Clin Obstet Gynecol. 2017 Sep;60(3):485-496.

Medical Management of Endometriosis.

Rafique S¹, Decherney AH.

 

Abstract

Endometriosis is a chronic medical condition that affects around 6% to 10% of reproductive age women. Pelvic pain, dysmenorrhea, and infertility are the most common presenting symptoms. The disease is characterized by estrogen-dependent growth of the endometrial glands and stroma outside the endometrial cavity. The diagnosis requires a high degree of suspicion and can be only confirmed on histopathology. Treatment includes medical and surgical options. Both hormonal and nonhormonal medical options are available and are tried at first with a goal to control pain and stop the growth of the endometriotic lesions. Nonsteroidal anti-inflammatory drugs, oral contraceptive pills, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors are some of the commonly used medications. With more research on the molecular and biochemical aspects of endometriosis, newer targets of therapy are being developed like selective progesterone receptor modulators, antiangiogenic factors and immunomodulators. In women who do not respond to medical therapy or have severe symptoms, surgical excision of the endometrial lesions and adhesions is often helpful and offers confirmatory diagnosis by histopathology.

 

 

Rev Med Inst Mex Seguro Soc. 2017 Jul-Aug;55(4):452-455.

Dienogest usefulness in pelvic pain due to endometriosis. A meta-analysis of its effectiveness.

García Uranga-Romano J¹, Hernández-Valencia M, Zárate A, Basavilvazo-Rodríguez MA.

Abstract

BACKGROUND:

Endometriosis is the presence of functional endometrial tissue in the pelvic peritoneum and it affects several age groups. That is why the impact of endometriosis in quality of life is considerable. The objective of this study was to evaluate the effectiveness of dienogest in patients with pelvic pain associated to endometriosis (PPAE).

METHODS:

The evaluation of the effectiveness was carried out through a systematic review using the Cochrane methodology. It was used Markov model, which considers two states of health (with and without PPAE), with the possibility of weekly transition. Women between 18 and 45 years with PPAE were included, in a temporary horizon of 26 weeks. A level of statistical significance of 95% was used for a p < 0.05, with a multivariate probabilistic analysis of sensibility, as well as a univariate analysis of sensibility in several scenarios.

RESULTS:

The probability that the female patient did not experience PPAE with the initial treatment was 87.91% with dienogest, 80.07% with danazol, 84.93% with medroxyprogesterone (injectable and oral) and 89.17% with gosereline. The probability that the female patient abandoned her initial treatment was 9% with dienogest, 12.07% with danazol, 9.6 and 6.75% with medroxyprogesterone injectable and oral, respectively, and 10.8 and 3.6% 3-monthly and monthly with gosereline.

CONCLUSION:

Compared to danazol, medroxiprogesterone and gosereline, dienogest is the most efficient alternative to treat PPAE.

 

 

Hum Reprod. 2017 Aug 1;32(8):1732-1742

Associations among body size across the life course, adult height and endometriosis.

Farland LV^1,2, Missmer SA^1,3,4, Bijon A^5,6, Gusto G^5,6, Gelot A^5,6, Clavel-Chapelon F^5,6, Mesrine S^5,6, Boutron-Ruault MC^5,6, Kvaskoff M^5,6.

Abstract

STUDY QUESTION:

Are body size across the life course and adult height associated with endometriosis?

SUMMARY ANSWER:

Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height.

WHAT IS KNOWN ALREADY:

The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis.

STUDY DESIGN, SIZE, DURATION:

We used a nested case-control design within E3N (Etude Epidémiologique auprès de femmes de l’Education Nationale), a prospective cohort of French women. Data were updated every 2-3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women.

MAIN RESULTS AND THE ROLE OF CHANCE:

The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20-25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (<158 cm) (162-164 cm: OR = 1.28, 95% CI = 1.12-1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18-1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05-1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis.

LIMITATIONS REASONS FOR CAUTION:

Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias.

WIDER IMPLICATIONS OF THE FINDINGS:

The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further.

STUDY FUNDING/COMPETING INTEREST(S):

The Mutuelle Générale de l’Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011-302078). The authors have no conflicts of interest to declare.

 

 

Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Jul;47(4):512-515.

Expressions of Livin and PTEN in Cancerous Tissues of Ovary Endometriosis.

Liu XY¹, Wang HJ¹, Xu P¹, Chen J¹, Pan HY¹, Liu Y¹.

Abstract

OBJECTIVES:

To investigate the expressions of Livin and phosphate and tension homology deleted on chromsome ten (PTEN) protein in the cancerous tissues of ovary endometriosis.

METHODS:

Immunohistochemistry EliVision was used to examine the expressions of Livin and PETN protein in 19 samples of ovary endometriosis cancerous tissues, 30 samples of ovary endometriosis tissues and 30 samples of ovarian benign tumor tissues.

RESULTS:

The positive expression rate of Livin in ovary endometriosis cancerous tissues (68%) was obviously higher than that in ovary endometriosis tissues (36%) and benign tumor tissues (13%)( P<0.05). The positive expression rate of PTEN in ovary endometriosis cancerous tissues (16%) was obviously lower than that in ovary endometriosis tissues (65%) and benign tumor tissues (80%)( P<0.01). There was no correlations between positive expressions of Livin and age, clinical stage, grading, histological type and lymphatic metastasis of ovary endometriosis cancer ( P>0.05), the same result was also found for PTEN. Livin and PTEN expression presented an obviously negative correlation in ovary endometriosis cancer ( r=-0.559, P=0.001).

CONCLUSIONS:

Up-regulation of Livin expression and down-regulation of PTEN may be involved in the occurrence and development of ovary endometriosis cancerization.

 

 

Reproduction. 2017 Sep;154(3):107-116.

Altered retinoid signaling compromises decidualization in human endometriotic stromal cells.

Pavone ME¹, Malpani S², Dyson M², Bulun SE².

 

Abstract

Decidualization alters multiple molecular pathways in endometrium to permit successful embryo implantation. We have reported that paracrine factors, including retinoids, secreted from progesterone-treated endometrial stromal cells, act on nearby epithelial cells to induce the estradiol metabolizing enzyme HSD17B2. This same induction is not seen in endometriotic stromal cells. We have also shown significant differences in retinoid uptake, metabolism and action in endometriotic tissue and stromal cells compared to normal endometrium. Here, we characterize retinoid signaling during decidualization in these cells. Endometrial and endometriotic cells were isolated, cultured and incubated and decidualized. Genes involved in retinoid metabolism and trafficking were examined using RT-PCR and Western blotting. Prolactin, a decidualization marker, was also examined. We found that both endometrial and endometriotic stromal cells express all intracellular proteins involved in retinoid uptake and metabolism. Decidualization significantly reduced the expression of the genes responsible for retinoid uptake and shuttling to the nucleus. However, expression of CRBP1, an intracellular carrier protein for retinol, increased, as did RBP4, a carrier protein for retinol in the blood, which can function in a paracrine manner. Secreted RBP4 was detected in the media from decidualized endometrial cells but not from endometriotic cells. We believe that retinoid trafficking in endometrial stromal cells during decidualization may shift to favor paracrine rather than intracrine signaling, which may enhance signaling to the adjacent epithelium. There is blunting of this signaling in endometriotic cells. These alterations in retinoid signaling may help explain the decidualization defects and deficient estradiol inactivation (via HSD17B2) seen in endometriosis.

 

 

Psychosomatics. 2017 Sep – Oct;58(5):533-543

Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study.

Castro-Marrero J¹, Faro M², Aliste L², Sáez-Francàs N³, Calvo N⁴, Martínez-Martínez A², de Sevilla TF², Alegre J².

Abstract

BACKGROUND:

Previous studies have shown evidence of comorbid conditions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

OBJECTIVE:

To estimate the prevalence of comorbidities and assess their associations using a nationwide population-based database of a Spanish CFS/ME cohort.

