Environ Toxicol Pharmacol. 2017 Apr;51:56-70.

Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

Sifakis S¹, Androutsopoulos VP², Tsatsakis AM³, Spandidos DA⁴.

 

Abstract

Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system.

 

 

Iran J Med Sci. 2017 Jan;42(1):98-101.

Ruptured Hemorrhagic Cyst of Undescended Ovary Mimicking Mucocele: A Rare Pediatric Case.

Sekmenli T¹, Gündüz M¹, Ciftci I¹.

 

Abstract

Undescended ovary is a rare entity and usually presentedas a case report. It is associated with urinary and uterine anomalies. Symptomatic patients are diagnosed during surgery. Most of the patients are asymptomatic and treatment is unnecessary. They are incidentally diagnosed during infertility evaluation and treatment such as ovarian hyperstimulation studies. A 15-year-old female patient presented with the diagnosis of renal cystic massas identifiedduring ultrasonography in another hospital. Abdominal computedtomography image was requested. A cystic lesion of about 48×34 mm with well-defined borders associated with the appendix and probably with mucocele of the appendix was reported in the lower right abdominal quadrant close to the cecum. During exploration, the right ovary was seen to be attached to the cecum and was higher in position as well as a right ovary originated cystic structure of 5×5 cm. Using needle aspiration, intraovarian hemorrhage was confirmed and partial cystectomy was performed. The present study reports on an undescended ovary that hadacute abdomen symptoms imitating mucocele. In girls referring to the hospital with abdominal pain, although quite rare, undescended ovaries are to be also considered. As the incidence of renal and uterine anomalies is higher in suchpatients, in symptomatic cases relevant organs are to be investigated carefully during surgical intervention.

 

 

Cancer Causes Control. 2017 May;28(5):437-445.

Endometriosis and risk o f ovarian and endometrial cancers in a large prospective cohort of U.S. nurses.

Poole EM¹, Lin WT², Kvaskoff M^3,4, De Vivo I^3,5, Terry KL^2,5, Missmer SA^3,2,5,6.

Abstract

PURPOSE:

Endometriosis is associated with ovarian cancer, but the relation with endometrial cancer is unclear. Prior studies generally were retrospective and had potential limitations, including use of self-reported endometriosis, failure to account for delays between symptom onset and endometriosis diagnosis, and changes in risk factors post-endometriosis diagnosis. We evaluated whether these limitations obscured a weak association with endometrial cancer and the extent to which these limitations impacted associations with ovarian cancer.

METHODS:

Cox proportional hazards regression models were used to assess associations between endometriosis and cancer risk, evaluating the impacts of self-reported vs. laparoscopically confirmed endometriosis, delayed diagnosis, and post-endometriosis diagnosis changes in risk factor exposures on relative risk estimates.

RESULTS:

Over 18 years of follow-up, we identified 228 ovarian and 166 endometrial cancers among 102,025 and 97,109 eligible women, respectively. Self-reported endometriosis was associated with ovarian cancer [relative risk (RR): 1.81; 95% confidence interval (CI): 1.26-2.58]; this association was stronger for laparoscopically confirmed endometriosis (HR: 2.14; 95% CI 1.45-3.15). No association was observed with endometrial cancer (self-report RR: 0.78; 95% CI 0.42-1.44; laparoscopic-confirmation RR: 0.76; 95% CI 0.35-1.64). Accounting for diagnosis delays or post-endometriosis diagnosis changes in risk factors had a little impact.

CONCLUSIONS:

This study adds to the evidence that endometriosis is not strongly linked to endometrial cancer risk and that the association with ovarian cancer is robust to misclassification, diagnostic delay, and changes in exposures post-endometriosis diagnosis. Our analysis suggests that confounding and misclassification do not obscure a weak association for endometrial cancer risk, although our results should be replicated.

 

 

Cell Death Dis. 2017 Mar 16;8(3

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis.

Chang KK^1,2, Liu LB¹, Jin LP^3,4, Zhang B¹, Mei J¹, Li H⁴, Wei CY¹, Zhou WJ^1,2, Zhu XY³, Shao J¹, Li DJ^1,2, Li MQ^1,2,3.

 

Abstract

Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10⁺Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β. Compared with peripheral CD4⁺ T cells, endometrial CD4⁺ T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-β) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10⁺Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10⁺Th17 cells.

 

 

J Pediatr Surg. 2017 Aug;52(8):1269-1272.

Unexpected findings after surgery for suspected appendicitis rarely change treatment in pediatric patients; Results from a cohort study.

Gorter RR¹, van Amstel P², van der Lee JH³, van der Voorn P⁴, Bakx R⁵, Heij HA⁶.

Abstract

BACKGROUND:

To determine if non-operative treatment is safe in children with acute appendicitis, we evaluated the incidence of unexpected findings after an appendectomy in children, and the influence they have on subsequent treatment.

METHODS:

A historical cohort study (January 2004-December 2014) was performed including children, aged 0-17 years, who underwent an appendectomy for the suspicion of acute appendicitis. Patients were divided based upon histopathological examination. Unexpected findings were reviewed, as well as the subsequent treatment plan.

RESULTS:

In total 484 patients were included in this study. In the overall group, unexpected findings were noted in 10 (2.1%) patients of which two patients intra-operatively with a non-inflamed appendix (Ileitis terminalis N=1 and ovarian torsion N=1) and in 8 patients on histopathological examination. The latter group consisted of 4 patients with concomitant simple appendicitis (parasitic infection N=3 and Walthard cell rest N=1), two with concomitant complex appendicitis (carcinoid N=1 and parasitic infection N=1) and two patients with a non-inflamed appendix (endometriosis N=1 and parasitic infection N=1). Treatment was changed in 4 patients (<1%).

CONCLUSIONS:

Results from this study corroborate the safety of non-operative strategy for acute simple appendicitis, as the occurrence of unexpected findings was low, with extremely few necessary changes of the treatment plan because of serious findings.

 

 

Aust N Z J Obstet Gynaecol. 2017 Apr;57(2):201-205.

Endometriosis in patients with irritable bowel syndrome: Specific symptomatic and demographic profile, and response to the low FODMAP diet.

Moore JS^1,2, Gibson PR¹, Perry RE², Burgell RE¹.

Abstract

BACKGROUND:

Women with endometriosis are frequently misdiagnosed with irritable bowel syndrome (IBS) for some time before a correct diagnosis is made. Visceral hypersensitivity is a key feature in both conditions.

AIMS:

To determine if there are distinct symptom patterns in women with IBS and endometriosis, and to determine the response of these women to a low FODMAP diet in comparison to those with IBS alone.

MATERIALS AND METHODS:

A retrospective analysis of prospectively collected data from women attending a specialist IBS service in Christchurch New Zealand. Data from those who met Rome III criteria for IBS were sorted into two groups: concurrent endometriosis and those with IBS alone. Demographics and symptom patterns were identified from a prospective questionnaire. A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet was taught to all women as the primary therapeutic intervention. Responses to the diet were noted against their ultimate disposition.

RESULTS:

Of the 160 women who met Rome III criteria for IBS, 36% had concurrent endometriosis. The presence of dyspareunia (P > 0.0001), referred pain (P = 0.005), bowel symptoms exacerbated by menstruation (P = 0.0004) and a family history of endometriosis (P = 0.0003) were associated with concurrent endometriosis. Seventy two percent of these women reported a >50% improvement in bowel symptoms after four weeks of a low FODMAP diet compared with 49% in those with no known endometriosis (P = 0.001, odds ratio 3.11, 95% CI, 1.5-6.2).

CONCLUSIONS:

Women with concurrent endometriosis and IBS report a unique symptom phenotype. The low FODMAP diet appears effective in women with gut symptoms and endometriosis.

 

 

Sci Rep. 2017 Mar 17;7:44616.

Effects of matrix stiffness on epithelial to mesenchymal transition-like processes of endometrial epithelial cells: Implications for the pathogenesis of endometriosis.

Matsuzaki S^1,2,3, Darcha C⁴, Pouly JL¹, Canis M^1,2,3.

 

Abstract

Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation. Increasing matrix stiffness with TGF-β1 stimulation reduced the number of cell-cell contacts. Cells that retained cell-cell contacts showed decreased expression of E-cadherin and zonula occludens 1 (ZO-1) to cell-cell junctions. Few deep endometriotic epithelial cells (DEE) grown on 30-kPa PGS, which may mimic in vivo tissue compliance of DIE, retained localization of E-cadherin to cell-cell junctions with TGF-β1 treatment. Immunohistochemical analysis showed no phosphorylated Smad 2/3 nuclear localization in E-cadherin+ epithelial cells of DIE. We hypothesize that EEE may undergo an EMT-like process after attachment of endometrium to peritoneum in a TGF-β1-rich microenvironment. However, TGF-β1 signaling may be absent in DIE, resulting in a more epithelial cell-like phenotype in a rigid microenvironment.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 May;212:9-12.

Effects of long-term postoperative dienogest use for treatment of endometriosis on bone mineral density.

Seo JW¹, Lee DY¹, Yoon BK¹, Choi D².

Abstract

OBJECTIVE:

This study was conducted to evaluate the effects of long-term postoperative dienogest (DNG) use for the treatment of endometriosis on bone mineral density (BMD).

STUDY DESIGN:

Sixty reproductive-aged women who underwent conservative surgery for endometriomas and received postoperative DNG (2mg/day) for at least 12 months to prevent recurrence were analyzed. BMD was measured before and after DNG treatment by using dual energy X-ray absorptiometry, and changes in BMD were evaluated.

RESULTS:

Mean patient age was 30.5 years, and mean duration of DNG treatment was 18.6 months. BMD at the lumbar spine significantly decreased after the first 6 months (-2.2%), and 1year (-2.7%) of DNG treatment, compared to baseline. The proportion of women who had significantly decreased BMD at the lumbar spine after 1year was 75% (45/60). In addition, BMD at the femur neck also decreased significantly after 1year (-2.8%). BMDs after 2 years were not different from those after 1year at both sites in 24 women who received DNG for ≥2years. In addition, there were no differences in baseline characteristics between women who had significantly reduced BMD at the lumbar spine after 1year (N=45) and women who did not (N=15).

CONCLUSION:

This study suggests that long-term postoperative DNG treatment might have an adverse effect on BMD in reproductive-aged women. Bone loss mostly occurs during the first 6 months of treatment with DNG. A clinical trial is warranted to establish the effects of long-term DNG treatment on bone mass.

 

 

Int J Surg Case Rep. 2017;33:139-142.

A case report of thoracic endometriosis – A rare cause of haemothorax.

Pankratjevaite L¹, Samiatina-Morkuniene D².

Abstract

INTRODUCTION:

The presence of endometrial tissue in airways, pleura and lung parenchyma is called thoracic endometriosis syndrome (TES). It is a rare pathology, and typically consists of catamenial pneumothorax, haemothorax, haemoptysis, and pulmonary nodules. We report a case of a 36-year-old woman with thoracic endometriosis causing catamenial haemothorax.

CONCLUSIONS:

The diagnosis of thoracic endometriosis is complicated and often delayed. TES should be suspected in a reproductive age woman with exacerbating symptoms during the menstruation. Treatment may be medical and surgical.

 

 

Abdom Radiol (NY). 2017 Jul;42(7):1975-1992.

Adnexal masses associated with peritoneal involvement: diagnosis with CT and MRI.

Ognong-Boulemo A^1,2, Dohan A³, Hoeffel C⁴, Stanek A⁵, Golfier F^1,6,7, Glehen O^1,6,8, Valette PJ^1,2,6, Rousset P^9,10,11.

Abstract

Given the unique intra-peritoneal anatomic location of the adnexa, tubo-ovarian diseases can commonly spread into the peritoneal cavity. Peritoneal seeding may occur in a spectrum of adnexal conditions including infectious diseases, endometriosis, and benign or malignant primary or secondary ovarian tumors. CT is usually the imaging modality on which the concomitant involvement of the peritoneum and the ovary is depicted. The first diagnosis to be considered by the radiologist is generally peritoneal carcinomatosis from ovarian cancer but other conditions cited above have also to be borne in mind and may be suggested on the basis of careful assessment of CT findings or on further MR findings. MRI may indeed help characterize the lesions in some cases. The purpose of this review is to describe the clinical and imaging patterns of peritoneal involvement that may be found in association with different ovarian lesions. Familiarity with these patterns and diagnoses will help the radiologist narrow the differential diagnosis and make an accurate diagnosis, thus facilitating patient management and avoiding unnecessary invasive treatment.

 

 

Int J Gynecol Pathol. 2018 Jan;37(1):44-51

Microcystic, Elongated, and Fragmented Pattern Invasion in Ovarian Endometrioid Carcinoma: Immunohistochemical Profile and Prognostic Implications.

Goldberg A¹, Hand L, DeCotiis D, Rosenblum N, Chan J.

 

Abstract

Microcystic, elongated, and fragmented (MELF) pattern invasion is a poor prognostic indicator in uterine endometrioid carcinoma, but its existence, biology, and prognostic value have not been described in ovarian endometrioid carcinoma. We evaluated cases of ovarian endometrioid carcinoma without synchronous uterine endometrioid carcinoma for MELF and other histologic features. To evaluate tumor biology, we assessed an immunohistochemical profile, including MLH1, PMS2, MSH2, MSH6, β-catenin, e-cadherin, CK19, and cyclin D1. A retrospective chart review evaluated clinical and demographic features and survival. The Fisher exact test analyzed data. The Kaplan-Meier method assessed overall survival. Forty-two patients met inclusion criteria. MELF was found in 45%. Two MELF cases showed MSH2/MSH6 deficiency and 2 conventional cases showed PMS2 deficiency. Clear cell features were seen exclusively in MELF cases (P-value=0.044). No difference was identified in overall survival, cancer recurrence, serous features, concurrent endometriosis, lymphovascular space invasion, lymph node metastasis, bilaterality of disease, extranodal metastasis, or remainder of immunohistochemical profile. MELF occurs at similar rates in ovarian endometrioid carcinoma and uterine endometrioid carcinoma and can be helpful in defining ovarian endometrioid carcinoma as it proves definitive invasion. Recurrence and overall survival in ovarian endometrioid carcinoma are not affected by MELF. Clear cell features are identified exclusively in MELF cases. Different mismatch repair proteins are lost in MELF compared with conventional ovarian endometrioid carcinomas. Given its association with clear cell features and mismatch repair protein loss, presence of MELF may be useful in clinical decisions regarding surgical staging and Lynch syndrome screening.

 

 

 

 

Reprod Sci. 2017 Aug;24(8):1121-1128.

Therapeutically Targeting the Inflammasome Product in a Chimeric Model of Endometriosis-Related Surgical Adhesions.

Stocks MM¹, Crispens MA¹, Ding T¹, Mokshagundam S¹, Bruner-Tran KL¹, Osteen KG^1,2,3.

 

Abstract

Development of adhesions commonly occurs in association with surgery for endometriosis. Even in the absence of surgery, women with endometriosis appear to be at an enhanced risk of developing adhesions. In the current study, we utilized a chimeric mouse model of experimental endometriosis in order to examine the role of inflammasome activation in the development of postsurgical adhesions. Mice were randomized to receive peritoneal injections of human endometrial tissue fragments or endometrial tissue conditioned media (CM) from women with or without endometriosis 16 hours after ovariectomy and placement of an estradiol-releasing silastic capsule. A subset of mice receiving CM was also treated with interleukin (IL) 1 receptor antagonist (IL-1ra). Our studies demonstrate that peritoneal injection of endometrial tissue fragments near the time of surgery resulted in extensive adhesive disease regardless of tissue origin. However, adhesion scores were significantly higher in mice receiving CM from tissues acquired from patients with endometriosis compared to control tissue CM ( P = .0001). Cytokine bead array analysis of endometrial CM revealed enhanced expression of IL-1β from patients with endometriosis compared to controls ( P < .01). Finally, the ability of human tissue CM to promote adhesive disease was dramatically reduced in mice cotreated with IL-1ra ( P < .0001). Our data implicate enhanced expression of IL-1β in women with endometriosis as a potential causal factor in their increased susceptibility of developing postsurgical adhesions. Thus, targeting inflammasome activation may be an effective strategy for the prevention of surgical adhesions in patients with endometriosis.

 

 

Brain Res. 2017 May 15;1663:132-140

Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogen-activated protein kinase activation.

Han H¹, Liang X¹, Wang J², Zhao Q¹, Yang M², Rong W², Zhang G³.

 

Abstract

The endocannabinoid system regulates neurite outgrowth and neurogenesis during development of the central nervous system. Cannabinoid receptor 1 (CB1R) is expressed in neurons, including the somata and fibers, that innervate the endometrial ectopic cyst in rats. Here, we investigated the contribution of CB1R and its downstream signaling to the innervation of endometrial ectopic growth. We found that intrathecal injection of a CB1R agonist enhanced both the density of protein gene product (PGP) 9.5-immunoreactive sprouted nerve fibers and the protein level of PGP 9.5 of the ectopic cyst, and the CB1R antagonist induced opposite effects. The CB1R agonist increased the expression of phosphorylated extracellular signal-regulated kinase (pERK) and c-Jun N-terminal kinase (pJNK), but not pp38, in dorsal root ganglion (DRG), whereas the CB1R antagonist only decreased the expression of pERK. In cultured DRG neurons, CB1R agonists dose-dependently increased neurite elongation. The mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) and JNK inhibitors, but not the p38 inhibitor, attenuated CB1R agonist-induced neurite elongation. The inhibitions of CB1R and its downstream ERK and JNK signaling pathways may alleviate the sprouted innervation that has been involved in ENDO-associated pain. This finding may provide a new therapeutic target for patients with endometriosis.

