Oman Med J. 2016 Sep;31(5):336-44.

Evaluation of HE4, CA-125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) in the Preoperative Assessment of Patients with Adnexal Mass.

Al Musalhi K¹, Al Kindi M¹, Al Aisary F¹, Ramadhan F², Al Rawahi T³, Al Hatali K³, Mula-Abed WA¹.

 

Abstract

OBJECTIVES:

To evaluate the validity and compare the performance of cancer antigen-125 (CA-125), human epididymis protein 4 (HE4), the risk of malignancy index (RMI), and the risk of ovarian malignancy algorithm (ROMA) in the diagnosis of ovarian cancer in patients with ovarian lesions discovered during their preoperative work-up investigations.

METHODS:

This prospective, cross-sectional study looked at patients who attended the gynecology department at the Royal Hospital, Muscat, from 1 March 2014 to 30 April 2015, for the evaluation of an ovarian lesion. The inclusion criteria included women who underwent surgical intervention and who had a preoperative pelvic ultrasound with laboratory investigation for CA-125 and HE4. The study validated the diagnostic performance of CA-125, RMI, HE4, and ROMA using histopathological diagnosis as the gold standard.

RESULTS:

The study population had a total of 213 cases of various types of benign (77%) and malignant (23%) ovarian tumors. CA-125 showed the highest sensitivity (79%) when looking at the total patient population. When divided by age, the sensitivity was 67% in premenopausal women. In postmenopausal women, CA-125 had lower sensitivity (89%) compared to RMI, HE4, and ROMA (93% each). A high specificity of 90% was found for HE4 in the total patient population, 93% in premenopausal women and 75% in postmenopausal women. CA-125 had the highest specificity (79%) in postmenopausal women. Both CA-125 and RMI were frequently elevated in benign gynecological conditions particularly in endometriosis when compared to HE4 and ROMA. We also studied modifications of the optimal cut-offs for the four parameters. Both CA-125 and RMI showed a significant increase in their specificity if the cut-off was increased to ≥ 60 U/mL for CA-125 and to ≥ 250 for RMI. For HE4, we noted an improvement in its specificity in postmenopausal women when its cut-off was increased to140 pmol/L.

CONCLUSIONS:

HE4 and ROMA showed a very high specificity, but were less sensitive than CA-125 and RMI in premenopausal women. However, they were of comparable sensitivity in postmenopausal women and were valuable in distinguishing benign ovarian tumors or endometriosis from ovarian cancer. Modifying the cut-off values of the different markers resulted in a higher accuracy compared to the standard cut-offs, but at the expense of reduced sensitivity.

 

 

Reprod Biol Endocrinol. 2016 Sep 7;14(1):56.

Chronic effects of an anti-angiogenic thrombospondin-1 mimetic peptide, ABT-898, on female mouse reproductive outcomes.

Edwards AK¹, Olariu I¹, Nakamura DS¹, Ahn SH¹, Tayade C².

 

Abstract

BACKGROUND:

Angiogenesis is an essential process in endometriosis disease progression. Earlier, we demonstrated that anti-angiogenic peptide, ABT-898 prevents neoangiogenesis of human endometriotic lesions in a xenograft mouse model. Since angiogenesis is essential for normal ovarian and uterine function, we evaluated effects of ABT-898 on normal female reproductive processes in mice.

METHODS:

Cycling female C57BL/6N mice were dosed with ABT-898 (100 mg/kg) or 5 % dextrose control for 21 consecutive days to cover multiple estrous cycles (average estrous cycle 4 to 5 days in mice). Pregnant female mice were dosed with ABT-898 (100 mg/kg) or control on alternate days over the course of gestation, beginning at gestation day 7.5 to 17.5 (gestation length 21 days). Histological analysis along with CD31 and Vimentin immunohistochemistry were performed on ovaries and uteri obtained from treated and control mice. To understand the influence of ABT-898 on systemic angiogenic factors, a Pro Mouse Cytokine 9-plex assay was performed on plasma samples obtained from mice prior to treatment, during the second week of ABAT-898 or control treatment and on the last day of treatment.

RESULTS:

ABT-898 did not affect the number of estrous cycles over the 21 day treatment compared to control. Histological analysis of ovaries found no difference in the number of primordial, primary, secondary, and antral follicles between ABT-898 treated and control groups. Similarly, no difference was observed in the microvessel density between ABT-898 treated and control uteri, ovarian follicles or corpus luteum when assessed using CD31 or vimentin immunohistochemistry. Electron microscopy revealed similar capillary structure and appearance in both ABT-898 treated and control uteri. Although peripheral blood angiogenic cytokine profiles (IL-15, IL-18, M-CSF, b-FGF, PDGF-bb, MIG, MIP-2, LIF and VEGF) changed over the course of the intervention, there was no significant difference between ABT-898 and control groups at any of the studied time points. Treatment with ABT-898 during pregnancy had no effect on litter size at birth, pup weight at birth or pup weight at weaning.

CONCLUSION:

Our findings suggest that ABT-898 may not alter angiogenesis dependent reproductive processes in female mice. However, an extensive reproductive toxicology screening is required to substantiate use of ABT-898 in future.

 

 

Breast Cancer Res Treat. 2016 Oct;159(3):545-52.

A prospective study of endometriosis and risk of benign breast disease.

Farland LV^1,2, Tamimi RM^3,4, Eliassen AH^3,4, Spiegelman D^3,4,5, Collins LC⁶, Schnitt SJ⁶, Missmer SA^3,7,4.

 

Abstract

PURPOSE:

Given the altered hormonal and inflammatory environment of women with endometriosis, several studies have suggested a positive association between endometriosis and breast cancer, although findings have been mixed. This study investigates the relationship between endometriosis and benign breast disease (BBD), benign lesions that are associated with an increased risk of breast cancer.

METHODS:

Among women in the Nurses’ Health Study II followed from 1991-2003 (n = 76,393), we investigated the association between laparoscopically confirmed endometriosis and biopsy-confirmed BBD. Cox proportional hazard models, adjusted for a priori potential confounding factors, were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI). Across follow-up, 2011 BBD biopsies were collected and centrally reviewed by study pathologists (nonproliferative = 675, proliferative = 1336). Effect modification by infertility history and use of screening mammography was investigated.

RESULTS:

Endometriosis was associated with a modest increased risk of biopsy-confirmed BBD in crude and multivariable adjusted models (HR 1.20, 95 % CI 1.00-1.43). When evaluating subtypes of BBD, we did not see different associations for nonproliferative or proliferative BBD lesions, as endometriosis was associated with a modest increased risk for both (HR nonproliferative 1.15, 95 % CI 0.84-1.57; HR proliferative 1.22, 95 % CI 0.98-1.52). The association between endometriosis and proliferative BBD appeared strongest among women who had ever experienced infertility (HR 1.50, 95 % CI 1.12-2.03; P value, test for heterogeneity = 0.05). Sensitivity analyses investigating screening behaviors between those with and without endometriosis did not significantly alter results.

CONCLUSION:

Endometriosis was associated with a modest increased risk of both proliferative and nonproliferative BBD, although future work should replicate this novel finding.

 

 

Eur Rev Med Pharmacol Sci. 2016 Aug;20(16):3319-26.

miRNA-15a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis.

Liu XJ¹, Bai XG, Teng YL, Song L, Lu N, Yang RQ.

 

Abstract

OBJECTIVE:

miRNAs have been recently reported to contribute to the etiology of endometriosis in stem cells. However, the mechanisms remain unclear. The aim of this investigation is to explore the expression of miR-15a-5p and VEGFA in endometrial samples from patients with or without endometriosis. And then examine the regulation by miR-15a-5p on the expression of VEGFA.

PATIENTS AND METHODS:

Here we collected 31 endometrial samples from patients with or without endometriosisand characterized the miRNAs expression profiles of these two groups. Then, we investigated the regulation by microRNA-15a-5p (miR-15a-5p) on the expression of vascular endothelial growth factor (VEGF) in endometrial mesenchymal stem cells.

RESULTS:

It was demonstrated that there was dramatically down-regulation of miR-15a-5p in the patients with endometriosis, compared with control patients. Moreover, we found that the up-regulation of miR-15a-5p suppressed cell proliferation, migration and invasion of these ectopic stem cells by targeting the 3′ untranslated region of VEGFA.

CONCLUSIONS:

Taken together, this newly identified miR-15a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility as well as angiogenesis, and may facilitate the development of potential therapeutics against endometriosis.

 

 

Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:584-97.

Cytotoxicity assessment of adipose-derived mesenchymal stem cells on synthesized biodegradable Mg-Zn-Ca alloys.

Fazel Anvari-Yazdi A¹, Tahermanesh K², Hadavi SM³, Talaei-Khozani T⁴, Razmkhah M⁵, Abed SM⁶, Mohtasebi MS⁵.

 

Abstract

Magnesium (Mg)-based alloys have been extensively considered as biodegradable implant materials for orthopedic surgery. Mg and its alloys are metallic biomaterials that can degrade in the body and promote new bone formation. In this study, the corrosion behavior and cytotoxicity of Mg-Zn-Ca alloys are evaluated with adipose-derived mesenchymal stem cells (ASCs). Mg-2Zn and Mg-2Zn-xCa (x=1, 2 and 3wt.%) alloys were designated. Mg alloys were analyzed with scanning electron microscopy and potentiodynamic polarization. To understand the in-vitro biocompatibility and cytotoxicity of Mg-2Zn and Mg-2Zn-xCa alloys, ASCs were cultured for 24 and 72h in contact with 10%, 50% and 100% extraction of all alloys prepared in DMEM. Cell cytotoxicity and viability of ASCs were examined by MTT assay. Alloying elements including Zn and Ca improved the corrosion resistance of alloys were compared with pure Mg. The cytotoxicity results showed that all alloys had no significant adverse effects on cell viability in 24h. After 72h, cell viability and proliferation increased in the cells exposed to pure Mg and Mg-2Zn-1Ca extracts. The release of Mg, Zn and Ca ions in culture media had no toxic impacts on ASCs viability and proliferation. Mg-2Zn-1Ca alloy can be suggested as a good candidate to be used in biomedical applications.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Oct;205:170-3.

Epithelial ovarian cancer and type of peritoneal insult: a case-control study.

Ruiz MP¹, Morales-Ramirez PB², Dziadek OL², Algren SD³.

 

Abstract

OBJECTIVE:

To evaluate the association between different types of peritoneal insults and the development of sporadic epithelial ovarian cancer (EOC) subtypes in the general population.