METHOD:

A nationally representative, retrospective, cross-sectional cohort study (2008-2015) assessed 1757 Spanish subjects who met both the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian Criteria for CFS/ME. Sociodemographic and clinical data, comorbidities, and patient-reported outcome measures at baseline were recorded. A cluster analysis based on baseline clinical variables was performed to classify patients with CFS/ME into 5 categories according to comorbidities. A multivariate logistic regression analysis was conducted adjusting for potential confounding effects such as age and sex; response and categorical predictor variables were also assessed.

RESULTS:

A total of 1757 CFS/ME patients completed surveys were collected. We identified 5 CFS/ME clusters: group 1-fibromyalgia, myofascial pain, multiple chemical hypersensitivity, sicca syndrome, epicondylitis, and thyroiditis; group 2-alterations of ligaments and subcutaneous tissue, hypovitaminosis D, psychopathology, ligamentous hyperlaxity, and endometriosis. These 2 subgroups comprised mainly older women, with low educational level, unemployment, high levels of fatigue, and poor quality of life; group 3-with hardly any comorbidities, comprising mainly younger women, university students or those already employed, with lower levels of fatigue, and better quality of life; group 4-poorly defined comorbidities; and group 5-hypercholesterolemia.

CONCLUSION:

Over 80% of a large population-based cohort of Spanish patients with CFS/ME presented comorbidities. Among the 5 subgroups created, the most interesting were groups 1-3. Future research should consider multidisciplinary approaches for the management and treatment of CFS/ME with comorbid conditions.

Acta Obstet Gynecol Scand. 2017 Sep;96(9):1128-1135.

ZEB1 expression is a potential indicator of invasive endometriosis.

Furuya M¹, Masuda H¹, Hara K², Uchida H¹, Sato K¹, Sato S¹, Asada H³, Maruyama T¹, Yoshimura Y¹, Katabuchi H⁴, Tanaka M¹, Saya H⁵.

Abstract

INTRODUCTION:

Although endometriosis is a benign disease, it shares some features with cancers, such as invasiveness and the potential to metastasize. This study sought to investigate the epithelial-mesenchymal transition status in human endometriotic lesions.

MATERIAL AND METHODS:

Thirteen endometriosis patients and 10 control women without endometriosis undergoing surgery for benign indications were recruited. We examined the expression of E-cadherin, vimentin, and epithelial-mesenchymal transition-induced transcriptional factors, such as Snail and ZEB1, by immunohistochemistry. We evaluated the expression of each marker in epithelial cells of both endometriotic lesions (ovarian endometrioma, deep infiltrating endometriosis, adenomyosis) and normal endometria. The correlation between ZEB1 expression and serum level of CA125 was also investigated.

RESULTS:

Immunohistochemical analysis revealed that although E-cadherin, vimentin, and Snail were expressed in epithelia of normal endometria and endometriotic lesions, ZEB1 expression was only expressed in epithelia of endometriotic lesions. Additionally, ZEB1 was most frequently observed in epithelial cells of invasive endometriosis. The endometriosis patients with high serum CA125 level were more likely to have ZEB1-positive lesions.

CONCLUSIONS:

This is the first observation of ZEB1 expression in epithelial cells of benign disease. The preferential expression of ZEB1 in epithelial cells of endometriotic lesions suggests that these cells may have, at least in part, a higher level of mesenchymal features possibly via ZEB1-driven epithelial-mesenchymal transition than normal endometria and that ZEB1 can be a potential indicator of invasiveness or severity of endometriosis.

 

 

Taiwan J Obstet Gynecol. 2017 Jun;56(3):371-373.

Does exist a correlation between endometriosis and thrombophilic disorders? A pilot study.

Paradisi R¹, Ferrini G², Matteucci C¹, Facchini C¹, Zannoni L¹, Seracchioli R¹.

Abstract

OBJECTIVE:

At present, there is growing evidence of the existence of a genetic predisposition in both thrombophilic disorders and endometriosis. The aim of our study was to evaluate for the first time the prevalence of some thrombophilic disorders in patients with endometriosis.

MATERIALS AND METHODS:

We conducted a retrospective study on 138 patients with endometriosis and 278 healthy control women. All women were subjected to a blood examination testing for thrombophilic screening and the variables examinated were: hyperhomocysteinemia, factor V Leiden and factor II prothrombin G20210A mutations in heterozygosis and homozigosis.

RESULTS:

A significant reduced prevalence (p < 0.05) of factor V Leiden mutation in endometriosis patients was found, whereas no significant differences (p = NS) for factor II and hyperhomocysteinemia were observed.

CONCLUSION:

Our preliminary data do not show any association between thrombophilic condition and endometriosis. Before assuming hormonal therapies, a thrombophilic plasmatic screening seems to be unnecessary in patients affected by endometriosis.

 

 

Reprod Biomed Online. 2017 Aug;35(2):145-151.

GnRH agonist administration prior to embryo transfer in freeze-all cycles of patients with endometriosis or aberrant endometrial integrin expression.

Surrey ES¹, Katz-Jaffe M², Kondapalli LV², Gustofson RL², Schoolcraft WB².

 

Abstract

Prolonged gonadotrophin-releasing hormone agonist (GnRHa) administration before IVF with fresh embryo transfer to patients with endometriosis or aberrant endometrial integrin expression (-integrin) improves outcomes but may suppress ovarian response and prevents elective cryopreservation of all embryos. This retrospective cohort pilot study evaluates freeze-all cycles with subsequent prolonged GnRHa before embryo transfer in these populations. Patients from 2010 to 2015 who met inclusion criteria and received a long-acting GnRHa every 28 days twice before FET were evaluated. A subset underwent comprehensive chromosomal screening (CCS) after trophectoderm biopsy. Three groups were identified: Group 1: + CCS, +endometriosis (20 patients, 20 transfers); Group 2: +CCS, -integrin (12 patients, 13 transfers); Group 3: no CCS, +endometriosis or -integrin (10 patients, 12 transfers); Group 4: all transfers after CCS for descriptive comparison only (n = 2809). Baseline characteristics were similar among Groups 1-3 except that the mean surgery to oocyte aspiration interval was longer for Group 1 than Group 3. Implantation and ongoing pregnancy rates were statistically similar among the three groups and compared favourably to Group 4. A non-significant trend towards improved outcomes was noted in Group 1. Prolonged GnRHa after freeze-all in these patients avoids excessive ovarian suppression and results in excellent outcomes.

 

 

Fertil Steril. 2017 Jul;108(1):19-27.

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why.

Lessey BA¹, Kim JJ².

 

Abstract

The endometrium maintains complex controls on proliferation and apoptosis as part of repetitive menstrual cycles that prepare the endometrium for the window of implantation and pregnancy. The reliance on inflammatory mechanisms for both implantation and menstruation creates the opportunity in the setting of endometriosis for establishment of chronic inflammation that is disruptive to endometrial receptivity, causing both infertility and abnormal bleeding. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation, and strong evidence exists to suggest that endometrial changes are associated with decreased cycle fecundity as a result of this disease. Here we provide unifying concepts regarding those changes and how they are coordinated to promote progesterone resistance and estrogen dominance through aberrant cell signaling pathways and reduced expression of key homeostatic proteins in eutopic endometrium of women with endometriosis.

 

 

 

 

 

J Gynecol Obstet Hum Reprod. 2017 Oct;46(8):665-666.

Spontaneous intergluteal cleft endometriosis.

Furet E¹, Bendifallah S², Ballester M², Darai E².

 

Abstract

Endometriosis is a condition where hormonal-responsive endometrial tissue grows outside the uterus usually within the pelvic cavity. Extra-abdominal endometriosis is less common and may involves the skin. Subcutaneous endometriosis is rare. We report the first case of spontaneous intergluteal cleft endometriosis revealed by pain and bleeding during menstruation.

 

 

Gynecol Surg. 2017;14(1):8

Spigelian hernia in gynaecology.

