrhoea. Based on the findings, imaging tests such as MRI and, if necessary, laparoscopy coinciding with menstruation, should be conducted before opting for surgical treatment.

 

 

Childs Nerv Syst. 2014 Apr;30(4):717-21.

Functional müllerian tissue within the conus medullaris generating cyclical neurological morbidity in an otherwise healthy female.

Scott WW1Ray BRickert KLMadden CJRaisanen JMMendelsohn DRogers DWhitworth TA.

 

Abstract

PURPOSE:

Endometriosis is a common disease; however, ectopic müllerian tissue within the spine is a rare entity with the potential for producing significant neurological compromise. There are several postulated etiologies for this phenomenon, and only a few case reports are available in the world literature. Knowledge of this rare phenomenon is of paramount importance, since early diagnosis can lead to lessened neurological morbidity.

METHODS:

In this manuscript, we present a case report, discuss gynecological and neurosurgical perspectives relating to the treatment strategies for managing this entity, and propose an alternative explanation for such an occurrence from a neurogenetic standpoint.

RESULTS:

We present a case of spinal müllerianosis within the conus medullaris which was managed symptomatically for several years with an intracystic drain and subcutaneous reservoir. Over the years, it became clear that there was a cyclical presentation to her clinical malady, which at times was severe. Ultimately, she required surgical resection which aided in her diagnosis and subsequent treatment.

CONCLUSION:

Intraspinal müllerianosis is a rare location for an otherwise common disease in women and has the potential to create significant neurological morbidity by creating a mass lesion. Although the exact etiology remains unclear, the histogenic theories of embryologic origin appear most plausible. Treatment strategies for this condition may include hormonal therapy, obstetrical surgery, or open spinal surgery. This unusual and poorly understood disease should be considered in the differential diagnosis for intraspinal lesions presenting with hemorrhage in the clinical context of cyclical neurological symptoms.

 

 

PLoS One. 2013 Sep 24;8(9):e75282.

Extracellular signal-regulated kinase 1/2 signaling pathway is required for endometrial decidualization in mice and human.

Lee CH1Kim THLee JHOh SJYoo JYKwon HSKim YIFerguson SDAhn JYKu BJFazleabas ATLim JMJeong JW.

 

Abstract

Decidualization is a crucial change required for successful embryo implantation and the maintenance of pregnancy. During this process, endometrial stromal cells differentiate into decidual cells in response to the ovarian steroid hormones of early pregnancy. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) are known to regulate cell proliferation and apoptosis in multiple cell types, including uterine endometrial cells. Aberrant activation of ERK1/2 has recently been implicated in the pathological processes of endometriosis and endometrial cancer. However, the function of ERK1/2 signaling during implantation and decidualization is still unknown. To determine the role and regulation of ERK1/2 signaling during implantation and decidualization, we examine ERK1/2 signaling in the mouse uterus during early pregnancy using immunostaining and qPCR. Interestingly, levels of phospho-ERK1/2 were highest within decidual cells located at the implantation sites. Expression levels of ERK1/2 target genes were also significantly higher at implantation sites, when compared to either inter-implantation sites. To determine if ERK1/2 signaling is also important during human endometrial decidualization, we examined levels of phospho-ERK1/2 in cultured human endometrial stromal cells during in vitro decidualization. Following treatment with a well-established decidualization-inducing steroidogenic cocktail, levels of phospho-ERK1/2 were markedly increased. Treatment with the ERK1/2 inhibitor, U0126, significantly decreased the expression of the known decidualization marker genes, IGFBP1 and PRL as well as inhibited the induction of known ERK1/2 target genes; FOS, MSK1, STAT1, and STAT3. Interestingly, the phosphorylation level of CCAAT/ enhancer binding protein β (C/EBPβ), a protein previously shown to be critical for decidualization, was significantly reduced in this model. These results suggest that ERK1/2 signaling is required for successful decidualization in mice as well as human endometrial stromal cells and implicates C/EBPβ as a downstream target of ERK1/2.