STUDY DESIGN:

Hospital based case control study comparing sporadic cases of EOC with age matched control group between 2003 and 2008. Medical, surgical, and gynecological histories were compared between 208 women with histological diagnosis of EOC and 224 women in the control group matched for age at presentation for well woman examination.

RESULTS:

18% patients in the study population and 5% patients in the control group had history of diverticulosis (OR 7.3, 95% CI 2.8-19.1). 10% patients in the study populations and 39% patients in the control group had history of diabetes mellitus (OR 0.41, 95% CI 0.23-0.75). Sub classification of EOC into type 1 and type 2 further revealed 12% patients (OR 0.44, 95% CI 0.22-0.87) in type 1 group, 35% patients (OR 0.43, 95% CI 0.27-0.69) in type 2 group, and 71% patients in the control group had no prior surgical history. Furthermore, 3% patients (OR 0.27; 95% CI 0.08-0.9) in the type 1 group, 48% patients (OR 2.0, CI 95% 1.24-3.24) in the type 2 group, and 41% patients in the control group had history of bilateral tubal ligation (BTL).

CONCLUSION:

A significant association was found between diverticulosis, hysterectomy and endometriosisincreasing the likelihood of type 1 EOC; while diverticulosis, exploratory laparotomy and hysterectomy increased the likelihood of type 2 EOC. BTL was significantly associated with decreasing the likelihood of type 1 EOC, but increasing the likelihood of type 2 EOC. Diabetes mellitus and no prior surgical history were found to significantly decrease the likelihood of all EOC.

 

 

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jan 4;72:60-72.

Histone deacetylases inhibitors (HDACis) as novel therapeutic application in various clinical diseases.

Qiu X¹, Xiao X¹, Li N¹, Li Y².

 

Abstract

Accumulating evidence suggests that histone hypoacetylation which is partly mediated by histone deacetylase (HDAC), plays a causative role in the etiology of various clinical disorders such as cancer and central nervous diseases. HDAC inhibitors (HDACis) are natural or synthetic small molecules that can inhibit the activities of HDACs and restore or increase the level of histone acetylation, thus may represent the potential approach to treating a number of clinical disorders. This manuscript reviewed the progress of the most recent experimental application of HDACis as novel potential drugs or agents in a large number of clinical disorders including various brain disorders including neurodegenerative and neurodevelopmental cognitive disorders and psychiatric diseases like depression, anxiety, fear and schizophrenia, and cancer, endometriosis and cell reprogramming in somatic cell nuclear transfer in human and animal models of disease, and concluded that HDACis as potential novel therapeutic agents could be used alone or in adjunct to other pharmacological agents in various clinical diseases.

 

 

J Assist Reprod Genet. 2016 Nov;33(11):1487-1492.

Polymorphisms of ICAM-1 and IL-6 genes related to endometriosis in a sample of Brazilian women.

Bessa NZ¹, Francisco DO¹, Andres MP², Gueuvoghlanian-Silva BY³, Podgaec S^2,3, Fridman C⁴.

 

Abstract

PURPOSE:

This study investigated the possibility of K469E (rs5498) and G241R (rs1799969) polymorphisms, in ICAM-1 gene, and G634C (rs1800796), in IL-6 gene, being associated with the occurrence of endometriosis in a sample of Brazilian women.

METHODS:

We genotyped 200 women (100 in control group and 100 in endometriosis group) by PCR-RFLP technique for G634C, K469E, and G241R polymorphisms.

RESULTS:

No significant difference was observed in genotypic frequency between control and endometriosisgroups for G634C and K469E polymorphisms (p = 0.61 and p = 0.22, respectively). In addition, no significant difference between stages I-II and III-IV of the disease was found for both SNPs (p = 0.63 and p = 0.24, respectively). All individuals were wild homozygotes for G241R polymorphism.

CONCLUSION:

This study suggests that polymorphisms K469E, G241R, and G634C are not associated with increased susceptibility to endometriosis in Brazilian women.

 

 

Expert Opin Pharmacother. 2016 Oct;17(15):2019-31.

Pharmacologic treatment of the ovarian endometrioma.

Benagiano G¹, Guo SW², Bianchi P³, Puttemans P⁴, Gordts S⁴, Petraglia F⁵, Brosens I⁶.

 

Abstract

INTRODUCTION:

Treatment of ovarian endometriomas is commonly achieved through laparoscopic surgery and this can be effective in eliminating the disease, although a majority of recent trials documented an adverse effect of surgery on ovarian reserve markers. With the advancement in imaging techniques, ovarian endometriomas are increasingly diagnosed at an earlier stage when the endometrioma may be smaller, less fibrotic and more responsive to medical treatment, making an evaluation of medical options critically important.

AREAS COVERED:

The review focuses on currently utilized pharmacologic therapies for endometrioma (oral contraceptives, the levonorgestrel-releasing IUS, the hormone-releasing subdermal implant, Implanon); experimental and future treatments are also mentioned (GnRH antagonists, progesterone receptor modulators, antioestrogens, newer subdermal implants and intracystic administration of pharmacologic agents). Finally, the usefulness of post-operative adjuvant medical treatments is discussed Expert opinion: Today, reliable, non-invasive diagnostic procedures of an ovarian endometrioma are available and should be utilized to identify its presence and type of pathology. In a young patient, classic medical therapies such as oral contraceptives and synthetic progestins should be tried first to alleviate symptoms. Only when these regimens fail, should a minimally invasive surgery be envisaged. Following endoscopic surgery, adjuvant medical treatment may reduce recurrence of both symptoms and the lesion.

 

 

Radiographics. 2016 Sep-Oct;36(5):1579-96

Pelvic Inflammatory Disease: Multimodality Imaging Approach with Clinical-Pathologic Correlation.

Revzin MV¹, Mathur M¹, Dave HB¹, Macer ML¹, Spektor M¹.

 

Abstract

Pelvic inflammatory disease (PID) is a common medical problem, with almost 1 million cases diagnosed annually. Historically, PID has been a clinical diagnosis supplemented with the findings from ultrasonography (US) or magnetic resonance (MR) imaging. However, the diagnosis of PID can be challenging because the clinical manifestations may mimic those of other pelvic and abdominal processes. Given the nonspecific clinical manifestations, computed tomography (CT) is commonly the first imaging examination performed. General CT findings of early- and late-stage PID include thickening of the uterosacral ligaments, pelvic fat stranding with obscuration of fascial planes, reactive lymphadenopathy, and pelvic free fluid. Recognition of these findings, as well as those seen with cervicitis, endometritis, acute salpingitis, oophoritis, pyosalpinx, hydrosalpinx, tubo-ovarian abscess, and pyometra, is crucial in allowing prompt and accurate diagnosis. Late complications of PID include tubal damage resulting in infertility and ectopic pregnancy, peritonitis caused by uterine and/or tubo-ovarian abscess rupture, development of peritoneal adhesions resulting in bowel obstruction and/or hydroureteronephrosis, right upper abdominal inflammation (Fitz-Hugh-Curtis syndrome), and septic thrombophlebitis. Recognition of these late manifestations at CT can also aid in proper patient management. At CT, careful assessment of common PID mimics, such as endometriosis, adnexal torsion, ruptured hemorrhagic ovarian cyst, adnexal neoplasms, appendicitis, and diverticulitis, is important to avoid misinterpretation, delay in management, and unnecessary surgery. Correlation with the findings from complementary imaging examinations, such as US and MR imaging, is useful for establishing a definitive diagnosis. (©)RSNA, 2016.

 

 

 

 

Gynecol Obstet Invest. 2017;82(2):105-112

Malignant Transformation of Vaginal Endometriosis – A Review of Literature.

Cozzolino M¹, Nasioudis D, Sisti G, Coccia ME.

 

Abstract

BACKGROUND:

The study aimed to examine all available evidence regarding primary vaginal cancer arising from endometriosis from an evidence-based perspective.

METHODS:

A literature search in Medline and EMBASE databases was conducted. The following key words were employed: ‘vaginal cancer’ AND ‘endometriosis malignant transformation’ OR ‘endometriosis’.

RESULTS:

A total of 23 eligible studies were identified and included in the present review providing information for 37 patients. Endometrioid adenocarcinoma (17 cases) was the most common histological subtype followed by endometrial stromal sarcoma (6 cases). The majority of patients received cancer-directed surgery while adjuvant treatment was commonly employed for patients with sarcomas.

CONCLUSION:

Vaginal cancer arising from endometriosis is exceedingly rare. The mainstay of treatment is surgical excision. Mean follow-up of patients was relative short. Tumor recurrence was often observed, and the outcome was less favorable for patients with non-epithelial tumors.

 

 

Orphanet J Rare Dis. 2016 Sep 13;11(1):124.

Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study.

Hugon-Rodin J¹, Lebègue G¹, Becourt S¹, Hamonet C², Gompel A³.

 

Abstract

BACKGROUND:

Hypermobile Ehlers-Danlos syndrome (hEDS), is probably the most common disease among heritable connective tissue disorders. It affects women more than men and causes symptoms in multiple organs. It is associated with chronic pain, skin fragility and abnormal bleeding. These characteristics may hamper reproductive life. We conducted a study to evaluate the gynecologic and obstetric outcomes in women with hEDS. We also explored a possible hormonal modulation of the hEDS symptoms. The gynecologic and obstetric history of 386 consecutive women diagnosed with hEDS was collected by a standardized questionnaire and a medical consultation performed by a senior gynecologist in an expert centre for hEDS between May 2012 and December 2014.

RESULTS:

We observed a high frequency of gynecologic complaints, specifically: menorrhagia (76 %), dysmenorrhea (72 %) and dyspareunia (43 %). Endometriosis was not highly prevalent in this population. The obstetric outcomes were similar to those of the general French population for deliveries by cesarean section (14.6 %) and premature births (6.2 %) but the incidence of multiple spontaneous abortion (13 %) and spontaneous abortion (28 %) were significantly higher. A subset of women were sensitive to hormonal fluctuations with more severe symptoms occurring during puberty, prior to menstruation, during the postpartum period as well as on oral contraception.

CONCLUSIONS:

Increased awareness of the gynecological symptomatology in women with hEDS can help discriminate between endometriosis and thus prevent useless, and potentially dangerous, surgery. This study also suggests that hormonal modulation may be an appropriate treatment for a subset of women with hEDS.

 

 

Hum Reprod. 2016 Nov;31(11):2598-2608.

miR-196a overexpression activates the MEK/ERK signal and represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis.