Ussia A^1,2, Imperato F¹, Schindler L³, Wattiez A³, Koninckx PR⁴.

Abstract

BACKGROUND:

A Spigelian hernia is a rare hernia through the Spigelian fascia between the rectus muscle and the semilunar line. This hernia is well known in surgery. Symptoms vary from insidious to localised pain, an intermittent mass and/or a bowel obstruction.

RESULTS:

The Spigelian hernia is poorly known in gynaecology. Spigelian hernias may be causally related to secondary trocar insertion. This review is written to increase awareness in gynaecology and is illustrated by a case report in which the diagnosis was missed for 4 years even by laparoscopy. Smaller hernias risk not to be diagnosed and will thus not be treated. Even larger Spigelian hernias might not be recognised and treated appropriately.

CONCLUSIONS:

The gynaecologist should consider a Spigelian hernia in women with localised pain in the abdominal wall lateral of the rectus muscle some 5 cm below the umbilicus. Smaller hernias can be closed by laparoscopy without a mesh. Larger hernias require a mesh repair.

 

 

Case Rep Pathol. 2017;2017:9752908

Benign Multicystic Peritoneal Mesothelioma: A Rare Condition in an Uncommon Gender.

Khurram MS¹, Shaikh H², Khan U¹, Edens J¹, Ibrar W¹, Hamza A¹, Zaka A³, Bano R¹, Hadid T¹.

 

Abstract

Benign Multicystic Peritoneal Mesothelioma (BMPM) is a rare condition that arises from the abdominal peritoneum. Fewer than 200 cases have been reported worldwide. BMPM usually affects premenopausal women and is extremely rare in men. Many factors are suspected to contribute to its development, such as previous surgery, endometriosis, and familial Mediterranean fever. The main management is surgical resection; however, it is estimated that the recurrence rate is up to 50%. Malignant transformation is rare. We report a case series of three male patients who were diagnosed with BMPM and were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

 

 

J Pathol. 2017 Aug;242(4):476-487.

Targeting hypoxia-mediated YAP1 nuclear translocation ameliorates pathogenesis of endometriosis without compromising maternal fertility.

Lin SC¹, Lee HC², Hou PC², Fu JL¹, Wu MH³, Tsai SJ¹.

 

Abstract

Endometriosis is a highly prevalent gynaecological disease that severely reduces women’s health and quality of life. Ectopic endometriotic lesions have evolved mechanisms to survive in the hypoxic peritoneal microenvironment by regulating the expression of a significant subset of genes. However, the master regulator controlling these genes remains to be characterized. Herein, by using bioinformatics analysis and experimental verification, we identified yes-associated protein 1 (YAP1) as a master regulator of endometriosis. Nuclear localization and transcriptional activity of YAP1 were up-regulated by hypoxia via down-regulation of LATS1, a kinase that inactivates YAP1. Disruption of hypoxia-induced YAP1 signalling by siRNA knockdown or inhibitor treatment abolished critical biological processes involved in endometriosis development such as steroidogenesis, angiogenesis, inflammation, migration, innervation, and cell proliferation. Treatment with a YAP1 inhibitor caused the regression of endometriotic lesions without affecting maternal fertility or the growth rate of offspring in the mouse model of endometriosis. Taken together, we identify hypoxia/LATS1/YAP1 as a novel pathway for the pathogenesis of endometriosis and demonstrate that targeting YAP1 might be an alternative approach to treat endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

 

 

Syst Biol Reprod Med. 2017 Oct;63(5):324-330.

The Impact of laparoscopic surgery of peritoneal endometriosis and endometrioma on the outcome of ICSI cycles.

Guler I¹, Erdem A¹, Oguz Y¹, Cevher F¹, Mutlu MF², Bozkurt N¹, Oktem M¹, Erdem M¹.

 

Abstract

Our objective was to assess the role of laparoscopic removal of ovarian endometriomas and ablation of peritoneal endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) – Embryo Transfer cycles by comparing with the results of patients with untreated endometriomas and tubal factor without underlying endometriosis confirmed by laparoscopy. For this purpose, between 2002 and 2015, outcomes of 257 ICSI cycles of 150 patients, including 91 cycles of 48 patients in minimal endometriosis, 57 cycles of 25 patients in endometrioma removal, 65 cycles of 53 patients in non-operated endometrioma, and 44 cycles of 24 patients in tubal factor groups were retrospectively analyzed. Basal ovarian reserve was significantly lower, mean starting and total gonadotropin consumption was significantly higher, and mean serum E2 on the day of hCG injection, number of dominant follicles, number of retrieved total, and MII oocytes were all significantly lower in the endometrioma cystectomy group. Fertilization and embryo cleavage rates were also significantly the lowest in the endometrioma cystectomy group, whereas clinical pregnancy and live birth rates were comparable among all groups. The number of transferred embryos and duration of infertility were the most significant predictors of clinical pregnancy and live birth. Basal antral follicle count was also significant in predicting live birth.

 

 

AJR Am J Roentgenol. 2017 Sep;209(3):690-696.

Cryoablation of Abdominal Wall Endometriosis: A Minimally Invasive Treatment.

Dibble EH¹, D’Amico KC¹, Bandera CA², Littrup PJ¹.

Abstract

OBJECTIVE:

The objective of this study is to present cryoablation as a minimally invasive definitive treatment for abdominal wall endometriosis. We describe our experience with the outpatient application of cryoablation to treat symptomatic abdominal wall endometriosis in three patients.

CONCLUSION:

This feasibility study shows that minimally invasive cryoablation treated abdominal wall endometriosis in three patients and provided a prompt clinical response.

 

 

JBRA Assist Reprod. 2017 Jun 1;21(2):120-125.

To operate or not to operate on women with deep infiltrating endometriosis (DIE) before in vitro fertilization (IVF).

Carneiro MM^1,2,3,4, Costa LMP^1,4, Ávila I^2,4.

 

Abstract

Deep infiltrating endometriosis (DIE) can cause infertility and pelvic pain. There is little evidence of a clear connection between DIE and infertility, and the absolute benefits of surgery for DIE have not been established. This paper aimed to review the current literature on the effect of surgery for DIE on fertility, pregnancy, and IVF outcomes. Clinicians should bear in mind that a comprehensive clinical history is useful to identify patients at risk for endometriosis, although many women remain asymptomatic. Imaging can be useful to plan surgery. The effect of surgery on the fertility of women with DIE remains unanswered due to the heterogeneous nature of the disease and the lack of trials with enough statistical power and adequate follow-up. Surgery is not recommended when the main goal is to treat infertility or to improve IVF results. Decisions should be tailored according to the individual needs of each woman. Patients must be provided information on the potential benefits, harm, and costs of each treatment alternative, while the medical team observes factors such as presence of pelvic pain, patient age, lesion location, and previous treatments. In this scenario, management by a multidisciplinary endometriosis team is a key step to achieving successful outcomes.

 

 

Metab Brain Dis. 2017 Oct;32(5):1603-1607.

Treadmill exercise alters ecstasy- induced long- term potentiation disruption in the hippocampus of male rats.

Sajadi A¹, Amiri I^2,3, Gharebaghi A¹, Komaki A¹, Asadbeigi M¹, Shahidi S¹, Mehdizadeh M⁴, Soleimani Asl S^5,6.

 

Abstract

3, 4-methylenedioxymethamphetamine (MDMA) or ecstasy is a derivative of amphetamine that leads to long term potentiation (LTP) disruption in the hippocampal dentate gyrus (DG). Exercise has been accepted as a treatment for the improvement of neurodegenerative disease. Herein, the effects of exercise on the MDMA- induced neurotoxicity were assessed. Male Wistar rats received intraperitoneal injection of MDMA (10 mg/kg) and exercised for one month on a treadmill (Simultaneously or asynchronously with MDMA). LTP and expression of BDNF were assessed using electrophysiology and western blotting methods, respectively. MDMA attenuated the field excitatory post-synaptic potential (fEPSP) slope in comparison with the control group, whereas treadmill exercise increased this parameter when compared to MDMA group. Furthermore, BDNF expression significantly decreased in MDMA group and treadmill exercise could increase that. In conclusion, results of this study suggest that synchronous exercise is able to improve MDMA-induced LTP changes through increase of BDNF expression in the hippocampus of rats.