 

 

Immunol Lett. 2017 May;185:52-55.

Interleukin-37 in endometriosis.

Kaabachi W¹, Kacem O¹, Belhaj R¹, Hamzaoui A¹, Hamzaoui K².

 

Abstract

Interleukin-37 (IL-37) has been identified as a novel anti-inflammatory cytokine. The present study aimed to evaluate the expression of IL-37 in serum and in peritoneal fluid to determine its clinical significance in endometriosis. Enzyme-linked immunosorbent assay (ELISA) was performed to examine serum IL-37 levels in patients with endometriosis and healthy controls. Peritoneal fluid IL-37 mRNA and NFκB expression were quantified by real-time reverse transcription polymerase chain reaction assays. The association of IL-37 levels with clinical factors and prognosis of endometriosis was analysed. We found that IL-37 levels in PF and in serum were significantly higher in patients with endometriosis compared to women without endometriosis (P=0.0005). IL-37 levels were highly expressed in PF [132.38±34.62pg/mL; P<0.0001] than in serum [74.10±13.49pg/mL] in endometriosis patients. IL-37 mRNA expression contrasted with NFκB mRNA expression in PF from patients with endometriosis. A significant inverse correlation was observed between IL-37 mRNA and NFκB mRNA expression. IL-37 expression correlates with endometriosis severity. The affected NFκB mRNA expression in endometriosiscontributed the to exhibited increase of IL-37. The increased levels of IL-37 may dampen NFκB activation in endometriosis patients.

 

 

 

 

Reprod Sci. 2017 Jan 1:

Stem Cell Markers Describe a Transition From Somatic to Pluripotent Cell States in a Rat Model of Endometriosis.

Othman ER^1,2, Meligy FY³, Sayed AA⁴, El-Mokhtar MA⁵, Refaiy AM⁶.

Abstract

OBJECTIVE:

To study Thy1 as a fibroblast marker, SSEA1 as a marker of intermediate pluripotency, and Oct4 as a marker of established pluripotency in rat model of endometriosis.

DESIGN:

In vivo animal study.

MATERIALS AND METHODS:

Endometriosis was induced in 20 albino female rats through autologous transplantation of one uterine horn to mesentery of intestine. Other 20 rats had their horn removed without transplantation (controls). Rats were sacrificed 4 weeks after induction surgery. Ectopic, eutopic, and control endometria were harvested from endometriosis and control animals respectively. Quantitative syber green based RT-PCR was used to detect expression of Thy-1 (CD90), FUT4 (SSEA1), and POU5F1 (Oct4) genes in tissues. Relative expression was normalized to that of β actin. Thy1, SSEA1, and Oct4 protein expression were detected by immunohistochemistry.

RESULTS:

Ectopic endometrium expressed significantly higher mRNA of Oct4 and SSEA1 as compared to control endometrium. Expression levels of Oct4 and SSEA1 were comparable between ectopic and eutopic endometria and between eutopic and control endometria. Thy1 (CD90) gene expression level was comparable among ectopic, eutopic, and control endometria. Oct4 immunoscore were significantly higher in ectopic (6.6±0.91) than eutopic (2.5±0.78) or control endometrium (3.7±0.1) (P value 0.02). Thy1 and SSEA1 immunoscores were comparable among all three types of endometria.

CONCLUSIONS:

Using rat model of endometriosis, ectopic endometrium showed significantly higher Oct4, and SSEA1, but similar Thy1 gene expression to that of control endometrium. This indicates increased transition from somatic to pluripotent cell states in ectopic endometrium which may play a role in endometriosis pathogenesis.

 

 

 

 

 

J Obstet Gynaecol. 2017 Jul;37(5):639-644.

Conservative management in ureteric hydronephrosis due to deep endometriosis: Could the levonorgestrel-intrauterine device be an option?

Simón E¹, Tejerizo Á¹, Muñoz JL¹, Álvarez C¹, Marqueta L¹, Jiménez JS¹.

 

Abstract

Endometriosis can affect up to 10% of women of reproductive age, in a wide range of clinical presentations that vary from mild to severe or deep endometriosis. Deep endometriosis can affect the urinary tract in 1-5% to 15-25% cases. Even though deep endometriosis’ surgeries are usually complex with higher rate of complications, conservative management is not always considered as an option because of its high failure rates. This paper describes two cases of deep endometriosis with ureteric involvement (hydronephrosis) treated conservatively with a double-pigtail stent plus a Levonorgestrel intrauterine device, after conservative surgery, who remained symptom free with no evidence of recurrence at 3 years follow-up, avoiding radical high-risk surgery. Impact statement Several treatments have been described for endometriosis. From a symptomatic perspective, conservative medical management has been proposed with a variable response. Concerning deep endometriosis(affecting the urinary or digestive tract), the definitive treatment has always been thought to be radical surgery. However, this can lead to several complications. To illustrate a possible more conservative approach this paper describes two cases of deep infiltrating endometriosis affecting the ureter, treated conservatively with a temporary pigtail ureter stent plus a Levonorgestrel intrauterine device. The management demonstrates that, in a selected population, conservative treatment solves the urinary disease avoiding the surgical complications and, what is more, improving patients’ symptoms in a permanent way. Further prospective studies are needed to confirm whether the introduction of this management in clinical practice would reduce the need for surgery thereby, avoiding high-risk surgery and improving the success rate of conservative management.

 

 

Ann Diagn Pathol. 2017 Apr;27:28-33

Seromucinous ovarian tumor A comparison with the rest of ovarian epithelial tumors.

Karpathiou G¹, Chauleur C², Corsini T², Venet M³, Habougit C³, Honeyman F³, Forest F³, Peoc’h M³.

Abstract

BACKGROUND:

Seromucinous ovarian tumors are rare and not adequately described in the literature and this is especially true for seromucinous carcinomas.

AIM OF THE STUDY:

To describe histological and clinical features of these tumors in comparison with the rest of ovarian epithelial tumors.

MATERIALS AND METHODS:

Two hundred and forty one (241) ovarian tumors, borderline (n=92) or malignant (n=149), treated surgically without neoadjuvant chemotherapy, were examined.

RESULTS:

Seromucinous borderline (SMBT) and malignant tumors (SMC) comprised 7.8% (n=7) and 4% (n=6) of all borderline tumors and carcinomas, respectively, studied. Mean age of diagnosis was 63.2 and 68.3years and mean size was 6.4cm and 12cm for SMBT and SMC, respectively. Seromucinous tumors were associated with endometriosis in 23.1% of the cases and they were bilateral in 30.8%. Microscopically, variety in cellular composition, papillary architecture and development into thick walled, occasionally muscular, cysts were the main findings. Medullary/paraovarian/tubal or deeply cortical localization was also characteristic. Stage predicted overall and progression-free survival (p<0.0001 and p=0.03, respectively). Five-year survival was 62% for patients with high grade serous carcinoma, 55% for seromucinous carcinoma, 100% for endometrioid carcinoma, 75% for clear cell carcinoma, and 80% for patients with mucinous carcinoma. Differences were not however statistically significant.

CONCLUSION:

Seromucinous tumors have unique features that support their classification as a different entity. Their localization and their often thick fibrous or/and muscular wall provides further evidence for an histogenesis from the secondary Müllerian system or vestigial structures.

 

 

Case Rep Obstet Gynecol. 2017;2017

Cesarean Scar Endometriosis: An Uncommon Surgical Complication on the Rise? Case Report and Literature Review.

Khachani I¹, Filali Adib A¹, Bezad R¹.

 

Abstract

Endometriosis is defined by the presence and growth of ectopic functional endometrial tissue outside the uterus. Scar endometriosis has been described following obstetrical and gynecological surgery. It is a rare condition, though probably on the rise, due to the considerable increase of cesarean sections performed worldwide. Its physiopathology is complex; its symptomatology is rich and diverse but thorough clinical examination along with ultrasound imaging and potentially pretherapeutic cytologic evaluation are usually efficient in diagnosing the condition. Treatment is mostly surgical. We report the case of a cesarean section scar endometriosis, managed at a tertiary level center and emphasize the diagnosis and treatment options.

 

 

Ginekol Pol. 2017;88(2):96-102.

Influence of diet on the risk of developing endometriosis.

Jurkiewicz-Przondziono J¹, Lemm M, Kwiatkowska-Pamuła A, Ziółko E, Wójtowicz MK.

 

Abstract

Endometriosis is a hormone-dependent chronic inflammatory disease characterized by the presence of endometrium beyond the uterine cavity. The disease affects 5-15% of women of child-bearing age, 30-50% of whom suffer from infertility. Understanding the role of dietary factors in the development of endometriosis is critical to development of effective dietary instructions for prevention. Existing studies concerning nutrition and endometriosis suggest that diet is a potentially modifiable risk factor for endometriosis. Fruits and vegetables, fish oils, dairy products rich in calcium and vitamin D, and Omega-3 fatty acids are likely connected with a lower risk of developing endometriosis. Risk factors that increase the risk of endometriosis include consumption of products rich in trans-unsaturated fatty acids, consumption of fats generally, and consumption of beef and other kinds of red meat and alcohol. Currently, there are no clear correlations between par-ticular food products and the risk of endometriosis. Further research is needed in order to fully understand the influence of consumed food products on the risk of development of this disease.

 

 

Hum Reprod. 2017 Apr 1;32(4):780-793

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.

Uimari O^1,2, Rahmioglu N^1,2, Nyholt DR³, Vincent K¹, Missmer SA⁴, Becker C¹, Morris AP^2,5, Montgomery GW⁶, Zondervan KT^1,2.

Abstract

STUDY QUESTION:

Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis?

SUMMARY ANSWER:

GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways.

WHAT IS KNOWN ALREADY:

Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis.

STUDY DESIGN SIZE, DURATION:

Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software.

MAIN RESULTS AND THE ROLE OF CHANCE:

The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10-4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10-5, FDR-P = 3.0 × 10-3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10-4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10-4, FDR-P = 5.0 × 10-4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology-Core matrisome (P = 1.4 × 10-3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10-3, FDR-P = 7.1 × 10-3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10-12), Apoptosis signaling pathway (P = 9.7 × 10-9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10-6); however, these pathways did not feature in the results based on GWAS data.

LARGE SCALE DATA:

Not applicable.

LIMITATIONS, REASONS FOR CAUTION:

The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry.

WIDER IMPLICATIONS OF THE FINDINGS:

The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis.

 

 

Hum Reprod. 2017 Apr 1;32(4):770-779.

Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis.

Kuessel L¹, Wenzl R¹, Proestling K¹, Balendran S², Pateisky P¹, Yotova 1st¹, Yerlikaya G^1,3, Streubel B², Husslein H¹.

Abstract

STUDY QUESTION:

Do cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis?

SUMMARY ANSWER:

Altered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker.

WHAT IS KNOWN ALREADY:

Cell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes. Altered expression of VCAM-1 and ICAM-1 in women with endometriosis has been investigated previously; however, gene expression levels in tissues and protein levels in the serum have not been investigated in the same patients.

STUDY DESIGN SIZE, DURATION:

We performed a prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent a laparoscopy for benign gynecological pathology in a university-based tertiary referral center for endometriosis. From a total of 138 women who were included in the study from July 2013 through September 2014, 97 had not received hormonal treatment for at least 3 months prior to recruitment and were included in the analysis; 49 (50.5%) of these women had endometriosis, and the 48 (49.5%) who did not have endometriosis served as a control group.

PARTICIPANTS/MATERIALS SETTING METHODS:

During laparoscopy, tissue samples were obtained from ectopic and eutopic endometrium, and from normal pelvic peritoneum. In addition, serum samples were collected immediately before and 6-10 weeks after surgery. The mRNA levels of VCAM-1, ICAM-1 and epithelial cell adhesion molecule (EpCAM) were measured using quantitative real-time PCR, and serum protein levels of soluble VCAM-1 (sVCAM-1), ICAM-1 (sICAM-1) and EpCAM (sEpCAM) were measured using ELISA and correlated with endometriosis status.

MAIN RESULTS AND THE ROLE OF CHANCE:

The mRNA levels of both VCAM-1 and ICAM-1 were higher in ectopic endometriotic lesions than in eutopic endometrium (P < 0.001). Moreover, the mRNA levels of both VCAM-1 and ICAM-1 were higher in normal peritoneum samples obtained from women with endometriosiscompared to those from controls (P = 0.038 and P = 0.009). The mRNA levels of VCAM-1 were also higher in the eutopic endometrium samples obtained from women with endometriosis compared to controls (P = 0.018). With respect to serum protein levels, compared to controls, the women with endometriosis had lower serum levels of sICAM-1 (P = 0.042) and higher levels of sVCAM-1 (P < 0.001). Our analysis revealed that the serum levels of sVCAM-1 were not affected by lesion entity, menstrual cycle phase or disease severity. An receiver operating characteristics curve, calculated to determine whether preoperative serum sVCAM-1 concentration can be used to predict endometriosis, found an AUC of 0.868 with 80% specificity and 84% sensitivity at a cutoff value of 370 pg/ml. This predictive performance can be further improved by calculation of the sVCAM-1/sICAM-1 ratio, leading to an AUC of 0.929 with 86.7% specificity and 90.3% sensitivity at a cutoff ratio value of 1.55.

LARGE SCALE DATA:

Not applicable.

LIMITATIONS REASONS FOR CAUTION:

The relatively small sample size in the expression analyses is a possible limitation of this study.

WIDER IMPLICATIONS OF THE FINDINGS:

Our findings could contribute to an improved understanding of the pathogenesis of endometriosis and the role of cell adhesion molecules. In addition, the results may lead to the development of new, non-invasive tools for diagnosing endometriosis. The ability to diagnose patients by measuring serum sVCAM-1 levels or the sVCAM-1/sICAM-1 ratio would have considerable clinical value.

STUDY FUNDING/COMPETING INTEREST(S):

The Ingrid Flick Foundation (Grant no. FA751C0801), which played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.

 

 

Hum Reprod. 2017 Apr 1;32(4):719-724.

‘Forever Young’-Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises.

Busnelli A^1,2, Somigliana E^1,2, Vercellini P^2,3.

 

Abstract

In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as ‘late-onset hypogonadism (LOH)’. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence.

 

 

 

Hum Reprod Update. 2017 May 1;23(3):276-288

Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery: a systematic review and meta-analysis.

van den Beukel BA¹, de Ree R¹, van Leuven S¹, Bakkum EA², Strik C¹, van Goor H¹, Ten Broek RPG¹.

Abstract

BACKGROUND:

Chronic pain is a frequent post-operative complication, affecting ~20-40% of patients who have undergone surgery of the female genital or alimentary tract. Chronic pain is an important risk factor for diminished quality of life after surgery. Adhesions are frequently associated with chronic post-operative pain; however, surgical treatment of adhesion-related pain is controversial.

OBJECTIVE AND RATIONALE:

The aim of this study was to investigate the efficacy and harms of surgical interventions for chronic post-operative pain attributable to adhesions.

SEARCH METHODS:

A search was conducted using PubMed, EMBASE and CENTRAL, without restrictions pertaining to date, publication status or language. Randomized trials and cohort studies from all surgical interventions for chronic post-operative pain were considered eligible. Patients with a concomitant diagnosis that could cause chronic pain (e.g. endometriosis or inflammatory conditions) were excluded. Outcome measures were graded according to clinical relevance, with improvement of pain at long-term follow-up regarded as most clinically relevant.

OUTCOMES:

A total of 4294 unique citations were identified, of which 13 studies met the criteria for inclusion. Two of the analysed studies were randomized trials, of which one had a low risk of bias. Only one trial, randomizing between laparoscopic adhesiolysis without an adhesion barrier and diagnostic laparoscopy, reported improvement of pain at long-term follow-up. In this trial, pain improved in 55.8% of patients after adhesiolysis and in 41.7% of patients in the control group; however, the difference was not significant (relative risk (RR) 1.34; 95% CI: 0.89-2.02). Most non-randomized studies had mid-length follow-up (6-12 months). In pooled analyses of trials and non-randomized studies, improvement of pain was reported in 72% of patients who underwent adhesiolysis (95% CI: 61-83%) at any follow-up longer than 3 months. The incidence of negative laparoscopies was 20% (95% CI: 10-30%). The overall incidence of complications following laparoscopic adhesiolysis was 4% (95% CI: 1-6%).

WIDER IMPLICATIONS:

Laparoscopic adhesiolysis reduces pain from adhesions in ~70% of patients in the initial phase after treatment. However, there is little evidence for long-term efficacy of adhesiolysis for chronic pain. Other drawbacks of laparoscopic adhesiolysis are the high rate of negative laparoscopies and the risk of bowel injury. At present, there is little evidence to support routine use of adhesiolysis in treatment for chronic pain. New research is needed to investigate whether the results of adhesiolysis can be improved with new techniques for diagnosis and prevention of adhesion reformation.

 

 

Hum Reprod Update. 2017 May 1;23(3):358-370.

Tubal anastomosis after previous sterilization: a systematic review.

van Seeters JAH¹, Chua SJ², Mol BWJ², Koks CAM³.