Zhou M^1,2, Fu J¹, Xiao L¹, Yang S¹, Song Y¹, Zhang X¹, Feng X¹, Sun H³, Xu W³, Huang W⁴.

 

Abstract

STUDY QUESTION:

Do microRNAs (miRNAs) contribute to aberrant progesterone receptor (PGR) expression in the eutopic endometrium of women with endometriosis? SUMMARY ANSWER: miR-196a upregulates MEK/ERK signalling, mediating a downregulation of PGR expression in the eutopic endometrium of women with minimal or mild endometriosis.

WHAT IS KNOWN ALREADY:

Implantation failure is strongly suggested as an underlying cause for the observed infertility in minimal or mild endometriosis. Progesterone resistance, which is mainly caused by aberrantly expressed progesterone receptor in the eutopic endometrium, is considered as a key factor of decreased endometrial receptivity; thus far, epigenetics, but not miRNA, has been shown to affect PGR expression in the endometrium.

STUDY DESIGN SIZE, DURATION:

Microarray analysis was used to analyse the eutopic endometrium. The differential expression of miR-196a was validated. Bioinformatics analysis predicted that miR-196a targets the 3′-untranslated region (UTR) of the PGR. The relationship between the miR-196a level and PGR expression was studied and the role of the MEK/ERK signal pathway was investigated.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Total RNA was extracted from eutopic endometrium samples in three infertile women with mild/minimal endometriosis and three disease-free control subjects. The miRNA and mRNA expression levels were analysed by microarray analysis. The miR-196a expression was validated by qRT-PCR [endometriosis (n = 22) and control (n = 20)], while functional analysis utilised in vitro transfection of endometrial stromal cells (ESCs), induction of decidualization of ESCs, and luciferase reporter assays in 293 T cell lines.

MAIN RESULTS AND THE ROLE OF CHANCE:

A total of 66 dysregulated miRNAs and 357 dysregulated mRNAs were screened by microarray analysis. miR-196a and P-MEK/P-ERK were both found to be significantly upregulated in the eutopic endometrium in patients with mild/minimal endometriosis. PGR and PGR-B mRNA were inhibited by miR-196a overexpression and upregulated by miR-196a inhibition. Luciferase reporter failed to confirm the target regulation of miR-196a on PGR. Transfection of ESCs with a miR-196a mimic led to an increase in the P-MEK/P-ERK protein levels, decrease in the PGR protein levels, and atypical decidualization. Following miR-196a inhibition, the P-MEK/P-ERK protein was downregulated and the PGR protein was upregulated. Inhibition of P-MEK/P-ERK also increased PGR expression.

LARGE SCALE DATA:

Data are presented in Supplementary Tables SI and SII.

LIMITATIONS REASONS FOR CAUTION:

This study focused on the role of miR-196a, and therefore does not involve other miRNAs; hence, it is possible that other miRNAs may also be responsible for progestin resistance in endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS:

Our data revealed altered miRNA expression and activated MEK/ERK signalling in the eutopic endometrium in minimal or mild endometriosis. We showed that the miR-196a level is associated with reduced expression of PGR isoforms through MEK/ERK, suggesting that miR-196a and MEK/ERK are both potential biomarkers of endometriosis. These results provide a novel approach to target the mechanisms behind progesterone resistance in endometriosis.

STUDY FUNDING/COMPETING INTERESTS:

This research was supported by the National Natural Science Foundation of China (No. 81370693). The authors have no conflicts of interest.

 

 

Hum Reprod. 2016 Nov;31(11):2577-2586.

Dyspareunia and depressive symptoms are associated with impaired sexual functioning in women with endometriosis, whereas sexual functioning in their male partners is not affected.

De Graaff AA¹, Van Lankveld J², Smits LJ³, Van Beek JJ⁴, Dunselman GA⁵.

 

Abstract

STUDY QUESTION:

To what extent are endometriosis and its related physical and mental symptoms associated with the perceived level of sexual functioning in women and their male partners?

SUMMARY ANSWER:

Dyspareunia and depressive symptoms are associated with impaired sexual functioning in women with endometriosis, whereas sexual functioning in their male partners is not affected.

WHAT IS KNOWN ALREADY:

Women with endometriosis suffer from more dyspareunia, lower sexual functioning, and lower quality of life. In qualitative studies, partners of women with endometriosis report that endometriosisaffected their quality of life and produced relational distress.

STUDY DESIGN SIZE, DURATION:

In this cross-sectional study, sexual functioning in women with endometriosis(n = 83) and their partners (n = 74) was compared with sexual functioning in a control group of women attending the outpatient department for issues related to contraception (n = 40), and their partners (n = 26).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women and partners were recruited in the Maastricht University Medical Centre (MUMC) and the VieCuri Medical Centre Venlo between June 2011 and December 2012. All participants were asked to complete a set of online questionnaires.

MAIN RESULTS AND THE ROLE OF CHANCE:

Response rates were 59.3% (83/140) for women with endometriosis and 52.3% (74/140) for their partners. Response rates in the control group were respectively 43.2% and 27.4% (41/95 and 27/95), of whom 40 women and 26 partners could be included in the study. Women with endometriosis as compared with the control group, reported significantly more frequent pain during intercourse (53% versus 15%, P < 0.001); higher levels of chronic pain (median VAS 2.0 cm versus 0.0 cm, P < 0.001); more impairment of sexual functioning (median Female Sexual Function Index 25.4 versus 30.6, P < 0.001); more impairment of quality of life (median Short Form-12 66.3 versus 87.2, P < 0.001); more pain catastrophizing (mean Pain Catastrophizing Scale 17.8 versus 8.5, P < 0.001), more depression and anxiety symptoms (median Hospital Anxiety and Depression Scale for depression 7 versus 4, P < 0.001 and for anxiety 4 versus 1, P < 0.001). Sexual functioning was comparable between male partners of women with endometriosis and male partners of the control group based on the International Index of Erectile Function. Logistic regression analyses showed that dyspareunia (OR 0.54; 95% CI 0.39-0.75) and depressive symptoms (OR 0.761; 95% CI 0.58-0.99) were independent and significant negative predictors for sexual functioning. Chronic pelvic pain (OR 0.53; 95% CI 0.35-0.81) and depressive symptoms (OR 0.65; 95% CI 0.44-0.96) were independent and significant negative predictors for quality of life.

LIMITATIONS, REASONS FOR CAUTION:

Patient recruitment was performed in one tertiary care centre and to a lesser extent one general hospital, possibly leading to an over-representation of patients with more severe endometriosis. All participating women had a partner and are therefore ‘survivors’ in relationship terms. This may have led to an underestimation of the impact of endometriosis on sexual functioning.

WIDER IMPLICATIONS OF THE FINDINGS:

It would be worthwhile to further explore the role of depressive symptoms in women with symptomatic endometriosis and to assess the effect of treatment of depressive symptoms on sexual functioning and quality of life. The fact that the partners did not report impaired sexual functioning could be a reassuring thought to women that might be discussed in the consulting room.

STUDY FUNDING/COMPETING INTERESTS:

The study was funded by the MUMC. An unconditional research grant was given by the Dutch Society of Psychosomatic Obstetrics and Gynaecology (21 June 2011).

 

 

Hum Reprod. 2016 Nov;31(11):2587-2597.

miR-503, a microRNA epigenetically repressed in endometriosis, induces apoptosis and cell-cycle arrest and inhibits cell proliferation, angiogenesis, and contractility of human ovarian endometriotic stromal cells.

Hirakawa T¹, Nasu K^2,3, Abe W^1,4, Aoyagi Y¹, Okamoto M¹, Kai K¹, Takebayashi K¹, Narahara H¹.

 

Abstract

STUDY QUESTION:

Is the micro-RNA (miRNA) miR-503, downregulated in endometriotic cyst stromal cells (ECSCs) and does this affect the cell cycle, cell proliferation, angiogenesis and contractility of these cells? SUMMARY ANSWER: miR-503 expression is downregulated in ECSCs by DNA hypermethylation and this contributes to their proliferation, resistance to apoptosis, extracellular matrix (ECM) contractility and angiogenesis through effects on cyclin D1, B-cell lymphoma/leukemia (Bcl)-2, Ras homology A  and vascular endothelial growth factor A (VEGF-A).

WHAT IS KNOWN ALREADY:

A variety of miRNAs are demonstrated to involve in the pathogenesis of endometriosis. miR-503 is a miRNA with tumor-suppressor functions, whose expression is suppressed in ECSCs.

STUDY DESIGN, SIZE, DURATION:

We isolated ECSCs and normal endometrial stromal cells (NESCs) from ovarian endometriotic tissues (n = 32) and eutopic endometrial tissues without endometriosis (n = 8), respectively.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

We investigated the functions of miR-503 by using miR-503-transfected ECSCs and the DNA methylation status of miR-503 gene in ECSCs and NESCs by combined bisulfite restriction analysis.

MAIN RESULTS AND THE ROLE OF CHANCE:

In ECSCs, miR-503 is downregulated by the DNA hypermethylation of its gene. The transfection of miR-503 into ECSCs resulted in the inhibition of cell proliferation and induction of cell-cycle arrest at G0/G1 phase through the suppression of cyclin D1, the induction of apoptosis through Bcl-2 suppression, the inhibition of VEGF-A production and the attenuation of ECM contractility via the suppression of Rho/Rho-associated coiled-coil-forming protein kinase-pathways.

LARGE SCALE DATA:

NA.

LIMITATIONS, REASONS FOR CAUTION:

The present experiments were carried out only with the stromal component of endometriosis and eutopic endometrium. The experiments with the eutopic endometrial stromal cells from women with endometriosis are not performed.

WIDER IMPLICATIONS OF THE FINDINGS:

Our findings indicate that epigenetically repressed miR-503 in ECSCs is involved in the acquisition of endometriosis-specific cellular functions.

STUDY FUNDING/COMPETING INTERESTS:

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 13237327 to K.N., no. 26861335 to K.K. and no. 23592407 to H.N.) and the Kanzawa Medical Research Foundation (to K.K.). There are no conflicts of interest to declare.

 

 

 

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Oct;205:174-88.

Associations between various possible promoter polymorphisms of MMPs genes and endometriosis risk: a meta-analysis.

Yang H¹, Liu J¹, Fan Y¹, Guo Q², Ge L¹, Yu N¹, Zheng X¹, Dou Y¹, Zheng S³.

 

Abstract

BACKGROUND:

Endometriosis is a common, benign gynecological disorder affecting life quality of reproductive-aged women. Several polymorphisms in the promoter regions of the MMPs genes have been reported that were related to endometriosis risk. However, there are many contradictory conclusions, and no meta-analysis focused on this association systematically.

