Minerva Ginecol. 2017 Aug;69(4):322-327.

Reproductive prognosis in women with endometriosis after conservative surgery: a single-center experience.

Cesana MC¹, Ferrari L², Passoni P², Polizzi S³, Brunetti F³, Milani R².

 

Abstract

BACKGROUND:

To evaluate the reproductive prognosis in women subjected to conservative surgical treatment for endometriosis seeking pregnancy during the first three years after surgery. We tried to identify operative findings which negative influences prognosis.

METHODS:

A total of 140 patients were retrospectively analyzed, who had a diagnosis of endometriosis, based on surgical and histological criteria and without other male or female infertility factors who underwent surgery between 01/2002 and 01/2012. For each patient, anatomic and surgical data, stage according to the revised classification of American Fertility Society (AFS), months of pregnancy research and the use of assisted reproductive technology (ART) after surgery were collected. A total of 109 patients had been diagnosed preoperatively as being infertile (group 1), 31 cases tried to conceive only after surgery (group 2). The study was approved by the Ethics Committee of San Gerardo Hospital, Monza.

RESULTS:

The pregnancy rate among infertile women (group 1) was 53% (58/109, 48 occurring naturally and 10 with ART), and 71% (22/31, 3 with ART) in patients of group 2. The overall cumulative probability of pregnancy at 3 years was 60% for group 1 and 76% for group 2. The prognosis was independent by the stage, presence of monolateral or bilateral endometriomas, tubal adhesions or superficial lesions while it is inversely correlated to Douglas’ pouch obliteration (DPO) (P=0.05).

CONCLUSIONS:

Surgery improves the reproductive prognosis in infertile women with endometriosis. In the studied population DPO obliteration had a high prevalence and it influenced negatively the pregnancy outcome.

 

 

PLoS One. 2016 Nov 16;11(11)

Euterpe oleracea Extract (Açaí) Is a Promising Novel Pharmacological Therapeutic Treatment for Experimental Endometriosis.

Machado DE¹, Rodrigues-Baptista KC^1,2, Alessandra-Perini J^1,2, Soares de Moura R³, Santos TA^1,4, Pereira KG¹, Marinho da Silva Y¹, Souza PJ⁵, Nasciutti LE⁶, Perini JA^1,2.

 

Abstract

This study investigated the therapeutic potential of Euterpe oleracea extract (açaí) on the growth and survival of endometriotic lesions using an experimental model. Twenty female Sprague-Dawley rats were randomized into two groups after the implantation and establishment of autologous endometrium onto the peritoneum abdominal wall and treated with 200 mg/kg hydroalcoholic solution extract from açaí stone or vehicle via gastric tube for 30 consecutive days. Body weight, lesion surface areas, histological and immunohistochemistry analyses of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and F4-80 were performed. Levels of VEGF, VEGFR-2, MMP-9 and COX-2 mRNA were measured. Flow cytometry of F4-80 was performed, and ELISA immunoassays measured prostaglandin E2 (PGE2), VEGF and nitric oxide (NO) and concentrations. Macrophage cell line J774.G8 was treated with 10, 20, and 40 μg/mL of açaí for 24, 48 and 72 h, and cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Açaí treatment significantly decreased the implant size, and histological examination indicated atrophy and regression. A reduction in immunostaining and mRNA expression of VEGF, MMP-9 and COX-2 was observed, and F4-80 was lower in the treated group than the control group. The treated group also exhibited lower concentrations of PGE2, VEGF and NO compared to the control group. Macrophages cells treated with 20 and 40 μg/ml of açaí reduced cell viability in about 50% after 24, 48 and 72 h. Our results suggest that açaí effectively suppressed the establishment and growth of endometriotic lesions, and this agent is a promising novel pharmacological therapeutic treatment for endometriosis.

 

 

Eur J Med Chem. 2017 Feb 15;127:944-957

Treatment of estrogen-dependent diseases: Design, synthesis and profiling of a selective 17β-HSD1 inhibitor with sub-nanomolar IC50 for a proof-of-principle study.

Abdelsamie AS¹, van Koppen CJ², Bey E², Salah M³, Börger C⁴, Siebenbürger L⁴, Laschke MW⁵, Menger MD⁵, Frotscher M⁶.

 

Abstract

Current endocrine therapeutics for the estrogen-dependent disease endometriosis often lead to considerable side-effects as they act by reducing estrogen action systemically. A more recent approach takes advantage of the fact that the weak estrogen estrone (E1) which is abundant in the plasma, is activated in the target cell to the highly estrogenic estradiol (E2) by 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). 17β-HSD1 is overexpressed in endometriosis and thus a promising target for the treatment of this disease, with the prospect of less target-associated side-effects. Potent inhibitors from the class of bicyclic substituted hydroxyphenylmethanones with sulfonamide moiety recently described by us suffered from high molecular weight and low selectivity over 17βHSD2, the physiological adversary of 17β-HSD1. We describe the structural optimizations leading to the discovery of (5-(3,5-dichloro-4-methoxyphenyl)thiophen-2-yl)(2,6-difluoro-3-hydroxyphenyl)methanone 20, which displayed a sub-nanomolar IC₅₀ towards 17β-HSD1 as well as high selectivity over the type 2 enzyme, the estrogen receptors α and β and a range of hepatic CYP enzymes. The compound did neither show cellular toxicity, nor PXR activation nor mutagenicity in the AMES II assay. Additional favourable pharmacokinetic properties (rat) make 20 a suitable candidate for proof-of-principle studies using xenotransplanted immunodeficient rats.

 

 

Int J Environ Res Public Health. 2016 Nov 14;13(11).

The Association between Endometriosis, Tubal Ligation, Hysterectomy and Epithelial Ovarian Cancer: Meta-Analyses.

Wang C¹, Liang Z², Liu X³, Zhang Q⁴, Li S⁵.

 

Abstract

To investigate the association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer. Relevant published literatures were searched in PubMed, ProQuest, Web of Science and Medline databases during 1995-2016. Heterogeneity was evaluated by I² statistic. Publication bias was tested by funnel plot and Egger’s test. Odds ratio and 95% CI were used to assess the association strength. The statistical analyses in this study were accomplished by STATA software package. A total of 40,609 cases of epithelial ovarian cancer and 368,452 controls in 38 publications were included. The result suggested that endometriosis was associated with an increased risk of epithelial ovarian cancer (OR = 1.42, 95% CI = 1.28-1.57), tubal ligation was associated with a decreased risk of epithelial ovarian cancer (OR = 0.70, 95% CI = 0.60-0.81), while hysterectomy show no relationship with epithelial ovarian cancer (OR = 0.97, 95% CI = 0.81-1.14). A stratified analysis showed there were associations between endometriosis and the increased risk of epithelial ovarian cancer for studies conducted in USA and Europe. Meanwhile, there were associations between tubal ligation and the decreased risk of epithelial ovarian cancer for studies conducted in USA, Asia, Europe and Australia. The result indicated that endometriosis was a risk factor of epithelial ovarian cancer whereas tubal ligation was a protective risk factor of epithelial ovarian cancer, hysterectomy may have no relationship with epithelial ovarian cancer.

 

 

 

Rev Med Inst Mex Seguro Soc. 2016;54 Suppl 3:S230-S237.

Association of ovarian tumors with CA-125.

Martínez-Acosta JE¹, Olguín-Cruces VA.

 

Abstract

in English, Spanish

BACKGROUND:

The tumor marker CA-125 is the most widely used serum marker for ovarian cancer screening. The aim of this paper was to establish the association between histopathologic result of ovarian tumors with serologic CA-125 and utility for the diagnosis of ovarian tumors at a Ginecoobstetric hospital.

METHODS:

An observational, retrospective, descriptive and longitudinal study, from September 1st 2010 to February 28 2013. All patients with histopathologic report ovarian tumor and CA-125 was selected to analyze the association of ovarian tumors with their histological type, biological behavior, range positivity of CA-125 and its relationship to the pre and postmenopausal state.

RESULTS:

Of 1213 patients, 334 were included. Utility of CA-125 in postmenopausal reported positive predictive value of 67.5%, with sensitivity (72%), specificity (82.6%) and negative predictive value (86.1%), both with p = 0.001, mainly in the epithelial origin. In premenopausal a low positive predictive value was reported.

CONCLUSIONS:

The CA-125 is useful for screening for ovarian cancer in postmenopausal women, mainly for epithelial origin.

 

 

PLoS One. 2016 Nov 17;11(11):e0166658.

Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis.

Liu S¹, Xin X¹, Hua T¹, Shi R¹, Chi S¹, Jin Z¹, Wang H¹.

 

Abstract

BACKGROUND/OBJECTIVE:

Vascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis.

METHODS:

A systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers.

RESULTS:

We identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) -0.96, 95% CI -1.31 to -0.62; P < 0.0001) and weight (SMD -1.70, 95% CI -2.75 to -0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD -1.17, 95% CI -1.65 to -0.69; P < 0.0001); the number of follicles were similar (SMD -0.78, 95% CI -1.65 to 0.09; P = 0.08).

CONCLUSIONS:

Anti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis.

 

 

J Minim Invasive Gynecol. 2017 Feb;24(2):201-202.

Mini-Laparoscopy for Removal (Partial) of Adnexae at the Time of Hysterectomy.

Setúbal AG¹, Alves JS², Lavado O², Faria J².

 

Abstract

STUDY OBJECTIVE:

To demonstrate our technique of mini-laparoscopic adnexectomy or salpingectomy at the time of total laparoscopic hysterectomy (TLH).

DESIGN:

Step-by-step video demonstration of our technique.