Abstract

BACKGROUND:

Female sterilization is one of the most common contraceptive methods. A small number of women, however, opt for reversal of sterilization procedures after they experience regret. Procedures can be performed by laparotomy or laparoscopy, with or without robotic assistance. Another commonly utilized alternative is IVF. The choice between surgery and IVF is often influenced by reimbursement politics for that particular geographic location.

OBJECTIVE AND RATIONALE:

We evaluated the fertility outcomes of different surgical methods available for the reversal of female sterilization, compared these to IVF and assessed the prognostic factors for success.

SEARCH METHODS:

Two search strategies were employed. Firstly, we searched for randomized and non-randomized clinical studies presenting fertility outcomes of sterilization reversal up to July 2016. Data on the following outcomes were collected: pregnancy rate, ectopic pregnancy rate, cost of the procedure and operative time. Eligible study designs included prospective or retrospective studies, randomized controlled trials, cohort studies, case-control studies and case series. No age restriction was applied. Exclusion criteria were patients suffering from tubal infertility from any other reason (e.g. infection, endometriosis and adhesions from previous surgery) and studies including <10 participants. The following factors likely to influence the success of sterilization reversal procedures were then evaluated: female age, BMI and duration and method of sterilization. Secondly, we searched for randomized and non-randomized clinical studies that compared reversal of sterilization to IVF and evaluated them for pregnancy outcomes and cost effectiveness.

OUTCOMES:

We included 37 studies that investigated a total of 10 689 women. No randomized controlled trials were found. Most studies were retrospective cohort studies of a moderate quality. The pooled pregnancy rate after sterilization reversal was 42-69%, with heterogeneity seen from the different methods utilized. The reported ectopic pregnancy rate was 4-8%. The only prognostic factor affecting the chance of conception was female age. The surgical approach (i.e. laparotomy [microscopic], laparoscopy or robotic) had no impact on the outcome, with the exception of the macroscopic laparotomic technique, which had inferior results and is not currently utilized. For older women, IVF could be a more cost-effective alternative for the reversal of sterilization. However, direct comparative data are lacking and a cut-off age cannot be stated.

WIDER IMPLICATIONS:

In sterilized women who suffer regret, surgical tubal re-anastomosis is an effective treatment, especially in younger women. However, there is a need for randomized controlled trials comparing the success rates and costs of surgical reversal with IVF.

 

 

Pol Merkur Lekarski. 2017 Mar 21;42(249):121-124.

Intestinal endometriosis – a case report.

Krzemiński S¹.

Abstract

Endometriosis intestines due to its non-specific symptoms can pose diagnostic problems, a lack of or incorrect treatment worsens the quality of life, sometimes leading to serious complications. The differential diagnosis of abdominal pain, especially in patients of reproductive age should be taken disease into account. Often abdominal pain in young women are classified as a functional gastrointestinal disorder, and only carefully collected intelligence allows you to focus on the diagnosis of endometriosis, especially if the symptoms significantly impair quality of life.

A CASE REPORT:

A woman 32 year old who was admitted to the department of gastroenterology because of increasing pain in the abdomen. Due to the deteriorating condition of the patient, the characteristics of mechanical obstruction on imaging studies was transferred to the surgical ward with suspected Crohn’s disease. She was treated surgically. Histopathological examination found endometriosis.

CONCLUSIONS:

Endometriosis outside the sex system can lead to serious complications.

 

 

Evid Based Complement Alternat Med. 2017;2017

Evaluation of Efficacy and Safety of Dan’e-Fukang Soft Extract in the Treatment of Endometriosis: A Meta-Analysis of 39 Randomized Controlled Trials Enrolling 5442 Patients.

Li Y¹, Li T², Song S³.

 

Abstract

Objective. To systematically evaluate the efficacy and safety of Dan’e-fukang soft extract in endometriosistreatment. Method. PubMed, CNKI, Wanfang Database, VIP, SinoMed, and Cochrane Library were searched. Randomized controlled trials (RCTs) comparing the efficacy of Dan’e-fukang soft extract and conventional western medicines for endometriosis treatment were included. The data were extracted independently by two people and analyzed using RevMan 5.2.0 software. The relative risk (RR) and mean difference (MD) with 95% confidence intervals were considered as effective outcome indicators. Results. Thirty-nine papers including 5442 patients with endometriosis were included in this study. A meta-analysis revealed that Dan’e-fukang soft extract was more efficient than gestrinone in the treatment of endometriosis (RR = 1.08, 95% CI = 1.03 to 1.15, I² = 71%, REM, 18 trials) and its efficacy was comparable to that of danazol and mifepristone. Dan’e-fukang soft extract was also as effective as gestrinone and mifepristone in terms of relapse rate and relieving dysmenorrhea. The incidence of adverse reactions was lower than that of conventional western medicines. Conclusions. The results of this study showed that Dan’e-fukang soft extract offers certain advantages in endometriosis treatment, but rigorously designed, strictly implemented RCTs are needed to further validate its efficacy.

 

 

Pain Physician. 2017 Mar;20(3):185-195.

Comparing the Efficacy of Surgery and Medical Therapy for Pain Management in Endometriosis: A Systematic Review and Meta-analysis.

Chaichian S¹, Kabir A², Mehdizadehkashi A³, Rahmani K⁴, Moghimi M⁵, Moazzami B⁶.

Abstract

BACKGROUND:

Pain is considered as one of the main symptoms of endometriosis. The treatment for endometriosis remains controversial.

OBJECTIVES:

The aim of this study is to compare the effect of medical or surgical treatments for pain-relief in patients with endometriosis.

STUDY DESIGN:

Systematic review and meta-analysis.

SETTING:

Published papers about evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar.

METHODS:

After searching all studies evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar, there were 23 related studies, containing 1,847 patients enrolled in our study. We used a variety of tests: fixed and random effects models, Q Cochrane test and I2 index, Egger and Begg tests, forest and funnel plots, Trim and fill method, and meta-regression in our analysis.

RESULTS:

There was no statistically significant difference in pain improvement between surgical and medical treatment. Interestingly, pain relief was more prominent longer after treatment. Both clinical trials and cross sectional studies showed higher improvement in pain than cohort studies. High quality studies and lower body mass index (BMI) had a greater effect on pain relief. All studies were heterogeneous, but there was no publication bias.

LIMITATIONS:

There was a higher probability of risk of bias in blinding, random sequence generation, and selective outcome reporting in clinical trial studies entered in our meta-analysis.

CONCLUSIONS:

Our results could not demonstrate the preference of each medical or surgical treatment effect for dysmenorrhea in endometriosis. Additional data is required before a standardized medical protocol can be offered, but we believe this study may encourage clinicians to consider a less invasive alternative for treating their patients’ chronic pelvic pain in the near future.Key words: Endometriosis, pain, meta-analysis, therapy, disease management.

 

 

Pain Physician. 2017 Mar;20(3)

Pulsed Radiofrequency Ablation of Pudendal Nerve for Treatment of a Case of Refractory Pelvic Pain.

Petrov-Kondratov V¹, Chhabra A², Jones S³.

Abstract

Pudendal neuralgia (PN) is a result of pudendal nerve entrapment or injury, also called “Alcock syndrome.” Pain that develops is often chronic, and at times debilitating. If conservative measures fail, invasive treatment modalities can be considered. The goal of this case report is to add to a small body of literature that a pulsed radiofrequency (PRF) ablation can be effectively used to treat PN and to show that high resolution MR neurography imaging can be used to detect pudendal neuropathy.

CASE PRESENTATION:

We present a case of a 51-year-old woman with 5 years of worsening right groin and vulva pain. Various medication trials only lead to limited improvement in pain. The first diagnostic right pudendal nerve block was done using 3 mL of 0.25% bupivacaine with 6mg of betamethasone using a transgluteal technique and a target of the right ischial spine; this procedure resulted in ~8 hours of > 50% pain relief. The patient was then referred for MR neurography of the lumbosacral plexus. This study revealed increased signal of the right pudendal nerve at the ischial spine and in the pudendal canal, findings consistent with the clinical picture of PN. Six weeks after the initial block, the patient underwent a second right transgluteal pudendal nerve block, utilizing 3 mL of 0.25% bupivacaine with 40 mg of triamcinolone acetonide; this procedure resulted in ~8 hours of 100% pain relief. Satisfied with these results the patient decided to undergo pudendal nerve PRF ablation for possible long-term relief. For this therapeutic procedure, a right transgluteal approach was again utilized. PRF ablation was performed for 240 seconds at 42° Celsius. Following this ablation the patient reported at least 6 weeks of significant (> 50%) pain relief.

DISCUSSION AND CONCLUSION:

In this paper we presented a case of successful treatment of PN with PRF ablation and detection of pudendal neuropathy on MR neurography. We believe that transgluteal PRF ablation for PN might be an effective, minimally invasive option for those patients that have failed conservative management. MR neurography employed in this case is not only helpful in confirming the diagnosis of PN but could also be useful in ruling out other causes of pelvic pain, such as genitofemoral neuropathy, endometriosis, adenomyosis, or pelvic mass lesion. To conclude, transgluteal PRF ablation can serve as a viable treatment option for mitigating symptoms of pudendal neuropathy and MR neurography is useful in confirming a clinically suspected diagnosis of PN.Key words: Pelvic pain, pudendal neuralgia, MR neurography, pulsed radiofrequency ablation, transgluteal technique, Alcock canal syndrome.

 

 

Biol Reprod. 2017 Apr 1;96(4):772-779.

Lipidomic profiling of endometrial fluid in women with ovarian endometriosis†.

Domínguez F^1,2, Ferrando M³, Díaz-Gimeno P^1,2, Quintana F³, Fernández G³, Castells I³, Simón C^2,4.

 

Abstract

The proteomic content of the endometrial fluid (EF) from patients with endometriosis has been investigated, but the lipidomic profile has not been analyzed yet in detail.This study is a comparative untargeted lipidomic analysis of human EF obtained from 35 patients (12 endometriosis and 23 controls). Global differential lipidomic profile was analyzed in both groups by ultrahigh performance liquid chromatography coupled to mass spectrometry. A total of 123 out of the 457 metabolites identified in the EF were found to be significantly differentially expressed between ovarian endometriosis (OE) versus controls. Univariate statistical analysis showed reduced levels of saturated diacylglycerols and saturated triacylglycerols in endometriosis patients. A predictive model was generated using the 123 differentially expressed metabolites. Using this model, we were able to correctly classify 86% of the samples. This study identified the lipidomic profile in the EF associated with OE, suggesting that EF analysis could be considered as a minimally invasive approach for the diagnosis of endometriosis. In conclusion, the lipidomic profile of the EF is different between samples from patients with OE and controls.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 May;212:69-74.

Value of the 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. A pilot study.

Fastrez M¹, Artigas C², Sirtaine N³, Wimana Z², Caillet M⁴, Rozenberg S⁴, Flamen P².

Abstract

OBJECTIVE:

The non-invasive diagnosis of endometriosis remains challenging. Recent data suggested that somatostatin might be involved in its pathogenesis. High sensitive visualization of somatostatin receptors expression is possible using PET-CT imaging after the administration of a ⁶⁸Ga-labeled somatostatin analog (DOTATATE) that will bind to the somatostatin receptor sub-types 2 and 5. The aim of the present study was to assess the usefulness of ⁶⁸Ga-DOTATATE PET-CT in the diagnosis of endometriosis.

STUDY DESIGN:

This is a prospective, single center pilot study. A pre operative ⁶⁸Ga-DOTATATE PET-CT was performed in all of the patients who presented with suspected endometriosis and who were scheduled for a laparoscopy. Surgical endometriosis staging and histopathological analysis, including somatostatin receptors SST1, 2 and 5 immunohistochemistry (IHC) of removed specimens, were confronted to the results of the ⁶⁸Ga-DOTATATE PET-CT.

RESULTS:

12 patients were included in this study. ⁶⁸Ga-DOTATATE PET-CT performed pre operatively showed increased pathologic uptake in four patients with a deep infiltrating endometriosis (DIE) recto-vaginal lesion and in another patient with an adenomyoma. Expression of SST1, 2 and 5 receptors in surgical specimens was confirmed by IHC in these five lesions. Neither superficial peritoneal endometriosis, nor ovarian endometrioma were found to show an increased pathologic uptake on ⁶⁸Ga-DOTATATE PET-CT. IHC analysis confirmed that SST1, 2, and 5 receptors were not present in these lesions.

CONCLUSION:

The results observed in this small size series of patients seem to confirm expression of somatostatin receptors only in recto-vaginal DIE and focal adenomyosis lesions. The usefulness of ⁶⁸Ga-DOTATATE PET-CT in the diagnosis of this entity is uncertain. Future research should concentrate on studying the role of somatostatin in the pathogenesis of DIE.

 

 

Obstet Gynecol Sci. 2017 Mar;60(2):236-239.

Catamenial hemoptysis accompanied by subcutaneous endometriosis treated with combination therapy.

Jang HI¹, Kim SE¹, Kim TJ¹, Lee YY¹, Choi CH¹, Lee JW¹, Kim BG¹, Bae DS¹.

 

Abstract

Extra pelvic endometriosis is considered to be rare. This paper reports a case of catamenial hemoptysis accompanied by subcutaneous endometriosis in 26-year-old woman. A computed tomography scan of the chest revealed a focal ground-glass opacity lesion in the posterior segment of the right upper lobe. Histopathology confirmed the diagnosis of endometriosis of right lung and concurrent subcutaneous endometriosis. She was treated with surgical resection of the endometriosis lesions on two different sites and perioperative gonadotropin-releasing hormone agonist therapy. The 6-month follow-up after combination treatment showed no recurrence. Though long-term follow-up result is needed, aggressive treatment using combination treatment (surgery and perioperative medication) should be considered for symptomatic extra pelvic endometriosis.

 

 

Reprod Sci. 2017 Dec;24(12):1577-1582

Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.

Carrarelli P¹, Funghi L¹, Ciarmela P^2,3, Centini G¹, Reis FM⁴, Dela Cruz C⁴, Mattei A⁵, Vannuccini S¹, Petraglia F¹.

 

Abstract

Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.

 

 

Exp Biol Med (Maywood). 2017 Apr;242(8):884-895

Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation’s fire?

Abouelkheir GR¹, Upchurch BD¹, Rutkowski JM¹.

 

Abstract

Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain. Depending on the tissue site, lymphangiogenic mechanism, or induction timeframe, however, evidence shows that inflammation-associated lymphangiogenesis (IAL) may worsen the pathology. Recent studies have identified lymphatic endothelial cells themselves to be local regulators of immune cell activity and its consequential phenotypes – a more active role in inflammation regulation than previously thought. Indeed, results focusing on the immunocentric roles of peripheral lymphatic function have revealed that the basic drainage task of lymphatic vessels is a complex balance of locally processed and transported antigens as well as interstitial cytokine and immune cell signaling: an interplay that likely defines the function of IAL. This review will summarize the latest findings on how IAL impacts a series of disease states in various tissues in both preclinical models and clinical studies. This discussion will serve to highlight some emerging areas of lymphatic research in an attempt to answer the question relevant to an array of scientists and clinicians of whether IAL helps to fuel or extinguish inflammation. Impact statement Inflammatory progression is present in acute and chronic tissue pathologies throughout the body. Lymphatic vessels play physiological roles relevant to all medical fields as important regulators of fluid balance, immune cell trafficking, and immune identity. Lymphangiogenesis is often concurrent with inflammation and can potentially aide or worsen disease progression. How new lymphatic vessels impact inflammation and by which mechanism is an important consideration in current and future clinical therapies targeting inflammation and/or vasculogenesis. This review identifies, across a range of tissue-specific pathologies, the current understanding of inflammation-associated lymphangiogenesis in the progression or resolution of inflammation.

 

 

Gynecol Endocrinol. 2017 Jul;33(7):544-547.

Endometriosis doubles the risk of sexual dysfunction: a cross-sectional study in a large amount of patients.

Fairbanks F¹, Abdo CH², Baracat EC¹, Podgaec S^1,3.

Abstract

INTRODUCTION:

Endometriosis affects several aspects of a woman’s life, including sexual function, but which specific aspects of sexual function remains unclear.

METHODS:

A cross-sectional study was performed involving 1001 women divided into two groups, according to the presence or absence of endometriosis. We assessed sexual function, anxiety and depression of patients and correlated these findings with symptoms, locations and types of endometriosis and the affected domains of sexual function. Eighteen completed the forms incorrectly, 294 women (29.9%) were excluded due to severe anxiety and depression. One hundred and six patients had symptoms that could have any relation to endometriosis, so they were also excluded. The final cohort was composed of 254 patients with endometriosisand 329 patients without the disease. Sexual function score was assessed using the female sexual quotient (FSQ); Beck inventories were used to assess anxiety and depression.

RESULTS:

Patients with endometriosis were affected in all phases of sexual response: desire, sexual arousal, genital-pelvic pain/ penetration and orgasm/ sexual satisfaction. In the overall assessment, 43.3% of patients with endometriosis had sexual dysfunction, while the population without endometriosis sexual dysfunction occurred in 17.6% of women.

CONCLUSIONS:

Patients with endometriosis have more than twice sexual dysfunctions as compared to women without the disease.

 

 

Reproduction. 2017 Jun;153(6):809-820.

Hypoxia-inducible factor-1α promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis.