 

 

BJOG. 2017 Jun 14. doi: 10.1111/1471-0528.14786.

Medical therapy for preventing recurrent endometriosis after conservative surgery: a cost-effectiveness analysis.

Wu B¹, Yang Z², Tobe RG³, Wang Y².

Abstract

OBJECTIVE:

To assess the cost-effectiveness of different strategies, including gonadotropin-releasing hormone agonist (GnRH-a) and oral contraceptive therapy, for the prevention of endometriosis recurrence after conservative surgery.

DESIGN:

Cost-effectiveness analysis from a health care perspective.

SETTING:

A health-resource-limited setting in China.

POPULATION:

Patients who underwent conservative laparoscopic or laparotomic surgery for endometriosis.

METHODS:

A Markov model was developed for the endometriosis disease course. Clinical data were obtained from published studies. Direct medical costs and resource utilization in the Chinese health care setting were taken into account. The health and economic outcomes were evaluated over a period from treatment initiation to menopause onset. Sensitivity analyses were carried out to test the impact of various parameters and assumptions on the model output.

MAIN OUTCOME MEASURES:

Quality-adjusted life years (QALYs) gained and costs from a health care perspective.

RESULTS:

The incremental cost-effectiveness ratio of 6-month GnRH-a therapy compared with no therapy ranged from $6,185 per QALY in deep endometriosis to $6,425 with peritoneal endometriosis. A one-way sensitivity analysis showed considerable influential factors, such as remission rates and utility values. Probabilistic sensitivity analysis indicated that 6-month GnRH-a therapy is cost-effective in most cases at a threshold of $7,400/QALY, regardless of the type of endometriosis.

CONCLUSION:

Six months of therapy with GnRH-a can be a highly cost-effective option for the prevention of endometriosis recurrence.

 

 

Rev Bras Ginecol Obstet. 2017 Jun;39(6):273-281.

Combined Effect of the PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis.

Cardoso JV^1,2, Machado DE¹, Ferrari R³, Silva MCD¹, Berardo PT⁴, Perini JA^1,2.

 

Abstract

Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis. Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression. Results The endometriosis patients were significantly younger than the controls (36.0 ± 7.3 versus 38.0 ± 8.5 respectively, p = 0.023), and they had a lower body mass index (26.3 ± 4.8 versus 27.9 ± 5.7 respectively, p = 0.006), higher average duration of the menstrual flow (7.4 ± 4.9 versus 6.1 ± 4.4 days respectively, p = 0.03), and lower average time intervals between menstrual periods (25.2 ± 9.6 versus 27.5 ± 11.1 days respectively, p = 0.05). A higher prevalence of symptoms of dysmenorrhea, dyspareunia, chronic pelvic pain, infertility and intestinal or urinary changes was observed in the case group when compared with the control group. The interval between the onset of symptoms and the definitive diagnosis of endometriosis was 5.2 ± 6.9 years. When comparing both groups, significant differences were not observed in the allelic and genotypic frequencies of the polymorphisms PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A, even when considering the symptoms, classification and stage of the endometriosis. The combined genotype PGR +331TT/CYP17A1 -34AA/CYP19A11531AA is positively associated with endometriosis (odds ratio [OR] = 1.72; 95% confidence interval [95%CI] = 1.09-2.72). Conclusions The combined analysis of the polymorphisms PGR-CYP17A1-CYP19A1 suggests a gene-gene interaction in the susceptibility to endometriosis. These results may contribute to the identification of biomarkers for the diagnosis and/or prognosis of the disease and of possible molecular targets for individualized treatments.

 

 

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017 Jun-.
2017 Apr 20.

Oral Contraceptive Pills.

Cooper D¹, Adigun R².

 

Excerpt

Currently, there are three types of oral contraceptive pills: combined estrogen-progesterone, progesterone only and the continuous or extended use pill.  The birth control pill is the most commonly prescribed form of contraception in the US.  Approximately 25% of women age 15-44 who currently use contraception reported using the pill as their method of choice.  The most commonly prescribed pill is the combined hormonal pill with estrogen and progesterone.  Progesterone is the hormone that prevents pregnancy, and the estrogen component will control menstrual bleeding.  Birth control pills are primarily used to prevent pregnancy.  The effectiveness of this form of birth control is referred to as typical and perfect use.  Typical use, meaning the method may not always be used consistently or correctly, results in a failure rate of 9 women out of 100 that will become pregnant during the first year of using this method.  Perfect use, meaning the method is used consistently and correctly every time, is less than one woman out of 100 will become pregnant in the first year of use.  Due to human error, the quoted failure rate for combined oral contraceptive pills is the typical use of 9%.  OCP’s can be used to address other health conditions particularly menstrual related disorders such as menstrual pain, irregular menstruation, fibroids, endometriosis-related pain and menstrual- related migraines.  Use of combined pills for acne has been formally approved by the FDA for specific brands.  The majority of women take OCP’s to prevent pregnancy, but 14% used them for non-contraceptive reasons.

 

 

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017 Jun-.
2017 Oct 2.

Intussusception, Child.

Fusco E¹, Bhimji S².

 

Excerpt

Intussusception is a condition in which part of the intestine folds into the section next to it. Intussusception usually involves the small bowel and rarely the large bowel. Symptoms include abdominal pain which may wax and wane, vomiting, bloating, and bloody stool. It may result in a small bowel obstruction. Other complications may include peritonitis or bowel perforation. The cause is typically unknown in children while in adults a lead point due to cancer is often present. Risk factors in children include infections, cystic fibrosis, and intestinal polyps. Risk factors in adults include endometriosis, bowel adhesions, and intestinal tumors. Medical imaging often supports a diagnosis. In children, ultrasound is a preferred the method to diagnose while in adults a CT scan is preferred. Intussusception requires rapid treatment. Treatment in children is typically by an enema with surgery if not successful. In adults removal of part of the bowel is more often required. Intussusception occurs more commonly in children than adults. In Intussusception occurs more commonly in children than adults, in children it is more common in males than females. The usual age of occurrence is six to 18 months old.

 

 

J Obstet Gynaecol. 2017 Oct;37(7):906-911

An evaluation of quality of life in women with endometriosis who underwent primary surgery: a 6-month follow up in Sabah Women & Children Hospital, Sabah, Malaysia.

M F A¹, Narwani H¹, Shuhaila A¹.

 

Abstract

Endometriosis is a complex disease primarily affecting women of reproductive age worldwide. The management goals are to improve the quality of life (QoL), alleviate the symptoms and prevent severe disease. This prospective cohort study was to assess the QoL in women with endometriosis that underwent primary surgery. A pre- and post-operative questionnaire via ED-5Q and general VAS score used for the evaluation for endometrial-like pain such as dysmenorrhoea and dyspareunia. A total of 280 patients underwent intervention; 224 laparoscopically and 56 via laparotomy mostly with stage II disease with ovarian endometriomas. Improvements in dysmenorrhoea pain scores from 5.7 to 4.15 and dyspareunia from 4.05 to 2.17 (p <.001) were observed. The Self Rate Assessment was improved; 6.66-4.68 post-operatively (p < .05). In EQ-5 D Index, the anxiety and activities outcomes showed a significant worsening post-intervention. There was no correlation between the stage of disease and endometrial pain; (p = .289), method of intervention (p = .290) and usage of post-operative hormonal therapy (p = .632). This study concluded that surgical treatment improved the QoL with added hormonal therapy post-intervention, despite not reaching statistical significance, showed a promising result. Impact statement Surgical intervention does improve the QoL for women with endometriosis however post interventional hormonal therapy is remain inconclusive.