SETTING:

The advantages of laparoscopic surgery have been widely recognized, including improved visualization and exposure, reduced operative trauma owing to smaller incisions and gentler tissue handling, and faster postoperative recovery. Continuing technological developments have allowed the use of smaller-caliber instruments while maintaining a high standard of surgical performance. Mini-laparoscopy requires the use of 3-mm or smaller ports. The main advantage of mini-laparoscopy is the reduced incision size, which can translate into a lower incidence of incision-related complications such as postoperative pain, infection, and trocar site herniation, along with superior cosmetic results. Today, in younger patients, prophylactic salpingectomy can be considered instead of adnexectomy, taking into account the well-known benefits of ovarian conservation. Prophylactic salpingectomy involves Fallopian tube removal for primary prevention of epithelial carcinoma of the fallopian tubes, ovaries, and peritoneum in women undergoing pelvic surgery for another indication. Other advantages of this intervention are the avoidance of hydrosalpinx (which affects ∼30% women after hysterectomy), the 7.8% lifetime risk of revision surgery [1], tubal infection, and benign and malignant Fallopian tube tumors. Finally, salpingectomy has no known physiological side effects, is safe and feasible, does not worsen surgical outcomes, does not significantly increase the operative time, and is not related to increased rates of intraoperative and postoperative complications or readmission.

INTERVENTIONS:

The patient is a 44-year-old woman with a history of 2 previous cesarean sections with adenomyosis and endometriosis infiltration of the uterosacral ligaments. After discussion about the risks and benefits of ovarian conservation with prophylactic salpingectomy versus adnexectomy, the patient opted to preserve her ovaries. A TLH with partial removal of the uterosacral ligaments nodules and prophylactic bilateral salpingectomy was performed. To begin, the patient was placed in lithotomy position with Allen stirrups at an angle of approximately 100 degrees. Standard trocar placement was used. A 5- or 10-mm 0° scope was placed at the level of the umbilicus and three 3-mm skin incisions were made for accessory lower quadrant trocar placement: 2 lateral, approximately 3 cm medial to the anterior superior iliac spine, and 1 suprapubic, slightly higher than the line made by the lateral trocars, ensuring that the distance between this port and the camera trocar exceeded 8 cm. This triangulation of the accessory ports allowed for good ergonomics for the surgeon. The procedure continued with abdominopelvic cavity inspection and bilateral transperitoneal ureter identification and eventual adhesiolysis, and then the following steps: The instruments used were a 10-mm scope, a 3-mm bipolar forceps, 3-mm cold scissors, a 3-mm suction-irrigation device and 3-mm grasping forceps.

CONCLUSION:

Mini-laparoscopy is an alternative to classic laparoscopy associated with greater patient satisfaction. Prophylactic salpingectomy has proven to reduce the risk of ovary, peritoneal, and tubal epithelial carcinomas as well as benign tubal diseases, and does not significantly increase the operative time or the incidence of postoperative complications.

 

 

 

Neuro Endocrinol Lett. 2016 Sep;37(4):295-300

Women’s fertility after laparoscopic cystectomy of endometrioma and other benign ovarian tumors – a 24-month follow-up retrospective study.

Kostrzewa M¹, Stachowiak G¹, Zyła M¹, Kolasa-Zwierzchowska D², Szpakowski A¹, Nowak M¹, Wilczynski JR¹.

 

Abstract

OBJECTIVES:

The golden standard in treatment benign ovarian cysts is laparoscopic cystectomy, but it may also influence women’s fertility. The aim of the study was to compare women’s fertility after laparoscopic cystectomy of endometrioma versus other benign ovarian tumors.

MATERIALS AND METHODS:

Out of the 123 patients operated because of benign ovarian tumor (OT), 66 underwent laparoscopic cystectomy of endometrioma (endometrioma group) and 57 underwent laparoscopic cystectomy of other benign ovarian tumor like: functional cyst, hemorrhagic cyst, yellow body cyst or mature teratoma (reference group). OT-related data were obtained from medical documentation (diagnostic tests, medical reproductive and surgical history, clinical status during OT surgery). Follow-up data were collected by means of a telephone interview. The survey included questions focused on women’s fertility during a 24-month period following the surgical treatment of OT (conception, subsequent pregnancies, recurrence of OT).

RESULTS:

A 24-month follow-up period revealed that the cumulative pregnancy rate was significantly higher in reference group (RG) as compared to endometrioma group (EG), i.e. 52.6% vs. 32.3%. Lower pregnancy risk was demonstrated in a EG group vs. other benign ovarian tumors, HR=0.57 (CI 0.33-0.99; p=0.049), log-rank test p=0.045. Benign OT returned in 19.3% vs. EG 36.3%, HR= 2.5 (CI 1.16-5.55 ; p=0.019) log-rank test: p=0.0136. The EG was divided on two subgroups: women with solitary endometrioma and women with endometrioma and coexistent peritoneal endometriosis. The study showed insignificantly lower risk of pregnancy in a group of advanced endometriosis vs. solitary endometrioma group (HR= 0.79 (CI 0.34-1.83; log-rank test p=0.57; pregnancy rate 29.3% vs. 40.0%). Statistically nonsignificant higher pregnancy rate occurred in a group of women with tumor ≤50mm in size among patients with benign ovarian tumor and solitary endometrioma vs. group of women with tumor >50mm (30% vs. 61%; p=0.09).

CONCLUSIONS:

There is a low pregnancy rate after laparoscopic cystectomy of benign OT. Moreover, pregnancy rate after cystectomy of endometrioma is significantly lower and the percentage of reccurence of endometrioma is significantly higher. That is why, the decision about surgical treatment among childbearing women must be well-considered because of the risk of subsequent surgery in the future.

 

 

 

 

Int J Appl Basic Med Res. 2016 Oct-Dec;6(4):300-302.

Successful pregnancy after excision of cesarean scar endometriosis with uterovesicocutaneous fistula: A rare case report.

Juneja SK¹, Tandon P¹, Chopra I¹.

 

Abstract

Scar endometriosis is an infrequent type of extrapelvic endometriosis. The most common extrapelvic form of endometriosis is cutaneous endometriosis, involving scar tissues occurring after obstetric or gynecologic procedures such as episiotomy, hysterotomy, cesarean section, and even laparoscopic surgery. The clinical presentation of scar endometriosis, i.e., tender swellings, mimics other dermatological and/or surgical conditions and delays the diagnosis. Scar endometriosis very rarely can get complicated with uterocutaneous fistula with a reported incidence of very few cases in world literature. We report a case of a 36-year-old woman presenting with scar endometriosis with complicated uterocutaneous fistula 11 years after her last lower segment cesarean section, managed successfully with laparotomy-fistulectomy and sleeve resection of the bladder with repair followed by successful subsequent spontaneous conception and pregnancy terminated by lower segment cesarean section.

 

 

Medicine (Baltimore). 2016 Nov;95(44):e5200.

Utility of T-cell interferon-γ release assays for the diagnosis of female genital tuberculosis in a tertiary referral hospital in Beijing, China.

Liu X¹, Bian S, Cheng X, Wang W, Tian Q, Zhang L, Zhang Y, Shi X, Zhang Y, Liang Z.

 

Abstract

Diagnosis of female genital tuberculosis (FGTB) remains a challenge. The aim of this study was to evaluate the diagnostic value of T-SPOT.TB on peripheral blood mononuclear cells (PBMCs) for diagnosing FGTB in an area with high TB burden.Patients with suspected FGTB were enrolled consecutively between August 2010 and August 2015. T-SPOT.TB on PBMCs and histopathology were performed in all patients. T-SPOT.TB results were evaluated against patients’ final diagnosis of FGTB which was made based on clinical manifestations, radiology, microbiological and histopathological evaluation, and response to anti-TB treatment. The sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB were analyzed.Among the 66 patients enrolled, 32 were diagnosed with confirmed FGTB, 33 with non-TB including ovarian tumor in 10 patients (30%), pelvic inflammatory diseases in 8 patients (24%), endometriosis in 7 patients (21%), endometrial polyps in 3 patients (9%), abscess of fallopian tube in 2 patients (6%), cyst of fallopian tube in 2 patients (6%), and endometrial carcinoma in 1 patient (3%). One patient with clinically indeterminate diagnosis was not included in the final analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio, and negative likelihood ratio of T-SPOT.TB on PBMCs for diagnosis of FGTB were 94%, 70%, 75%, 92%, 3.09, and 0.09, respectively. Frequencies of spot forming cells (SFCs) of T-SPOT.TB were 430 (interquartile range [IQR] 155-706) SFCs/10 PBMCs and 124 (IQR 61-313) SFCs/10 PBMCs in FGTB and non-TB patients, respectively, and the difference was statistically significant (P = 2.14 × 10). By receiver operating characteristic curve analysis, a cutoff value of 40 SFCs/10 PBMCs of T-SPOT.TB had a sensitivity of 94% and specificity of 76% for the diagnosis of FGTB.T-SPOT.TB on PBMCs appeared to be a valuable and rapid diagnostic method for FGTB in TB endemic settings with high sensitivity and NPV.

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):702-706

Endometriosis and uterine malformations: infertility may increase severity of endometriosis.

Boujenah J^1,2, Salakos E¹, Pinto M¹, Shore J¹, Sifer C^1,2, Poncelet C^1,2, Bricou A¹.

 

Abstract

INTRODUCTION:

The aim of our study was to compare the stage and severity of endometriosis in fertile and infertile women with congenital uterine malformations.

MATERIAL AND METHODS:

We performed an observational study from September 2007 to December 2015 in a tertiary care university hospital and assisted reproductive technology center. A total of 52 patients with surgically proven uterine malformations were included. We compared 41 infertile patients with uterine malformations with 11 fertile patients with uterine malformation. The main outcome was the stage, score and type of endometriosis in regard to infertility and class of uterine malformation.