Liu H¹, Zhang Z², Xiong W¹, Zhang L¹, Xiong Y¹, Li N¹, He H¹, Du Y¹, Liu Y³.

 

Abstract

Endometriosis is a benign gynecological disease that shares some characteristics with malignancy like migration and invasion. It has been reported that both hypoxia-inducible factor-1α (HIF-1α) and autophagy were upregulated in ectopic endometrium of patients with ovarian endometriosis. However, the crosstalk between HIF-1α and autophagy in the pathogenesis of endometriosis remains to be clarified. Accordingly, we investigated whether autophagy was regulated by HIF-1α, as well as whether the effect of HIF-1α on cell migration and invasion is mediated through autophagy upregulation. Here, we found that ectopic endometrium from patients with endometriosis highly expressed HIF-1α and autophagy-related protein LC3. In cultured human endometrial stromal cells (HESCs), autophagy was induced by hypoxia in a time-dependent manner and autophagy activation was dependent on HIF-1α. In addition, migration and invasion ability of HESCs were enhanced by hypoxia treatment, whereas knockdown of HIF-1α attenuated this effect. Furthermore, inhibiting autophagy with specific inhibitors and Beclin1 siRNA attenuated hypoxia triggered migration and invasion of HESCs. Taken together, these results suggest that HIF-1α promotes HESCs invasion and metastasis by upregulating autophagy. Thus, autophagy may be involved in the pathogenesis of endometriosis and inhibition of autophagy might be a novel therapeutic approach to the treatment of endometriosis.

 

 

Aust N Z J Obstet Gynaecol. 2017 Aug;57(4):452-457.

Endometriosis education in schools: A New Zealand model examining the impact of an education program in schools on early recognition of symptoms suggesting endometriosis.

Bush D^1,2, Brick E¹, East MC², Johnson N^3,4.

Abstract

BACKGROUND:

Menstrual morbidity plays a significant role in adolescent females’ lives. There are no studies to date reporting such data from menstrual health education programs in schools.

AIMS:

The aim of our study was to report results from an audit of a menstrual health and endometriosis education program in secondary schools and observe age patterns of young women presenting for menstrual morbidity care.

MATERIALS AND METHODS:

Audit data from education in secondary schools and audit data of patients from an Endometriosis and Pelvic Pain Coaching clinic operating in a private endometriosis specialised centre are reported.

RESULTS:

In a region of consistent delivery of the education program, student awareness of endometriosis was 32% in 2015. Overall in 2015, 13% of students experienced distressing menstrual symptoms and 27% of students sometimes or always missed school due to menstrual symptoms. Further, in one region of consistent delivery of the menstrual health education program, data show an increase in younger patients attending for specialised endometriosis care.

CONCLUSIONS:

There is strong suggestive evidence that consistent delivery of a menstrual health education program in schools increases adolescent student awareness of endometriosis. In addition, there is suggestive evidence that in a geographical area of consistent delivery of the program, a shift in earlier presentation of young women to a specialised health service is observed.

 

 

Gynecol Obstet Invest. 2017;82(4):313-321.

Decidual Bleeding as a Cause of Spontaneous Hemoperitoneum in Pregnancy and Risk of Preterm Birth.

Lier MCI¹, Brosens IA, Mijatovic V, Habiba M, Benagiano G.

Abstract

BACKGROUND:

Spontaneous hemoperitoneum in pregnancy (SHiP) is a rare, life-threatening event, particularly relevant to women with endometriosis or deciduosis.

METHODS:

To determine the type of lesions leading to SHiP, a literature search was conducted among all published SHiP cases. From a total of 1,339 publications, information on pathological findings at the bleeding site with histological data was found in 24 case reports (16 pregnant, 8 postpartum).

RESULTS:

Among pregnant women (81% primigravida), 75% had a diagnosis of endometriosis and 25% of deciduosis. Among postpartum women (38% primiparous), 63% had a diagnosis of deciduosis and 25% of endometriosis. In all cases except one, decidual cells, with or without glandular structures, were present at the bleeding site. Decidual vessels were described in 7 cases and all exhibited vascular changes, including distension of the lumen, medial disorganization, or loss of vascular integrity. These vessels were significantly different from arteries seen in the secretory endometrium, showing that structural modifications take place during the initial stage of the remodelling of placental bed spiral arteries.

CONCLUSIONS:

During pregnancy, a link seems to exist between ectopic decidualization, particularly that occurring in endometriotic foci, and occurrence of SHiP. In addition, subclinical decidual bleeding may be a potential risk factor for preterm labour.

 

 

 

Abdominal Wall Endometriosis in a Rhesus Macaque (Macaca mulatta).

Atkins HM, Caudell DL, Hutchison AR, LeGrande AC, Kock ND.

 

Abstract

Endometriosis is the presence of endometrium outside of the uterus. Although endometriosis occurs in both pelvic and extrapelvic locations, extrapelvic locations are less common. The development of abdominal wall or incisional endometriosis in women is associated with gynecologic surgeries and is often misdiagnosed. Because they naturally develop endometriosis similar to women,Old World NHP, including rhesus macaques, provide excellent opportunities for studying endometriosis. Here, we describe a case of abdominal wall endometriosis in a rhesus macaque that had undergone cesarean section. Microscopically, the tissue consisted of pseudocolumnar epithelium-lined glands within a decidualized stroma, which dissected through the abdominal wall musculature and into the adjacent subcutaneous tissue. The stroma was strongly positive for vimentin and CD10 but was rarely, weakly positive for estrogen receptors and negative for progesterone. Close examination of extrapelvic endometriosis in rhesus macaques and other NHP may promote increased understanding of endometriosis in women.

 

 

Zhonghua Fu Chan Ke Za Zhi. 2017 Mar 25;52(3):164-167.

Clinical analysis of pelvic abscess with endometriosis.

Liu YT¹, Shi HH, Yu X, Wang S, Fan QB, Liu HY.

 

Abstract

Objective: To investigate the clinical features, diagnosis and treatments of pelvic abscess with endometriosis. Methods: A retrospective analysis was performed on 129 cases of pelvic abscess in Peking Union Medical College Hospital from January 2000 to January 2016. Among them, 34 women with endometriosis were divided into the study group and the others were in the control group. The clinical characteristics, therapeutic regimens and outcomes were compared. Results: (1) General conditions: there were no statistic differences between the two groups in age, WBC, serum CA(125), intrauterine device in use, pelvic inflammatory disease history; while incidence rates of dysmenorrhea (65%, 22/34) and infertility (21%, 7/34) in the study group were higher than those in the control group (all P<0.05). (2) Clinical manifestations: fever, abdominal pain and pelvic mass were the main symptoms in two groups. The incidence rates of septic shock were 12% (4/34) in the study group and 2% (2/95) in the control group (P<0.05). (3) Treatment: treatment with puncture all failed in the study group (7/7) and surgeries were required. In contrast, there was only 1/19 treatment failure with puncture in the control group. The puncture failure rates were statistically significant (P<0.05). Compared with the study group and the control group, there were significant differences (P<0.05) in the operation time of laparoscopic surgery [(76±41) versus (53±21) minutes] and of laparotomy [(168±58) versus (116±35) minutes], intra-operative blood loss of laparoscopic surgery [(216±296) versus (43±36) ml] and of laparotomy [(448±431) versus (145±24) ml]. Conclusions: Pelvic abscess in women with endometriosis is more severe and refractory to antibiotics and puncture treatment. Active surgical intervention is required. Although surgical procedures are often difficult, prognosis is comparatively satisfied.

 

 

 

Int J Womens Health. 2017 Mar 23;9:157-161.

Robotic-assisted hysterectomy: patient selection and perspectives.

Smorgick N¹.

 

Abstract

Minimally invasive hysterectomy via the laparoscopic or vaginal approach is beneficial to patients when compared with laparotomy, but has not been offered in the past to all women because of the technical difficulties and the long learning curve required for laparoscopic hysterectomy. Robotic-assisted hysterectomy for benign indications may allow for a shorter learning curve but does not offer clear advantages over conventional laparoscopic hysterectomy in terms of surgical outcomes. In addition, robotic hysterectomy is invariably associated with increased costs. Nevertheless, this surgical approach has been widely adopted by gynecologic surgeons. The aim of this review is to describe specific indications and patients who may benefit from robotic-assisted hysterectomy. These include hysterectomy for benign conditions in cases with high surgical complexity (such as pelvic adhesive disease and endometriosis), hysterectomy and lymphadenectomy for treatment of endometrial carcinoma, and obese patients. In the future, additional evidence regarding the benefits of single-site robotic hysterectomy may further modify the indications for robotic-assisted hysterectomy.

 

 

J Affect Disord. 2017 Aug 1;217:34-41.

Preconception gynecological risk factors of postpartum depression among Japanese women: The Japan Environment and Children’s Study (JECS).

Muchanga SMJ¹, Yasumitsu-Lovell K², Eitoku M³, Mbelambela EP³, Ninomiya H⁴, Komori K³, Tozin R⁵, Maeda N⁶, Fujieda M⁷, Suganuma N⁸; Japan Environment and Children’s Study Group.

Abstract

BACKGROUND:

Postpartum depression is one of the major causes of disability among women who are on their childbearing years. Identifying people at risk of postpartum depression may improve its management. The objective of this study was to determine the probable association between postpartum depression and some preconception gynecological morbidities.

METHODS:

Data from a nationwide birth cohort study, the Japan Environment and Children’s study (JECS), up to one month of postpartum were analyzed. To assess postpartum depression, the Edinburgh Postnatal Depression Scale (EPDS) was used; 11 preconception gynecological morbidities were considered as risk factors. Covariates included psychiatric illness history, psychosocial factors, some pregnancy adverse outcomes, birth outcomes, socio-demographic and health behavioral factors.

RESULTS:

Except for the prevalence of previous miscarriage, leiomyoma and polycystic ovarian syndrome, depressive women had more gynecological morbidities compared to non-depressive ones. In logistic regression model, endometriosis (OR, 1.27; 95%CI: 1.15-1.41), dysmenorrhea (OR, 1.13; 95%CI: 1.06-1.21) and abnormal uterine bleeding (OR, 1.21; 95%CI: 1.15-1.29) were associated with postpartum depression.

LIMITATIONS:

CONCLUSION: Women with endometriosis and menstrual problems were at risk of developing postpartum depression. This study suggests a perinatal mental health screening for predisposed women.

 

 

Fertil Steril. 2017 Apr;107(4):969-976.

Spontaneous fertility after expectant or surgical management of rectovaginal endometriosis in women with or without ovarian endometrioma: a retrospective analysis.

Leone Roberti Maggiore U¹, Scala C¹, Tafi E¹, Racca A¹, Biscaldi E², Vellone VG³, Venturini PL¹, Ferrero S⁴.

Abstract

OBJECTIVE:

To investigate spontaneous pregnancy rate (SPRs) of women with rectovaginal endometriosis (RV) with/without ovarian endometrioma (OMA) and treated with the use of expectant or surgical management.

DESIGN:

Retrospective study.

SETTING:

University hospital.

PATIENT(S):

The study included patients with RV with or without OMA who tried to conceive spontaneously for 1 year either without undergoing surgery (group E; n = 284) or after surgery (group S; n = 221). The study population was further divided into four subgroups: women with RV without OMA who directly tried to conceive (group eRV; n = 121) or tried to conceive after surgery (group sRV; n = 96), and women with RV with OMA who directly tried to conceive (group eOMA; n = 163) or tried to conceive after surgery (group sOMA; n = 125).

INTERVENTIONS(S):

Expectant or surgical management.

MAIN OUTCOME MEASURE(S):

Crude and cumulative SPRs.

RESULT(S):

At 1 year, crude and cumulative SPRs were lower in group E (17.3% and 23.8%, respectively) than in group S (35.7% and 39.5%). Similarly, crude and cumulative SPRs were lower in group eRV (24.8% and 30.6%) than in group sRV (42.7% and 45.7%, respectively) and in group eOMA (11.7% and 18.0%) than group sOMA (30.4% and 34.5%). At 1 year, crude and cumulative SPRs were higher in group eRV (24.8% and 30.6%) than in group eOMA (11.7% and 18.0%), and in group sRV (42.7% and 45.7%) than in group sOMA (30.4% and 34.5%).

CONCLUSION(S):

Crude and cumulative SPRs are lower in women treated with the use of expectant rather than surgical management. The presence of OMAs decreases SPRs independently from the treatment modality adopted.

 

 

Case Rep Neurol Med. 2017;2017

Sacral Neuromodulation: Foray into Chronic Pelvic Pain in End Stage Endometriosis.

Lavonius M¹, Suvitie P¹, Varpe P¹, Huhtinen H¹.

 

Abstract

Excision of all endometriotic lesions is the method of choice in the treatment of severe endometriosis resistant to medical therapy. The infiltrating nature of the disease as well as extensive surgery may, however, cause chronic pain that cannot be relieved by either surgery or hormonal treatment. As a pilot treatment, we tested the effect of sacral neuromodulation (SNM) for four endometriosis patients suffering chronic pelvic pain and pelvic organ dysfunction after radical surgical treatment. Three out of four patients reported improvement in their symptoms during the neuromodulation testing period and a permanent pulse generator was installed. After 2.5 years, all three patients report better quality of life and want to continue with SNM.

 

 

Cell J. 2017 Apr-Jun;19(1):50-64.

Lovastatin Reduces Stemness via Epigenetic Reprograming of BMP2 and GATA2 in Human Endometrium and Endometriosis.

Taghizadeh M¹, Noruzinia M¹.

Abstract

OBJECTIVE:

The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers.

MATERIALS AND METHODS:

In this experimental investigation, MSCs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. To investigate the osteogenic and adipogenic differentiation of eMSCs treated with the different concentration of lovastatin and decitabin, BMP2, RUNX2 and GATA2 expressions were measured by real-time polymerase chain reaction (PCR). To determine involvement of DNA methylation in BMP2 and GATA2 gene regulations of eMSCs, we used quantitative Methylation Specific PCR (qMSP) for evaluation of the BMP2 promoter status and differentially methylated region of GATA2 exon 4.

RESULTS:

In the present study, treatment with lovastatin increased expression of BMP2 and RUNX2 and induced BMP2 promoter demethylation. We also demonstrated that lovastatin treatment down-regulated GATA2expression via inducing methylation. In addition, the results indicated that CD146 cell marker was decreased to 53% in response to lovastatin treatment compared to untreated group.

CONCLUSION:

These findings indicated that lovastatin treatment could increase the differentiation of eMSCs toward osteogenic and adiogenic lineages, while it decreased expression of eMSCs markers and subsequently reduced the stemness.

 

 

 

Gynecol Oncol Rep. 2017 Mar 14;20:78-80.

Clear cell carcinoma arising from abdominal wall endometriosis – Brief report and review of the literature.

Marques C¹, Silva TS², Dias MF³.

 

Abstract

• Endometriosis-associated abdominal wall cancer is a rare entity with poor prognosis.•Personal history of C-section is extremely relevant.•The treatment consists in a wide local excision with adjuvant chemotherapy.•Proper treatment of abdominal endometriosiscould prevent these situations.

 

 

Biomaterials. 2017 Jun;130:90-103.

On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial-stromal communication networks.

Valdez J¹, Cook CD¹, Ahrens CC², Wang AJ¹, Brown A¹, Kumar M¹, Stockdale L¹, Rothenberg D¹, Renggli K¹, Gordon E¹, Lauffenburger D³, White F¹, Griffith L⁴.

 

Abstract

Methods to parse paracrine epithelial-stromal communication networks are a vital need in drug development, as disruption of these networks underlies diseases ranging from cancer to endometriosis. Here, we describe a modular, synthetic, and dissolvable extracellular matrix (MSD-ECM) hydrogel that fosters functional 3D epithelial-stromal co-culture, and that can be dissolved on-demand to recover cells and paracrine signaling proteins intact for subsequent analysis. Specifically, synthetic polymer hydrogels, modified with cell-interacting adhesion motifs and crosslinked with peptides that include a substrate for cell-mediated proteolytic remodeling, can be rapidly dissolved by an engineered version of the microbial transpeptidase Sortase A (SrtA) if the crosslinking peptide includes a SrtA substrate motif and a soluble second substrate. SrtA-mediated dissolution affected only 1 of 31 cytokines and growth factors assayed, whereas standard protease degradation methods destroyed about half of these same molecules. Using co-encapsulated endometrial epithelial and stromal cells as one model system, we show that the dynamic cytokine and growth factor response of co-cultures to an inflammatory cue is richer and more nuanced when measured from SrtA-dissolved gel microenvironments than from the culture supernate. This system employs accessible, reproducible reagents and facile protocols; hence, has potential as a tool in identifying and validating therapeutic targets in complex diseases.

 

 

Reprod Sci. 2017 Aug;24(8):1129-1138.

KLF11 is an Epigenetic Mediator of DRD2/Dopaminergic Signaling in Endometriosis.

Richards EG¹, Zheng Y¹, Shenoy CC¹, Ainsworth AJ¹, Delaney AA¹, Jones TL¹, Khan Z¹, Daftary GS¹.