OBJECTIVES:

To evaluate the associations between various possible polymorphisms of MMPs genes and endometriosis risk, and confirm which kinds of MMPs genetic polymorphisms are associated with endometriosisrisk, in order to identify the etiology and pathogenesis of endometriosis and the potential effective markers for predicting the predisposition to endometriosis.

SEARCH STRATEGY:

An exhaustive electronic literature search was conducted, using keywords MMP, endometriosis and SNP, in English and Chinese.

SELECTION CRITERIA:

All eligible case-control studies by written in English or Chinese of the associations of MMPs polymorphisms with endometriosis risk, which had sufficient data for examining an odds ratio (OR) with 95% confidence interval (CI), were identified up to March 1, 2015.

DATA COLLECTION AND ANALYSIS:

A total of 1833 patients and 2190 controls from 12 studies were included. Allele frequency differences between cases and controls were performed with the use of odds ratios (ORs) and their respective 95% confidence intervals (CIs) for five genetic models.

MAIN RESULTS:

For MMP-1 -1607 1G>2G (rs1799750) polymorphism, significant associations were observed both in overall comparison and subgroup analyses based on the stage of endometriosis, ethnicity of each study population and method of genotyping under four genetic models. In contrast, for MMP-2 15918 T>C (rs243847), MMP-2 -753 C>T (rs2285053), MMP-7 -181 A>G (rs11568818), MMP-9 -1562 C>T (rs3918242) and MMP-9 R279Q (rs17576) polymorphisms, no association was found in overall comparison, but in subgroup analyses based on source of control, stage of endometriosis, or ethnicity.

CONCLUSIONS:

MMP-1 -1607 1G>2G polymorphism might modulate risk of endometriosis, so does the MMP-2 15918 T>C, MMP-2 -753 C>T, MMP-7 -181 A>G, MMP-9 -1562 C>T and MMP-9 R279Q polymorphisms in some subgroups.

 

 

Pediatr Ann. 2016 Sep 1;45(9):e332-5

Endometriosis in Adolescence: Practical Rules for an Earlier Diagnosis.

Zannoni L, Forno SD, Paradisi R, Seracchioli R.

 

Abstract

Dysmenorrhea, cyclic pelvic pain, and acyclic pelvic pain are common in adolescent girls, and at least 10% of these girls are at risk for subsequent development of endometriosis. In this article we highlight practical tips for the management of dysmenorrhea and chronic pelvic pain and how to diagnose endometriosis as early as possible and detect patients at risk for developing the disease in the future. We suggest five practical rules for managing adolescents with dysmenorrhea and chronic pelvic pain: (1) Never underestimate the pain; (2) Always consider endometriosis as a possible cause of severe cyclic pain; (3) Obtain a detailed and accurate history before performing clinical evaluation and pelvic sonography; (4) Treat the pain with hormonal therapies (combined oral contraceptives or progestogen-only pill) and analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs); and (5) Plan frequent follow-up visits to re-evaluate the patient. [Pediatr Ann. 2016;45(9):e332-e335.].

 

 

Int J Clin Oncol. 2017 Feb;22(1):118-125.

Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

Miyagi E¹, Maruyama Y², Mogami T², Numazaki R², Ikeda A³, Yamamoto H³, Hirahara F².

 

Abstract

BACKGROUND:

We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths.

METHODS:

API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves.

RESULTS:

The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05).

CONCLUSIONS:

API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

 

 

Abdom Radiol (NY). 2016 Dec;41(12):2364-2379.

Sonographic evaluation of deep endometriosis: protocol for a US radiology practice.

Young SW¹, Saphier NB², Dahiya N², Menias CO², Bridge AA², Czaplicki CD², Patel MD².

 

Abstract

Endometriosis is a common condition with significant morbidity, including pain and subfertility, which is often subject to a delay in diagnosis. Ultrasound has been successfully utilized, mostly outside North America, to preoperatively stage deep endometriosis, but in these international settings, imaging is typically performed solely by expert radiologists and gynecologists. We outline a method for detailed sonographic survey of the lower abdomen and pelvis to ensure optimum detection and communication of disease extent that is geared to radiologists practicing ultrasound in the United States, with the use of diagnostic medical sonographers.

 

 

 

 

Surg Case Rep. 2016 Dec;2(1):97

A case of small intestinal endometrioid adenocarcinoma.

Ogi Y¹, Yamaguchi T², Kinugasa Y¹, Shiomi A¹, Kagawa H¹, Yamakawa Y¹, Numata M¹, Furutani A¹, Abe M³.

 

Abstract

Endometriosis generally occurs in the ovary. Intestinal endometriosis is rare. About 1 % of all endometriosis cases become malignant. Malignant transformation of small intestinal endometriosis is very rare. A 55-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and omentectomy for endometriosis 7 years ago presented to her primary care doctor with melena. A tumor was detected in the right lower abdomen by ultrasonography. The doctor referred her to our hospital. Computed tomography demonstrated a lobulated tumor ventral to the right common iliac vessels. Magnetic resonance imaging demonstrated that the tumor had heterogeneous intensity on T2-weighted images. Several small cysts with high intensity were observed caudal to the tumor on T2-weighted images. We performed partial small intestinal resection for the lesion. The tumor was diagnosed as endometrioid adenocarcinoma of the small intestine. She has been relapse-free for 5 years after surgery. Only three cases of malignant transformation of small intestinal endometriosis have been reported previously. It is very rare for long-term survival to be obtained with surgery alone, as in our case. This case report highlights the imaging findings for malignant transformation of intestinal endometriosis.

 

 

BJOG. 2016 Sep;123 Suppl 3:76-81.

Endometriosis has no negative impact on outcomes of in vitro fertilisation in women with poor ovarian response.

Yang X¹, Huang R¹, Cai M¹, Liang X².

 

Abstract

OBJECTIVE:

To compare the in vitro fertilisation (IVF) outcomes of poor ovarian responders among women with laparoscopically diagnosed minimal-mild endometriosis (Group A), moderate-severe endometriosis (Group B) and those without endometriosis (Group C). The comparisons were made separately for age groups younger than 35 years and 35 years or older.

DESIGN:

Retrospective study.

SETTING:

A university-affiliated hospital in Guangzhou, China.

POPULATION:

495 women younger than 35 years old and 543 women aged 35 or older who had poor ovarian response with or without laparoscopically diagnosed endometriosis.

METHODS:

Poor ovarian response (POR) was diagnosed using the Bologna criteria. First cycle parameters were analysed over the same period of time from January 2011 to October 2014.

MAIN OUTCOME MEASURES:

The primary endpoint was the live birth rate per embryo transfer cycle. Secondary outcome measures were clinical pregnancy rate, cycle cancellation rate and miscarriage rate.

RESULTS:

In women aged 35 or older no differences were found among the three subgroups in terms of live birth rate, clinical pregnancy rate, cycle cancellation rate or miscarriage rate; in women aged younger than 35 years, the clinical pregnancy rates were 62.96, 45.45 and 43.27% for Groups A, B and C, respectively (P = 0.028). The live birth rate, cycle cancellation rate and miscarriage rate were not significantly different. Compared with the older group of women, the younger women had a significantly higher live birth rate (P < 0.001).

CONCLUSIONS:

A woman’s age is the most important factor governing the live birth rate with IVF. Endometriosishas no consistent impact on IVF outcomes in women with POR.

 

 

Biotechnol Lett. 2017 Jan;39(1):39-44.

Promigratory and proangiogenic effects of AdipoRon on bone marrow-derived mesenchymal stem cells: an in vitro study.

Malih S¹, Saidijam M¹, Mansouri K², Pourjafar M¹, Tafakh MS¹, Talebzadeh F¹, Najafi R^3,4.

 

Abstract

OBJECTIVES:

To investigate the effect of AdipoRon on major factors involved in survival, migration and neovascularization of rat bone marrow-derived mesenchymal stem cells.

RESULTS:

AdipoRon promoted the MSCs viability. Real-time PCR indicated that the expression of cyclooxygenase-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 matrix metalloproteinase-2 (MMP-2) and MMP-9 were upregulated in AdipoRon-treated MSCs compared to control groups. Prostaglandin E2 (PGE2) level, as well as migration ability of MSCs (scratch assay) was enhanced by AdipoRon preconditioning.

CONCLUSION:

Preconditioning of MSCs with AdipoRon prior to transplantation could enhance cell survival, angiogenesis and migration via activating the COX-2/PGE2/HIF-1 pathway and other contributing factors.

 

 

Biol Reprod. 2016 Dec;95(6):115.

Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice.

Goetz LG¹, Mamillapalli R², Taylor HS¹.

 

Abstract

The gynecological disease endometriosis is characterized by the deposition and proliferation of endometrial cells outside the uterus and clinically is linked to low body mass index (BMI). Gene expression in the liver of these women has not been reported. We hypothesized that endometriosis may impact hepatic gene expression, promoting a low BMI. To determine the effect of endometriosis on liver gene expression, we induced endometriosisin female mice by suturing donor mouse endometrium into the peritoneal cavity and measuring the weight of these mice. Dual-energy X-ray absorptiometry (DEXA) scanning of these mice showed lower body weight and lower total body fat than controls. Microarray analysis identified 26 genes differentially regulated in the livers of mice with endometriosis. Six of 26 genes were involved in metabolism. Four of six genes were upregulated and were related to weight loss, whereas two genes were downregulated and linked to obesity. Expression levels of Cyp2r1, Fabp4, Mrc1, and Rock2 were increased, whereas Igfbp1 and Mmd2 expression levels were decreased. Lep and Pparg, key metabolic genes in the pathways of the six genes identified from the microarray, were also upregulated. This dysregulation was specific to metabolic pathways. Here we demonstrate that endometriosis causes reduced body weight and body fat and disrupts expression of liver genes. We suggest that altered metabolism mediated by the liver contributes to the clinically observed low BMI that is characteristic of women with endometriosis. These findings reveal the systemic and multiorgan nature of endometriosis.

 

 

Arch Gynecol Obstet. 2016 Nov;294(5):897-904.

Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives.

Vetvicka V¹, Laganà AS², Salmeri FM³, Triolo O⁴, Palmara VI⁴, Vitale SG⁴, Sofo V³, Králíčková M⁵.

 

Abstract

PURPOSE:

Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease. Considering the pivotal role of interaction between immune and endometriotic cells, in this paper, we aim to shed light about the role of apoptosis pathways in modulating the fine-regulated peritoneal microenvironment during endometriosis.