 

 

Ann Ist Super Sanita. 2017 Apr-Jun;53(2):125-134.

Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis.

Indraccolo U¹, Indraccolo SR², Mignini F³.

Abstract

AIM:

To demonstrate clinical effectiveness of micronized palmitoylethanolamide-trans-polydatin combination in reducing endometriotic chronic pelvic pain. Other endometriotic-pains were also assessed.

METHODS:

Systematic reviews of PubMed, SCIELO, Scopus, and AJOL. Randomized trials and observational studies reporting a visual analogue scale for pain or similar in endometriotic patients were reviewed. A mean improvement of visual analogue scale (or visual analogue scale-like) scores at enrollment and at a three-month follow-up was assessed and interpreted clinically.

RESULTS:

Four studies of poor quality were available. In a heterogeneous sample of endometriotic patients with pain, the administration of micronized palmitoylethanolamide/trans-polydatin (400 mg/40 mg) twice a day for three months provided a clinically relevant improvement of chronic pelvic pain and dysmenorrhea while improving deep dyspareunia to a limited degree. No clinically relevant improvement was found for dyschezia.

CONCLUSION:

More studies are warranted for assessing the drugs-related efficacy.

 

 

J Cell Physiol. 2018 Apr;233(4):3055-3065

Apigenin induces ROS-dependent apoptosis and ER stress in human endometriosis cells.

Park S^1,2, Lim W³, Bazer FW⁴, Song G^1,2.

 

Abstract

Apigenin is a plant-derived flavonoid having antiproliferative, anti-inflammatory, and anti-angiogenic properties in chronic and metabolic diseases, and cancers. However, the functional role of apigenin remains to be identified in human endometriosis that is a benign inflammatory disease causing infertility, dysmenorrhea, dyspareunia, and chronic abdominal or pelvic pain. In the present study, we determined the effects of apigenin on two well-established human endometriosis cell lines (VK2/E6E7 and End1/E6E7). Apigenin reduced proliferation and induced cell cycle arrest and apoptosis in the both endometriosis cell lines. In addition, it disrupted mitochondrial membrane potential (MMP) which was accompanied by an increase in concentration of calcium ions in the cytosol and in pro-apoptotic proteins including Bax and cytochrome c in the VK2/E6E7 and End1/E6E7 cells. Moreover, apigenin treated cells accumulated excessive reactive oxygen species (ROS), and experienced lipid peroxidation and endoplasmic reticulum (ER) stress with activation of the unfolded protein response (UPR) regulatory proteins. Furthermore, the apigenin-induced apoptosis in endometriosis cells was regulated via the ERK1/2, JNK, and AKT cell signaling pathways. Taken together, apigenin is a potential novel therapeutic agent to overcome current limitations in the treatment to endometriosis.

 

 

J Obstet Gynaecol Res. 2017 Jun;43(6):1048-1053.

Exploring the impact of endometriosis on partners.

Ameratunga D¹, Flemming T¹, Angstetra D¹, Ng SK^1,2, Sneddon A¹.

Abstract

AIM:

This study aimed to determine how endometriosis affects the quality of life of partners of women who suffer from this disease and how it impacts their relationships, finances, mental states, and daily living.

METHODS:

This was a questionnaire-based cohort study that took place at a large tertiary hospital gynecology unit, which covered two sites. Fifty-one partners of women who had surgically diagnosed endometriosis agreed to participate in the study and returned completed surveys.

RESULTS:

Ninety-two percent (n = 46) of partners reported negative feelings about the diagnosis of endometriosis. Seventy percent (n = 35) reported that endometriosis affected their day-to-day life either moderately or severely. Over half (52%) also felt that their finances were affected. Only 34% (n = 17) of partners felt that health professionals had engaged them in decision-making processes and had been supportive of them. Eighty percent (n = 40) of partners reported that they had received no information about the impact of endometriosis on couples. Partners reported a significant affect on their sex life (74%) and their relationship as a whole (56%). Participants whose relationships had been affected by endometriosis had also more likely had their day-to-day life (P = 0.027), sex life (P = 0.001), and finances (P = 0.002) affected.

CONCLUSION:

Overall, our findings suggest that endometriosis can have a significant impact on partners with respect to day-to-day living, finances, sex lives, and relationships. Improvements can be made to engage partners in the treatment process, and to provide better education, support, and holistic management to women and families who suffer with endometriosis.

 

 

Fertil Steril. 2017 Aug;108(2):289-295

Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link.

Cicinelli E¹, Trojano G², Mastromauro M³, Vimercati A², Marinaccio M², Mitola PC², Resta L³, de Ziegler D⁴.

Abstract

OBJECTIVE:

To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry.

DESIGN:

Case-control study.

SETTING:

University hospital.

PATIENT(S):

Women with and without endometriosis who have undergone hysterectomy.

INTERVENTION(S):

Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis.

MAIN OUTCOME MEASURE(S):

CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells.

RESULT(S):

The prevalence of CE was statistically significantly higher in the women with endometriosis as compared with the women who did not have endometriosis (33 of 78, 42.3% vs. 12 of 78, 15.4% according to hysteroscopy; and 30 of 78, 38.5% vs. 11 of 78, 14.1% according to histology). The women were divided into two groups, 115 patients without CE and 41 patients with CE. With univariate analysis, parity was associated with a lower risk for CE, and endometriosis was associated with a statistically significantly elevated risk of CE. Using multivariate analysis, parity continued to be associated with a lower incidence of CE, whereas endometriosis was associated with a 2.7 fold higher risk.

CONCLUSION(S):

The diagnosis of CE is more frequent in women with endometriosis. Although no etiologic relationships between CE and endometriosis can be established, this study suggests that CE should be considered and if necessary ruled out in women with endometriosis, particularly if they have abnormal uterine bleeding. Identification and appropriate treatment of CE may avoid unnecessary surgery.

 

 

Reprod Biomed Online. 2017 Oct;35(4):435-444.

‘Money for nothing’. The role of robotic assisted laparoscopy for the treatment of endometriosis.

Berlanda N¹, Frattaruolo MP², Aimi G², Farella M², Barbara G², Buggio L², Vercellini P².

 

Abstract

Despite higher costs for robotic assisted laparoscopy (RAL) than standard laparoscopy (SL), RAL treatment of endometriosis is performed without established indications. PubMed/MEDLINE was searched for ‘robotic surgery’ and ‘endometriosis’ or ‘gynaecological benign disease’ from January 2000 to December 2016. Full-length studies in English reporting original data were considered. Among 178 articles retrieved, 17 were eligible: 11 non-comparative (RAL only) and six comparative (RAL versus SL). Non-comparative studies included 445 patients. Mean operating time, blood loss and hospital stay were 226 min, 168 ml and 4 days. Major complications and laparotomy conversions were 3.1% and 1.3%. Eight studies reported pain improvement at 15-month follow-up. Comparative studies were all retrospective; 749 women underwent RAL and 705 SL. Operating time was longer for RAL in five studies. Major complications and laparotomy conversions for RAL and SL were 1.5% versus 0.3% and 0.3% versus 0.5%. One study reported pain reduction for RAL at 6-month follow-up. RAL treatment of endometriosis did not provide benefits over SL, overall and among subgroups of women with severe endometriosis, peritoneal endometriosis and obesity. Available evidence is low-quality, and data regarding long-term pain relief and pregnancy rates are lacking. RAL treatment of endometriosis should be performed only within controlled studies.

 

 

J Minim Invasive Gynecol. 2017 Sep – Oct;24(6):998-1006.

Surgical Outcomes of Urinary Tract Deep Infiltrating Endometriosis.

Darwish B¹, Stochino-Loi E², Pasquier G³, Dugardin F³, Defortescu G³, Abo C¹, Roman H⁴.