 

Abstract

Endometriosis is a heterogeneous, recalcitrant disease that affects 10% of reproductive-age women. Resistance to conventional therapy critically raises the need for novel treatment options that target specific, dysregulated underlying molecular mechanisms. Dopamine receptor 2 (DRD2) has been shown to be associated with vascularity and fibrosis in endometriosis. Transcription factor KLF11 has been implicated in the pathogenesis of several human endocrine and reproductive tract diseases including endometriosis. KLF11 recruits epigenetic cofactors for regulation of target genes; dysregulation of critical target genes and associated signaling pathways results in diverse disease phenotypes. KLF11 regulates the expression of DRD2 in neurons. We investigated the regulation of DRD2 by KLF11 in the established eutopic and ectopic endometrial cell lines as well as in an animal model of endometriosis. KLF11 binding and activation of the DRD2 promoter was conserved across species. Promoter activation was reflected in correspondingly increased gene expression in an endometrial cell line and in primary endometriotic cells. In vivo, disease relevance was further evaluated in a surgically induced murine endometriotic model using Klf11-/- and wild-type mice. Consistent with loss of Klf11-mediated activation, lesions in Klf11-/- animals were associated with progressive fibrosis and decreased Drd2 expression. KLF11 binds specific epigenetic corepressors to repress several target genes. Activation of DRD2 by KLF11 could not be explained simply by loss of corepressor binding and is thus likely due to selective coactivator recruitment; identification of the precise pathway is the focus of ongoing investigation. Characterization of pharmacologically reversible epigenetic regulatory mechanisms has translational relevance in health and disease.

 

 

Arch Gynecol Obstet. 2017 May;295(5):1277-1285.

Major and minor complications after anterior rectal resection for deeply infiltrating endometriosis.

Renner SP¹, Kessler H², Topal N¹, Proske K¹, Adler W³, Burghaus S¹, Haupt W⁴, Beckmann MW¹, Lermann J⁵.

Abstract

PURPOSE:

The aim of the present study was to analyze major and minor complications-including long-term impairment of intestinal, bladder, and sexual function-following surgery for deeply infiltrating endometriosis using anterior rectal resection.

METHODS:

Patients who had undergone anterior rectal resection due to endometriosis between 2001 and 2011 were included (n = 113). Clinical and surgical data, as well as minor and major complications, were recorded. A questionnaire was sent to the patients and also to a healthy control group (n = 100).

RESULTS:

Major complications occurred in 15.9% of cases and minor complications in 15%. Patients with postoperative ileostomies (n = 8) initially had ultralow anastomoses significantly more often. The questionnaire response rate was 77%, with a mean follow-up period of 85.9 months. Weak urinary flow was reported by 22.4% of the patients: a feeling of residual urine by 18.4%; more than one bowel movement/day by 57.5%; and insufficient lubrication during intercourse by 36.5%. These results differed significantly from the control group. Subgroup analysis showed no statistical associations between questionnaire responses and major or minor complications, ultralow anastomoses, bilateral dissection of the sacrouterine ligaments, or dissection of the vagina and rectovaginal space.

CONCLUSIONS:

The major complication rate was consistent with the literature, but there were fewer minor complications. Patients with bowel anastomoses below 6 cm (ultralow) should receive information postoperatively about the high risk of insufficiency and should be closely monitored. The high rate of bladder, bowel, and sexual function impairment, and inadequate data make further prospective studies on this topic necessary.

 

 

J Ovarian Res. 2017 Apr 4;10(1):25.

Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies.

Sipak-Szmigiel O¹, Włodarski P², Ronin-Walknowska E³, Niedzielski A², Karakiewicz B⁴, Słuczanowska-Głąbowska S⁵, Laszczyńska M⁶, Malinowski W⁷.

Abstract

BACKGROUND:

Although immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases.

CASE PRESENTATION:

The study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers.

CONCLUSIONS:

Elevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid concentrations of sHLA-G have no diagnostic value in differentiating between ovarian malignancies and endometriomas.

 

 

Int J Gynaecol Obstet. 2017 Jul;138(1):37-41.

Review of clinical indicators, including serum anti-Müllerian hormone levels, for identification of women who should consider egg freezing.

Martyn F^1,2, O’Brien YM^1,2, Wingfield M^1,2,3.

Abstract

OBJECTIVE:

To identify women, on the basis of clinical history and serum anti-Müllerian hormone (AMH) levels, who are at risk of premature ovarian insufficiency and thereby guide appropriate early referral for egg freezing.

METHODS:

In a retrospective study, data were reviewed from women attending two fertility clinics in Dublin, Ireland, between August 2011 and December 2012. Case histories of women aged 35 years or younger were assessed to identify risk factors for reduced ovarian reserve, including endometriosis, ovarian surgery, and family history of premature ovarian failure (POF).

RESULTS:

Among 490 women aged 35 years or younger, 195 (39.7%) had an AMH level below 10 pmol/L, 94 (19.2%) had an AMH below 5 pmol/L, and 21 (4.3%) had an AMH below 1 pmol/L. Among 104 women aged 30 years or younger, the respective numbers were 28 (26.9%), 15 (14.4%), and 9 (8.7%). Among the 490 women, significantly lower AMH levels were observed for those with endometriosis (P=0.017) and a family history of POF (P=0.006). However, 53 (56.4%) of 94 women aged 35 years or younger with low AMH levels had no clinical risk factors.

CONCLUSION:

Universal AMH screening should be considered for all women in their 30s who are not ready to try to conceive; clinical risk factors will only identify approximately 50% of women at risk of low ovarian reserve.

 

 

Ned Tijdschr Geneeskd. 2017;161

A woman with severe abdominal pain and endometriosis in the past.

 

Schuurs TC¹, Vandewalle EM, Dickhoff C.

 

Abstract

A 44-year-old woman came to the emergency department with severe pain in the right upper abdomen. Her medical history mentioned a low anterior resection 8 years ago because of severe endometriosis. The CT scan showed a ruptured right hemidiaphragm with herniation of the small intestine.

 

 

Minerva Ginecol. 2017 Aug;69(4):381-389.

Sexual pain in women: quality of sex life and marital relations.

Ghizzani A¹, Orlandini C¹, Bernardi MG¹, Cevenini G², Luisi S³.

 

Abstract

Common gynecological and dermatological conditions resulting in sexual pain are often observed in gynecological practice and are easily diagnosed with visual observation and laboratory tests. The lower genital tract diseases we are referring to are vaginitis, vaginoses, dermatoses, hypoestrogenism and endometriosis. All of them affect the vaginal mucosa with diverse mechanisms, their effects lasting for only few days or many months. Furthermore, they change the women’s sense of wellbeing sometimes significantly and for a long period. The conditions we mentioned above are recognized promptly with basic gynecological interventions but when burning or sharp pain occurs with light pressure (as in case of penetration attempts) without physical signs we must suspect the genitopelvic pain penetration disorder. This condition was defined for the first time in the Diagnostic and Statistical Manual of Mental Disorders-5 and its dimensions include difficulty or pain at penetration associated with fear, anxiety, and pelvic floor hypertonus. Pain is most often localized at the vulvar vestibule and described as burning, pressure, and itching. These dimensions are iconic of sexual pain associated with vulvodyina and vaginismus but are common also in fibromyalgia, a syndrome of widespread chronic pain of unknown origin; sexual pain in fibromyalgia is mostly attributed both to the joint pathology and to the lower sensitive threshold that are the pathognomonic signs of this condition. In our study we analyzed the characteristics of pain as reported for each disease to evaluate its influence on sexuality and marital relations.

 

 

Minerva Ginecol. 2017 Oct;69(5):477-487.

Complications of colorectal resection for endometriosis.

Bouaziz J¹, Soriano D².

 

Abstract

Based on a review of the current literature, we will discuss early and late (more than three months postoperative) complications associated with surgery for colorectal endometriosis resection. The most common surgical complications are: rectovaginal fistulae, anastomotic leakages and abscesses. Postoperative bleeding occurs rarely but has also been reported; and usually requires blood transfusion without surgical interventions. The selection of patients for surgery requires a multidisciplinary approach and complete preoperative imaging work-up by an experienced physician. The surgical procedure is challenging, including resection of all extrarectal DIE lesions, often in a context of patients who already underwent operations. Considering the major complications that may occur, there are three frequently observed risk factors. First is the opening of the vagina at the time of the bowel surgical procedure. However, this is a matter of debate, and experts commonly open the vagina during the procedure, as appropriate, without increasing the rate of complications. Second is excessive use of electrocoagulation, which increases the risk of rectovaginal fistulae and abscesses, due to the risk of necrosis of the posterior vaginal cuff. Third is surgical treatment of low rectal lesions (5-8 cm from the anal verge), which increases the risk of anastomotic leaks. In addition, we refuse to consider functional postoperative complications that affect gastrointestinal and sexual function, as minor complications. These can have a severe impact on the quality of life of young women. Further research is needed to prevent and treat such complications.

 

 

Minerva Ginecol. 2017 Oct;69(5):468-476.

Bladder endometriosis: a summary of current evidence.

Saccardi C¹, Vitagliano A², Litta P¹.

 

Abstract

Bladder endometriosis is a specific form of endometriosis characterized by the presence of endometrial glands and stroma in the detrusor muscle. Such disease may involve different sites of the bladder, most frequently the base and the dome, with various grade of infiltration. Bladder nodules typically coexists with other localizations of deep pelvic endometriosis, resulting in a wide variety of abdominal and urinary symptoms that may be overlooked by clinicians. In spite of advances in understanding the genetic and molecular development of endometriosis, the clinical approach to bladder lesions is very challenging and may require the use of different diagnostic tools in order to set up a comprehensive diagnostic workup and direct towards the most appropriate treatment. The aim of this paper was to portray the state of art of diagnosis and management of bladder endometriosis, starting from the current evidence about epidemiology, pathophysiology, clinical signs and providing all the available strategies for medical and surgical treatment.

 

 

Arch Gynecol Obstet. 2017 Jun;295(6):1413-1419.

Correlation of polypeptide N-acetylgalactosamine transferases-3 and -6 to different stages of endometriosis.

Xu X^1,2, Fei X³, Ma J³, Qu Y³, Zhou C⁴, Xu K⁵, Lin J⁶.

Abstract

PURPOSE:

To investigate the expression patterns of N-acetyl galactosamine transferases (GalNAc-Ts)-3 and GalNAc-T6 in clinicopathologically characterized endometriosis (EMS), and to explore their clinical significance.

METHODS:

Ectopic and eutopic endometrial tissue samples were obtained and confirmed with CD-10 immunohistochemistry in patients with EMS (n = 12), whereas normal control endometrium was obtained from patients with uterine septum (n = 12). The mRNA and protein levels of GalNAc-T3 and GalNAc-T6 were detected in these samples using quantitative real-time PCR, immunohistochemistry, and western blotting.

RESULTS:

GalNAc-T3 and GalNAc-T6 were expressed in the endometrium of all groups, with no significant changes observed during the menstrual cycle. The expression of GalNAc-T3 and GalNAc-T6 in ectopic endometrium was significantly lower than that in eutopic (P < 0.05) or control endometrium (P < 0.05), whereas there were no significant differences (P > 0.05) between eutopic and control endometria. Furthermore, the expression of GalNAc-T3 and GalNAc-T6 was significantly lower in patients with stage III/IV EMS compared to patients with stage I/II (P < 0.05).

CONCLUSIONS:

Both GalNAc-T3 and GalNAc-T6 expression levels were downregulated in ectopic endometrium, which may increase the adhesion and invasion of endometrial cells and contribute to the development of EMS. Moreover, we found a strong correlation between the expression of GalNAc-T3 and GalNAc-T6 and different stages of EMS.

 

 

 

Uterus-like Masses in a Rhesus Macaque (Macaca mulatta).

Dickerson MF, Martin LD, Lewis AD.

 

Abstract

Endometriosis is a relatively common condition in women and some populations of adult female rhesus macaques. However,endometriosis with extensive smooth muscle proliferation, as occurs in endomyometrioma and uterus-like mass (ULM), is rare inwomen. This report describes a case of endometriosis with extensive smooth muscle metaplasia resembling multiple ULM in a20-y-old female rhesus macaque. During a protocol-related procedure, a large, smooth, globoid, freely moveable mass was palpated in the midabdomen. Ultrasonography revealed a cystic structure from which dark brown fluid was aspirated. During exploratory laparotomy, an 8-cm spherical mass in the greater omentum and 3 additional masses (diameter, 2 to 5 cm) attached to the omentum were excised. Microscopic examination of the masses revealed numerous foci of ectopic endometrial glands and stroma frequently surrounded by bundles of smooth muscle and fibrous connective tissue. The gross and histologic lesions in this macaque bore many similarities to ULM in women. To our knowledge, this case represents the first report of endometriosis resembling a uteruslike mass in a NHP.

 

 

Hum Reprod. 2017 Jun 1;32(6):1258-1269.

Measuring health-related quality of life in women with endometriosis: comparing the clinimetric properties of the Endometriosis Health Profile-5 (EHP-5) and the EuroQol-5D (EQ-5D).

Aubry G¹, Panel P², Thiollier G³, Huchon C^1,3, Fauconnier A^1,3.

Abstract

STUDY QUESTION:

Which of the Endometriosis Health Profile-5 (EHP-5) and the EuroQol-5D (EQ-5D) is the most efficient to assess quality of life in women suffering from endometriosis?

SUMMARY ANSWER:

Although EHP-5 and EQ-5D instruments had an excellent responsiveness, EHP-5 has a better discriminative ability than EQ-5 to measure health-related quality of life (HrQoL).

WHAT IS KNOWN ALREADY:

Proper measurement of HrQoL is important in endometriosis. While many quality of life instruments are available, few have been completely validated in endometriosis. The EHP-5 and the EQ-5D are short and practical scales, which may be useful. Literature is lacking to determine which one is the most suitable in clinical practice or in clinical research.

STUDY DESIGN, SIZE, DURATION:

This prospective and observational study conducted between 1 January 2012 and 31 December 2013 included a total of 253 consecutive women with proven endometriosis, undergoing medical or surgical treatment, in 2 French tertiary care centers.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS:

Women over 18 years consulting for painful symptoms of at least 3 months’ duration or for infertility, with endometriosis proven histologically or radiologically, were requested to fill in the 2 scales before (T0) and 12 months after treatment (T1). Construct validity consisted in testing presupposed relationships between the scales and the characteristics of the patients or the endometriosis. Responsiveness to change was calculated for all patients and in each treatment group. Effect sizes were used according to Cohen’s d method.

MAIN RESULTS AND THE ROLE OF CHANCE:

A total of 216 women filled in completely all the questionnaires at T0 and 133 (61.6%) at T1. EHP-5 and EQ-5D had good discriminative abilities regarding the patients’ symptoms, with significant superiority of EHP-5 concerning three of the nine hypotheses. The largest difference was that calculated for the ‘intensity of dysmenorrhea’ using the Visual Analogic Scale, with respectively effect size from Cohen’s d (ES) = 0.86 95% CI (0.54-1.17) for EHP-5 versus 0.48 95% CI (0.16-0.79) for EQ-5D. There were no differences in EHP-5 or in EQ-5D scores between subgroups according to the characteristics of endometriosis. Overall responsiveness was excellent and equivalent for EHP-5 and for EQ-5D, with, respectively, ES = 0.81 95% CI (0.56-1.56) versus ES = 0.95 95% CI (0.68-1.20). In subgroup analyses, EHP-5 was responsive in case of medical treatment with ES = 0.93 95% CI (0.07-1.70), whereas EQ-5D was not, ES = 0.73 95% CI (-0.06-1.47).

LIMITATIONS, REASONS FOR CAUTION:

Our study population included patients with symptomatic and mainly severe forms of endometriosis, which may suggest a spectrum bias. The evaluation of responsiveness in case of medical treatment was based on a small number of patients, which limits the interpretation of the difference found between the two scales in this subgroup.

WIDER IMPLICATIONS OF THE FINDINGS:

EHP-5 is a simple, efficient and valid tool for evaluating quality of life in daily practice and also valuable to provide a primary outcome in clinical studies evaluating treatment efficacy.

STUDY FUNDING/COMPETING INTEREST(S):

This work was funded by the Direction à la Recherche Clinique et à l’Innovation of Versailles, France. The authors have no conflicts of interest.

 

 

Hum Reprod. 2017 Jun 1;32(6):1304-1317

Synergistic effect of regulatory T cells and proinflammatory cytokines in angiogenesis in the endometriotic milieu.

Wang XQ¹, Zhou WJ¹, Luo XZ¹, Tao Y¹, Li DJ¹.

Abstract

STUDY QUESTION:

Do regulatory T cells (Tregs) contribute to angiogenesis in endometriosis?

SUMMARY ANSWER:

High levels of CCL17 and CCL22 cause the recruitment of Tregs, upregulate the immunosuppression of Tregs and, in turn, may promote angiogenesis in endometrial cells in synergy with proinflammatory cytokines.

WHAT IS ALREADY KNOWN:

The peritoneal fluid of patients with endometriosis has a higher percentage of Tregs than that of normal individuals; however, the regulatory role of Tregs in the disease remains unclear.

STUDY DESIGN, SIZE, DURATION:

This study used primary human endometrial stromal cells (ESCs), monocytes (Mo), Tregs and human umbilical vein endothelial cells (HUVECs). All experiments were performed at least three times.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The migration of Tregs was evaluated by the transwell migration assay. The activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase and p38 signaling pathways was examined using the In-Cell WesternTM (LI-COR®) western blot analysis system, as well as by traditional western blot analysis. Changes in the expression of CCL22, CCL17, transforming growth factor-beta 1 (TGF-β1), Interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), IL-8 and vascular endothelial growth factor (VEGF) in cell-culture supernatant were detected by ELISA. We analyzed the Tregs by multicolor flow cytometry to directly test the expression of CCR4, CD4, CD25, Foxp3, CTLA-4, CD39 and CD73.