 

 

Biomed Res Int. 2013;2013:564153.

Clinical prediction of deeply infiltrating endometriosis before surgery: is it feasible? A review of the literature.

Carneiro MM1Filogônio IDCosta LMde Ávila IFerreira MC.

 

Abstract

BACKGROUND:

Endometriosis is a chronic benign gynecologic disease that can cause pelvic pain and infertility affecting almost 10% of reproductive-age women. Deeply infiltrating endometriosis (DIE) is a specific entity responsible for painful symptoms which are related to the anatomic location of the lesions. Definitive diagnosis requires surgery, and histological confirmation is advisable. The aim of this paper is to review the current literature regarding the possibility of diagnosing DIE accurately before surgery. Despite its low sensitivity and specificity, vaginal examination and evaluation of specific symptoms should not be completely omitted as a basic diagnostic tool in detecting endometriosis and planning further therapeutic interventions. Recently, transvaginal ultrasound (TVUS) has been reported as an excellent tool to diagnose DIE lesions in different locations (rectovaginal septum, retrocervical and paracervical areas, rectum and sigmoid, and vesical wall) with good accuracy.

CONCLUSION:

There are neither sufficiently sensitive and specific signs and symptoms nor diagnostic tests for the clinical diagnosis of DIE, resulting in a great delay between onset of symptoms and diagnosis. Digital examination, in addition to TVS, may help to gain better understanding of the anatomical extent and dimension of DIE which is of crucial importance in defining the best surgical approach.

 

 

Chest. 2014 Feb;145(2):354-360.

Pneumothorax in women of child-bearing age: an update classification based on clinical and pathologic findings.

Legras A1Mansuet-Lupo A2Rousset-Jablonski C3Bobbio A1Magdeleinat P1Roche N4Regnard JF1Gompel A3Damotte D2Alifano M5.

 

Abstract

BACKGROUND:

A significant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known.

METHODS:

Clinical and pathologic records of all consecutive women of reproductive age operated on for pneumothorax between 2000 and 2011 were retrospectively reviewed.

RESULTS:

Two hundred twenty-nine women (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed pelvic endometriosis was associated in 29 cases. At pathology, thoracic endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of 54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis were positive for progesterone and/or estrogen receptors (intense and nuclear). Catamenial pneumothoraces (n = 80, 34.9%) were endometriosisrelated in 50% of cases (n = 40, 17% of the whole population). Pneumothoraces were noncatamenial but endometriosis related in 6% of cases (n = 14) and merely idiopathic in 60% of patients (n = 135). Multivariate analysis showed that right side, presence of diaphragmatic abnormalities, relapse after unilateral surgery, and presence of hemosiderin-laden macrophages were independent variables associated with thoracic endometriosis(all, P &lt; .02). Apical emphysema-like changes were found in 184 of the 213 patients (86%) with apical resection and were significantly associated with the absence of thoracic endometriosis (P &lt; .001).

CONCLUSIONS:

In women with surgically treated pneumothorax, prevalence of catamenial/endometriosis-related pneumothorax is high. Clinicians and pathologists must be aware to recognize such a difficult diagnosis.

 

 

MSMR. 2013 Sep;20(9):20-4.

Menorrhagia, active component service women, U.S. Armed Forces, 1998-2012.

Dorsey KA.

Abstract

Menorrhagia (excessive menstrual bleeding) is relatively common among women of reproductive age and may be caused by a wide range of different conditions. Menorrhagia symptoms can interfere with work and quality of life and may result in iron deficiency anemia due to chronic blood loss. This analysis of active component service women of the U.S. Armed Forces found that, during the surveillance period of 1998 through 2012, the crude incidence rate of menorrhagia was 6.2 cases per 1,000 person years. Annual incidence rates rose steadily throughout the period. Compared to their respective counterparts, rates were highest in women who were aged 40 to 49 or were of black, non-Hispanic ethnicity. Among women with menorrhagia whose records documented co-ocurring conditions, the most common such conditions were uterine disorders (e.g., fibroids) and ovarian cysts. Less than one percent of cases had underlying bleeding disorders documented. Of women hospitalized with the diagnosis of menorrhagia, 79 percent underwent hysterectomy during their hospitalizations. Limitations of the analysis and possible future studies are discussed.