RESULTS:

The rate of endometriosis did not differ between the two groups (43.9 vs. 36.4%). The mean revised American Fertility Society score was higher in infertile patients with uterine malformations (19.02 vs. 6, p < 0.05). No significant difference was found in the rate of superficial peritoneal endometriosis (43.9 vs. 37.5%). Endometrioma and deep infiltrating endometriosis were associated with uterine malformations in infertile women, respectively 14.6 and 0%. No difference in the characteristics of endometriosis was found regarding the class of malformation.

CONCLUSIONS:

The association of uterine malformations and infertility may increase the severity of endometriosis and raise the issue of their diagnosis and management.

 

 

Cell Prolif. 2017 Feb;50(1).

All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo.

Pourjafar M¹, Saidijam M¹, Mansouri K², Ghasemibasir H³, Karimi Dermani F¹, Najafi R^1,4.

 

Abstract

OBJECTIVES:

Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model.

MATERIALS AND METHODS:

MSCs were treated with a variety of concentrations of ATRA, and mRNA expression of cyclo-oxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Ang-4 were examined by qRT-PCR. Prostaglandin E2 (PGE2) levels were measured using an ELISA kit and MSC angiogenic potential was evaluated using three-dimensional tube formation assay. Finally, benefit of ATRA-treated MSCs in wound healing was determined with a rat excisional wound model.

RESULTS:

In ATRA-treated MSCs, expressions of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2 and Ang-4 increased compared to control groups. Overexpression of the related genes was reversed by celecoxib, a selective COX-2 inhibitor. Tube formation and in vivo wound healing of ATRA-treated MSCs were also significantly enhanced compared to untreated MSCs.

CONCLUSION:

Pre-conditioning of MSCs with ATRA increased efficacy of cell therapy by activation of survival signalling pathways, trophic factors and release of pro-angiogenic molecules.

 

 

BJOG. 2017 Feb;124(3):381-392.

Lesbian and bisexual women’s gynaecological conditions: a systematic review and exploratory meta-analysis.

Robinson K¹, Galloway KY¹, Bewley S¹, Meads C².

 

Abstract

BACKGROUND:

Little is known about the gynaecological health of lesbian and bisexual (LB) women.

OBJECTIVES:

To examine differences in incidence and/or prevalence of gynaecological conditions in LB compared with heterosexual women.

SEARCH STRATEGY:

The systematic review protocol was prospectively registered (PROSPERO-CRD42015027091) and searches conducted in seven databases.

SELECTION CRITERIA:

Comparative studies published 2000-2015, reporting any benign (non-infectious) and/or malignant gynaecological conditions with no language or setting restrictions.

DATA COLLECTION AND ANALYSIS:

Inclusions, data extraction and quality assessment were conducted in duplicate. Meta-analyses of condition prevalence rates were conducted where ≥3 studies reported results.

MAIN RESULTS:

From 567 records, 47 full papers were examined and 11 studies of mixed designs included. No studies directly addressing the question were found. Two chronic pelvic pain studies reported higher rates in bisexual compared with heterosexual women (38.5 versus 28.2% and 18.6 versus 6.4%). Meta-analyses showed no statistically significant differences in polycystic ovarian syndrome, endometriosis and fibroids. There was a higher rate of cervical cancer in bisexual than heterosexual women [odds ratio (OR) = 1.94; 95% CI 1.46-2.59] but no difference overall (OR = 0.76; 95% CI 0.15-3.92). There was a lower rate of uterine cancer in lesbian than heterosexual women (OR = 0.28; 95% CI 0.11-0.73) and overall (OR = 0.36; 95% CI 0.13-0.97), but no difference in bisexual women (OR = 0.43; 95% CI 0.06-3.07).

CONCLUSIONS:

More bisexual women may experience chronic pelvic pain and cervical cancer than heterosexual women. There is no information on potential confounders. Better evidence is required, preferably monitoring sexual orientation in research using the existing validated measure and fully reporting results.

TWEETABLE ABSTRACT:

Lesbians have less uterine cancer than heterosexual women; bisexuals have more pelvic pain and cervical cancer.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Dec;207:141-146.

Comparison of combined hormonal vaginal ring and low dose combined oral hormonal pill for the treatment of idiopathic chronic pelvic pain: a randomised trial.

Priya K¹, Rajaram S², Goel N².

 

Abstract

OBJECTIVE:

To compare the efficacy and acceptability of combined hormonal vaginal ring with combined oral hormonal pill in women with idiopathic chronic pelvic pain.

STUDY DESIGN:

Randomised prospective interventional trial conducted in 60 women with idiopathic chronic pelvic pain. Women were randomised into two groups of 30 each. In each group, treatment was given for 84 days using either combined vaginal ring or combined oral hormonal pill. Hormonal vaginal ring releases 15mcg of ethinyl estradiol and 120mcg of the etonogestrel per day while the hormonal pill contained 30mcg of ethinyl estradiol and 150mcg of levonorgestrel. There was no ring or pill free week. After every 28 days, pain relief was measured using visual analogue scale (VAS), and verbal rating score (VRS) calculated by summing dysmenorrhea, non-cyclic pelvic pain (NCCP) and deep dyspareunia scores. Side effects, compliance, satisfaction, and user acceptability were also measured. Data was analyzed using various parametric and non-parametric tests.

RESULTS:

Reduction in mean VAS score at end of treatment in ring group was 6.23 (95% confidence interval [CI], 5.45-7.01; p<0.001) as compared to 5.53 in pill group (95% CI, 4.83-6.23; p<0.001). Reduction in mean VRS score was 5.63 in ring users (95% CI, 4.84-6.42; p<0.001) versus 4.36 in pill users (95% CI, 3.63-5.10; p<0.001). A significantly higher persistent relief in NCPP score was observed in vaginal ring group as compared to oral pill group at end of one month after stopping treatment. Compliance, satisfaction, and user acceptability were higher in ring users (80%) than pill users (70%) and a higher incidence of nausea was seen in pill group.

CONCLUSION:

Present study demonstrates for first time that both vaginal and oral hormonal therapy are effective in treatment of idiopathic chronic pelvic pain and vaginal ring may be a better choice with higher satisfaction rate and fewer side effects.

 

 

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016 May 25;45(4):439-445.

Research progress on the role of epithelial-mesenchymal transition in pathogenesis of endometriosis.

Zhu T¹, Zhang X².

 

Abstract

Epithelial-mesenchymal transition plays an important role in the development and progression of endometriosis. Mesenchymal-epithelial transition is involved in forming localized lesions of endometriosis, while EMT is involved in the injury, repair and fibrosis induced by local inflammation of endometriosis and the process of cell invasion and metastasis. The studies of signal transduction pathway and related proteins of epithelial-mesenchymal transition in the process of endometriosis may provide new targets for diagnosis and treatment of endometriosis.

 

 

J Altern Complement Med. 2017 Jan;23(1):45-52

The Practice of Hatha Yoga for the Treatment of Pain Associated with Endometriosis.

Gonçalves AV¹, Barros NF², Bahamondes L¹.

 

Abstract

OBJECTIVES:

The aim of this study was to compare chronic pelvic pain, menstrual patterns, and quality of life (QoL) in two groups of women with endometriosis: those who did and those who did not participate in a specific 8-week yoga intervention.

METHOD:

This was a randomized controlled trial. It was conducted at the University of Campinas Medical School, Campinas, SP, Brazil. Forty women were randomly divided into two groups: an intervention group of women who practiced yoga (n = 28), and a control group of women who did not practice yoga (n = 12). Participants attended 90-min scheduled yoga sessions twice a week for 8 weeks. Additionally, an Endometriosis Health Profile (EHP)-30 questionnaire was applied to evaluate women’s QoL at admission and 2 months later upon completion of the yoga program. Menstrual and daily pain patterns were evaluated through a daily calendar (visual analog scale).

RESULTS:

The degree of daily pain was significantly lower among the women who practiced yoga compared with the non-yoga group (p = 0.0007). There was an improvement of QoL in both groups between baseline and the end of the study evaluation. In relation to EHP-30 domains, pain (p = 0.0046), impotence (p = 0.0006), well-being (p = 0.0009), and image (p = 0.0087) from the central questionnaire, and work (p = 0.0027) and treatment (p = 0.0245) from the modular questionnaire were significantly different between the study groups over time. There was no significant difference between the two groups regarding the diary of menstrual patterns (p = 0.96).

CONCLUSIONS:

Yoga practice was associated with a reduction in levels of chronic pelvic pain and an improvement in QoL in women with endometriosis.

 

 

FASEB J. 2017 Feb;31(2):447-456.

Involvement of serum glucocorticoid-regulated kinase 1 in reproductive success.

Lou Y^1,2, Hu M¹, Mao L¹, Zheng Y¹, Jin F^3,4,5,6.

 

Abstract

Reproductive processes, in particular events that concern pregnancy, are fine-tuned to produce offspring. Reproductive success is of prime importance for the survival of every species. The highly conserved and ubiquitously expressed serum glucocorticoid-regulated kinase 1 (SGK1) was first implicated in infertility as a regulator of a Na⁺ channel. In this review, we emphasize the prominent role of SGK1 during early pregnancy: 1) balancing uterine luminal fluid secretion and reabsorption to aid blastocyst adhesion and to import nutrients and energy; 2) transducing signals from the blastocyst to the receptive endometrium; 3) inducing multiple genes that are involved in uterine receptivity and trophoblast invasion; 4) regulating cell differentiation and antioxidant defenses at the fetomaternal interface; and 5) contributing to the proliferation and survival of decidual stromal cells. Accordingly, SGK1 coordinates many cellular processes that are crucial to reproductive activities. Aberrant expression or function of SGK1 results in implantation failure and early pregnancy loss. Further investigation of the molecular mechanisms of the function of SGK1 might provide novel diagnostic tools and interventions for reproductive complications.-Lou, Y., Hu, M., Mao, L., Zheng, Y., Jin, F. Involvement of serum glucocorticoid-regulated kinase 1 in reproductive success.