MAIN RESULTS AND THE ROLE OF CHANCE:

Our results showed that ESCs-Mo co-culture produced significantly higher levels of CCL22 and CCL17 than ESCs or Mo cultured alone, and that estradiol (E2) or progesterone (P) further promoted this upregulation, demonstrating stronger chemotaxis on Tregs. The co-culture of ESCs with Mo stimulated TGF-β1 secretion by Tregs, which could be inhibited by anti-CCL22 or/and anti-CCL17 neutralizing antibodies (Abs). The expression of CCR4 by Tregs was upregulated in ESCs-Mo co-culture, especially by treatment with E2 and/or P, and this effect could be abolished by anti-CCL22 and/or anti-CCL17-neutralizing Abs. The Treg-ESCs-Mo co-culture treated with E2 (10-8 mol/l) and P (10-8 mol/l) could enhance the immunosuppression of Tregs, as proved by the elevated expression of Foxp3, CTLA-4, CD39 and CD73 on Tregs. ESCs-Mo co-culture could significantly promote the secretion of IL-1β and TNF-α. TGF-β1 from Tregs could activate p38/ERK1/2 signaling pathways in ESCs, and IL-1β and TNF-α produced by ESCs-Mo co-culture had synergistic roles with TGF-β1. TGF-β1 and the proinflammatory cytokines IL-1β or TNF-α could synergistically promote IL-8 and VEGF expression in ESCs via the p38/ERK1/2 signaling pathways. The high levels of IL-8 and VEGF in the supernatant of ESCs stimulated the angiogenesis of HUVECs.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Jun;213:4-10.

Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis.

Morotti M¹, Venturini PL¹, Biscaldi E², Racca A¹, Calanni L¹, Vellone VG³, Stabilini C³, Ferrero S⁴.

Abstract

OBJECTIVE:

To study the efficacy of long-term treatment with norethindrone acetate (NETA) in patients with rectovaginal endometriosis.

STUDY DESIGN:

This retrospective cohort study included 103 women with pain symptoms caused by rectovaginal endometriosis. Patients received NETA alone (2.5mg/day up to 5mg/day) for 5 years. Primary outcome was the degree of satisfaction with treatment after 5 years of progestin therapy. Secondary outcomes were the assessment of any variation in pain symptoms and the volumetric assessment of the disease by magnetic resonance imaging (MRI).

RESULTS:

Sixty-one women completed the 5-year follow-up (61/103, 59.2%) with 16 women withdrawing because of adverse effects (38.1%). Overall, 68.8% (42/61) of the women who completed the study were satisfied or very satisfied of this long term NETA treatment. This represents a 40.8% (42/103) of the patients enrolled. Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (p<0.001 versus baseline at 1 and 5year). Dyschezia improved after 1-year respect to baseline (p=0.008) but remained stable between first and second year (p=0.409). At the end of 5 years treatment, a radiological partial response was observed in 33 patients (55.9%, n 33/59); a stable disease in 19 patients (32.2%, n 19/59). Seven women (7/59, 11.9%) displayed a volumetric increase of rectovaginal endometriosis under NETA treatment.

CONCLUSION:

Five-year therapy with NETA is safe and well tolerated by women with rectovaginal endometriosis. Due to its low cost and good pharmacological profile, it represents a good candidate for long-term treatment in this setting.

 

 

Environ Health. 2017 Apr 7;16(1):37.

Environmental pollutants, a possible etiology for premature ovarian insufficiency: a narrative review of animal and human data.

Vabre P¹, Gatimel N^1,2, Moreau J¹, Gayrard V^3,4, Picard-Hagen N^3,4, Parinaud J^5,6, Leandri RD^1,2.

Abstract

BACKGROUND:

Because only 25% of cases of premature ovarian insufficiency (POI) have a known etiology, the aim of this review was to summarize the associations and mechanisms of the impact of the environment on this pathology. Eligible studies were selected from an electronic literature search from the PUBMED database from January 2000 to February 2016 and associated references in published studies. Search terms included ovary, follicle, oocyte, endocrine disruptor, environmental exposure, occupational exposure, environmental contaminant, pesticide, polyaromatic hydrocarbon, polychlorinated biphenyl PCB, phenol, bisphenol, flame retardant, phthalate, dioxin, phytoestrogen, tobacco, smoke, cigarette, cosmetic, xenobiotic. The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We have included the human and animal studies corresponding to the terms and published in English. We have excluded articles that included results that did not concern ovarian pathology and those focused on ovarian cancer, polycystic ovary syndrome, endometriosis or precocious puberty. We have also excluded genetic, auto-immune or iatrogenic causes from our analysis. Finally, we have excluded animal data that does not concern mammals and studies based on results from in vitro culture. Data have been grouped according to the studied pollutants in order to synthetize their impact on follicular development and follicular atresia and the molecular pathways involved. Ninety-seven studies appeared to be eligible and were included in the present study, even though few directly address POI. Phthalates, bisphenol A, pesticides and tobacco were the most reported substances having a negative impact on ovarian function with an increased follicular depletion leading to an earlier age of menopause onset. These effects were found when exposure occured at different times throughout the lifetime from the prenatal to the adult period, possibly due to different mechanisms. The main mechanism seemed to be an increase in atresia of pre-antral follicles.

CONCLUSION:

Environmental pollutants are probably a cause of POI. Health officials and the general public must be aware of this environmental effect in order to implement individual and global preventive actions.

 

 

Cell Signal. 2018 Jan;41:89-96.

Niclosamide: Beyond an antihelminthic drug.

Chen W¹, Mook RA Jr², Premont RT², Wang J².

 

Abstract

Niclosamide is an oral antihelminthic drug used to treat parasitic infections in millions of people worldwide. However recent studies have indicated that niclosamide may have broad clinical applications for the treatment of diseases other than those caused by parasites. These diseases and symptoms may include cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, and systemic sclerosis. Among the underlying mechanisms associated with the drug actions of niclosamide are uncoupling of oxidative phosphorylation, and modulation of Wnt/β-catenin, mTORC1, STAT3, NF-κB and Notch signaling pathways. Here we provide a brief overview of the biological activities of niclosamide, its potential clinical applications, and its challenges for use as a new therapy for systemic diseases.

 

 

Med Sci Monit. 2017 Apr 8;23:1701-1706.

Leonurine Attenuates Hyperalgesia in Mice with Induced Adenomyosis.

Nie J¹, Liu X¹.

 

Abstract

BACKGROUND Adenomyosis, defined as the invasion of endometrial glands and stroma into the myometrium, is a common gynecological disorder. In the present study we report on the effect of leonurine on ICR mice with adenomyosis induced by neonatal tamoxifen. MATERIAL AND METHODS After being treated with tamoxifen for 4, 8, and 12 weeks, we assessed body weight and pain modulation in mice in hotplate tests. The mice were divided into 5 groups: a low-dose leonurine treatment group, a high-dose leonurine treatment group, a valproic acid (VPA) treatment group, a vehicle only treatment group, and a blank control group. We evaluated body weight, pain modulation in hotplate tests, and the depth of myometrial infiltration. Immunoreactivity staining of progesterone receptor (PR), nuclear factor-κB phosphorylated-p65 (p-p65), cyclooxygenase-2 (COX-2), and oxytocin receptor (OTR) was evaluated by immunohistochemistry. RESULTS The measurement of the body weight, myometrial infiltration, and pain modulation showed that neonatal tamoxifen treatment led to adenomyosis. Leonurine treatment appeared to decrease hyperalgesia and myometrial infiltration. Immunoreactivity staining showed decreased p-p65, COX-2, and OTR protein expressions. CONCLUSIONS Our results indicate that leonurine attenuates hyperalgesia in mice with induced adenomyosis via down-regulating expressions of p-P65, COX-2, and OTR, and could be beneficial for treating adenomyosis.

 

 

Environ Int. 2017 Jul;104:118-121.

Quantitative bias analysis of a reported association between perfluoroalkyl substances (PFAS) and endometriosis: The influence of oral contraceptive use.

Ngueta G¹, Longnecker MP², Yoon M³, Ruark CD⁴, Clewell HJ Rd⁵, Andersen ME⁶, Verner MA⁷.

 

Abstract

An association between serum levels of perfluoroalkyl substances (PFAS) and endometriosis has recently been reported in an epidemiologic study. Oral contraceptive use to treat dysmenorrhea (pelvic pain associated with endometriosis) could potentially influence this association by reducing menstrual fluid loss, a route of excretion for PFAS. In this study, we aimed to evaluate the influence of differential oral contraceptive use on the association between PFAS and endometriosis. We used a published life-stage physiologically based pharmacokinetic (PBPK) model to simulate plasma levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from birth to age at study participation (range 18-44years). In the simulated population, PFAS level distributions matched those for controls in the epidemiologic study. Prevalence and geometric mean duration (standard deviation [SD]) of oral contraceptive use in the simulated women were based on data from the National Health and Nutrition Examination Survey; among the women with endometriosis the values were, respectively, 29% and 6.8 (3.1) years; among those without endometriosis these values were 18% and 5.3 (2.8) years. In simulations, menstrual fluid loss (ml/cycle) in women taking oral contraceptives was assumed to be 56% of loss in non-users. We evaluated the association between simulated plasma PFAS concentration and endometriosis in the simulated population using logistic regression. Based on the simulations, the association between PFAS levels and endometriosis attributable to differential contraceptive use had an odds ratio (95% CI) of 1.05 (1.02, 1.07) for a log_e unit increase in PFOA and 1.03 (1.02, 1.05) for PFOS. In comparison, the epidemiologic study reported odds ratios of 1.62 (0.99, 2.66) for PFOA and 1.25 (0.87, 1.80) for PFOS. Our results suggest that the influence of oral contraceptive use on the association between PFAS levels and endometriosis is relatively small.

 

 

Nat Cell Biol. 2017 May;19(5):568-577.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

Turco MY^1,2, Gardner L^1,2, Hughes J³, Cindrova-Davies T^2,4, Gomez MJ¹, Farrell L^1,2, Hollinshead M¹, Marsh SGE⁵, Brosens JJ⁶, Critchley HO⁷, Simons BD^8,9, Hemberger M^2,10, Koo BK^9,11, Moffett A^1,2, Burton GJ^2,4.

 

Abstract

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

 

 

Biol Reprod. 2017 Jan 1;96(1):46-57.

Interaction of macrophages and endometrial cells induces epithelial-mesenchymal transition-like processes in adenomyosis.

An M¹, Li D², Yuan M¹, Li Q¹, Zhang L¹, Wang G¹.

 

Abstract

Adenomyosis is a nonneoplastic condition characterized by the benign invasion of ectopic endometrium into the myometrium. Macrophages play significant roles in epithelial-mesenchymal transition (EMT) and adenomyosis. An EMT associated with adenomyosis has been extensively studied. This study investigated the process by which the interaction of macrophages with endometrial cells induces EMT in Ishikawa cells and epithelial cells of adenomyosis. Specimens were collected after hysterectomy or resection of adenomyosis lesions from women with adenomyosis and curettage from women without adenomyosis or endometriosis. Immunohistochemistry and immunofluorescent staining demonstrated that CD68-positive macrophages aggregated in adenomyosis lesions, along with the increased protein expressions of n-cadherin, vimentin, and S100A4. By contrast, the protein expressions of e-cadherin and CK7 were decreased. After the primary endometrium cells were cocultured with THP-1-derived macrophages, the protein expression levels of n-cadherin, vimentin, and S100A4 of endometrium cells were increased, whereas the protein expression levels of e-cadherin and CK7 were decreased. The proportion of alternatively activated (M2) macrophages derived from THP-1 macrophages was also increased. The M2 macrophages elicited a bidirectional effect on Ishikawa cells by inducing EMT-like or mesenchymal-epithelial transition-like processes. The apoptotic rate of the Ishikawa cells cocultured with macrophages was increased, whereas their cell proliferation rate was decreased. Transmission electron microscopy indicated that the number of intercellular junctions of the cocultured Ishikawa cells was reduced. Microarray-based gene expression analysis revealed that transforming growth factor-β1/Smad3 and interleukin-6/JAK2/STAT3 signaling pathways were upregulated. Therefore, macrophages can induce EMT-like processes in adenomyosis and undergo polarization to M2.

 

 

J Obstet Gynaecol. 2017 Aug;37(6):775-778.

Prospective study concerning 71 cases of caesarean scar endometriosis(CSE).

Pas K¹, Joanna SM¹, Renata R¹, Skręt A¹, Barnaś E².

 

Abstract

A prospective study was undertaken involving 71 patients with caesarean scar endometriosis (CSE) between the years 2007 and 2013. A prospective study enabled us to find out: mean age of patients with CSE; 34.0 years (range 22.0-48.0), time between CS and diagnosis of CSE; 12.0 months (range 19.0-39.0), duration between symptoms and surgery; 24.0 months (range 1.0-204.0), mean operation time; 40.0 min. (range 15.0-160.0), and mean lesion size; 54.4 ± 42.3 mm³. In three patients (4.2%) a large deficit in the abdominal wall was closed by means of polypropylene mesh. One of them conceived a year later. Surgical excision is the only effective treatment in patients with CSE. Wide local excision with clear margins is the key to prevent recurrence. Repair of large post-excisional deficits with mesh may also be offered to woman planning their next pregnancy. Impact statement • What is already known on this subject? Endometriosis in the scar may occur after various abdominal surgeries, more frequently after caesarean sections. The excision of large nodules is connected with suboptimal cosmetic outcomes and the possibility of recurrence. • What the results of this study add? In this study including 71 patients with CSE, wide excision with electrocoagulatory was associated with a single recurrence in 12-month follow-up. In three patients (4.2%) large deficits in the abdominal wall were closed with the use of polypropylene mesh. One of them conceived a year later and had a successful pregnancy. • What the implications are of these findings for clinical practice and/or futher research? Surgical excision is the only effective treatment in patients with CSE. Wide local excision with clear margins is the key to preventing recurrence. Repair of large post excisional deficit with mesh may be offered also to woman planning pregnancy.

 

 

Eur Radiol. 2017 Oct;27(10):4298-4306.

Mid-term outcomes after percutaneous cryoablation of symptomatic abdominal wall endometriosis: comparison with surgery alone in a single institution.

Maillot J¹, Brun JL², Dubuisson V³, Bazot M⁴, Grenier N¹, Cornelis FH^5,6.

Abstract

OBJECTIVES:

To compare the outcomes of percutaneous image-guided cryoablation of symptomatic abdominal wall endometriosis (AWE) versus surgery alone.

METHODS:

From 2004 to 2016, cryoablation or surgery alone was performed under local (n = 5) or general anaesthesia (n = 15) for AWE in a single institution in 7 (mean age, 36.1 years) and 13 (mean age, 31.9 years) patients, respectively. Fifteen lesions were treated by cryoablation (mean size, 2.3 cm; range, 0.5-7 cm) and 16 by surgery (2.5 cm; 1.1-3.4 cm). Tolerance, efficacy and patient and procedural characteristics were compared.

RESULTS:

Median follow-up was 22.5 (range, 6-42) months after cryoablation and 54 (14-149) after surgery. The median procedure and hospitalisation durations were 41.5 min (24-66) and 0.8 days (0-1) after cryoablation, and 73.5 min (35-160) and 2.8 days (1-12 days) after surgery (both P = 0.01). Three patients (23.1%) had severe complications and nine aesthetic sequels (69.2%) after surgery, none after cryoablation (P = 0.05). The median 12- and 24-month symptom free-survival rates were 100% and 66.7% (95% CI, 5.4; 94.5) after cryoablation and 92% (55.3; 98.9) after surgery at both time points (P = 0.45).

CONCLUSIONS:

Cryoablation presents similar effectiveness to surgery alone for local control of AWE while reducing hospitalisation duration and complications. Any aesthetic sequels were associated with the cryoablation treatment.

KEY POINTS:

• Hospitalisation is shorter after cryoablation than after surgery of abdominal wall endometriosis. • A significantly lower rate of complications is observed after cryoablation compared to surgery. • Cryoablation of abdominal wall endometriosispresents similar effectiveness to surgery alone. • A significant reduction of pain is observed 6 months after treatment. • A significant reduction of abdominal wall endometriosisis observed at 6 months.

 

 

Chin Med J (Engl). 2017 Apr 20;130(8):950-956.

Transforming Growth Factor-beta 1 Involved in the Pathogenesis of Endometriosis through Regulating Expression of Vascular Endothelial Growth Factor under Hypoxia.

Yu YX¹, Xiu YL², Chen X², Li YL³.

Abstract

BACKGROUND:

Endometriosis (EMs) is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. Transforming growth factor-beta 1 (TGF-β1) plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions.

METHODS:

Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA (mRNA) and protein expression levels of TGF-β1, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) were measured. A Dual-Luciferase Reporter Assay was used to examine the effect of TGF-β1 and hypoxia on a VEGF promoter construct. Student’s t-test was performed for comparison among groups (one-sided or two-sided) and a value of P < 0.05 was considered statistically significant.