METHODS:

Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.

RESULTS:

In normal conditions, endometriotic cells, refluxed through the fallopian tubes into the peritoneal cavity, should be attacked and removed by phagocytes and NK cells. During endometriosis, the breakdown of peritoneal homeostasis causes the failure of scavenging mechanisms, allowing the survival of endometriotic cells. The consequent so-called “immunoescaping” of endometriotic cells could be due, at least in part, to the reduction of apoptotic-mediated pathways previously described.

CONCLUSION:

Considering the large amount of evidence retrieved from in vitro as well as in vivo models, the reduced apoptosis of endometriotic cells together with the increased apoptosis of peritoneal fluid mononuclear cells may address the peritoneal homeostasis to a permissive environment for the progression of the disease.

 

 

Intern Med. 2016;55(18):2595-9

Acute Small Bowel Obstruction and Small Bowel Perforation as a Clinical Debut of Intestinal Endometriosis: A Report of Four Cases and Review of the Literature.

Torralba-Morón A¹, Urbanowicz M, Ibarrola-De Andres C, Lopez-Alonso G, Colina-Ruizdelgado F, Guerra-Vales JM.

 

Abstract

Endometriosis is a quite common pathology, however, intestinal endometriosis is a rare condition, which typically occurs with chronic symptoms. Its acute presentation is very infrequent. We herein report four cases of intestinal endometriosis, in which the clinical debut occurred acutely: two as an acute small bowel obstruction and two as a small bowel perforation. None of the cases had a preoperative diagnosis of endometriosis. The interest of these cases lies in this exceptional form of presentation, such as a surgical acute abdomen. Therefore, intestinal endometriosis should be taken into account in the differential diagnosis of an acute obstructive or perforative process of the small or large bowel.

 

 

J Womens Health (Larchmt). 2017 Feb;26(2):152-158.

Reproductive and Lifestyle Factors Associated with Endometriosis in a Large Cross-Sectional Population Sample.

Saha R¹, Kuja-Halkola R², Tornvall P¹, Marions L¹.

 

Abstract

OBJECTIVES:

Despite the high prevalence of endometriosis among women of reproductive age, risk factors or markers for developing the condition remain largely unknown. Many of the published studies are based on small selected samples. We therefore investigated the relationships of reproductive and lifestyle factors with endometriosis in a large sample of Swedish female twins.

MATERIAL AND METHODS:

This cross-sectional study included 28,822 women. Among these, endometriosis was reported by 1,228 women and the self-reported diagnosis was confirmed by medical records. Potential risk factors or markers for risk considered were age at menarche, level of education, body mass index (BMI), parity, oral contraceptive (OC) use, infertility, coffee consumption, smoking, and alcohol intake, which were investigated using logistic regression with crude and adjusted analyses. We performed within-pair analysis to examine the sensitivity of the results.

RESULTS:

Late age at menarche and higher parity showed an inverse association and infertility showed a strong association with endometriosis. We observed positive associations with coffee consumption and smoking and an inverse association with OC use in crude analysis but not in adjusted analysis. There were no significant associations between level of education, BMI, or alcohol intake and endometriosis. Within-pair analysis showed persistent inverse association of parity and association of infertility with endometriosis.

CONCLUSIONS:

Our study suggests that late age at menarche and higher parity are inversely associated and infertility is strongly associated with endometriosis. Future studies are needed to explore the significance of these factors in the diagnosis of endometriosis and understanding of its etiology.

 

 

Womens Health (Lond). 2016 Jul;12(4):404-6.

Clinical implications of accessory fallopian tube ostium in endometriosis and primary infertility.

Pereira N¹, Kligman I².

 

Abstract

Several variations in fallopian tube anatomy may be noted during the evaluation of infertility. Some anatomical variants such as accessory tubal ostia are rare. A 31-year-old woman presented to our center with a 2-year history of primary infertility. Given her history of dysmenorrhea, a diagnostic laparoscopy was performed. Laparoscopy revealed a left utero-sacral endometriosis implant, which was resected. Although the left fallopian tube was normal, the right fallopian tube was noted to have two prongs with individual ostia. Tubal cannulation confirmed two separate ostia, with chromotubation showing free flow of dye through separate fimbrial ostia of the right fallopian tube. The current case highlights that accessory tubal ostia are rare müllerian duct anomalies seen during laparoscopy and can be associated with endometriois or primary infertility.

 

 

Pan Afr Med J. 2016 May 25;24:79.

Parietal-scar endometriosis after cesarean section: a rare entity.

El Fahssi M¹, Lomdo M¹, Bounaim A¹, Ali AA¹, Sair K¹.

 

Abstract

Wall endometriosis is a rare clinical entity whose pathophysiology remains unclear. It occurs most frequently after gynecologic or obstetric surgery. We report the case of a patient with cyclic pain at the caesarean section scar. Clinical examination showed a 5 cm mass in the right iliac fossa. Tomodensitometry revealed a tissue density mass (45mm on the major axis). Hence, the decision to perform a wide excision of the lesion. Anatomo-pathological examination confirmed the diagnosis of parietal endometriosis. Postoperative sequelae were simple with a follow-up period of 20 months with no recurrence of the mass or of the pain. Our study highlights the characteristics of this disease to allow the health practitioner to understand the importance of diagnosis, of early treatment of this disease as well as of the possibility to prevent it during each gynecologic or obstetric surgery.

 

 

J Endometr Pelvic Pain Disord. 2016 Apr-Jun;8(2):62-66.

Retroperitoneal anatomy during excision of pelvic side wall endometriosis.

Gingold JA¹, Falcone T¹.

 

Abstract

Surgical management of endometriosis has been shown to improve dysmenorrhea at all disease stages and is recommended in severe disease for treatment of infertility. Deeply infiltrating endometriosis (DIE) produces thick inflammatory tissue that precludes visualization of anatomical landmarks and distorts normal anatomy. Excision of DIE poses several technical and surgical challenges that mandate a clear understanding of the anatomy of the pelvic sidewall. This review details relevant surgical anatomy and addresses the principles of safe retroperitoneal entry, ureterolysis and excision of endometriotic lesions. Proper use of these techniques should facilitate safe and successful surgery for management of DIE.

 

 

J Reprod Immunol. 2016 Nov;118:42-49.

Correlation between Cyr61 expression and clinicopathologic parameters in adenomyosis.

Zhang D¹, Xia W¹, Tong T¹, Li C¹, Shi W¹, Yan MX¹, Xue RH¹, Guan XM², Zhang J³.

 

Abstract

Adenomyosis, a benign invasion of endometrium, is closely related to endometriosis. Cysteine-rich 61 (Cyr61), a protein present in all endometrial tissues and menstrual effluents, is known to be associated with endometriosis. However, its relation to adenomyosis has not been determined thus far. Therefore, here, we aimed to investigate the expression of Cyr61 protein in adenomyosis and determine the correlation between Cyr61 expression and clinicopathologic parameters in patients with adenomyosis. One hundred and twenty patients with histologically diagnosed adenomyosis, who underwent hysterectomy for non-endometrial disease were enrolled in this study. Patients were interviewed using a standard questionnaire consisting of sociodemographic characteristics and reproduction history. The severity of dysmenorrhea and menorrhagia was evaluated using the visual analogue scale (VAS) and pictorial blood-loss assessment chart (PBAC). Samples of serum, endometrial tissue, and peritoneal fluid were collected, and Cyr61 mRNA levels were determined by RT-PCR. The Cyr61 protein levels in endometrial and ectopic lesions were determined by immunohistochemistry and those in serum and peritoneal fluid, by ELISA. We found that expression of Cyr61 was higher in the ectopic endometrium than in the eutopic endometrium. Cyr61 expression in the endometrium was correlated with age, number of natural labors, PBAC score, VAS score, uterine volume, adenomyosis type, and concurrent endometriosis. The Cyr61 protein level in the ascites was higher than that in serum, and no correlation existed between them. Our results suggest that the expression of Cyr61 may be indirectly related to the degree of dysmenorrhea and Cyr61 may be involved in the pathogenesis of adenomyosis.

 

 

Reprod Biol Endocrinol. 2016 Sep 20;14(1):60.

Adenomyosis in infertile women: prevalence and the role of 3D ultrasound as a marker of severity of the disease.

Puente JM¹, Fabris A², Patel J², Patel A², Cerrillo M², Requena A², Garcia-Velasco JA³.

 

Abstract

BACKGROUND:

Adenomyosis is linked to infertility, but the mechanisms behind this relationship are not clearly established. Similarly, the impact of adenomyosis on ART outcome is not fully understood. Our main objective was to use ultrasound imaging to investigate adenomyosis prevalence and severity in a population of infertile women, as well as specifically among women experiencing recurrent miscarriages (RM) or repeated implantation failure (RIF) in ART.

METHODS:

Cross-sectional study conducted in 1015 patients undergoing ART from January 2009 to December 2013 and referred for 3D ultrasound to complete study prior to initiating an ART cycle, or after ≥3 IVF failures or ≥2 miscarriages at diagnostic imaging unit at university-affiliated private IVF unit. Adenomyosis was diagnosed in presence of globular uterine configuration, myometrial anterior-posterior asymmetry, heterogeneous myometrial echotexture, poor definition of the endometrial-myometrial interface (junction zone) or subendometrial cysts. Shape of endometrial cavity was classified in three categories: 1.-normal (triangular morphology); 2.- moderate distortion of the triangular aspect and 3.- “pseudo T-shaped” morphology.

RESULTS:

The prevalence of adenomyosis was 24.4 % (n = 248) [29.7 % (94/316) in women aged ≥40 y.o and 22 % (154/699) in women aged <40 y.o., p = 0.003)]. Its prevalence was higher in those cases of recurrent pregnancy loss [38.2 % (26/68) vs 22.3 % (172/769), p < 0.005] and previous ART failure [34.7 % (107/308) vs 24.4 % (248/1015), p < 0.0001]. The presence of adenomyosis has been shown to be associated to endometriosis[35.1 % (34/97)]. Adenomyosis was diagnosed as a primary finding “de novo” in 80.6 % (n = 200) of the infertile patients. The impact on the uterine cavity was mild, moderate and severe in 63.7, 22.6 and 10.1 % of the cases, respectively.

CONCLUSIONS:

Our results indicate that adenomyosis is a clinical condition with a high prevalence that may affect the reproductive results. The described severity criteria may help future validating studies for better counseling of infertile couples.