 

 

 

 

Gynecol Oncol. 2017 Jan;144(1):83-89.

Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Müllerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors.

Haltia UM¹, Hallamaa M², Tapper J³, Hynninen J², Alfthan H⁴, Kalra B⁵, Ritvos O⁶, Heikinheimo M⁷, Unkila-Kallio L³, Perheentupa A⁸, Färkkilä A⁹.

 

Abstract

OBJECTIVE:

Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs).

METHODS:

The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared.

RESULTS:

HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT.

CONCLUSIONS:

HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.

 

 

J Adv Res. 2017 Jan;8(1):1-5.

Thrombosis of iliac vessels, a rare complication of endometriosis: Case report and review of literature.

Chiaramonte R¹, Castorina S², Castorina EG³, Panarello A⁴, Antoci SA⁴.

 

Abstract

A young women presented with iliac vein thrombosis, as extrapelvic endometriosis complication. Endometriosismass had a subfascial position at the level of external oblique muscle and extended to the iliac vein. This paper reviewed the literature on endometriosis cases localized into striated muscles and cases of deep vein thrombosis due to this disease. There are not similar cases in the literature. The diagnostic role of ultrasound, in obtaining the definitive histological diagnosis, may be further enhanced through Elasticity Imaging Techniques and ultrasound-guided biopsy.

 

 

Yonsei Med J. 2017 Jan;58(1):59-66.

Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression.

Choi JY¹, Han HH^1,2, Kim YT³, Lee JH^1,2, Kim BG^1,2, Kang S^1,4, Cho NH^1,2,5.

 

Abstract

PURPOSE:

Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart.

MATERIALS AND METHODS:

Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed.

RESULTS:

Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as “ARID1A-negative.” The other 22 (31%) O-CCCs were designated as “ARID1A-positive.” ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either.

CONCLUSION:

We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.

Hum Fertil (Camb). 2017 Jun;20(2):140-146.

Prognostic factors for patients undergoing vitrified-warmed human embryo transfer cycles: a retrospective cohort study.

Takahashi T¹, Hasegawa A¹, Igarashi H¹, Amita M¹, Matsukawa J¹, Takehara I¹, Suzuki S¹, Nagase S¹.

 

Abstract

We examined the prognostic factors for pregnancy in 210 vitrified-warmed embryo transfer (ET) cycles in 121 patients. The univariate analysis showed that age, gravida, the number of cycles associated with infertility caused by endometriosis, the number of previous assisted reproductive technology (ART) treatment cycles, and the number of ICSI procedures were significantly lower in pregnant cycles compared with non-pregnant cycles. The percentages of ET using at least one intact embryo and of ET using at least one embryo that had developed further after warming were significantly higher in pregnant cycles compared with non-pregnant cycles. Multivariate logistic regression analysis showed that previous ART treatment cycles, ET with at least one intact embryo, and ET using at least one embryo that had developed further were independent prognostic factors for pregnancy in vitrified-warmed ET cycles. We conclude that fewer previous ART treatment cycles, ET using at least one intact embryo, and ET with embryos that have developed further after warming might be favourable prognostic factors for pregnancy in vitrified-warmed ET cycles.

 

 

Reprod Sci. 2016 Nov 21.

Effects of Supplementation of Human Endometriotic Fluids on In Vitro Mouse Preantral Follicle Culture.

Kim SK^1,2, Jee BC^1,2, Kim SH^3,4.

 

Abstract

This study aimed to investigate the potential detrimental effect of human endometriotic fluids (EFs) on in vitro growth of mouse preantral follicles. Preantral follicles (isolated from ovaries of 7- to 8-week-old mice) were cultured in growth medium for 10 days and then in maturation medium for 2 days. During in vitro culture, EF supernatants (0%, 2.5%, 5%, and 10%) were supplemented. Meiotic spindle integrity of metaphase II (MII) oocytes was analyzed. Hormone (17β-estradiol and anti-Müllerian hormone [AMH]) levels in the final spent media were measured by enzyme-linked immunosorbent assay. The survival rates of follicles at day 10 were significantly lower in 3 EF-supplemented groups (56.1%, 30.6%, and 6.2%; 83.6% in the nonsupplemented group). The production of total oocytes per initiated follicle was also significantly lower in the 3 EF-supplemented groups (34.7%, 18.4%, and 4.1%; 68.1% in the nonsupplemented group). Proportions of the oocyte with normal spindles were significantly lower in the 3 EF-supplemented groups (10%, 0% and 0%; 52% in the nonsupplemented group). In the final spent media, the level of 17β-estradiol was significantly lower only in the 10% EF-supplemented group, and the level of AMH was significantly lower in all 3 EF-supplemented groups, when compared with the nonsupplemented group. During in vitro culture of mouse preantral follicles, the survival rate, oocyte acquisition, spindle integrity of MII oocytes, and AMH production were greatly affected by EF supplementation. These findings suggest a possibility of detrimental effects of endometriotic cysts on folliculogenesis in adjacent ovarian tissues.

 

 

Reprod Biol Endocrinol. 2016 Nov 24;14(1):81.

Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients.

Proestling K¹, Birner P², Balendran S², Nirtl N¹, Marton E¹, Yerlikaya G³, Kuessel L¹, Reischer T¹, Wenzl R¹, Streubel B⁴, Husslein H¹.

 

Abstract

BACKGROUND:

Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis.

METHODS:

Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP) endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used.

RESULTS:

We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p = 0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%). The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001).

CONCLUSION:

Our findings support the hypothesis that upregulation of stem cell-related factors contribute to the establishment of endometriotic lesions.

 

 

Pak J Med Sci. 2016 Sep-Oct;32(5):1268-1272.

Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis.

Xue HL¹, Yu N², Wang J³, Hao WJ⁴, Li Y⁵, Liu MY⁶.

 

Abstract

OBJECTIVE:

To evaluate the clinical therapeutic effects of mifepristone combined with gestrinone on patients with endometriosis.

METHODS:

A total of 150 endometriotic patients treated in our hospital between January 2014 and December 2015 were randomly divided into a control group and a treatment group (n=75). The control group began to orally take gestrinone capsules on the second day after menstruation started (2.5 mg/time, twice/week). The treatment group orally took mifepristone tablets (12.5 mg/time, once/day), and the dosage and administration of gestrinone capsules were the same as those of the control group. After 24 weeks of consecutive treatment, the clinical therapeutic effects of the two groups were assessed, and the pelvic symptom score, clinical sign score, serum sex hormone levels and pregnancy outcomes were compared.

RESULTS:

The total effective rates of control and treatment groups were 77.3% and 90.7% respectively, between which the difference was statistically significant (P<0.05). After treatment, the scores of pelvic symptoms (dysmenorrhea, dyspareunia, pelvic pain) and clinical signs (pelvic tenderness, induration) significantly reduced (P<0.05). Each score of the treatment group decreased more significantly than that of the control group did (P<0.05). The serum follicle hormone, luteinizing hormone, estrogen and progesterone levels were significantly lower than those before treatment (P<0.05). Each level of the treatment group dropped more significantly than that of the control group did (P<0.05). The pregnancy rates in the 6th and 12th months of follow-up were 28.0% and 13.3% in the control group respectively, and 42.7% and 29.3% in the treatment group respectively. Such rates of the two groups were significantly different at each follow-up time point (P<0.05).

CONCLUSION:

Mifepristone combined with gestrinone had satisfactory clinical therapeutic effects on endometriosis by reducing hormone levels and improving pregnancy outcomes. Therefore, this regimen is worthy of promotion and application in clinical practice.

 

 

Biomed Rep. 2016 Nov;5(5):531-540.

Endometriosis research using capture microdissection techniques: Progress and future applications.

Zhao L¹, Gu C², Huang K¹, Han W³, Fu M⁴, Meng Y¹.

 

Abstract

Endometriosis is a common gynecological disease with high prevalence, while its etiology and pathophysiology have remained to be fully elucidated. Previous evidence suggested that this disorder may be in part or completely of somatic origin. However, traditional endometrial samples may not be ideal for investigation, as target cells, including epithelial and stromal cells, in endometriotic lesions are too sparse to be analyzed. Recently, capture microdissection techniques have been used to overcome these limitations and eliminate tissue heterogeneity in endometriosis research. Therefore, the present review summarized the alterations in epithelial and stromal cells in endometriosis tissues isolated through capture microdissection, outlined recent progress and provided directions for future investigation of the pathogenesis of endometriosis.

 

 

BBA Clin. 2016 Nov 5;6:143-152

Ovarian-like differentiation in eutopic and ectopic endometrioses with aberrant FSH receptor, INSL3 and GATA4/6 expression.

Fouquet B¹, Santulli P¹, Noel JC², Misrahi M¹.