Abstract

OBJECTIVE:

To report the outcomes of surgical management of urinary tract endometriosis.

DESIGN:

Retrospective study based on prospectively recorded data (NCT02294825).

DESIGN:

Classification: II-3 SETTING: University Tertiary referral center.

PATIENTS:

81 women treated for urinary tract endometriosis from July 2009 to December 2015 were included of whom 39 had bladder endometriosis, 31 ureteral endometriosis and 11 both ureteral and bladder endometriosis. Due to bilateral ureteral localizations in 8 women, 50 different ureteral procedures were recorded.

INTERVENTION:

Resection of bladder endometriosis nodules, advanced ureterolysis, ureteral resection followed by end-to-end anastomosis or ureteroneocysostomy were performed.

MAIN OUTCOME MEASURES:

Outcomes of the surgical management of urinary tract endometriosis.

RESULTS:

50 women presented with DIE of the bladder, and underwent either full-thickness excision of the nodule (70%) or excision of the bladder wall without opening of the bladder (30%). Ureterolysis was performed in 78% of ureteral lesions, and 22% ureteral involvements were treated by primary segmental resection. No nephrectomy was required. Intrinsic ureteral endometriosis was histologically revealed in 54.5% of cases. 16% of the patients who had surgery for ureteral nodules had a Clavien-Dindo grade 3 complication and, in those operated for bladder endometriosis 8% had Clavien-Dindo grade 3 complications. Overall delayed postoperative outcomes were favourable as regards urinary symptoms and fertility. Patients were followed up for a minimum of 12 months and up to 7 years postoperatively with no recorded recurrence.

CONCLUSION:

Surgical outcomes of urinary tract endometriosis are generally satisfactory; however, the risk of postoperative complications should be taken into consideration. Therefore, such procedures should be managed by an experienced multidisciplinary team.

 

 

J Obstet Gynaecol Can. 2017 Jul;39(7):585-595.

Primary Dysmenorrhea Consensus Guideline.

Burnett M¹, Lemyre M².

Abstract

OBJECTIVE:

This guideline reviews the investigation and treatment of primary dysmenorrhea.

INTENDED USERS:

Health care providers.

TARGET POPULATION:

Women and adolescents experiencing menstrual pain for which no underlying cause has been identified.

EVIDENCE:

Published clinical trials, population studies, and review articles cited in PubMed or the Cochrane database from January 2005 to March 2016.

VALIDATION METHODS:

Seven clinical questions were generated by the authors and reviewed by the SOGC Clinical Practice-Gynaecology Committee. The available literature was searched. Guideline No. 169 was reviewed and rewritten in order to incorporate current evidence. Recommendations addressing the identified clinical questions were formulated and evaluated using the ranking of the Canadian Task Force on Preventive Health Care.

BENEFITS, HARMS, AND COSTS:

Primary dysmenorrhea is common and frequently undertreated. Effective therapy is widely available at minimal cost. Treatment has the potential to improve quality of life and to decrease time lost from school or work.

 

 

Mol Med Rep. 2017 Aug;16(2):1920-1926.

Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis.

Lian YL¹, Cheng MJ¹, Zhang XX¹, Wang L¹.

 

Abstract

Pain is the most pronounced complaint of women with endometriosis, however the underlying mechanism is still poorly understood. In the present study, the authors evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) of dorsal root ganglia (DRG) on endometriosis-associated pain. A total of 36 SD rats were randomly divided into a sham group (n=9) and a Model group (n=27), accepted auto‑transplanted pieces of fat or uterus to the pelvic cavity. At 4 weeks, the Model group was randomly subdivided into the following groups: ENDO group (no treatment, n=9), BCTC group (Model + BCTC, an antagonist of TRPV1, n=9), Vehicle group (Model + cyclodextrin, the vehicle of BCTC, n=9). Tail‑flick test was performed prior to surgery, 1 h prior to and following treatment of BCTC or cyclodextrin. The expression of TRPV1, substance P (SP), calcitonin gene‑related peptide (CGRP) in L1‑L6 DRG was measured via immunohistochemistry, western blotting and RT‑qPCR. The results indicated that the Model group exhibited a significant decrease in tail flick latency compared to pre‑surgical baseline, and the expression of TRPV1, SP, CGRP protein and mRNA in L1‑L6 DRG significantly increased compared to the sham group. BCTC significantly improved tail flick latency, and downregulated the expression of TRPV1, SP and CGRP protein and mRNA levels in L1‑L6 DRG compared to ENDO group. However, there were no significant differences of those in Vehicle group compared with the ENDO group. Taken together, the current study provides evidence that TRPV1 expressed in DRG may serve an important role in endometriosis-associated pain.

 

 

BMJ Case Rep. 2017 Jun 18;2017.

Port site endometrioma: a rare cause of abdominal wall pain following laparoscopic surgery.

Siddiqui ZA¹, Husain F², Siddiqui Z³, Siddiqui M⁴.

 

Abstract

Endometriomas are a rare cause of abdominal wall pain. We report a case of a port site endometrioma presenting with an umbilical swelling. The patient underwent a laparoscopy for pelvic endometriosis 6 months previously and presented with a swelling around her umbilical port site scar associated with cyclical pain during menses. Ultrasound scan reported a well-defined lesion in the umbilicus and MRI scanning excluded other pathology. As she was symptomatic, she underwent an exploration of the scar and excision of the endometrioma with resolution of her symptoms. Precautions should be taken to reduce the risk of endometrial seeding during laparoscopic surgery. All tissues should be removed in an appropriate retrieval bag and the pneumoperitoneum should be deflated completely before removing ports to reduce the chimney effect of tissue being forced through the port site. The diagnosis should be considered in all women of reproductive age presenting with a painful port site scar.

 

J Minim Invasive Gynecol. 2017 Nov – Dec;24(7):1239-1242.

Case Report: Three-Dimensional Printed Model for Deep Infiltrating Endometriosis.

Ajao MO¹, Clark NV², Kelil T³, Cohen SL², Einarsson JI².

 

Abstract

The combination of a thorough physical examination and imaging with either magnetic resonance imaging (MRI) or pelvic ultrasound are important in the preoperative planning for deep infiltrating endometriosis (DIE). A 2-dimensional (2D) rendering of the pathology by imaging does not always accurately represent intraoperative findings. The detailed topographical relationship and extent of surrounding tissue invasion can be better appreciated by 3-dimensional (3D) modeling. A 49-year-old patient with history of endometriosis and persistent pain underwent preoperative MRI that showed features consistent with DIE endometriosis. Surgery was performed, and the findings were documented. A 3D printed model of the DIE was generated from the MRI and retrospectively compared with intraoperative findings. The 3D model demonstrated both the laterality and spatial relationship of the endometriotic nodule to the posterior uterine wall and rectum. Three-dimensional printing of DIE may be a beneficial adjunct to 2D imaging and can identify further structural relationships to support surgical planning.

 

 

 

Sci Rep. 2017 Jun 20;7(1):3916.

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase.

Kukushkina V^1,2,3, Modhukur V⁴, Suhorutšenko M^1,5, Peters M^1,5, Mägi R³, Rahmioglu N⁶, Velthut-Meikas A¹, Altmäe S^1,7, Esteban FJ⁸, Vilo J⁴, Zondervan K^6,9, Salumets A^1,5,10,11, Laisk-Podar T^12,13.

 

Abstract

The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR < 0.05). Of differentially methylated CpG sites with the largest absolute changes in methylation level, approximately 30% correlated with gene expression measured by RNA sequencing, with negative correlations being more common in 5′ UTR and positive correlations in the gene ‘Body’ region. According to our results, extracellular matrix organization and immune response are the pathways most affected by methylation changes during the transition from pre-receptive to receptive phase.

 

 

J Psychosom Obstet Gynaecol. 2017 Dec;38(4):238-248.

The burden of endometriosis symptoms on health-related quality of life in women in the United States: a cross-sectional study.