 

 

Magn Reson Med Sci. 2017 Apr 10;16(2):137-145

Transverse Relaxation Rate of Cyst Fluid Can Predict Malignant Transformation of Ovarian Endometriosis.

Yoshimoto C¹, Takahama J, Iwabuchi T, Uchikoshi M, Shigetomi H, Kobayashi H.

 

Abstract

PURPOSE:

Heme and iron accumulation due to repeated hemorrhage in endometriosis may contribute to a pivotal role in carcinogenesis. We evaluate the clinical application of MR relaxometry in a series of ovarian endometriosis(OE) and endometriosis-associated ovarian cancer (EAOC).

MATERIALS AND METHODS:

A prospective study of diagnostic accuracy was conducted among 82 patients (67 OE and 15 EAOC) to compare MR relaxometry and biochemical measurement of cyst fluid total iron concentration. Transverse relaxation rate R2 value was determined using a single-voxel, multi-echo MR sequence (HISTO) by a 3T-MR system. Phantom experiments were also performed to assess the correlation between the ex vivo R2 values and total iron concentrations.

RESULTS:

Both the results of phantom experiments and in vivo human data confirmed that in vivo R2 values were highly correlated with total iron concentrations. Compared to OE, EAOC exhibit decreased in vivo R2 values and total iron levels, regardless of their age, menopausal status and cyst size. The use of in vivo R2 values retained excellent accuracy in distinguishing EAOC versus OE (sensitivity and specificity: 86% and 94%).

CONCLUSIONS:

We have demonstrated that MR relaxometry provides a noninvasive predictive tool to discriminate between EAOC and OE.

 

 

 

 

Ups J Med Sci. 2016 Sep 20:1-4

Prevention of unintended pregnancy and use of contraception-important factors for preconception care.

Kallner HK^1,2, Danielsson KG¹.

 

Abstract

Preservation of fertility and optimizing health before pregnancy is becoming increasingly important in societies where childbirth often is postponed. Research shows that as women postpone childbirth they achieve higher levels of education and higher incomes. This leads to advantages for their children and for society. However, as women postpone childbearing they are at risk for contracting conditions which may affect fertility and/or pregnancies, pregnancy outcome, and the newborn child. Preconception counseling is therefore becoming increasingly important. Women are often unaware of the added health benefits of contraception and have the right to be well informed so they can make decisions to fulfill their reproductive desires. Contraception can reduce the risk of unintended pregnancies, ectopic and molar pregnancies, and sexually transmitted infections. In addition, hormonal contraceptives reduce the risk of some types of cancer, dysmenorrhea, heavy menstrual bleeding, and anemia and are a treatment for endometriosis. Contraception should increasingly be looked upon as a means of preserving fertility and optimizing health status before a planned pregnancy. Thus, effective contraception can provide women with a possibility of achieving their long-term reproductive goals, although childbearing is actually postponed. The most effective contraceptive methods are the long-acting reversible contraceptives, which have been shown to be highly effective especially in young women who have difficulties with adherence to user-dependent methods. Therefore, these methods should increasingly be promoted in all age groups.

 

 

J Ethnopharmacol. 2016 Dec 4;193:450-455

Viburnum opulus L.: A remedy for the treatment of endometriosisdemonstrated by rat model of surgically-induced endometriosis.

Saltan G¹, Süntar I², Ozbilgin S¹, Ilhan M², Demirel MA³, Oz BE¹, Keleş H⁴, Akkol EK⁵.

 

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Endometriosis is a gynecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. The fruits of Viburnum opulus L. have been used to treat gynecological disorders including primary and secondary dysmenorrhea and ovarian cysts.

MATERIALS AND METHODS:

Air-dried and powdered fruits of V. opulus were extracted sequentially with n-hexane, ethyl acetate (EtOAc), and methanol (MeOH), respectively for four days. Endometriosis was induced by suturing 15mm piece of endometrium into abdominal wall of Sprague Dawley rats. In second laparotomy, the dimensions of endometrial implants were measured and intra-abdominal adhesions were scored. The abdomen was closed. Extracts were daily administered to the rats. At the end of the experiment, rats were sacrified and endometriotic foci areas and intra-abdominal adhesions were re-evaluated. The tissues were also histopathologically investigated. Furthermore, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels of peritoneal fluid were measured. HPLC analyses were conducted on the most potent EtOAc and MeOH extracts to determine the amount of the major compound, chlorogenic acid.

RESULTS:

The endometriotic volumes were found to be reduced significantly in the EtOAc extract-administered group to 30.1mm³ and in the MeOH extract-administered group to 34.7mm³ as compared to the control group. No adhesion was observed in the reference and EtOAc groups. Histopathological data also supported the results. Both EtOAc and MeOH extract-administered groups displayed significant remission in the levels of TNF-α, VEGF and IL-6. When the active extracts were subjected to HPLC analysis, chlorogenic acid was found to be the major compound and the amount of this compound was calculated as 0.5112±0.0012mg and 1.7072±0.0277mg/100mg extract, repectively.

CONCLUSIONS:

The results of the present study indicate that the effectiveness of the fruit extract of V. opulus could be partially attributed chlorogenic acid. Other phenolic compounds could potentiate the activity due to their amount.

 

 

JSLS. 2016 Jul-Sep;20

Strong Association Between Endometriosis and Symptomatic Leiomyomas.

Nezhat C¹, Li A¹, Abed S², Balassiano E¹, Soliemannjad R¹, Nezhat A¹, Nezhat CH³, Nezhat F⁴.

 

Abstract

BACKGROUND AND OBJECTIVES:

The relationship between leiomyoma and endometriosis is poorly understood. Both contribute to considerable pain and may cause subfertility or infertility in women. We conducted this retrospective study to assess the rate of coexistence of endometriosis in women with symptomatic leiomyoma. The primary outcome measured was the coexistence of histology-proven endometriosis in women with symptomatic leiomyoma.

METHODS:

This is a retrospective review of a data-based collection of medical records of 244 patients treated at a tertiary medical center, who were evaluated for symptomatic leiomyoma from March 2011 through December 2015. Of those, 208 patients underwent laparoscopic or laparoscopic-assisted myomectomy or hysterectomy. All patients provided consent for possible concomitant diagnosis and treatment of endometriosis. The remaining 36 patients underwent medical therapy and were excluded from the study. All patients who had myomectomy or supracervical hysterectomy underwent minilaparotomy for extracorporeal morcellation and specimen removal beginning in April 2012.

RESULTS:

Of the 208 patients with the presenting chief concern of symptomatic leiomyoma and who underwent surgical therapy, 181 had concomitant diagnoses of leiomyoma and endometriosis, whereas 27 had leiomyoma. Of the 27 patients, 9 also had adenomyosis. Patients with only fibroid tumors were, on average, 4.0 years older than those with endometriosis and fibroids (mean age, 44 vs 40 ± SD). Patients with both pathologies were also more likely to present with pelvic pain and nulliparity than those with fibroid tumors alone.

CONCLUSIONS:

In our patient population, 87.1% of patients with a chief concern of symptomatic fibroids also had a diagnosis of histology-proven endometriosis, which affirms the need for concomitant diagnosis and intraoperative treatment of both conditions. Overlooking the coexistence of endometriosis in women with symptomatic leiomyoma may lead to suboptimal treatment of fertility and persistent pelvic pain. It is important for physicians to be aware of the possibility of this association and to thoroughly evaluate the abdomen and pelvis for endometriosis at the time of myomectomy or hysterectomy in an effort to avoid the need for reoperation.

 

 

J Obstet Gynaecol India. 2016 Oct;66

A Prospective Randomized Comparative Study of Vaginal, Abdominal, and Laparoscopic Hysterectomies.

Nanavati AM¹, Gokral SB².

 

Abstract

PURPOSE:

The present study is a prospective, randomized comparative study of abdominal, vaginal and laparoscopic hysterectomies comparing various parameters such as indications, blood loss, post operative pain, time taken for surgery, intraoperative and postoperative complications and total hospital stay.

MATERIALS AND METHODS:

50 patients were selected in each group over a period of 18 months. The patients were selected in such a way that they could be operated by all 3 routes. Thus patients undergoing hysterectomy for non malignant conditions, having no adnexal masses, having no severe endometriosis, uterine size not more than 12 weeks and uterine descent of not more than 1st degree were selected.

RESULTS:

The most common indication for hysterectomy was found to be DUB, the maximum time taken was in TLH, the minimum blood loss was found in TLH. There was significant difference in the pain scores using VAS among the three groups on day 0 and day 1, where the scores were significantly lower in VH group, the hospital stay was maximum in TAH group while there was no difference between VH and TLH groups.

CONCLUSION:

TLH is a better alternative for TAH and with good equipment, expertise and excellent teamwork TLH will be the future candidate for mode of surgery.

 

 

J Obstet Gynaecol India. 2016 Oct;66(Suppl 1):466-70.

Comparison of Serum Leptin Level in Women with Unexplained Infertility and Fertile Women in Iran.

Tafvizi F¹, Masomi M¹.

 

Abstract

BACKGROUND:

Various studies have been conducted on the role of leptin in the different types of infertility, including endometriosis, polycystic ovaries and male infertility; however, only a few studies have been conducted on the effect of leptin on unexplained infertility. The purpose of the present study was therefore to compare serum leptin levels in women with unexplained infertility and fertile women as a contributing factor to female infertility in Iran.

METHODS:

The present case-control study was conducted on 40 women with unexplained infertility and 30 fertile women who met the inclusion criteria (FSH < 10, BMI < 30, normal AMH and AFC and age under 35). Serum leptin levels were analyzed on the third day of menstruation by ELISA method.

RESULTS:

Although the mean serum leptin level was higher in women with unexplained infertility (31.20 ± 2.83 ng/ml) than in fertile women (24.89 ± 2.93 ng/ml), no statistically significant differences were observed between the two groups (P = 0.13).

CONCLUSIONS:

No statistically significant relationship was found between serum leptin levels in the two groups. In addition, there were no significant relationships between leptin and other predisposing factors such as hormone profile and antral follicle count.

 

 

J Obstet Gynaecol India. 2016 Oct;66(Suppl 1):478-81.

Hysterolaparoscopy in the Evaluation and Management of Female Infertility.

Kabadi YM¹, Harsha B².

 

Abstract

OBJECTIVE:

To study the role of hysterolaparoscopy in the evaluation and management of female infertility.