 

 

Reprod Sci. 2014 May;21(5):582-9.

Human ovarian tissue cortex surrounding benign and malignant lesions.

Pavone ME1Hirshfeld-Cytron JTingen CThomas CThomas JLowe MPSchink JCWoodruff TK.

 

Abstract

OBJECTIVE:

To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts.

MATERIALS AND METHODS:

Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer. In all, 10 women were either pregnant or immediately postpartum.

RESULTS:

Patients undergoing risk-reducing surgery had significantly decreased follicle count compared to physiologic control. Patients with cancer had significantly decreased counts compared to all other groups. There were no differences within the benign cohort.

CONCLUSIONS:

When compared to benign masses, the cortex surrounding an ovarian malignancy has decreased follicle density. The stretch impact may minimize any impact on total follicle numbers. Furthermore, there may be a proliferation of ovarian stroma, with the same number of follicles spread over a larger surface area. This information is important when counseling women with ovarian masses regarding the use of ovarian tissue cryopreservation.

 

 

 

J Obstet Gynaecol Res. 2014 Jan;40(1):230-6.

Recurrence of ovarian endometrioma after laparoscopic excision: risk factors and prevention.

Ouchi N1Akira SMine KIchikawa MTakeshita T.

 

Abstract

AIM:

The aim of this study was to assess the cut-off age of the risk factors for postoperative recurrence of ovarian endometriomas and to evaluate the end-points of follow-up after laparoscopic excision of ovarian endometriomas.

MATERIAL AND METHODS:

We retrospectively reviewed 167 patients who underwent laparoscopic excision of ovarian endometriomas at our hospital between 2000 and 2009, and followed up the patients until 2010. Following surgery, patients chose to receive gonadotrophin-releasing hormone agonist, oral contraceptive pills (OCP), dienogest, or no medication and underwent regular ultrasonographic examinations. Potential risk factors for recurrence, including age at surgery, were assessed in the patients receiving no medication. Postoperative recurrence, defined as re-appearance of an ovarian endometrioma > 2 cm in size, was assessed for each treatment group.

RESULTS:

Age at surgery was the only significant risk factor for recurrence, at a cut-off of 32 years, obtained through receiver-operator curve analysis. In patients not receiving medication, the recurrence rate gradually increased up to 50% over 5 years; there was no recurrence 5 years after surgery. Although no recurrence was seen in patients during continuous treatment with OCP or dienogest, the disease recurred in 55.5% of patients after discontinuing OCP.

CONCLUSIONS:

Although adjuvant therapy for all patients may represent overtreatment, the findings of the present study suggest that, in the interest of fertility preservation, continuous postoperative hormonal treatment should be administered, at least to patients younger than 32 years. In patients who decline hormonal treatment, we recommend that they undergo follow-up for recurrence until 5 years after surgery.

 

 

 

Zhonghua Fu Chan Ke Za Zhi. 2013 Jun;48(6):447-52.

Role of epidermal growth factor signaling system in the pathogenesis of endometriosis under estrogen deprivation conditions.

Wang YQ1Yin LRGuo RMSheng W.

 

Abstract

OBJECTIVE:

To study the role of epidermal growth factor (EGF) , epidermal growth factor receptor(EGFR), extracellular signal-regulated kinase 1/2 (p-ERK1/2) in the pathogenesis of endometriosis under estrogen deprivation conditions.