 

Abstract

Endometriosis, the hormone-dependent extrauterine dissemination of endometrial tissue outside the uterus, affects 5-15% of women of reproductive age. Pathogenesis remains poorly understood as well as the estrogen production by endometriotic tissue yielding autocrine growth. Estrogens (E2) are normally produced by the ovaries. We investigated whether aberrant “ovarian-like” differentiation occurred in endometriosis. 69 women, with (n = 38) and without (n = 31) histologically proven endometriosis were recruited. Comparative RT-qPCR was performed on 20 genes in paired eutopic and ectopic lesions, together with immunohistochemistry. Functional studies were performed in primary cultures of epithelial endometriotic cells (EEC). A broaden ovarian-like differentiation was found in half eutopic and all ectopic endometriosis with aberrant expression of transcripts and protein for the transcription factors GATA4 and GATA6 triggering ovarian differentiation, for the FSH receptor (FSHR) and the ovarian hormone INSL3. Like in ovaries the FSHR induced aromatase, the key enzyme in E2 production, and vascular factors in EEC. The LH receptor (LHR) was also aberrantly expressed in a subset of ectopic endometriosis (21%) and induced strongly androgen-synthesizing enzymes and INSL3 in EEC, as in ovaries, as well as endometriotic cell growth. The ERK pathway mediates signaling by both hormones. A positive feedback loop occurred through FSHR and LHR-dependent induction of GATA4/6 in EEC, as in ovaries, enhancing the production of the steroidogenic cascade. This work highlights a novel pathophysiological mechanism with a broadly ovarian pattern of differentiation in half eutopic and all ectopic endometriosis. This study provides new tools that might improve the diagnosis of endometriosis in the future.

 

 

 

Ceska Gynekol. 2016 Summer;81(3):182-185.

Surgical treatment of endometriomas and ovarian reserve.

Barátová D, Mekiňová L, Slabá K, Crha I.

 

Abstract

OBJECTIVE:

To present an overview of affect an ovarian reserve in women after laparoscopic surgery for ovarian endometriosis.

SUBJECT:

Review.

SETTING:

Department of Obstetric and Gynecology, Hospital Kyjov; Department of Obstetric and Gynecology, University Hospital, Brno.

METHODS:

Summary of the results of recent studies.

RESULTS:

The decrease in ovarian reserve has been detected in 8 of 9 evaluated studies, specifically in one retrospective study, six prospective studies and in one systematic review, the results of the meta-analysis don´t prove the reduction of ovarian reserve after the surgery for endometrioma, reduced ovarian reserve evaluated by the antral follicle count has been proven in the affect ovary before the surgery.

CONCLUSION:

Endometriosis is among the most frequent benign gynecological diseases, affecting the women in reproductive age. Laparoscopic surgery techniques are currently the method of choice in the treatment of endometriotic ovarian cysts. Excision of endometriotic cyst is associated with significant reduction in ovarian reserve. The women with previous surgery of endometrioma have significantly fewer mature oocytes capable of fertilization, the ovarian response to stimulation is reduced and the number of live births is lower.

 

 

Gynecol Obstet Invest. 2016 Nov 25.

The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic Agent.

Akyol A¹, Kavak E, Akyol H, Pala Ş, Gürsu F.

 

Abstract

AIM:

The study aimed to investigate the efficacy of a dopamine agonist, quinagolide, on experimentally induced endometriosis in a rat model.

METHODS:

Twenty female Wistar rats were used in this experiment. Endometriosis was surgically induced by transplantation of autologous endometrial tissue. A second laparotomy was performed 4 weeks after the first one to assess the pre-treatment implant volumes, and peritoneal lavage with saline solution was performed to assess the peritoneal cytokine levels. Rats were randomized to treatment with quinagolide or saline. At the end of the treatment period, a third laparotomy was performed to compare pre- and post-treatment implant volumes and cytokine levels within the groups. Implants were excised to compare glandular tissue (GT) and stromal tissue (ST) scores between the groups.

RESULTS:

In the quinagolide group, post-treatment volume was statistically significantly reduced compared with pre-treatment volume (p = 0.01). There were significant decreases in interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels in peritoneal fluid samples in quinagolide-treated rats when compared to pre-treatment levels (p = 0.03 and p < 0.01). Histopathologically, both GT and ST scores were significantly lower in the quinagolide group compared to the control group (p = 0.01 and p = 0.02).

CONCLUSIONS:

Quinagolide caused a significant regression in endometriotic implants and it also significantly reduced the levels of IL-6 and VEGF in peritoneal fluid.

 

 

Colorectal Dis. 2017 Jun;19(6):576-581

Transanal minimally invasive rectal resection for deep endometriosis: a promising technique.

Vlek SL^1,2, Lier MCI^1,3, Koedam TWA², Melgers I^1,3, Dekker JJML^1,3, Bonjer JH², Mijatovic V^1,3, Tuynman JB^1,2.

 

Abstract

AIM:

Surgical management of patients with deep endometriosis (DE) of the rectum is difficult. Inflammation and subsequent adhesions due to DE impede access to the lower pelvis and may lead to complications during laparoscopic low anterior resection (LAR). Transanal minimally invasive surgery (TAMIS) is an alternative to an abdominal approach with potential advantages. The aim of this study was to provide a description of the TAMIS technique and to present the perioperative results of TAMIS and of conventional LAR in patients with DE.

METHOD:

A prospective consecutive cohort of patients undergoing rectal resection for DE had either conventional laparoscopic LAR or TAMIS rectal excision. Pre-, intra- and postoperative parameters, such as patient symptomatology, operating time and postoperative complications were compared between the groups. Quality of life was assessed using the EORTC-QLQ-29/30 questionnaires.

RESULTS:

Between May 2014 and March 2016 a total of 11 rectal resections were performed, including five TAMIS procedures. No differences were found in the pre-, intra- or postoperative parameters. Two major complications occurred after conventional LAR and none after TAMIS. No differences in quality of life were found between the groups.

CONCLUSION:

Transanal minimally invasive surgery for DE of the rectum is feasible. Potential advantages include better surgical access to the pelvis, possibly fewer complications than LAR and no extraction incision with no difference in quality of life. Larger prospective studies are required to compare TAMIS with conventional rectal resection.

 

 

Sci Rep. 2016 Nov 25;6:37792.

An evolutionary conserved interaction between the Gcm transcription factor and the SF1 nuclear receptor in the female reproductive system.

Cattenoz PB, Delaporte C, Bazzi W, Giangrande A

 

Abstract

NR5A1 is essential for the development and for the function of steroid producing glands of the reproductive system. Moreover, its misregulation is associated with endometriosis, which is the first cause of infertility in women. Hr39, the Drosophila ortholog of NR5A1, is expressed and required in the secretory cells of the spermatheca, the female exocrine gland that ensures fertility by secreting substances that attract and capacitate the spermatozoids. We here identify a direct regulator of Hr39 in the spermatheca: the Gcm transcription factor. Furthermore, lack of Gcm prevents the production of the secretory cells and leads to female sterility in Drosophila. Hr39 regulation by Gcm seems conserved in mammals and involves the modification of the DNA methylation profile of mNr5a1. This study identifies a new molecular pathway in female reproductive system development and suggests a role for hGCM in the progression of reproductive tract diseases in humans.

 

 

Fertil Steril. 2017 Feb;107(2):e11-e12.

Magnetic resonance imaging correlation to intraoperative findings of deeply infiltrative endometriosis.

Ito TE¹, Abi Khalil ED², Taffel M², Moawad GN².

 

Abstract

OBJECTIVE:

To show characteristics of deeply infiltrative endometriosis (DIE) on magnetic resonance imaging (MRI) and how they correlate with intraoperative findings.

DESIGN:

Overview of still and dynamic MRI images of four different patients with DIE. We then used videos from their surgeries to highlight the appearance of endometriosis corresponding to these images (educational video).

SETTING:

University hospital.

PATIENT(S):

Four different patients with DIE were included in this video. These were all women of reproductive age who suffered from debilitating deeply infiltrative endometriosis. These patients had a pelvic MRI performed at our institution and subsequently underwent surgery with one of our minimally invasive gynecologic surgeons.

INTERVENTION(S):

The MRI endometriosis protocol includes T1-weighted fat and nonfat saturated as well as T2-weighted sequences. Images are taken along all three planes (axial, sagittal, and coronal) before and after contrast. What distinguishes the standard MRI from the endometriosis-protocol MRI is the thickness of the slices taken. For the evaluation of endometriosis, T1 nonfat saturated images are taken in 6-mm slices with no skip sections in between. Then, T1 fat saturated images and T2-weighted images are taken in 5-mm slices with a 1-mm skip section in between slices. The areas that are suspicious for lesions consistent with DIE are corroborated on videos taken during surgery.

MAIN OUTCOME MEASURE(S):

Value of accurate mapping of lesions with the use of preoperative MRI in surgical planning and complete resection of diseased tissue.

RESULT(S):

Results from a previously published prospective study by Bazot et al. reported sensitivity, specificity, positive predictive value, and negative predictive value of 90.3%, 91%, 92.1%, and 89%, respectively. Similarly to our institution, that study used a 1.5-T MRI, and the protocol of our institution closely mimicked the technique used in that study. Another prospective study published by Hottat et al. showed sensitivity, specificity, and positive and negative predictive values of MRI predicting intraoperative disease of 96.3%, 100%, 100%, and 93.3% respectively. Those results were gathered with the use of a 3.0-T MRI. The high accuracy in these studies of prediction of deep pelvic endometriosis in specific locations shows that MRI is effective for preoperative planning, as was the case for the four patients in our video.

CONCLUSION(S):

Preoperative planning for DIE with the use of MRI is integral in surgical planning. Other imaging modalities to diagnose DIE, such as transvaginal ultrasound, endoanal ultrasound, barium enema, cystoscopy, and rectoscopy, have all been used and studied for the evaluation of endometriosis. However, given its accuracy for mapping lesions, MRI could potentially replace multiple types of imaging while offering the best option for preoperative planning. Accurate mapping would result in greater success of resection and allow for multidisciplinary planning if necessary. Furthermore, being able to train the eye to identify lesions on MRI that are consistent with DIE is an asset to the gynecologic surgeon.

 

Arch Gynecol Obstet. 2017 Mar;295(3):631-639.

Elevated RON protein expression in endometriosis and disease-associated ovarian cancers.

Xu P¹, Ding S¹, Zhu L¹, Le F¹, Huang X¹, Tian Y¹, Zhang X².