MATERIALS AND METHODS:

A retrospective study of the 94 case files of all the patients who underwent diagnostic hysterolaparoscopy for infertility between January 2014 to June 2015 in the department of Obstetrics and Gynecology, Karnataka Institute of Medical Sciences, Hubli. These infertile women were confirmed to have normal ovulatory cycles, hormonal assays and seminogram report. Dye studies as well as inspection for abnormal pelvic and intrauterine pathology and necessary therapeutic interventions were done during the procedure. Abnormal pelvic and intrauterine pathology by hysterolaparoscopy were categorized.

RESULTS:

Out of 94 cases, 53.1 % patients had primary, 17.1 % patients had secondary infertility, and 29.8 % came for tubal recanalization. As a whole pelvic pathology was confirmed in 51.7 % and intrauterine pathology in 18.1 % patients by hysterolaparoscopy. The most common laparoscopic abnormality detected was ovarian pathology (20.8 %), followed by pelvic inflammatory disease (17.5 %). Tubal block comprised 7.7 % whereas distorted uterus by fibroid in 6.6 % and pelvic endometriosis in 5.4 %. In hysteroscopy, the incidence of uterine anomaly was 13 (13.8 %). Septate uterus is the most common with a mean incidence of approximately 7 (53.8 %).

CONCLUSION:

Diagnostic hysterolaparoscopy is an effective diagnostic and therapeutic modality for certain significant and correctable abnormalities in pelvis, tubes and uterus which are missed by other imaging modalities.

 

 

 

J Turk Ger Gynecol Assoc. 2016 Sep 1;17(3):150-4.

The effect of adenomyosis on the outcomes of laparoscopic hysterectomy.

Yavuzcan A¹, Başbuğ A¹, Baştan M¹, Çağlar M¹, Özdemir ݹ.

 

Abstract

OBJECTIVE:

The presence of adenomyosis (ADS) may increase complication rates associated with laparoscopic hysterectomy (LH) due to an increased weight of the uterus, increased vascularization of the uterus, impaired myometrial tissue, and presence of additional gynecological pathologies such as leiomyoma or endometriosis. The aim of the present study was to evaluate perioperative and early postoperative parameters in patients with or without adenomyotic lesions.

MATERIAL AND METHODS:

The study included patients who underwent LH in a university hospital. Patient data were retrieved from the hospital records and reviewed retrospectively. Sixty-one patients (85.9%) without adenomyotic lesions comprised the control group. Ten patients with adenomyotic lesions (14.1%) were regarded as the study group.

RESULTS:

In this study, the mean age of the patients was 50.93±9.39 years. The mean uterus size was significantly higher in patients with ADS (p=0.02). There was no statistically significant difference in perioperative variables such as delta hemoglobin (Hb), insertion of pelvic drainage catheter, and invasive assessment of the urinary tract between both the groups (p=0.27, p=1.0, and p=0.67, respectively). The difference between the groups in terms of postoperative blood transfusion was not statistically significant (p=0.25). There was no statistically significant difference in the postoperative maximum body temperature, length of hospital stay, and duration of urinary catheterization between both the groups (p=0.77, p=0.36, and p=0.75, respectively).

CONCLUSION:

LH appears to be a safe alternative for patients with ADS. Large-scale, prospective, and randomized trials are required in order to suggest the routine use of LH in patients preoperatively diagnosed with ADS.

 

 

BMC Womens Health. 2016 Sep 21;16(1):64.

Endometriosis and its global research architecture: an in-depth density-equalizing mapping analysis.

Brüggmann D^1,2, Elizabeth-Martinez A³, Klingelhöfer D³, Quarcoo D³, Jaque JM⁴, Groneberg DA³.

 

Abstract

BACKGROUND:

Endometriosis is one of the most common gynecological diseases. It is still a chameleon in many aspects and urges intense research activities in the fields of diagnosis, therapy and prevention. Despite the need to foster research in this area, no in-depth analysis of the global architecture of endometriosis research exists yet.

METHODS:

We here used the NewQIS platform to conduct a density equalizing mapping study, using the Web of Science as database with endometriosis related entries between 1900 and 2009. Density equalizing maps of global endometriosis research encompassing country-specific publication activities, and semi-qualitative indices such as country specific citations, citation rates, h-Indices were created.

RESULTS:

In total, 11,056 entries related to endometriosis were found. The USA was leading the field with 3705 publications followed by the United Kingdom (952) and Japan (846). Concerning overall citations and country-specific h-Indices, the USA again was the leading nation with 74,592 citations and a modified h-Index of 103, followed by the UK with 15,175 citations (h-Index 57). Regarding the citation rate, Sweden and Belgium were at top positions with rates of 22.46 and 22.26, respectively. Concerning collaborative studies, there was a steep increase in numbers present; analysis of the chronological evolution indicated a strong increase in international collaborations in the past 10 years.

CONCLUSIONS:

This study is the first analysis that illustrates the global endometriosis research architecture. It shows that endometriosis research is constantly gaining importance but also underlines the need for further efforts and investments to foster research and ultimately improve endometriosis management on a global scale.

 

 

J Biol Regul Homeost Agents. 2016 Jul-Sep;30(3):877-882.

Endometriosis and Glanzmann’s thrombasthenia.

Imperiale L¹, Manganaro L², Ticino A¹, Piacenti I¹, Anastasi E³, Resta S¹, Benedetti Panici P¹, Porpora MG¹.

 

Abstract

Glanzmann’s thrombasthenia (GT) is a rare bleeding syndrome characterized by deficiency or defect of platelet aggregation complex. The pathogenesis of endometriosis is controversial but the strongest evidence leans towards retrograde menstruation. GT probably predisposes to endometriosis. The management of women affected by this disease can be difficult due to the risk of bleeding complications, especially during surgical treatment. We describe the cases of three sisters affected by endometriosis and GT, referred to our Department, who received different therapeutic management.

 

 

 

Reprod Sci. 2017 Mar;24(3):376-381.

Circulating miRNAs in Murine Experimental Endometriosis.

Seifer BJ¹, Su D¹, Taylor HS¹.

 

Abstract

Endometriosis is a chronic disease that commonly affects women of reproductive age; however, diagnosis is often delayed due to lack of appreciation of early signs and symptoms. Development of a noninvasive biomarker would significantly reduce delays in diagnosis and treatment. Circulating microRNAs (miRNAs) have been implicated as biomarkers for several diseases including endometriosis. Here, we use an miRNA array to investigate differential miRNA abundance in the serum of mice after induction of experimental endometriosis. let-7a-5p was decreased in the serum of mice with endometriosis. let-7b-5p, c-5p, and e-5p also showed a trend toward downregulation. Serum let-7 family miRNA shows similar dysregulation in endometriosis in both humans and mice. Diminished circulating let-7 implies a complex regulation that potentially involves multiple organs. Further investigation is necessary to determine the functional roles of let-7 miRNAs in this disease.

 

 

J Genet. 2016 Sep;95(3):611-9.

Effect of matrix metalloproteinase promoter polymorphisms on endometriosisand adenomyosis risk: evidence from a meta-analysis.

Ye H¹, He Y, Wang J, Song T, Lan Z, Zhao Y, Xi M.

 

Abstract

Matrix metalloproteinase (MMP) promoter polymorphisms are considered to play roles in the aetiology of endometriosis and adenomyosis, however, the evidence available are inconsistent. We aimed to systematically review the asscociation between MMP-1 -1607 1G/2G MMP-2 -735 C/T, MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms and the risk of endometriosis and adenomyosis. A systemic search was conducted in Ovid, PubMed, Chinese National Knowledge Infrastructure and ChineseWanfang Database.We used the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) to calculate the statistical power. Besides, we evaluated the quality of individual studies based on Newcastle-Ottawa scale. A total of 13 papers with 18 studies conformed to our inclusion criteria. We observed a significant association between MMP-1 -1607 1G/2G polymorphism and the susceptibility of endometriosis and adenomyosis under recessive model (OR = 1.25, 95%CI = 1.03-1.53, P = 0.03). While no significant association was found in MMP-2 -735 C/T, MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms. This systemic review and meta-analysis suggested that theMMP-1 -1607 1G/2G polymorphism might play an important role in the risk of endometriosis and adenomyosis. Further, more well-designed and large-scale studies regarding gene-gene and gene-environment interactions are needed in the future.

 

 

Gynecol Oncol Rep. 2016 Aug 30;18:8-10.

Vesical clear cell adenocarcinoma arising from endometriosis: A mullerian tumor, indistinguishable from ovarian clear cell adenocarcinoma.

Miller EM¹, Sun Y², Richardson I³, Frimer M¹.

 

Abstract

Endometriosis is associated with increased rates of ovarian, particularly clear cell, adenocarcinomas. Malignant transformation of ovarian endometriosis is most common but rare cases have been reported in the bladder, abdominal wall, diaphragm, and rectum. We present the case of a 44-year-old female with vesical clear cell adenocarcinoma arising in a background of endometriosis in the absence of other pelvic endometriosis. The malignancy was diagnosed on transurethral resection of bladder tumor and managed with radical surgery. Histology and immunohistochemical findings were consistent mullerian origin and indistinguishable from similar tumors arising in the female genital tract. Extrapolating from the gynecologic literature, the recommendation was made for adjuvant chemotherapy. Further studies are needed to clarify the optimal treatment paradigm for ovarian and bladder clear cell adenocarcinomas.

 

 

Reprod Sci. 2017 Apr;24(4):619-626.

Myeloperoxidase as a Potential Target in Women With EndometriosisUndergoing IVF.

Santanam N^1,2, Zoneraich N^1,3, Parthasarathy S^1,4.

 

Abstract

As infertility is intimately associated with endometriosis, the levels of myeloperoxidase (MPO), a leukocyte enzyme and an oxidative stress marker, were determined in a case-control prospective study of 68 women with and without endometriosis undergoing in vitro fertilization in the outpatient fertility center within a tertiary care academic medical center. Measured values included plasma and follicular fluid (FF) concentrations of MPO, plasma estradiol, as well as oocyte quality, fertilization, implantation, and pregnancy rates in these women. In FF (mean ± standard error of mean [SEM]), the MPO concentrations (ng/mL) for controls were 4.3 ± 0.37, mild endometriosis (stages I-II) 3.9 ± 0.17, and moderate/severe endometriosis (stages III-IV) 16.6 ± 12.5 ( P < 0.0143). In FF, among patients supplemented with vitamins E and C, the MPO levels decreased significantly only in moderate/severe endometriosis from 25.3 ± 22.0 ng/mL to 4.9 ± 1.61 ng/mL, respectively. Plasma levels of MPO between groups did not change. Outcome data revealed a trend toward decreased percentage of mature oocytes, implantation rate, and clinical pregnancy rate with severity of endometriosis and MPO levels. Myeloperoxidase may be a potential oxidative stress target for endometriosis-associated infertility.