METHODS:

The estrogen was quickly-stripped in medium and the female nude mice were castrated by bilateral oophorectomy to build estrogen deprivation in vitro and in vivo experimental models, respectively. (1) In vitro experiments:according to different treatments the estrogen deprived ectopic endometrial cells were classified into 4 groups: a. EGF group:the ectopic endometrial cells were cultured for 72 hours with different concentrations of EGF (0.01, 0.1, 1, 10, 50, 100 ng/ml), the results of EGF group were represented by the result of cells treated by 10 ng/ml EGF cultured for 72 hours; b. EGF+PD98059 group:the ectopic endometrial cells were cultured for 72 hours with 5×10(-2) mol/L PD98059 (inhibitor of ERK), followed by a cultivation for 72 hours treated by 10 ng/ml EGF+5×10(-2) mol/L PD98059; c. EGF+ ICI182780 group: the ectopic endometrial cells were cultured for 72 hours with 10(-6) mol/L ICI182780 [inhibitor of estrogen receptor(ER)], followed by a cultivation for 72 hours treated by 10 ng/ml EGF+10(-6) mol/L ICI182780; d. Blank control group:the ectopic endometrial cells were cultured with no treatment. The proliferation activity of ectopic endometrial cells in all groups after treatment were examined by methyl thiazolyl tetrazolium (MTT) method represented by absorbance value (A). The expression of p-ERK1/2 protein were detected by western blot. (2) In vivo experiments: 64 female nude mice were randomly divided into control and castration groups (both n=32) using random number chart. The mice in castration group were castrated by bilateral oophorectomy on 3 weeks after the endometriosis model was established. The levels of EGF, EGFR, p-ERK1/2 protein in ectopic lesions of both groups were measured on 4, 6, 8 and 10 weeks after the endometriosis model was established by western blot.

RESULTS:

(1) The proliferation activity of ectopic endometrial cells:the proliferation activity of ectopic endometrial cells treated by different concentrations of EGF (0.01, 0.1, 1, 10, 50, 100 ng/ml) for 72 hours were 0.310±0.010, 0.340±0.020, 0.670±0.010, 0.980±0.030, 1.360±0.020, 1.670±0.020, respectively, the proliferation activity was increased along with of EGF concentrations.The proliferation activity was 0.680±0.030 at EGF+ PD98059 group, the differences exhibited significant difference when compared with that at EGF group with 100 ng/ml for 72 hours (P<0.01) .The proliferation activity of EGF+ ICI182780 and blank control groups were 0.330±0.030 and 0.310±0.030, respectively, which did not reached statistical differences (P>0.05). (2) The expression of EGF, EGFR, pERK1/2 protein: a. In vitro experiments:the levels of p-ERK1/2 protein in EGF and blank control groups were 0.670±0.020 and 0.600±0.010, respectively, which reached statistical differences (P<0.05). The level of p-ERK1/2 protein in EGF+ PD98059 group was 0.610±0.020, which exhibited significant differences with that at blank control group (P>0.05). b. In vivo experiments:at 4, 6 and 8 weeks after the endometriosis models were established, the expression of EGF protein in the ectopic lesions of castration group and control group were (0.530±0.015 versus 0.610±0.015), (0.400±0.029 versus 0.620±0.018), (0.560±0.026 versus 0.630±0.021), respectively, the levels of EGFR protein were (0.500±0.030 versus 0.640±0.030), (0.470±0.020 versus 0.630±0.020), (0.510±0.030 versus 0.610±0.020) respectively, and the level of p-ERK1/2 protein were (0.500±0.020 versus 0.580±0.020), (0.490±0.020 versus 0.580±0.020), (0.570±0.020 versus 0.590±0.020), respectively. The difference of EGF, EGFR, p-ERK1/2 protein expression levels between two groups did not exhibited significant difference (P<0.01, P<0.01, P<0.05). At 10 weeks after the endometriosis models were established, the levels of EGF protein in castration group and control group were both 0.620±0.020, the levels of EGFR protein were both 0.610±0.020, and the level of p-ERK1/2 protein were 0.590±0.010 and 0.600±0.020. No statistical difference (P>0.05) was found between those two groups (P>0.05).