RESULTS:

TGF-β1, VEGF, HIF-1α mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue (t = 2.16, P = 0.042). EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein (t = 6.84, P = 0.023). VEGF mRNA levels increased 12.5% in response to TGF-β, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production (87.5% increases) of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 (2.6-fold, t = 6.08, P = 0.032) or hypoxia (11.2-fold, t = 32.70, P < 0.001), whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect (18.5-fold, t = 33.50, P < 0.001).

CONCLUSIONS:

The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-β1 and hypoxia is taking place at the transcriptional level.

 

 

Int J Mol Sci. 2017 Apr 8;18(4).

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology.

Guzel E¹, Arlier S^2,3, Guzeloglu-Kayisli O⁴, Tabak MS⁵, Ekiz T⁶, Semerci N⁷, Larsen K⁸, Schatz F⁹, Lockwood CJ¹⁰, Kayisli UA¹¹.

 

Abstract

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis.

 

 

Hum Reprod. 2017 Jun 1;32(6):1238-1243.

Elective embryo transfers on Day 6 reduce implantation compared with transfers on Day 5.

Poulsen V¹, Ingerslev HJ^1,2, Kirkegaard K³.

Abstract

STUDY QUESTION:

Is there a difference in pregnancy rates between embryos transferred electively on Day 5 and Day 6, respectively?

SUMMARY ANSWER:

The chance of pregnancy is significantly reduced (odds ratio (OR): 0.34; 95% CI 0.22-0.52) if transfer is performed on Day 6 compared with Day 5.

WHAT IS KNOWN ALREADY:

Several studies report that Day 5 transfers have higher implantation rates (IRs) when compared with Day 6 transfers. These studies were based on non-elective Day 6 transfers, where transfers on Day 6 were performed with developmentally delayed embryos. Traditionally, difference in IRs has therefore been explained by an impaired embryo quality. An alternative explanation is that endometrial receptivity is higher on Day 5 compared with Day 6.

STUDY DESIGN, SIZE, DURATION:

The study was conducted as a retrospective cohort follow-up study on single blastocyst transfers from February 2011 until August 2015 in patients aged <38 years, with ≥eight oocytes retrieved and no diagnosis of endometriosis. Non-elective Day 6 transfers were excluded. Post hoc power-calculations (two-sided level of significance 0.05, power of 0.80) indicate that 91 embryos were needed in each group to detect a reduction in IR (primary outcome) from 40 to 20%.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Day 5 or Day 6 transfers were implemented accordingly: from 2011 till 2013, transfers were performed on Day 6. If Day 6 was a Sunday, patients received Day 5 transfers. From 2013 onward, blastocysts were transferred on Day 5. If Day 5 was a Sunday, the transfer was delayed to Day 6. Univariable logistic regression analysis was performed to identify potential confounders. Factors with a P-value <0.1 were included in the multivariable logistic regression analysis.

MAIN RESULTS AND THE ROLE OF CHANCE:

We included 334 single elective Day 5 and 268 elective Day 6 transfers. The unadjusted odds for implantation between Day 5 and Day 6 groups were 0.35 (95% CI 0.25-0.49). A univariable logistic regression analysis identified maternal age, BMI, cumulative FSH dose, number of cryopreserved embryos, score of inner cell mass and trophectoderm and day of transfer as predictors of clinical pregnancy. When adjusting for these variables in a multivariable logistic regression analysis, the implantation odds for Day 5 transfer remained significantly higher than Day 6 (OR 0.34; 95% CI 0.22-0.52).

LIMITATIONS, REASONS FOR CAUTION:

The study was conducted on good prognosis patients. The majority of Day 6 transfers were performed in the beginning of the study period. Day 5 transfers were generally performed in the end of the study period. This difference in time of recruitment may cause a minor variation in the data but a subanalysis indicates that this potential variation is negligible. Day 5 scores were higher in the Day 5 transfer group.

WIDER IMPLICATIONS OF THE FINDINGS:

Based on the findings in this study, transfers should be performed on Day 5. If Day 5 transfers are logistically impossible to perform, it is be preferable to cryopreserve the blastocyst and transfer in another cycle on Day 5, as Day 6 transfers should be avoided.

 

 

Rev Bras Ginecol Obstet. 2017 May;39(5):217-223.

The Effect of Mesenchymal Stem Cells on Fertility in Experimental Retrocervical Endometriosis.

Abreu JP¹, Rebelatto CLK², Savari CA¹, Capriglione LGA³, Miyague L³, Noronha L¹, Amaral VFD⁴.

 

Abstract

Purpose To evaluate the effect of mesenchymal stem cells (MSCs) on fertility in experimental retrocervical endometriosis. Methods A total of 27 New Zealand rabbits were divided into three groups: endometriosis, in which endometrial implants were created; mesenchymal, in which MSCs were applied in addition to the creation of endometrial implants; and control, the group without endometriosis. Fisher’s exact test was performed to compare the dichotomous qualitative variables among the groups. The quantitative variables were compared by the nonparametric Mann-Whitney and Kruskal-Wallis tests. The Mann-Whitney test was used for post-hoc multiple comparison with Boniferroni correction. Results Regarding the beginning of the fertile period, the three groups had medians of 14 ± 12.7, 40 ± 5, and 33 ± 8.9 days respectively (p = 0.005). With regard to fertility (number of pregnancies), the endometriosis and control groups showed a rate of 77.78%, whereas the mesenchymal group showed a rate of 11.20% (p = 0.015). No differences in Keenan’s histological classification were observed among the groups (p = 0.730). With regard to the macroscopic appearance of the lesions, the mesenchymal group showed the most pelvic adhesions. Conclusion The use of MSCs in endometriosisnegatively contributed to fertility, suggesting the role of these cells in the development of this disease.

 

 

J Pediatr Adolesc Gynecol. 2017 Aug;30(4):503-504.

Bladder Involvement in Stage I Endometriosis.

Brady PC¹, Missmer SA², Laufer MR³.

Abstract

BACKGROUND:

Endometriosis-the ectopic implantation of endometrial-like tissue-affects 10% of adolescent females and adults. Bladder involvement, causing dysuria and hematuria, occurs in a very small number of endometriosis patients.

CASE:

The patient presented at age 12 years with dysuria and pelvic pain. Laparoscopy revealed stage I endometriosis. Postoperatively, she reported persistent dysuria and passage of tissue in her urine. Cystoscopy showed diffuse erythema; urine cytology revealed glandular and spindle cells suggestive of endometriosis. She was transitioned from oral contraceptives to an intranasal gonadotropin-releasing hormone agonist, with symptom resolution.

SUMMARY AND CONCLUSION:

Intravesicular endometriosis coinciding with stage I disease supports a mechanism of endometriosis dissemination other than direct bladder infiltration. Patients with endometriosis who complain of urinary symptoms warrant assessment, because intravesicular bladder involvement cannot be excluded using pelviscopy.

 

 

 

 

J Res Med Sci. 2017 Jan 27;22:7.

A case-control study of bisphenol A and endometrioma among subgroup of Iranian women.

Rashidi BH¹, Amanlou M², Lak TB³, Ghazizadeh M¹, Eslami B¹.

Abstract

BACKGROUND:

Endometriosis is a multifactorial hormonally related complex disease with unknown etiology. Epidemiologic data were suggested the possible effects of endocrine disrupting chemicals such as bisphenol A (BPA) on endometriosis. BPA is similar to endogenous estrogen and has the ability to interact with estrogen receptors and stimulate estrogen production. Our aim was to evaluate the relationship between urinary BPA concentrations in women with endometrioma.

MATERIALS AND METHODS:

This case-control study consisted of fifty women who have been referred to gynecology and infertility center with endometrioma and were candidates for operative laparoscopy and ovarian cystectomy as cases. Fifty women who had not any evidence of endometrioma in clinical and ultrasound evaluation and came to the same clinic for routine check-up were selected as controls. One-time urine sample was collected after receiving informed consent before surgery and medical intervention. Total BPA in urine was measured with high-performance liquid chromatography method and detection limit was 0.33 ng/mL.

RESULTS:

Percentage of urine samples containing BPA was 86% of cases and 82.4% of control. Urinary BPA showed a right-skewed distribution. The mean concentration of BPA was 5.53 ± 3.47 ng/mL and 1.43 ± 1.57 ng/mL in endometriosis and control group, respectively (P < 0.0001, Mann-Whitney U-test). The logistic regression showed that the odds ratio of the BPA was 1.74 (95% confidence interval: 1.40-2.16) after adjustment of age, parity, body mass index <30, and educational status.

CONCLUSION:

This study showed a positive association between urinary BPA concentrations and endometrioma. However, further large-scale studies are needed to confirm this hypothesis.

 

 

 

Open Med (Wars). 2017 Mar 9;12:12-18

Live Birth Pregnancy Outcome after First In Vitro Fertilization Treatment in a Patient with Systemic Lupus Erythematosus and Isolated High Positive IgA Anti-β2glycoprotein I Antibodies: A Case Report.

Andreeva H¹, Seip M², Koycheva S¹.

 

Abstract

IgA anti-β2glycoprotein I antibodies (IgA-anti-β2GPI) seems to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE) with a significant association to thrombotic events. Both SLE and antiphospholipid syndrome (APS) can be associated with implantation failure, fetal loss and obstetric complications. Recent reports highlight the clinical value of IgA-anti-β2GPI determination in supporting in vitro fertilization (IVF) treatment and IVF pregnancy outcomes. We report a 36-year-old female diagnosed with SLE, endometriosis and unexplained infertility. Conventional APS markers were consistently negative: anti-cardiolipin (aCL) and anti-β2GPI: IgG/IgM. She was then tested with reports of repeatedly high IgA-anti-β2GPI and tested positive from 2014 after IgA (aCL; anti-β2GPI) were established in our APS diagnostic panel. She underwent successful first IVF procedure with a 30 week live birth pregnancy outcome. During the follow up no lupus flare, thrombosis or ovarian hyperstimulation syndrome were registered. Serum IgA anti-β2GPI and anti-dsDNA levels declined statistically significant during the second and third trimester. Titres of IgA-anti-β2GPI remained lower postpartum as well. This case highlights the clinical importance of IgA-anti-β2GPI testing for family planning, assisted reproduction and pregnancy in women with SLE and/or APS.

 

 

J Laparoendosc Adv Surg Tech A. 2017 Jul;27(7):691-695.

Ureteroscopy-Assisted Laparoscopic Segmental Resection of Ureteral Stricture with a Modified Flank Position: Clinical Experience.

Hung SC¹, Chiu KY¹, Cheng CL¹, Ou YC^1,2, Ho HC¹, Wang SS¹, Chen CS¹, Li JR¹, Yang CK¹, Chang LW¹.

Abstract

PURPOSE:

To share the surgical technique that possesses the advantage of a perioperative ureteroscope without position change, which allows for a laparoscopic segmental resection of the ureteral stricture to be performed more precisely.

PATIENTS AND METHODS:

Between 2006 January and 2015 December, 10 patients with a ureteral stricture received a laparoscopic segmental resection and ureteroureterostomy in our clinical institute. The etiology included stone, endometriosis, crossing vessel, and idiopathic benign ureteral polyp. With the advance of bilateral lower extremities extended and abducted, 1 assistant used a ureteroscope as a direct guide to the precise location of the stricture affected ureter. Thus, the surgeon was able to perform a more specific resection without an unnecessary excision, which may have compromised the blood supply or increased the tension at anastomosis.

RESULTS:

Five patients received the traditional transperitoneal laparoscopic approach, whereas the other 5 patients received a ureteroscopy-assisted laparoscopic segmental resection and ureteroureterostomy. The operating time appears to be no different between the two groups (124 minutes versus 142 minutes, P = .351), and, thus, no additional time is consumed for the ureteroscope procedure. After at least 1 year of follow-up, only 1 patient in the traditional laparoscopic group suffered from recurrence. One patient had a right ureteral stricture due to stone impaction, where with the advantage of a ureteroscope guide without change position, the operator was able to make a limited excision at the affected location. No complications related to the decubitus and bilateral leg in the extended position were noted.

CONCLUSIONS:

Ureteroscopy-assisted laparoscopic segmental resection of the ureter without a change in position is a feasible and safe procedure when dealing with a refractory ureter stricture. Although it is convenient, the surgeon should be aware of possible pressure sores at the dependent part.

 

 

J Gynecol Obstet Hum Reprod. 2017 Mar;46(3):203-209.

Conservative management of endometrioma in women undergoing in vitro fertilization.

Santulli P¹, Somigliana E², Bourdon M³, Maignien C⁴, Marcellin L⁵, Gayet V⁴, Chapron C⁶.

 

Abstract

Endometriosis is a chronic disease. The pathogenesis is actually still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical). Among the different phenotypes of endometriosis, the ovarian endometrioma seems to most important lesion in the management of endometriosis-related infertility. Surgical treatment is associated to a decrease of the ovarian reserve and a potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the choice between conservative or surgical management of endometrioma before IVF is actually debated. The advantages and drawback of surgical and conservative management should be discussed before to plan the treatment. In the present review, we aimed at assessing the risks of a conservative management of endometrioma as compared to surgery before IVF.

 

 

J Gynecol Obstet Hum Reprod. 2017 Mar;46(3):219-227.

Trauma and endometriosis. A review. May we explain surgical phenotypes and natural history of the disease?

Canis M¹, Bourdel N², Houlle C², Gremeau AS², Botchorishvili R², Matsuzaki S².

Abstract

OBJECTIVE:

The study was performed to evaluate whether trauma is an initial event of development of endometriosis.

METHOD:

Using Medline database from January 1960 up to December 2014, a systematic review was made of all published studies using the keywords trauma, healing, injury, infection, hyperperistaltism, stretch and endometriosis, adenomyosis and trauma. Studies and review articles written in French and/or in English related to the topic were included and reviewed independently by two authors.

RESULTS:

The role of trauma is well-established for endometriotic lesions diagnosed in surgical scars. Various traumas including delivery, uterine curettage or incision, intraperitoneal hemorrhage, or occult pelvic inflammatory diseases could be involved to explain other localizations of the disease. Many data suggested that the healing process, particularly growth factors and the associated estrogen production, may facilitate the implantation and the growth of ectopic endometrial cells. After the initial, a traumatic event, the phenotype of the disease would depend on the tissue in which the endometriotic lesion grows.

CONCLUSIONS:

The present literature review may support a potential role of a trauma as an initial event of endometriosis.

 

 

J Gynecol Obstet Hum Reprod. 2017 Mar;46(3):229-233.

Ureterovesical reimplantation for ureteral deep infiltrating endometriosis: A retrospective study.

Chudzinski A¹, Collinet P², Flamand V³, Rubod C².

Abstract

INTRODUCTION AND HYPOTHESIS:

Symptoms of endometriosis of the urinary tract consist of nonspecific signs that are often trivialized. However, late diagnosis may be responsible for an upstream impact. The aim of this study is to describe a population of patients who received ureterovesical reimplantation for deep infiltrating endometriosis. We evaluate the preoperative clinical and radiological symptoms and long-term surgical outcomes.

METHODS:

All the endometriotic patients who underwent ureterovesical reimplantation at Lille university hospital between 2003 and 2013 were included retrospectively.

RESULTS:

Seventeen patients were included. Urological symptoms of endometriosis were present in 53% of patients and 29% had a history of urological surgery. Delay between diagnosis and ureteral reimplantation was 64±65 months on average. Forty-seven percent of patients had urinary functional symptoms consisting mainly of lower back pain. The ureteral lesion was known preoperatively and associated with hydroureteronephrosis in 82% of cases. Thirty-five percent of patients had renal atrophy and renal function was impaired in 23% of cases. Mean follow-up was 45±27 months. Forty-one percent of patients presented at least one immediate postoperative complication-fistula, postoperative infection or nerve compression. Also, urinary functional symptoms, dyspareunia and dysmenorrhea were maintained in 47%.

CONCLUSION:

Ureterovesical reimplantation in a context of endometriosis is major surgery with frequent complications. It requires close collaboration between gynecologists, radiologists and urologists. Prior comprehensive patient information is essential. Diagnosis and early treatment of ureteral endometriosis lesions should help reduce the morbidity of this disease.

 

 

J Gynecol Obstet Hum Reprod. 2017 Mar;46(3):235-242.

Psychometric properties of the French version of the Endometriosis Health Profile-30, a health-related quality of life instrument.

Chauvet P¹, Auclair C², Mourgues C², Canis M¹, Gerbaud L², Bourdel N³.

Abstract

INTRODUCTION:

The objectives were to evaluate the acceptability, reliability and validity of the cross-cultural adaptation of the Endometriosis Health Profile-30 instrument into French.

METHODS:

This cross-sectional study was conducted between July and October 2015. We created an online link (REDCap platform) with the questionnaires. An endometriosis patients association spread the link on its website and with social networks. The translation and cultural adaptation of the EHP-30 was performed according to guidelines. Psychometric evaluation included data completeness, score distributions, floor and ceiling effects, factor analysis, internal consistency, item-total correlations corrected for overlap, convergent validity and test-retest reliability.

RESULTS:

The study included 913 women with endometriosis. In our results, data completeness was excellent. No floor effects were found and one ceiling effect was observed for the ‘Infertility’ scale. The highest means scores were found for ‘Control and powerlessness’ and ‘Infertility’ scales. Factor analysis confirmed the structure of the original EHP-30 questionnaire. Internal consistency was good (Cronbach’s α range=0.72-0.96). The correlations of similar scale scores between EHP-30 and SF-36 were all significant (Spearman correlation coefficients ranging from -0.52 to -0.75). Test-retest reliability was good (intraclass correlation coefficients range=0.51-0.98).