Soliman AM¹, Coyne KS², Zaiser E², Castelli-Haley J¹, Fuldeore MJ¹.

Abstract

INTRODUCTION:

To examine the symptomatic burden of endometriosis on health-related quality of life (HRQL) in women in the United States (US).

METHODS:

A cross sectional web-based survey study was conducted among women using survey panels. The survey included study-specific questions and standardized HRQL questionnaires. Participants reviewed a list of endometriosis symptoms and selected all symptoms they had ever or were currently experiencing. For current symptoms, participants rated the severity and bothersomeness of each symptom. Participants completed the endometriosis health profile (EHP-30) core questionnaire. Descriptive analyzes were performed and multivariate regressions were run with each EHP subscale as a dependent variable to examine the impact of symptoms while controlling for age and comorbid conditions.

RESULTS:

Mean age of the 1269 women was 34.3 ± 0.3; 78% were white. At least 75% reported having ever experienced: pelvic pain/cramping during their menstrual period, anxiety/stress, lower back pain or fatigue/weariness/anemia. EHP-30 scores ranged from 33.6 (95% CI: 31.4, 35.8) (social support) to 37.8 (95% CI: 35.5, 40.1) (control and powerlessness), indicating moderate HRQL impact. For all but one domain and one symptom, EHP-30 scores were significantly higher (worse) for women who had individual endometriosis-related symptoms than for those who did not. EHP-30 scores consistently deteriorated with each increase in the number of symptoms experienced and by increasing perceived disease severity. Pelvic pain/cramping during menstrual period, irregular periods and general abdominal pain were significantly associated with the EHP-30 domain scores in the regression models.

CONCLUSION:

Experiencing endometriosis symptoms is associated with lower HRQL. Importantly, as symptom severity and number of symptoms increase, HRQL further deteriorates.

 

 

Rev Bras Ginecol Obstet. 2017 Aug;39(8):403-407

Evaluation of Cases of Abdominal Wall Endometriosis at Universidade Estadual de Campinas in a period of 10 Years.

Yela DA¹, Trigo L¹, Benetti-Pinto CL¹.

 

Abstract

Purpose To determine the clinical and epidemiological characteristics of abdominal wall endometriosis (AWE), as well as the rate and recurrence factors for the disease. Methods A retrospective study of 52 women with AWE was performed at Universidade Estadual de Campinas from 2004 to 2014. Of the 231 surgeries performed for the diagnosis of endometriosis, 52 women were found to have abdominal wall endometriosis (AWE). The frequencies, means and standard deviations of the clinical characteristics of these women were calculated, as well as the recurrence rate of AWE. To determine the risk factors for disease recurrence, Fisher’s exact test was used. Results The mean age of the patients was 30.71 ± 5.91 years. The main clinical manifestations were pain (98%) and sensation of a mass (36.5%). We observed that 94% of these women had undergone at least 1 cesarean section, and 73% had used medication for the postoperative control of endometriosis. The lesion was most commonly located in the cesarean section scar (65%). The recurrence rate of the disease was of 26.9%. All 14 women who had relapsed had surgical margins compromised in the previous surgery. There was no correlation between recurrent AWE and a previous cesarean section (p = 0.18), previous laparotomy (p = 0.11), previous laparoscopy (p = 0.12) and postoperative hormone therapy (p = 0.51). Conclusion Women with previous cesarean sections with local pain or lumps should be investigated for AWE. The recurrence of AWE is high, especially when the first surgery is not appropriate and leaves compromised surgical margins.

 

 

Hum Reprod. 2017 Aug 1;32(8):1667-1673.

A qualitative study of the impact of endometriosis on male partners.

Culley L¹, Law C¹, Hudson N¹, Mitchell H¹, Denny E², Raine-Fenning N^3,4.

Abstract

STUDY QUESTION:

What is the impact of endometrioses on male partners of women with the condition?

SUMMARY ANSWER:

Endometriosis significantly impacts men across several life domains and can negatively impact emotional well-being.

WHAT IS KNOWN ALREADY:

Endometriosis has been shown to negatively impact women’s quality of life and may strain intimate relationships. Little is known about the impact on male partners.

STUDY DESIGN, SIZE, DURATION:

The ENDOPART study was a cross-sectional, qualitative study of 22 women with endometriosis and their male partners (n = 44) in the UK (2012-2013).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Inclusion criteria: laparoscopic diagnosis of endometriosis; the presence of symptoms for at least a year; partners living together. Data were collected via face to face, semi structured interviews with partners interviewed separately. Data were analysed thematically, assisted by NVivo 10.

MAIN RESULTS AND THE ROLE OF CHANCE:

Men reported that endometriosis affected many life domains including sex and intimacy, planning for and having children, working lives and household income. It also required them to take on additional support tasks and roles. Endometriosis also had an impact on men’s emotions, with responses including helplessness, frustration, worry and anger. The absence of professional or wider societal recognition of the impact on male partners, and a lack of support available to men, results in male partners having a marginalized status in endometriosis care.

LIMITATIONS REASONS FOR CAUTION:

Self-selection of participants may have resulted in a sample representing those with more severe symptoms. Couples included are in effect ‘survivors’ in relationship terms, therefore, findings may underestimate the contribution of endometriosis to relationship breakdown.

WIDER IMPLICATIONS OF THE FINDINGS:

The study extends knowledge about the impact of endometriosis on relationships, which thus far has been drawn largely from studies with women, by providing new insights about how this condition affects male partners. Healthcare practitioners need to take a more couple-centred, biopsychosocial approach toward the treatment of endometriosis, inclusive of partners and relationship issues. The findings demonstrate a need for information and support resources aimed at partners and couples.

STUDY FUNDING/COMPETING INTEREST(S):

This study was funded by the Economic and Social Research Council (reference ES/J003662/1). The authors have no conflicts of interest.

 

 

 

Biol Reprod. 2017 Jul 1;97(1):32-38.

Effect of Simvastatin on Baboon Endometriosis.

Taylor HS¹, Alderman M¹, D’Hooghe TM^2,3, Fazleabas AT⁴, Duleba AJ⁵.

 

Abstract

Endometriosis, a common disorder affecting women of reproductive age is characterized by ectopic growth of the endometrial tissues, altered steroid hormone response and inflammation. Previous studies revealed that statins, selective inhibitors of the key step of mevalonate pathway, inhibit growth of endometrial stromal cells in vitro and reduce endometriotic lesions in murine models of endometriosis. This study evaluated the effects of simvastatin on the development of endometriosis in a baboon model of this disease. Sixteen baboons were randomly assigned to the treatment group (simvastatin, 20 mg daily) or to the control group. Endometriotic lesions were evaluated by laparoscopy after three months. The volume of red, orange-red and white endometriotic lesions was significantly reduced by 78% in animals treated with simvastatin. The expression of a marker of proliferation, proliferating cell nuclear antigen (PCNA) was significantly reduced in animals receiving simvastatin in red lesions, white lesions, black lesions and in adhesions. Simvastatin was also associated with an increase in the expression of estrogen receptor alpha in red lesions, and a decrease in the expression of estrogen receptor beta in black lesions, in adhesions, and in eutopic endometrium. Furthermore, simvastatin significantly reduced the expression of neopterin, a marker of inflammation, oxidative stress and immune system activation. Collectively, the present findings indicate that the inhibition of the mevalonate pathway by simvastatin reduces the risk of developing endometriosis in the primate model of this disease by decreasing the growth of endometrial lesions, by modulating the expression of genes encoding for estrogen receptors, and by reducing inflammation.

 

 

Eurasian J Med. 2017 Jun;49(2):107-112.

Evaluation of the Ki-67 Proliferation Index and Urocortin Expression in Women with Ovarian Endometriomas.

Yalcin SE¹, Ocal I², Yalcin Y³, Selim HS⁴, Caltekin MD⁵, Aydogmus H⁶, Kelekci S⁷.