 

 

Arch Toxicol. 2017 Apr;91(4):1915-1924.

Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions.

Huang Q¹, Chen Y², Chen Q³, Zhang H², Lin Y², Zhu M³, Dong S⁴.

 

Abstract

Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure-activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model. Dioxin-like CB126, but not non-dioxin-like CB153, significantly enhanced 17β-estradiol (E2) biosynthesis in a dose-dependent manner. Among the genes related to estrogen metabolism, the level of 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) showed significant increase following CB126 exposure. We further found that CB126 exposure decreased the methylation of the HSD17B7 promoter. Elevated expression of HSD17B7 was observed in the eutopic endometrium of EM patients. CB126 rather than CB153 triggered the inflammatory response by directly stimulating the secretion of inflammatory factors and indirectly reducing the level of lipoxin A₄ (LXA₄). Furthermore, the inflammation enhanced the expression of HSD17B7. Antagonism of the aryl hydrocarbon receptor (AhR) diminished the effects induced by CB126. In vivo, the PCB-treated EM mouse model confirmed that CB126 rather than CB153 increased the levels of both E2 and inflammatory factors in peritoneal fluid and promoted the development of endometriotic lesions. In all, CB126, but not CB153, triggered EM development by stimulating estrogen biosynthesis, inflammation and their interactions and that these effects were mediated by the AhR receptor.

 

 

Hum Reprod. 2016 Dec;31(12):2730-2736.

Pregnancy outcome in women with endometriosis achieving pregnancy with IVF.

Benaglia L¹, Candotti G^2,3, Papaleo E³, Pagliardini L³, Leonardi M², Reschini M², Quaranta L³, Munaretto M³, Viganò P³, Candiani M³, Vercellini P^2,4, Somigliana E^2,4.

 

Abstract

STUDY QUESTION:

Are women with endometriosis who conceive with IVF at increased risk of preterm birth?

SUMMARY ANSWER:

Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth.

WHAT IS KNOWN ALREADY:

The eutopic endometrium of women with endometriosis has been repeatedly shown to present molecular and cellular alterations. On this basis, it has been hypothesized that pregnancy outcome may be altered in affected women. However, to date, available evidence from epidemiological studies is scanty and conflicting. Data tended to be partly consistent only for an increased risk of preterm birth and placenta previa.

STUDY DESIGN, SIZE, DURATION:

Retrospective matched case-control study of women achieving an IVF singleton pregnancy progressing beyond 12 weeks’ gestation.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women achieving IVF singleton pregnancies that progressed beyond 12 weeks’ gestation at two infertility units were reviewed. Cases were women with a history of surgery for endometriosis and/or with a sonographic diagnosis of the disease at the time of the IVF cycle. Controls were women without current or past evidence of endometriosis who were matched to cases by age (± 6 months), type of cycle (fresh or frozen cycle) and study period. Male factor and unexplained infertility were the most common diagnoses in the control group. Two hundred and thirty-nine women with endometriosis and 239 controls were selected. The main outcome of the study was the rate of preterm birth (birth < 37 weeks’ gestation) regardless of the cause. Secondary analyses were performed for the most common obstetrical complications.

MAIN RESULTS AND THE ROLE OF CHANCE:

The rate of preterm birth was similar in the two study groups (14% and 14%, respectively, p = 0.89). The rate of live birth and the incidence of hypertensive disorders, gestational diabetes, small and large for gestational age newborns and neonatal problems also did not differ. In contrast, placenta previa was more common in women with endometriosis than controls (6% versus 1%, respectively; p = 0.006): The adjusted odds ratio was 4.8 (95% confidence interval: 1.4-17.2).

LIMITATIONS, REASONS FOR CAUTION:

As for all observational studies, confounders cannot be totally excluded. Moreover, the retrospective study design exposes the findings to some inaccuracies. For example, the independent role of adenomyosis could not be reliably assessed because this diagnosis is complex and would necessitate a prospective recruitment. Second, the selection of controls may also be a matter of concern because some affected women may have been erroneously included in this group. Third, even if the sample size is significant, it is insufficient for robust subgroup analyses. Finally, it is mandatory to point out that our conclusions are valid for IVF pregnancies only, and specific data from properly designed studies are required to support any inference for natural pregnancies.

WIDER IMPLICATIONS OF THE FINDINGS:

The results of our study suggest that women with endometriosisconceiving with IVF can be reassured regarding the risk of preterm birth. The observed association with placenta previa requires further investigation and may open a new avenue of research.

 

 

Hum Reprod. 2016 Nov;31(11):2506-2519.

Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor β2.

Long Q¹, Liu X^1,2, Qi Q¹, Guo SW^3,2.

 

Abstract

STUDY QUESTION:

Does chronic stress in mice accelerate the development of endometriosis, and, if so, through what mechanism?

SUMMARY ANSWER:

Exposure to chronic stress accelerates the development of endometriosis and exacerbates the endometriosis-associated generalized hyperalgesia, most likely through activation of the adrenoceptor β2 (ADRB2) and cAMP responsive element-binding protein (CREB).

WHAT IS KNOWN ALREADY:

Women with endometriosis tend to have higher levels of psychological stress, which is known to impact negatively on health in general and to promote tumor growth and metastasis in particular. Exposure to chronic stress before and after the induction of endometriosis is reported to increase lesion sizes in rodents, but it is unclear whether adrenoceptors are involved or not in the stress-promoted development of endometriosis.

STUDY DESIGN, SIZE, DURATION:

Three independent, prospective, randomized mouse experimentations. A total of 184 virgin female Balb/C mice were used.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

In Experiment 1, the mice were randomly divided into four groups: the control group, which received no stress; the before, after and both groups, which received immobilization stress before, after and both before and after the induction of endometriosis, respectively. In Experiment 2, mice were randomly divided into four groups one day after the induction of endometriosis: phosphate buffer saline (PBS) and propranolol (PROP) groups, which received the mini-pump containing, respectively, PBS only and propranolol (a non-selective ADRB antagonist) but no stress, STR+PROP and STR+PBS groups, which received stress and the mini-pump containing, respectively, propranolol and PBS. The immobilization stress started after the insertion of mini-pumps. In Experiment 3, mice were induced with endometriosis. Three days after the induction, they were randomly divided into four groups: control, ADRAa, ADRB2a, and ADRBa, which received the mini-pump containing solution only, metaraminol (a non-specific α adrenoceptor agonist), tebutaline (a specific ADRB2 agonist), or isoproterenol (a non-specific ADRB agonist), respectively. In all three experiments, the bodyweight and hotplate latency were evaluated before sacrifice 14 days after the induction. In all experimentations, the lesion weight was evaluated and the harvested ectopic endometrial tissue samples were subjected to immunohistochemistry analysis of vascular endothelial growth factor (VEGF), CD31-positive microvessels, proliferating cell nuclear antigen (PCNA), phosphorylated CREB, ADRB1, ADRB2, ADRB3, adrenergic receptor α1 (ADRA1) and ADRA2.

MAIN RESULTS AND THE ROLE OF CHANCE:

Exposure to chronic stress accelerated the development of endometriosis and exacerbated the endometriosis-associated generalized hyperalgesia. This promotional effect is likely to be mediated through the systemic activation of the sympatho-adreno-medullary (SAM) axis, which results in subsequent release of catecholamines. The surging catecholamines may activate ADRB2 and CREB, yielding increased angiogenesis and cellular proliferation in ectopic endometrium in mice with induced endometriosis. In addition, β adrenergic receptor blockade completely abolished the promotional effect of chronic stress, likely through suppression of ADRB2 and CREB activation, thus suppressing angiogenesis and proliferation. Moreover, a non-specific adrenergic β agonist and a specific adrenergic β2 agonist, but not non-specific adrenergic α agonist, acted similarly to chronic stress, accelerating the development of endometriosis and exacerbating the generalized hyperalgesia in mice with pre-existing endometriosis.

LARGE SCALE DATA:

NA.

LIMITATIONS, REASONS FOR CAUTION:

This study is limited by the use of immunohistochemistry analyses only and the lack of molecular data.

WIDER IMPLICATIONS OF THE FINDINGS:

The present study provides the experimental evidence that chronic stress can promote the development of endometriosis through the activation of ADRB2. Given ADRB2 is also expressed in human endometriosis and appears to be functional, and in light of recent awareness that adrenergic signaling plays critical roles in tumorigenesis, it is likely that adrenergic signaling may play important roles in the development of endometriosis and is potentially a target for intervention.

 

 

J Magn Reson Imaging. 2017 Apr;45(4):1225-1231.

Evaluation of the sacral nerve plexus in pelvic endometriosis by three-dimensional MR neurography.

Zhang X¹, Li M¹, Guan J¹, Wang H¹, Li S¹, Guo Y¹, Liu M¹.

 

Abstract

PURPOSE:

To investigate the feasibility of three-dimensional MR neurography (3D MRN) for the sacral plexus using sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences, and to demonstrate structural abnormalities in the pelvic nerve of women with pelvic endometriosis.

MATERIALS AND METHODS:

Twenty patients with pelvic endometriosis and 20 healthy controls were examined by contrast-enhanced 3D short time inversion recovery T2-weighted imaging (CE 3D STIR T2WI) SPACE sequences on 3 Tesla MRI. Image quality and diagnostic confidence of the sequences in identifying abnormalities of the sacral plexus were analyzed and compared with conventional three-plane images of 2D turbo-spin echo T2-weighted images (2D TSE T2WI). The changes in the sacral plexus caused by endometrial lesions were evaluated.

RESULTS:

The sacral plexus was clearly revealed in both healthy controls and patients with endometriosis on 3D STIR SPACE images. A good agreement was reached in the evaluation of both imaging quality (Kappa value [κ] = 0.73-1.00) and diagnostic confidence (κ = 0.66-0.81) when compared between the two independent readers. Abnormalities caused by endometriosis were identified in 17 patients, unilaterally in 10 patients, and bilaterally in 7 patients. Nerve fiber abnormalities of lumbar 5 (L5) were detected in 11 patients, of sacral 1 (S1) in 14 patients and of sacral 2 (S2) in 9 patients.

CONCLUSION:

CE 3D STIR SPACE sequences demonstrate its significant capacity to investigate and map the sacral plexus, and reveal the compression and adhesion of the sacral plexus nerve as a result of ectopic lesions.