CONCLUSIONS:

EGF could stimulate the proliferation of ectopic endometrial cells by activating the ERK pathway under estrogen deprivation conditions. The inhibition of EGF signaling system in ectopic lesions was alleviated along with the prolongation of the period of estrogen deprivation.

 

 

 

Ned Tijdschr Geneeskd. 2013;157(41):A5421.

Van Heerden: the first female doctor in South Africa.

Lammes FB1.

 

Abstract

Petronella van Heerden (1887-1975) was born in South Africa. She studied medicine in Amsterdam from 1908 to 1915 and then worked as the first female doctor in her native country for 4 years before specialising in gynaecology in London. She then returned to Amsterdam, where she gained a PhD in 1923 on a thesis on endometriosis that was written in Afrikaans. She settled in Cape Town and participated in many political and emancipatory activities alongside her work as a doctor. She wrote two autobiographies.

 

Eur J Obstet Gynecol Reprod Biol. 2013 Dec;171(2):329-32.

Role of the aromatase inhibitor letrozole in the management of uterine leiomyomas in premenopausal women.

Duhan N1Madaan SSen J.

 

Abstract

BACKGROUND:

Uterine myomas are benign tumours affecting 20-40% women. Various medical and surgical therapeutic options are available but the search for an ideal medical option continues. Aromatase inhibitors have recently been reported to have a potential role in the management of oestrogen-dependent conditions like endometriosis and leiomyoma.

OBJECTIVE:

To evaluate the effect of letrozole on uterine myoma size and symptomatology in perimenopausal women.

STUDY DESIGN:

Prospective interventional study conducted on 30 premenopausal women aged between 30 and 55 years with menstrual or pressure symptoms and having a single intrauterine myoma of size 4 cm or more with or without one or more additional myomata each of size 2 cm or less. They received tablet letrozole 2.5 mg a day for 12 weeks, and the effect of the drug on myoma size and volume and symptomatology was studied along with the adverse effect profile and patient satisfaction.

RESULTS:

The mean myoma size reduced from 5.4±1.3 cm to 4.3±0.9 cm (p<0.05) and the myoma volume exhibited a reduction of 52.45% (p=0.00) at the end of 3 months. The symptomatology score showed a significant improvement that persisted up to 3 months after cessation of therapy. No significant effect was observed on lipid profile, serum estradiol, progesterone, testosterone and FSH and LH levels during the therapy. Nausea and hot flushes were the main adverse effects observed and were self-limiting.

CONCLUSION:

Letrozole significantly reduces myoma size and volume and also improves the associated symptoms. It has a good adverse effect profile and appears to be a promising medical option for management of uterine myomas.

 

 

 

Obstet Gynecol. 2013 Nov;122(5):1047-55.

Increased pressure pain sensitivity in women with chronic pelvic pain.

As-Sanie S1Harris REHarte SETu FFNeshewat GClauw DJ.

 

Abstract

OBJECTIVE:

To determine whether women with chronic pelvic pain and variable degrees of endometriosisdemonstrate altered pain sensitivity relative to pain-free healthy women in a control group and whether such differences are related to the presence or severity of endometriosis or comorbid pain syndromes.

METHODS:

Four patient subgroups (endometriosis with chronic pelvic pain [n=42], endometriosis with dysmenorrhea [n=15], pain-free endometriosis [n=35], and chronic pelvic pain without endometriosis [n=22]) were each compared with 30 healthy women in a control group in this cross-sectional study. All patients completed validated questionnaires regarding pain symptoms and underwent screening for comorbid pain disorders. Pain sensitivity was assessed by applying discrete pressure stimuli to the thumbnail using a previously validated protocol.