Abstract

OBJECTIVE:

The reasons why endometriosis is more aggressive and invasive in some patients are unknown. Despite the importance of population-based clinically defined risk factors in the prediction of recurrence, biochemical markers obtained from the patient are more valuable for prediction on an individual basis. Therefore, the discovery of significant potential biomarkers could be useful to clinicians for shedding light on the pathogenesis of endometriosis and in the monitoring recurrence.

MATERIALS AND METHODS:

This study included 50 patients who underwent surgery for ovarian cysts that were diagnosed as endometrioma. The age of the patients, stage of the endometriosis, diameter and localization of endometriomas, type of surgery, and pre- and postoperative cancer antigen 125 (CA125) levels were compared between patients with and without recurrence. The archived pathology slides were stained with Ki-67 and anti-urocortin antibodies for reevaluation. By comparing the pathology parameters of the patients with and without recurrence, the association between these parameters and recurrence was investigated.

RESULTS:

The median Ki-67 proliferation index of the patients with recurrence (7.5±6.5) was statistically significant compared with that of the patients without recurrence (1±4) (p=0.003). The urocortin epithelial staining intensity and percentage were not found to be statistically significant in comparison. A statistically significant difference was determined between postoperative CA125 median levels of patients without recurrence (10±17.6) and those of patients with recurrence (29.9±18.1) (p=0.003).

CONCLUSION:

The Ki-67 proliferation index may be useful for predicting prognosis and recurrence risk.

 

 

Front Endocrinol (Lausanne). 2017 Jun 7;8:110.

Gonadotropin-Releasing Hormone and Its Role in the Enteric Nervous System.

Ohlsson B^1,2.

 

Abstract

Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone, and luteinizing hormone orchestrate the reproduction cycle and regulate the sex steroid secretion from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neurotransmitters/peptides in various tissues, where the peptides exert many different effects. mRNA coding for GnRH1 and GnRH2 have been described in the human gastrointestinal tract, and GnRH has been found in both submucosal and myenteric neurons. mRNA coding for GnRH and the fully expressed peptide have been found in rat enteric neurons by some researchers but not by others. mRNA coding for GnRH receptors, but not the fully expressed receptor, has been found in one rat study. GnRH influences gastrointestinal motility and secretion. GnRH analogs are clinically used in the treatment of sex hormone-dependent diseases, i.e., endometriosis and malignancies, and as pretreatment for in vitro fertilization. Reduced numbers of enteric neurons and IgM antibodies against GnRH and progonadoliberin-2 (precursor of GnRH2) have been observed after such treatment, with the clinical picture of gastrointestinal dysmotility. Similarly, a rat model of enteric neurodegeneration has been developed after administration of the GnRH analog buserelin. Serum IgM antibodies against GnRH1, progonadoliberin-2, and GnRH receptors have been described in patients with signs and symptoms of gastrointestinal dysmotility and/or autonomic dysfunction, such as irritable bowel syndrome, enteric dysmotility, diabetes mellitus, and primary Sjögren’s syndrome. Thus, apart from regulation of reproduction and sex hormone secretion, GnRH also constitutes a part of enteric nervous system (ENS) and its functions during physiological and pathological conditions. This review aimed to describe the role of GnRH in the ENS.

 

 

Obstet Gynecol Int. 2017;2017

Uterine Cavity Abnormalities in Patients with Endometriosis in Alexandria: A Diagnostic Test Accuracy Study.

Abd El Fattah EA¹.

 

Abstract

Endometriosis is strongly associated with infertility. Endometrial polyps are prevalent in infertile women and they have similar pathological characteristics to endometriosis, suggesting a possible association. Uterine malformations as uterine septum and hypoplastic uterus are also linked to endometriosis. Hysterosalpingogram and transvaginal ultrasonography are used to diagnose endometrial lesions. Hysteroscopy can detect small lesions that might be missed. Recently, 4D ultrasonography is being used, but which is superior has not been established yet. We aim to compare 4D ultrasonography to office hysteroscopy in evaluating uterine cavity in cases with endometriosis; also we aim at correlating these findings with the stage of endometriosis. 50 cases of endometriosis diagnosed by laparoscopy were randomly selected from El Shatby fertility clinic, Alexandria University, Egypt, with exclusion of cases with any previous intrauterine surgery or any hormonal treatment. Transvaginal 4D ultrasonography and office hysteroscopy were done. 4D ultrasonography agreed with office hysteroscopy in diagnosing abnormal uterine findings in 14 cases and four additional cases were diagnosed by hysteroscopy alone. Conclusion. Endometrial polyps, septate uterus, and hypoplastic uterus are more prevalent among infertile women who happen to have endometriosis. 4D ultrasonography and office hysteroscopy are equally successful in assessing the uterine cavity.

 

 

J Obstet Gynaecol Can. 2017 Sep;39(9):764-768.

Dienogest Therapy as a Treatment for Catamenial Pneumothorax: Case Report and Review of Hormonal Options.

Lalani S¹, Black A², Hodge MC³, Tulandi T⁴, Chen I².

Abstract

BACKGROUND:

Catamenial pneumothorax is a rare but serious condition for women of reproductive age. We describe a trial of dienogest as hormonal therapy for catamenial pneumothorax and review the literature on hormonal suppressive therapy for this condition.

CASE:

A 39-year-old female, gravida 0 para 0, presented with recurrent pneumothoraces coinciding with her menses. After surgical therapy, she was started on leuprolide acetate injections for 6 months to reduce recurrence. To reduce long-term side effects of leuprolide acetate, the patient was started on dienogest 4 mg orally once daily instead of leuprolide acetate for hormonal suppression and experienced resolution of recurrent pneumothoraces.

CONCLUSION:

For women with recurrent catamenial pneumothorax, dienogest may be an effective hormonal treatment option and alternative to long-term GnRH agonist therapy for long-term suppression.

 

 

J Minim Invasive Gynecol. 2018 Jan;25(1):26-27.

A Modified Technique of Temporary Suspension of the Ovary to the Anterior Abdominal Wall.

Abuzeid OM¹, Raju R², Hebert J², Ashraf M³, Abuzeid MI³.

Abstract

STUDY OBJECTIVE:

To demonstrate a modified technique of temporary suspension of the ovary to the fascia of the anterior abdominal wall after operative laparoscopy for advanced stage-endometriosis to reduce postoperative adhesion formation.

DESIGN:

Video illustrating this modified technique of ovarian suspension (Canadian Task Force classification III).

SETTING:

A previous study described a technique of temporary suspension of the ovary to the abdominal wall using nylon suture [1]. Here we demonstrate a modification of this technique involving underwent temporary suspension of the right ovary, using dissolvable 3-0 plain catgut suture, after operative laparoscopy for advanced-stage endometriosis (American Society for Reproductive Medicine stage III classification).

INTERVENTIONS:

This patient underwent right ovariolysis for stage III endometriosis. A CO₂ laser was used to evaporate spots of endometriosis on the surface of the ovary, ovarian fossa, and the wall of a small endometrioma. A 3-0 plain catgut suture was placed in the right ovarian ligament, and the needle was cut and removed from the peritoneal cavity. The ends of the sutures were brought out of the peritoneal cavity through a 3-mm skin incision using an Endo Close device (Medtronic, Minneapolis, Minnesota). The suture was tied over the fascia while allowing CO₂ gas out of the peritoneal cavity, to ensure that the suture remained under tension and the ovary was well suspended without touching the abdominal wall. The suture was used to elevate the ovary away from the ovarian fossa, to avoid recurrence of adhesions between it and the ovary. Postoperatively the patient did well and was discharged home on oral pain medication on the same day of surgery. No postoperative complications related to the suspension procedure were reported. The patient had an uneventful recovery.

CONCLUSION:

This modified approach of temporary ovarian suspension to the fascia of the anterior abdominal wall appears to be simple, safe, and easy to learn.