 

Abstract

BACKGROUND:

Recepteur d’origine nantais (RON) protein expression has been demonstrated to correlate with tumor progression, metastasis, and prognosis, and its mRNA expression increases in deeply infiltrating endometriotic lesions. However, it remains unclear whether RON protein expression also increases in endometriotic lesions, and may be a risk factor of malignant transformation in endometriotic lesions.

METHODS:

The protein expression of RON in control (n = 19), eutopic (n = 16), and ectopic (n = 51) endometria, as well as in endometriosis-associated ovarian cancers (EAOC, n = 16) was determined by immunohistochemical (IHC) staining.

RESULTS:

Endometriotic lesions expressed low levels of RON protein, but no RON protein expression appeared in matched eutopic or control endometrium. EAOC exhibited high levels of RON protein. The frequency and IHC score of RON protein expression were both significantly higher in EAOC [100.0% (14/14), 5.37 ± 0.74] than those in endometriotic lesions [51.0% (26/51), 2.15 ± 1.12; P = 0.002, 0.001]. Multivariate analysis of covariance only revealed a correlation of RON protein expression and EAOC (P = 0.006), but no correlations of RON protein expression and clinical parameters (P > 0.05).

CONCLUSIONS:

These obtained results suggest that increased RON expression might be involved in the pathogenesis of endometriosis and disease-associated ovarian cancers.

 

 

Med Sci Monit. 2016 Nov 27;22:4596-4603.

Effect of Natural Cycle Endometrial Preparation for Frozen-Thawed Embryo Transfer in Patients with Advanced Endometriosis.

Guo H¹, Wang Y¹, Chen Q¹, Chai W¹, Lv Q¹, Kuang Y¹.

 

Abstract

BACKGROUND The aim of this study was to investigate the effect of natural cycle (NC) endometrial preparation for frozen-thawed embryo transfer (FET) in women with advanced endometriosis. MATERIAL AND METHODS This retrospective study included 179 patients with stage III-IV endometriosis who underwent 233 FET cycles at a tertiary care academic reproductive medical center between March 2011 and August 2013 (group A). The control group included 258 patients with tubal factor infertility who underwent 300 FET cycles (group B). Both groups were prepared for FET using a NC protocol. Rates of implantation, clinical pregnancy, live birth, ongoing pregnancy, miscarriage, and pregnancy complication were recorded. RESULTS The implantation rate (A: 36.0%, B: 30.4%, P=0.06), the pregnancy rate (A: 50.2%, B: 45.3%, P=0.263), and the live birth rate (A: 39.91%, B: 39.0%, P=0.428) were similar between the stage III-IV endometriosis and tubal factor infertility groups. No differences were observed in ongoing rates of pregnancy, miscarriage, and pregnancy complications, independent of endometriosis severity. No congenital birth defects were found. When high-quality embryos are transferred, pregnancy results were not affected by active endometriosis. Although severe endometriosis did not affect birth rate, higher frequencies of premature delivery (mean gestational age A: 37 weeks, B: 38.3 weeks, P=0.044) and low birth weight were observed (<2500 g A: 26.4%, B: 16.6%, P=0.047). CONCLUSIONS There was no difference in pregnancy outcomes between patients with endometriosis and those with tubal infertility. Pregnancy outcomes in patients with endometriosis were not affected by endometriosis severity. Pregnancy outcomes were not affected by active endometrial cyst.

 

 

J Clin Diagn Res. 2016 Oct;10(10)

Is There Any Impact of Copper Intrauterine Device on Female Sexual Functioning?

Koseoglu SB¹, Deveer R², Akin MN³, Gurbuz AS⁴, Kasap B³, Guvey H⁵.

 

Abstract

INTRODUCTION:

Intrauterine Device (IUD) is the most preferred modern contraceptive method in Turkey. Female Sexual Dysfunction (FSD) is defined as lack of one or more of the components in the sexual response cycle which includes sexual desire, impaired arousal and inability achieving an orgasm or pain with intercourse. FSD has multi-factorial aetiology. Advanced age and menopause, fatigue and stress, psychiatric and neurologic disease, childbirth, pelvic floor or bladder dysfunction, endometriosis, uterine fibroids, hypertension obesity, medication and substances, hormonal contraceptives, relationship factors are known risk factors for FSD.

AIM:

To investigate if IUD has any impact on female sexual functioning.

MATERIALS AND METHODS:

In this cross-sectional study subjects were divided into two groups. Study group consisted of 92 IUD-users (mean 5.1±1.2 years) and the control group consisted of 83 women with no contraception. Female Sexual Function Index (FSFI) questionnaire was performed to both two groups. Women with a total score lower than 26.5 were considered as having sexual dysfunction.

RESULTS:

The prevalence of FSD was 57.1% among participants. IUD users had a lower total FSFI score comparing to control group but the difference was not statistically different (p=0.983). A positive correlation was found between total FSFI score and duration of IUD (p=0.003).

CONCLUSION:

No difference was found in terms of sexual dysfunction between IUD users and women with no contraception. The prevalence of FSD was very high in both groups which may be attributed to the socio-cultural factors such as embarrassment of women due to conservatism.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Jan;208:81-85.

The age-related recurrence of endometrioma after conservative surgery.

Seo JW¹, Lee DY¹, Yoon BK¹, Choi D².

 

Abstract

OBJECTIVE:

As endometrioma frequently recurs after conservative surgery, long-term postoperative medical treatment for the prevention of recurrence is necessary. However, it has not been elucidated whether long-term postoperative medical treatment is crucial to all patients until menopause. Thereupon, this study was conducted to evaluate the age-related recurrence patterns after conservative surgery for endometrioma.

STUDY DESIGN:

A retrospective cohort study was performed on a total of 420 reproductive-aged women who underwent conservative surgery for endometrioma between January 2000 and December 2010. Ultrasonography was used during the follow-up period to detect endometrioma recurrence. Patients were classified into two groups according to the use of postoperative medications. The first group was observation only, while the second received gonadotropin releasing hormone agonists followed by cyclic oral contraceptives. The cumulative recurrence rate of endometrioma was compared according to the age at surgery (20-29 years, 30-39 years, 40-45 years) within each group. Subgroup analysis was performed according to the age between the two groups.

RESULTS:

The median follow-up duration after surgery was 29.0 months (range 6-159 months) for all patients. After adjusting for parity, size and bilaterality of cyst, and stage with American Society for Reproductive Medicine classification of endometriosis which was statistically different, within the group of no treatment, the cumulative recurrence rate in 40-45 years (10.2%) was significantly lower compared with those in 20-29 years (43.3%; hazard ratio (HR)=0.04; 95% confidence interval (CI)=0.01-0.52) and 30-39 years (22.5%; HR=0.19; 95% CI=0.04-0.92). However, there were no differences within the group of postoperative medical treatment. When we compared between the two groups, the cumulative recurrence rate was significantly different in 20-29 years (8.1 vs 43.3%; p<0.001) and 30-39 years (5.4 vs 22.5%; p=0.007), but there was no difference in 40-45 years (4.5 vs 10.2%; p=0.901).

CONCLUSIONS:

Our preliminary results demonstrate that the risk of endometrioma recurrence decreases with age. After the age of forty, the recurrence rate does not differ according to the use of postoperative medication. Based on our results, postoperative medical treatment may be individualized according to the patient’s age at the time of surgery. Further studies are needed to identify patients who may benefit from postoperative medication.

 

 

Obstet Gynecol Sci. 2016 Nov;59(6):506-511

Study of dienogest for dysmenorrhea and pelvic pain associated with endometriosis.

Kim SA¹, Um MJ², Kim HK², Kim SJ², Moon SJ², Jung H¹.

 

Abstract

OBJECTIVE:

To evaluate the effect of orally administered dienogest (DNG) for dysmenorrhea and pelvic pain associated with endometriosis.

METHODS:

For this study we recruited 89 patients with dysmenorrhea and pelvic pain associated with endometriosis diagnosed by laparoscopy. All patients complained of persistent dysmenorrhea and pelvic pain despite surgical treatment 6 months previously. After 6 months of DNG treatment, we used a 0 to 3 point verbal rating scale to measure the severity of disability in daily life due to dysmenorrhea and pelvic pain, and the use of analgesics. Weight gain, serum lipid and liver enzyme tests were performed before treatment and after 6 months of DNG treatment.

RESULTS:

Total dysmenorrhea scores assessed by the verbal rating scale significantly decreased by the end of treatment (P<0.001). The mean (±standard deviation) pain score for dysmenorrhea before and after treatment were 1.42±1.1 and 0.1±0.3, respectively. The mean non-menstrual pelvic pain scores before and after treatment were 0.52±0.6 and 0.18±0.3, respectively, showing a significant difference (P<0.001). The use of analgesics significantly decreased by the end of the treatment (P<0.001). The associated adverse effects were weight gains (in 56 of 89 patients, 63%) and uterine bleeding (in 28 of 89 patients, 31.5%). The weight gain (before treatment, 57.9±9.7; after treatment, 61.1±12.6) was statistically significant (P<0.040).

CONCLUSION:

This study demonstrated that orally administered DNG could be used to effectively treat dysmenorrhea and pelvic pain associated with endometriosis although the side effects of weight gain and uterine bleeding should be considered.

 

 

Ann Ital Chir. 2016 Nov 28;87.

Delayed Coloanal Anastomosis for rectovaginal fistula after colorectal resection for deep endometriosis.

Gallo G, Luc AR, Tutino R, Clerico G, Trompetto M.