RESULTS:

While adjusting for age and education, pain thresholds were lower in all subgroups of women with pelvic pain relative to healthy women in the control group (all P values <.01). There was no difference in pain thresholds when comparing patients with endometriosis without pelvic pain with healthy women in the control group (mean difference 0.02 kg/m2, 95% confidence interval -0.43 to 0.47). The presence and severity of endometriosis and number of comorbid pain syndromes were not associated with a difference in pain thresholds.

CONCLUSION:

Women with chronic pelvic pain demonstrate increased pain sensitivity at a nonpelvic site compared with healthy women in a control group, which is independent of the presence or severity of endometriosis or comorbid pain syndromes. These findings support the notion that central pain amplification may play a role in the development of pelvic pain and may explain why some women with pelvic pain do not respond to therapies aimed at eliminating endometriosis lesions.

 

 

 

J Membr Biol. 2013 Dec;246(12):869-75.

Recent reports of Wi-Fi and mobile phone-induced radiation on oxidative stress and reproductive signaling pathways in females and males.

Nazıroğlu M1Yüksel MKöse SAÖzkaya MO.

 

Abstract

Environmental exposure to electromagnetic radiation (EMR) has been increasing with the increasing demand for communication devices. The aim of the study was to discuss the mechanisms and risk factors of EMR changes on reproductive functions and membrane oxidative biology in females and males. It was reported that even chronic exposure to EMR did not increase the risk of reproductive functions such as increased levels of neoantigens abort. However, the results of some studies indicate that EMR induced endometriosis and inflammation and decreased the number of follicles in the ovarium or uterus of rats. In studies with male rats, exposure caused degeneration in the seminiferous tubules, reduction in the number of Leydig cells and testosterone production as well as increases in luteinizing hormone levels and apoptotic cells. In some cases of male and female infertility, increased levels of oxidative stress and lipid peroxidation and decreased values of antioxidants such as melatonin, vitamin E and glutathione peroxidase were reported in animals exposed to EMR. In conclusion, the results of current studies indicate that oxidative stress from exposure to Wi-Fi and mobile phone-induced EMR is a significant mechanism affecting female and male reproductive systems. However, there is no evidence to this date to support an increased risk of female and male infertility related to EMR exposure.

 

 

Mol Carcinog. 2015 Jan;54(1):35-49.

Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma.

Okamoto T1Mandai MMatsumura NYamaguchi KKondoh HAmano YBaba THamanishi JAbiko KKosaka KMurphy SKMori SKonishi I.

 

Abstract

Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically distinct subtype of ovarian carcinomas that often arises in ovarian endometriosis. We previously reported that a unique carcinogenic environment, especially iron-induced oxidative stress in endometriotic cysts may promote development of OCCC. We also identified a gene expression profile characteristic of OCCC (the “OCCC signature”). This 320-gene OCCC signature is enriched in genes associated with stress response and sugar metabolism. However, the biological implication of this profile is unclear. In this study, we have focused on the biological role of the HNF-1β gene within the OCCC signature, which was previously shown to be overexpressed in OCCC. Suppression of HNF-1β in the HNF-1β-overexpressing human ovarian cancer cell line RMG2 using short hairpin RNA resulted in a significant increase in proliferation. It also facilitated glucose uptake, glycolytic activity, and lactate secretion along with increased expression of the glucose transporter-1 (GLUT-1) gene and several key enzymes in the glycolytic process. Conversely, forced expression of HNF-1β in the serous ovarian cancer cell line, Hey, resulted in slowed cellular growth and repressed glycolytic activity. These data suggest that HNF-1β represses cell growth, and at the same time, it promotes aerobic glycolysis which is known as the “Warburg effect.” As the Warburg effect is regarded as a characteristic metabolic process in cancer which may contribute to cell survival under hypoxic conditions or in a stressful environment, overexpression of HNF-1β may play an inevitable role in the occurrence of OCCC in stressful environment.

 

 

 

 

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