CONCLUSION:

The French version of the EHP-30 is an acceptable, reliable and valid instrument for measuring health-related quality of life in women with endometriosis.

 

 

J Gynecol Obstet Hum Reprod. 2017 Jan;46(1):9-18.

Management of deep infiltrating endometriosis by laparoscopic route with robotic assistance: 3-year experience.

Abo C¹, Roman H², Bridoux V³, Huet E³, Tuech JJ³, Resch B¹, Stochino E¹, Marpeau L¹, Darwish B¹.

Abstract

OBJECTIVE:

To assess the feasibility of deep endometriosis surgery using robotic assistance, benefits and limits of this approach.

METHOD:

Case-series study enrolling patients managed for deep infiltrating endometriosis (DIE) using robotic assistance in our department between September 2011 and March 2014 (NCT02294825). Self-questionnaires including pain and digestive symptoms were filled in preoperatively and 1 year after surgery.

RESULTS:

Thirty-five patients were enrolled in the series. They represented 54% of patients managed for gynecological disease by laparoscopic route with robotic assistance during the study period, and 14% of patients managed for deep endometriosis in our department. Follow-up averaged 24±8 months, and no patient was lost to follow-up. Thirty-two patients had rectal involvement: rectal shaving was performed in 25 patients, disc excision in 3 and colorectal resection in 4. Three patients had bladder resection. Thirteen patients presented with deep endometriosis of the ureters: ureterolysis was performed in 11 of them, and resection of the ureter followed by reimplantation into the bladder in 2 patients. One major complication (Clavien IIIb) was recorded in a patient presenting with necrosis of the right ureter on postoperative day 5. Nine patients tried to conceive after surgery and 8 have already become pregnant (88.9%). One year after surgery, self-questionnaires revealed a significant decrease in pain symptoms and significant improvement in several item values of gastrointestinal standardized questionnaires.

CONCLUSIONS:

Surgical management of DIE is feasible using robotic assistance. However, data available in the literature and our own experience do not definitively support the hypothesis of the superiority of robotic assistance in the management of DIE.

 

 

J Gynecol Obstet Hum Reprod. 2017 Feb;46(2):137-142.

SF-36 preoperative interest of predicting improvement of quality of life after laparoscopic management of minimal endometriosis.

Valentin L¹, Canis M², Pouly JL³, Lasnier C⁴, Jaffeux P⁵, Aublet-Cuvelier B⁶, Bourdel N⁷.

Abstract

THE PURPOSE OF THE STUDY:

To study preoperative thresholds of the SF-36 components above which we can predict a high risk of failure in order to improve the quality of life after surgery for patients with minimal endometriosis.

MATERIAL AND METHODS:

Design: prospective and multicenter observational study between February 2004 and 2011.

PATIENTS:

167 patients with operated minimal endometriosis.

SETTING:

for the Physical Component Summary (PCS) or the Mental Component Summary (MCS) subscales of the SF-36 questionnaire, an improvement defined by an increase of 5 points.

INTERVENTION:

evaluation by the SF-36 questionnaire the week before and one year after surgery.

MEASUREMENT AND MAIN RESULTS:

Success of surgery measured by an improvement in both components. We found significantly different initial variables between patients with improvement and those without: initial MCS score (P=0.0003), initial PCS score (P<0.0001) and dyspareunia (P=0.004). Multivariate analysis revealed only two significant variables. Initial MCS higher than 40 (OR=4.6) and initial PCS higher than 50 (OR=10.6) are risk factors for failure of improvement after surgery.

CONCLUSION:

Surgery is seldom a good treatment for improving QOL in minimal endometriosis. We set two thresholds for SF-36, 50 for PCS and 40 for MCS: above there is a very high risk of failure (86% of failure in our population). Under, the risk of failure remains high (54.3%).

CANADIAN TASK FORCE CLASSIFICATION OF STUDY DESIGN:

Evidence obtained from well-designed cohort or case-control studies, preferably from more than one center or research group.

 

 

J Gynecol Obstet Hum Reprod. 2017 Feb;46(2):143-146.

Fertility after surgery for deep infiltrating endometriosis.

Blanc M¹, von Theobald P².

Abstract

OBJECTIVES:

The population of Reunion Island has a high prevalence of endometriosis impacting fertility. The aim of this series is to assess the fertility of women undergoing surgical approach of deep infiltrating endometriosis and to study the characteristics of the pregnancy outcomes.

MATERIAL AND METHODS:

This is a retrospective 2 centers study, including all women wanting to be pregnant and operated for deep endometriosis in any of the 2 hospitals of the CHU of Reunion Island between January 2012 and May 2013.

RESULTS:

Sixty-three women were included. Twenty-four (38%) had more than one operation and 16 (25.4%) experienced one or more complications. Fifty-eight (92%) had complete resection of the endometriosis. Twenty-seven (42.9%) women became pregnant at least once, spontaneously in 44.4%. Average delay for first pregnancy was 14.2 months. Twenty-two (34.9%) women became pregnant before 24 months. Among the 34 pregnancies, 20 ended with a live newborn. Premature delivery rate was 35%, cesarean section rate 10% and average birth weight was at 45th percentile.

CONCLUSION:

Fertility remains good after surgery for deep infiltrating endometriosis but the delay between operation and pregnancy is increased when a surgical complication occurs. Premature delivery rate is high. No pregnancy occurred in case of incomplete resection or after age of 36.

 

 

J Gynecol Obstet Hum Reprod. 2017 Feb;46(2):159-165.

A national snapshot of the surgical management of deep infiltrating endometriosis of the rectum and colon in France in 2015: A multicenter series of 1135 cases.

Roman H¹; FRIENDS group (French coloRectal Infiltrating ENDometriosis Study group).

Abstract

OBJECTIVE:

To perform a survey on the characteristics of the surgical management of patients with deep infiltrating endometriosis of the rectum and the sigmoid colon (DIERS) in France in 2015.

METHOD:

Case-series study enrolling patients with DIERS involving muscularis, submucosa or mucosa, operated on from January 1st to December 31st 2015, in 56 healthcare facilities in France. Surgeons filled in questionnaires concerning the number of patients, deep endometriosis localizations, surgical route and techniques used on digestive tract, associated surgical procedures and major complications. Data were pooled in a single database.

RESULTS:

A total of 1135 patients from 56 healthcare facilities were enrolled in the series (33 university hospitals, 4 general hospitals and 19 private hospitals). Deep endometriosis infiltrated only the rectum in 56.8% of cases, the rectum and the sigmoid colon in 36.3% and only the sigmoid colon in 6.9%. Associated localizations involved the cecum in 6.6% of cases, small bowel in 4.7%, bladder in 9%, and were responsible for stenosis of the ureters in 13.4% and for hydronephrosis in 6.8%. Surgery was performed using conventional laparoscopy in 82.2% of cases, robotic-assisted laparoscopy in 9.7% and open surgery in 8.1%. Rectal shaving was carried out in 48.1% of cases, disc excision in 7.3%, colorectal segmental resection in 40.4% and sigmoid colon segmental resection in 6.4% (2 different procedures could be associated in the same patient). Ureter resection was carried out in only 4% of cases, representing 29.6% of cases with stenosis of the ureters. Bladder resection was carried out in 6.9%. Vaginal resection and hysterectomy were performed in 33 and 14.7% of cases respectively, while temporary stoma was used in 19.1%. Anastomotic leakage occurred in 0.8% of cases, pelvic abscess in 3.4%, rectovaginal fistula in 2.7%, ureter fistula in 0.7%, while 8.6% of patients either required catheterization after recovery or had a post-voiding bladder volume superior to 100mL. According to the surgical procedure used, the risk of rectovaginal fistula was 1.3, 3.6 and 3.9% after shaving, disc excision and segmental resection respectively. Intensive care was required in 1.1% and blood transfusion in 2.2%. One patient died (0.1%) after rectal shaving.

CONCLUSIONS:

Our 2015 survey of a large number of patients managed for DIERS in France confirms that DIERS is far from being a rare disease. Even in the setting of complex procedures requiring multidisciplinary teams, a laparoscopic approach can achieve successful surgical treatment in 9 out of 10 patients with an acceptable risk of major postoperative complications.

 

 

J Gynecol Obstet Hum Reprod. 2017 Feb;46(2):197-200.

Pelvic nodules in a young woman: All is not endometriosis!

Buisson G¹, Maissiat E², Dubernard G³, Boussel L².

 

Abstract

Splenosis is a pathology resulting from a rupture of the spleen due to a trauma or a surgery. We report the case of a patient presenting with a splenosis, initially diagnosed as endometriosis-related pelvic nodules, the most frequent cause of pelvic nodules in women. We will describe the imaging strategy that led to the final diagnosis of splenosis.

 

 

J Assist Reprod Genet. 2017 Jun;34(6):789-794.

Involvement of 17β-hydroxysteroid dehydrogenase type gene 1 937 A>G polymorphism in infertility in Polish Caucasian women with endometriosis.

Osiński M¹, Mostowska A², Wirstlein P¹, Skrzypczak J¹, Jagodziński PP², Szczepańska M³.

Abstract

PURPOSE:

Endometriosis is considered to be an estrogen-related chronic inflammatory disease. The 17β-hydroxysteroid dehydrogenase 1 (HSD17B1) converts estrone to 17β estradiol. The role of HSD17B1 937 A>G (rs605059) single nucleotide polymorphism (SNP) in development of endometriosis is still disputable. This study evaluated the association of the HSD17B1 937 A>G (rs605059) SNP with infertile women affected by endometriosis from Polish Caucasian population.

METHODS:

The genotyping of cases (n = 290) and fertile women (n = 410) was conducted by high-resolution melting curve analysis.

RESULTS:

Statistical analysis demonstrated that the HSD17B1 937 A>G SNP is associated with endometriosis in stages I and II. The p _trend and p _allelic values calculated for the HSD17B1 937 A>G polymorphism were statistically significant and were equal to 0.001 and 0.0009, respectively. There was a significant association for the dominant model: (AG + GG vs AA) OR = 1.973 (95% CI = 1.178-3.304), p = 0.009, and for the recessive model: (GG vs AG + AA) OR = 1.806 (95% CI = 1.178-2.770), p = 0.006. However, we did not find statistical association of HSD17B1 937 A>G polymorphism with all infertile women with endometriosis or infertile women with endometriosis in stages III and IV.

CONCLUSION:

Our genetic study demonstrated HSD17B1 937 G variant as a risk factor for infertility in women with stage I and II endometriosis in Polish Caucasian patients.

 

 

J Med Chem. 2017 May 11;60(9):4086-4092.

First Dual Inhibitors of Steroid Sulfatase (STS) and 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1): Designed Multiple Ligands as Novel Potential Therapeutics for Estrogen-Dependent Diseases.

Salah M¹, Abdelsamie AS^1,2, Frotscher M¹.

 

Abstract

STS and 17β-HSD1 are attractive targets for the treatment of estrogen-dependent diseases like endometriosisand breast cancer. The simultaneous inhibition of both enzymes appears more promising than blockage of either protein alone. We describe a designed multiple ligand approach resulting in highly potent dual inhibitors. The most interesting compound 9 showed nanomolar IC₅₀ values for both proteins, membrane permeability, and no interference with estrogen receptors. It efficiently reversed E1S- and E1-induced T47D cell proliferation.

 

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Jun;213:17-21.

Impact of large ovarian endometriomas on the response to superovulation for in vitro fertilization: A retrospective study.

Ferrero S¹, Scala C¹, Tafi E², Racca A², Venturini PL², Leone Roberti Maggiore U³.

Abstract

OBJECTIVE:

To assess the response to superovulation for in vitro fertilization (IVF) in patients with unilateral endometriomas with diameter ≥5cm and in the contralateral healthy ovary.

STUDY DESIGN:

This retrospective analysis of a prospectively collected database included patients who underwent superovulation for IVF/ICSI cycles and had unoperated single unilateral endometrioma with diameter ≥5cm and healthy contralateral ovary. The primary outcome of the study was to compare the number of oocyte retrieved in the ovary with the endometrioma and the contralateral healthy ovary.

RESULTS:

The total number of follicles was lower in ovaries with endometriomas (2.6±1.3) than in healthy ovaries (4.8±2.0; p<0.001). The number of codominant follicles and the total number of oocytes retrieved were lower in ovaries with endometriomas (1.5±0.9 and 2.0±1.2) than in the contralateral ovaries (3.7±1.5 and 4.2±1.7; p<0.001, respectively). The number of oocytes retrieved suitable for fertilization was lower in ovaries with endometriomas (1.5±1.1) than in the healthy ovaries (3.3±1.5; p<0.001). The total number of oocytes retrieved and the number of oocytes retrieved suitable for fertilization were lower in ovaries with endometriomas respectively in 21 (80.8%) and in 20 (76.9%) cases. The decreased responsiveness to ovarian superovulation was confirmed considering women with ultrasonographic diagnosis of deep infiltrating endometriosis. 30.8% of patients had positive HCG; the pregnancy rate was 23.1%.

CONCLUSION:

The presence of large endometriomas (≥5cm) at time of IVF significantly decreases the number of oocyte retrieved compared with the contralateral healthy ovaries.

 

 

Int Immunopharmacol. 2017 Jun;47:150-158.

Expansion of monocytic myeloid-derived suppressor cells in endometriosispatients: A pilot study.

Chen H¹, Qin S², Lei A¹, Li X¹, Gao Q², Dong J³, Xiao Q⁴, Zhou J⁵.

 

Abstract

Endometriosis is a chronic inflammation disease and is closely associated with immune dysregulation. Myeloid-derived suppressor cells (MDSCs) are a negative regulator of the immune system. The aim of this study was to evaluate the possible role of MDSCs in endometriosis patients. We collected the peripheral blood and peritoneal fluid from endometriosis patients and controls and analyzed M-MDSCs level using specific monoclonal antibodies recognizing HLA-DR, CD33, CD11b, CD14 markers by flow cytometry. We found that there existed abnormal expansion of monocytic MDSCs (M-MDSCs) (HLA-DR^-/lowCD33⁺CD11b⁺ CD14⁺) in peripheral blood and peritoneal fluid of patients with endometriosis. Functional studies revealed that M-MDSCs from endometriosispatients significantly suppressed T-cell responses and produced high level of reactive oxygen species (ROS). The elevation of M-MDSCs from endometriosis patients may contribute to the disease progression.

 

 

Biomed Pharmacother. 2017 Jun;90:575-585.

A peek into the drug development scenario of endometriosis – A systematic review.

Goenka L¹, George M², Sen M³.

Abstract

PURPOSE AND OBJECTIVE:

Endometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis.

METHODS:

A systematic review was done and all the RCTs were selected from the identified hits. We included studies that explored the usage of therapeutic drugs on endometriosis patients from inception till November 2016. The search term used was ‘Endometriosis’ using PubMed and Clinicaltrials.gov. For the final analysis, 60 articles were analyzed and we identified the newly emerging drug therapies for endometriosis treatment and have briefed their current status and challenges in drug development for endometriosis. The quality of the selected studies was assessed based on the degree of bias.

RESULTS:

The current classes of drugs that have shown promising therapeutic results include Gonadotropin- releasing hormone (GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs that failed midway during development include tanezumab, rosiglitazone, infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene.

CONCLUSION:

From the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist’s armamentarium against endometriosis.

 

 

Am J Pathol. 2017 Jun;187(6):1200-1210.

RNA-Binding Proteins in Female Reproductive Pathologies.

Khalaj K¹, Miller JE¹, Fenn CR¹, Ahn S¹, Luna RL², Symons L¹, Monsanto SP¹, Koti M¹, Tayade C³.

 

Abstract

RNA-binding proteins are key regulatory molecules involved primarily in post-transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is critical for adequate cellular growth and survival. Recent reports have shown key interactions between these RNA-binding proteins and other regulatory elements, such as miRNAs and long noncoding RNAs, either enhancing or diminishing their response to RNA stabilization. Many RNA-binding proteins have been reported to play a functional role in mediation of cytokines involved in inflammation and immune dysfunction, and some have been classified as global post-transcriptional regulators of inflammation. The ubiquitous expression of RNA-binding proteins in a wide variety of cell types and their unique mechanisms of degradative action provide evidence that they are involved in reproductive tract pathologies. Aberrant inflammation and immune dysfunction are major contributors to the pathogenesis and disease pathophysiology of many reproductive pathologies, including ovarian and endometrial cancers in the female reproductive tract. Herein, we discuss various RNA-binding proteins and their unique contributions to female reproductive pathologies with a focus on those mediated by aberrant inflammation and immune dysfunction.

 

 

J Gynecol Obstet Hum Reprod. 2017 May;46(5):463-464.

Pelvic tuberculosis mimicking deep endometriosis.

Koch A¹, Lecointre L², Garbin O².

 

Abstract

Pelvic tuberculosis is most frequently observed in developing countries and often leads to the misdiagnosis of pelvic malignancy. We report the first case of pelvic tuberculosis mimicking deep endometriosis.

 

 

Pathol Oncol Res. 2018 Jan;24(1):145-151.

The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer.

Heydari K¹, Saidijam M¹, Sharifi MR², Dermani FK¹, Soleimani Asl S^3,4, Shabab N¹, Najafi R^5,6.

 

Abstract

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.