Abstract

AIM:

The deep infiltrating endometriosis, defined as a subperitoneal infiltration of endometrial implants of ≥ 5 mm involving not only the colorectal tract but also rectovaginal septum, vagina and bladder often requires a challenging surgery. Endometriosis nodes of the rectovaginal septum, if symptomatic, need a resection of the involved colorectal tract with colorectal or coloanal anastomosis. Unfortunately in these cases is not uncommon the possibility of a postoperative rectovaginal fistula (RVF), caused by the weakness of the septum that must be skeletonized to completely remove the endometriosis nodes. Here we present a case of anastomotic leakage with high RVF after colorectal resection and low colorectal anastomosis for deep endometriosis in which, for a chronic pelvic sepsis and a high risk of failure of a new immediate coloanal anastomosis, a Turnbull-Cutait pull-through with delayed coloanal anastomosis (DCAA) has been performed.

CASE REPORT:

A now 34 years old woman was admitted to our Clinic because of a RVF due to recto-sigmoid resection with colorectal anastomosis for endometriosis. An evaluation in anesthesia confirmed the RVF. In this case we avoided an immediate new colorectal anastomosis for the high risk of a recurrent anastomotic leakage and performed a DCAA.

RESULTS:

The outcome of the two-steps operation has been satisfactory both for the healing of the RVF and for the functional results bringing the young patient to a completely restored social, sexual and working life.

CONCLUSIONS:

In our opinion Turnbull-Cutait pull-through with delayed coloanal anastomosis is a good choice in patients with RVF in which a new colorectal or coloanal anastomosis can bring to a recurrent leakage.

KEY WORDS:

Delayed coloanal anastomosis, Deep endometriosis, Rectovaginal fistula.

 

 

Int J Surg Case Rep. 2017;30:1-5.

Spontaneous endometriosis associated with an umbilical hernia: A case report and review of the literature.

Ismael H¹, Ragoza Y², Harden A², Cox S².

 

Abstract

INTRODUCTION:

Umbilical endometriosis occurring in the presence of an underlying hernia is extremely rare and presents a diagnostic challenge for the general surgeon. We present an interesting case and perform a comprehensive review of the literature.

METHODS:

Medline and PubMed were queried for all cases of spontaneous umbilical endometriosis associated with an umbilical hernia. Data was analyzed and is presented along with an interesting case.

RESULTS:

Only 7 cases have been reported in the literature. Median age was 38 years. Time to presentation was long (up to 5 years) and the majority had cyclical symptoms related to menstruation. All patients, including our case, were treated surgically.

DISCUSSION:

Spontaneous umbilical endometriosis with an underlying hernia is often missed preoperatively. Preoperative suspicion warrants axial imaging for better operative planning and patient counseling. Surgery consists of enbloc excision of the umbilicus, implant and the hernia sac to avoid residual disease and reduce recurrence. The hernia defect can be repaired primarily or using mesh and the umbilicus reconstructed using skin flaps if necessary.

CONCLUSIONS:

Surgery is the mainstay of therapy for umbilical endometriosis associated with an underlying hernia. Clinical suspicion warrants preoperative imaging, and follow-up with a gynecologist is essential to address any pelvic disease.

 

 

Am J Obstet Gynecol. 2017 Mar;216(3):280.e1-280.

Prognostic factors for assisted reproductive technology in women with endometriosis-related infertility.

Maignien C¹, Santulli P², Gayet V¹, Lafay-Pillet MC¹, Korb D¹, Bourdon M¹, Marcellin L³, de Ziegler D¹, Chapron C³.

 

Abstract

BACKGROUND:

Assisted reproductive technology is one of the therapeutic options offered for managing endometriosis-associated infertility. Yet, published data on assisted reproductive technology outcome in women affected by endometriosis are conflicting and the determinant factors for pregnancy chances unclear.

OBJECTIVE:

We sought to evaluate assisted reproductive technology outcomes in a series of 359 endometriosispatients, to identify prognostic factors and determine if there is an impact of the endometriosis phenotype.

STUDY DESIGN:

This was a retrospective observational cohort study, including 359 consecutive endometriosispatients undergoing in vitro fertilization or intracytoplasmic sperm injection, from June 2005 through February 2013 at a university hospital. Endometriotic lesions were classified into 3 phenotypes-superficial peritoneal endometriosis, endometrioma, or deep infiltrating endometriosis-based on imaging criteria (transvaginal ultrasound, magnetic resonance imaging); histological proof confirmed the diagnosis in women with a history of surgery for endometriosis. Main outcome measures were clinical pregnancy rates and live birth rates per cycle and per embryo transfer. Prognostic factors of assisted reproductive technology outcome were identified by comparing women who became pregnant and those who did not, using univariate and adjusted multiple logistic regression models.

RESULTS:

In all, 359 endometriosis patients underwent 720 assisted reproductive technology cycles. In all, 158 (44%) patients became pregnant, and 114 (31.8%) had a live birth. The clinical pregnancy rate and the live birth rate per embryo transfer were 36.4% and 22.8%, respectively. The endometriosis phenotype (superficial endometriosis, endometrioma, or deep infiltrating endometriosis) had no impact on assisted reproductive technology outcomes. After multivariate analysis, history of surgery for endometriosis (odds ratio, 0.14; 95% confidence ratio, 0.06-0.38) or past surgery for endometrioma (odds ratio, 0.39; 95% confidence ratio, 0.18-0.84) were independent factors associated with lower pregnancy rates. Anti-müllerian hormone levels <2 ng/mL (odds ratio, 0.51; 95% confidence ratio, 0.28-0.91) and antral follicle count <10 (odds ratio, 0.27; 95% confidence ratio, 0.14-0.53) were also associated with negative assisted reproductive technology outcomes.

CONCLUSION:

The endometriosis phenotype seems to have no impact on assisted reproductive technology results. An altered ovarian reserve and a previous surgery for endometriosis and/or endometrioma are associated with decreased pregnancy rates.

 

 

Ecancermedicalscience. 2016 Oct 4;10:678.

The first case of benign multicystic mesothelioma presenting as a splenic mass.

D’Antonio A¹, Baldi C¹, Addesso M², Napolitano C³.

 

Abstract

Multicystic mesothelioma (MM) is a relatively rare tumour arising in the pelvic peritoneum of the tuboovarian region of young woman. Exceptionally, MM occurs on the serosal surfaces of various organs including kidney, bladder, lymph nodes, and liver. We report here the first case of MM wherein a 58-year-old woman with a previous history of endometriosis of the right ovary presented with a large multicystic mass of the spleen. The diagnosis of MM was made on a surgical specimen after splenectomy. A histopathologic examination is always necessary for the diagnosis of MM which should be differentiated from other lesions particularly from cystic lymphangioma. At one year follow-up, the patient had no evidence of recurrence. Despite the high frequency of local recurrences, MM is a benign lesion and ‘en bloc’ surgical excision with prolonged follow-ups is the treatment of choice.

 

 

Oncol Lett. 2016 Nov;12(5):3101-3114.

Diagnostic usefulness of the Risk of Ovarian Malignancy Algorithm using the electrochemiluminescence immunoassay for HE4 and the chemiluminescence microparticle immunoassay for CA125.

Chudecka-Głaz A¹, Cymbaluk-Płoska A¹, Luterek-Puszyńska K¹, Menkiszak J¹.

 

Abstract

The present study aimed to investigate the usefulness of the Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative stratification of patients with ovarian tumors using a novel combination of laboratory tests. The study group (n=619) consisted of 354 premenopausal and 265 postmenopausal patients. The levels of carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) were determined, and ROMA calculations were performed for each pre- and postmenopausal patient. HE4 levels were determined using an electrochemiluminescence immunoassay, while CA125 levels were determined by a chemiluminescence microparticle immunoassay. A contingency table was applied to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic curves were also constructed, and areas under the curves (AUCs) were compared between the marker determinations and ROMA algorithms. In terms of distinguishing between ovarian cancer and benign disease, the sensitivity of ROMA was 88.3%, specificity was 88.2%, PPV was 75.3% and NPV was 94.9% among all patients. The respective parameters were 71.1, 90.1, 48.2 and 91.1% in premenopausal patients and 93.6, 82.9, 86.6 and 91.6% in postmenopausal patients. The AUC value for the ROMA algorithm was 0.926 for the ovarian cancer vs. benign groups in all patients, 0.813 in premenopausal patients and 0.939 in postmenopausal patients. The respective AUC values were 0.911, 0.879 and 0.934 for CA125; and 0.879, 0.783 and 0.889 for HE4. In this combination, the ROMA algorithm is characterized by an extremely high sensitivity of prediction of ovarian cancer in women with pelvic masses, and may constitute a precise tool with which to support the qualification of patients to appropriate surgical procedures. The ROMA may be useful in diagnosing ovarian endometrial changes in young patients.

 

 

Regen Med. 2017 Jan;12(1):69-76.

Mesenchymal stem cells: a promising tool for targeted gene therapy of endometriosis.

Koippallil Gopalakrishnan AR¹, Kishore U², Madan T¹.

 

Abstract

Endometriosis is a leading, benign gynecological disorder around the world. Last few years have witnessed tremendous growth in the field of endometriosis and endometrial stem-cell research. Despite advancements in the biology and pathology of endometriosis, disease recurrence is still an enigma. Gene therapy holds promise in treating many pathologic conditions including endometriosis. Mesenchymal stem cells (MSCs) serve as ideal candidates for regenerative medicine and cell-based therapies. Owing to their specificity to the endometrium, residing endometrial MSC populations could be utilized as ideal candidates for targeting endometrial disorders. Recently, we demonstrated their flexibility for gene transduction using adenoviral vectors. The review highlights the potential of endometrial MSCs in devising targeted gene therapies for endometriosis.

 

 

Reprod Sci. 2017 Aug;24(8):1176-1186.

Decreased Endometrial Expression of Leukemia Inhibitory Factor Receptor Disrupts the STAT3 Signaling in Adenomyosis During the Implantation Window.

Yen CF^1,2, Liao SK^2,3, Huang SJ^4,5, Tabak S⁶, Arcuri F⁷, Lee CL⁸, Arici A⁶, Petraglia F⁷, Wang HS^1,2, Kayisli UA⁵.

 

Abstract

BACKGROUND:

Adenomyosis was found to have negative impacts on embryo implantation. Leukemia inhibitory factor (LIF), proposed to be a molecular marker for endometrial receptivity, works through the LIF receptor (LIFR) on both the embryo and the endometrium. We aimed to evaluate the endometrial expression of LIF and LIFR and its subsequent signaling in patients with adenomyosis during the window of implantation (WOI).

METHODS:

Endometrium was obtained during the WOI from patients with adenomyosis (age <45 years) who underwent hysterectomy and from age-matched controls who had no endometriosis or adenomyosis. The LIF and LIFR expressions were measured by polymerase chain reaction for messenger RNA expression, immunohistochemistry for protein intensity and localization, and immunofluorescent staining for colocalization. The ratio of signal transducer and activator of transcription 3 (STAT3) to extracellular signal-regulated kinase (ERK) phosphorylation was measured by Western blot of both the endometrium and the isolated human endometrial stromal cells (ESCs).

RESULTS:

Patients with adenomyosis showed significantly and parallelly reduced LIF and LIFR expressions in the eutopic endometrium during WOI as compared with the control women and subsequently with remarkably reduced activation of STAT3 and ERK signaling. The significantly increased STAT3 and ERK phosphorylation induced by the LIF treatment in the cultured ESCs supported the linkage between the LIF-LIFR reaction and the signaling cascade.

CONCLUSION:

Significant reduction in LIFR expression and the reduced activation of subsequent signaling strongly suggest a working model of how the implantation markers, LIF, may affect the endometrium of patients with adenomyosis. These molecular changes supported the declined implantation rates reported in patients with adenomyosis.

 

 

 

Intern Med. 2016;55(23):3491-3493.

Two Young Women with Left-sided Pneumothorax Due to Thoracic Endometriosis.

Yukumi S¹, Suzuki H, Morimoto M, Shigematsu H, Okazaki M, Abe M, Kitazawa S, Nakamura K, Sano Y.

 

Abstract

Pneumothorax associated with thoracic endometriosis (TE) generally occurs in women around 30 years old and it usually affects the right pleural cavity. We herein report two cases of TE associated with left-sided pneumothorax in young women. The prevalence of TE in younger patients may be underestimated if these cases are treated as spontaneous pneumothorax. Pneumothorax occurring in younger patients has not been reported to show laterality. TE-related or catamenial pneumothorax in young women must therefore represent a different clinical entity from the condition seen in older patients.

 

 

Minerva Ginecol. 2017 Apr;69(2):178-189.

Management of infertile women with pelvic endometriosis: a literature review.

Guinard E¹, Collinet P^2,3, Lefebvre C⁴, Robin G⁴, Rubod C^2,3.

 

Abstract

INTRODUCTION:

Endometriosis is a condition that affects women’s fertility. Several mechanisms are involved in this process: anatomical changes, mechanical, immune or inflammatory factors, ovarian reserve alterations… There are different types of strategies to treat endometriosis-related infertility: medical treatment, surgical treatment and/or techniques of medically assisted procreation.

EVIDENCE ACQUISITION:

We tried to consider various therapeutic strategies depending on the stage of the disease in order to offer appropriate management to patients with endometriosis who wish to become pregnant: we reviewed 58 articles between 1985 to 2016 searching in medline using the key words «endometriosis and infertility» and «infertility and endometriosis treatment». And we divided the patients in subgroups mild and severe endometriosis, in vitro fertilization (IVF) versus surgery in deep infiltrating endometriosis (DIE) and others.

EVIDENCE SYNTHESIS:

Surgery appears to be the chief treatment for minimal to mild endometriosis in a context of infertility. Concerning deep infiltrating endometriosis, data in insufficient to decide on the best treatment although surgery associated with IVF seems to bring clinical benefit.

CONCLUSIONS:

Regarding optimal management of infertility – in case of stage III or IV endometriosis, there is yet no consensus. A multidisciplinary approach is essential in order to consider the various treatment options and provide optimum care and individualized to patients according to different parameters (patient age, degree of damage and location of DIE lesions, presence or absence of ovarian failure or other factors associated with subfertility, male infertility factors in the couple…). Indeed, optimal care of patients should be multidisciplinary and personalized.

 

 

Cell Death Dis. 2016 Dec 1;7(12):e2489.

1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis.

Wei C¹, Mei J², Tang L¹, Liu Y¹, Li D¹, Li M¹, Zhu X^1,3.

 

Abstract

Foxp3⁺ regulatory T (T_reg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal T_reg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal T_reg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of T_reg cells, mainly IL-10⁺ T_reg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated T_reg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of T_reg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for T_reg differentiation in the ectopic lesion, especially that for CD4^high T_reg. Therefore, MRC2-silenced ESCs-educated T_reg manifested a stronger suppressive function in vitro. Consistently, the percentage of T_reg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of T_reg and is involved in the development of endometriosis. Thus, blockage of IDO1 in the ectopic lesion, which does not influence physiological functions of estrogen, may be considered a potential therapy for endometriosis.

 

 

 

World J Surg Oncol. 2016 Dec 3;14(1):300.

Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature.

Ferrandina G^1,2, Palluzzi E³, Fanfani F⁴, Gentileschi S⁵, Valentini AL⁶, Mattoli MV⁷, Pennacchia I⁸, Scambia G³, Zannoni G⁸.

 

Abstract

BACKGROUND:

Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar.

CASE PRESENTATION:

In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the rectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed irregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal lymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered neo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide resection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy. The muscular gap was repaired employing a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous anterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis foci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for CK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after 2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m², biweekly administration), the death of the patient disease occurred 1 month later.

CONCLUSIONS:

Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules.

 

 

Pathol Res Pract. 2017 Jan;213(1):39-44.

Intestinal metaplasia of appendiceal endometriosis is not uncommon and may mimic appendiceal mucinous neoplasm.

Vyas M¹, Wong S¹, Zhang X².

 

Abstract

Endometriosis of the appendix can be an incidental finding or a cause of appendicitis, intussusception, perforation or retention mucocele. Intestinal metaplasia of appendiceal endometriosis may occur, which can lead to a misdiagnosis of low-grade appendiceal mucinous neoplasm. On a retrospective search of the pathology database from 2001 to 2015, we identified 78 appendiceal endometriosis cases and intestinal metaplasia was present in 10/78 (13%) cases. In most of the cases (90%), the foci of intestinal metaplasia were mainly localized close to the mucosa. Intestinal and endometrial hybrid glands were present in 9/10 (90%) cases. These cases were often associated with marked appendiceal distortion, luminal obliteration and mass formation, causing concern for a mucinous neoplasm clinically and pathologically. Our findings indicate that intestinal metaplasia in appendiceal endometriosis is not an uncommon phenomenon, which can be mistaken for a mucinous neoplasm. Endometriosis should be kept in mind when a diagnosis of appendiceal mucinous neoplasm is made, especially in a young woman with a clinical history of endometriosis.

 

 

Pathol Res Pract. 2017 Jan;213(1):79-81.

Histomorphological changes in endometriosis in a patient treated with ulipristal: A case report.

Bateman J¹, Bougie O², Singh S², Islam S³.

 

Abstract

BACKGROUND:

Selective progesterone receptor modulators have shown efficacy in the treatment of endometriosis, however they are not currently licensed in Canada for this purpose. Their histomorphological effects have been well documented in the endometrium, but not in endometriosis.

CASE REPORT:

The patient presented with uterine fibroids and heavy menstrual bleeding, and was treated with ulipristal acetate over three 90-day courses. She eventually elected to undergo definitive surgical management. On pathological examination, she was found to have a focus of endometriosis in the para-tubal soft tissue showing a morphology similar to progesterone receptor modulator associated endometrial changes (PAEC).

CONCLUSIONS:

To our knowledge this is the first reported case of PAEC involving a focus of endometriosis. This case demonstrates histomorphological evidence of the effects of ulipristal acetate on endometriosis, and thus provides evidence of a pharmacological effect.

 

 

Reprod Biomed Online. 2017 Feb;34(2):124-136.

Progressive development of endometriosis and its hindrance by anti-platelet treatment in mice with induced endometriosis.

Zhang Q¹, Liu X², Guo SW³.

 

Abstract

We have recently shown that platelets drive smooth muscle metaplasia (SMM) and fibrogenesis in endometriosisthrough epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). To see whether this is true in vivo, this prospective, randomized, and serially evaluated mouse investigation was conducted. Endometriosis was induced in female Balb/C mice, which were then randomly divided into two groups: Tanshinone IIA (TAN) and control (CTL) groups. TAN mice were treated with TAN but CTL mice received none. Every week until the 6th week after induction, five mice from each group were killed. Lesion weight was measured and lesion samples were subjected to immunohistochemistry and histochemistry analysis of platelet aggregation (CD41), E-cadherin, TGF-β1, phosphorylated Smad3, α-SMA, collagen I, CCN2, LOX, desmin and SM-MHC, and the extent of fibrosis was evaluated by Masson trichrome staining. It was found that endometriotic lesions exhibited progressive cellular changes consistent with the progressive EMT, FMT, SMM, and fibrogenesis. TAN treatment resulted in significant hindrance of EMT, FMT, SMM and fibrogenesis, and reduced lesion weight (all P-values <0.05). These data corroborate the notion that endometriotic lesions undergo progressive EMT and FMT, giving rise to SMM and ultimately fibrosis. This understanding sheds new light onto the natural history of endometriosis.