Zhonghua Fu Chan Ke Za Zhi. 2016 Mar;51(3):180-5.

Effects of cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome of in vitro fertilization-embryo transfer cycle.

Zhang XR1Ding LLTang RSheng YQin YYChen ZJ.

 

Abstract

OBJECTIVE:

To investigate the impact of previous cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles.

METHODS:

Totally 622 infertility patients were retrospectively investigated who underwent first IVF/ICSI-ET cycle in Reproductive Hospital Affiliated to Shandong University from January 2013 to June 2014. There were 153 cases who had been removed ovarian cyst by cystectomy surgeries recruited as study group, in which 44 cases of ovarian endometriosis cyst, 35 cases of benign ovarian teratomas, 67 cases of simple ovarian cyst and 7 cases of ovarian mucinous cystadenoma. In contrast, 469 infertility patients with tubal-factor infertility or male factor were included as control group. The age-matched women in the control group had no ovarian surgery previously. The indicators of ovarian reserve and pregnancy outcome were analyzed between two groups. The influence of different types of ovarian cysts on ovarian reserve and pregnancy outcome in IVF/ICSI-ET cycles were also studied, ovarian endometriosis cyst was studied as Group A, and Group B consisted of benign ovarian teratomas, simple ovarian cyst and mucinous cystadenoma.

RESULTS:

(1) The significantly lower serum antimullerian hormone (AMH) level (median: 1.92 versus 2.90 mg/L), antral follicle count (AFC; median: 12.0 versus 13.0), retrieved oocytes (12±5 versus 13±6) and the number of embryo cryopreserved (median: 1.0 versus 3.0) were found in study group compared with control group (all P<0.05). There was no statistical difference between two group for the following parameters, such as basal FSH level, the total dosage of gonadotropin duration and the total dosage of gonadotropin (all P>0.05). A better clinical pregnancy rate was achieved in control group (61.6%, 241/391) than that in study group (61.4%, 81/132), but no significant difference was existed (P=0.96). (2) Compared to Group B, Group A had fewer AFC, lower serum AMH level, retrieved oocytes and the number of embryo cryopreserved (11±4 versus 13±5; 1.65 versus 2.15 mg/L; 9±4 versus 13±5; 0 versus 2.0; all P< 0.01). There was a lower clinical pregnancy rate in Group A than that in Group B [50.0% (19/38) versus 66.0% (62/94)], accompanying with higher abortion rate [3/19 versus 9.7% (6/62)], but no differences were observed (all P>0.05).

CONCLUSIONS:

Ovarian reserve declines after the cystectomy for ovarian benign cysts and the cystectomy has a negative impact on IVF/ICSI-ET cycle, resulting in a decrease of the number of retrieved oocytes and the number of embryo cryopreserved, but do not influence clinical pregnancy outcome. Ovarian reserve is impaired more seriously by cystectomy for ovarian endometriosis cyst than other ovarian benign cyst.

 

 

J Obstet Gynaecol Can. 2016 Feb;38(2):154-9.

Abdominal Wall Pain in Women With Chronic Pelvic Pain.

Mui J1Allaire C2Williams C2Yong PJ2.

 

Abstract

OBJECTIVE:

To investigate the role of abdominal wall pain (AWP) in women with pelvic pain.

METHODS:

We conducted a retrospective review of consecutive patients with pelvic pain seen in a tertiary referral centre between January and December 2012. AWP was defined as abdominal wall tenderness with a positive Carnett test (i.e., tenderness that worsened or remained the same with abdominal wall contraction). Pairwise comparisons were carried out between clinical variables (e.g., chronic pelvic pain) and AWP. This was followed by multiple logistic regression to identify the clinical variables with an independent association with AWP.

RESULTS:

The prevalence of AWP in women with pelvic pain was 67% (127/190). On multiple logistic regression, AWP was independently associated with chronic pelvic pain (OR 13.8; 95% CI 3.71 to 51.2, P < 0.001), but not with other symptoms including dysmenorrhea, deep and superficial dyspareunia, or bowel and bladder symptomology. In a corollary analysis, women with AWP were more likely to require opioids or pain adjuvants than women without AWP (P = 0.015 and P < 0.001).

CONCLUSION:

AWP is common in women with pelvic pain and may contribute specifically to the symptom of chronic pelvic pain.

 

 

Gynecol Obstet Fertil. 2016 Jun;44(6):315-21.

Partial cystectomy for bladder endometriosis: Robotic assisted laparoscopy versus standard laparoscopy.

le Carpentier M1Merlot B2Bot Robin V2Rubod C2Collinet P2.

Abstract

OBJECTIVES:

To compare robot-assisted laparoscopy (RL) and conventional laparoscopy (CL) in surgery for bladder endometriosis.

METHODS:

A retrospective study was conducted between January 2007 and December 2013, including patients with bladder endometriosis receiving at least a partial cystectomy by RL or CL. The primary endpoint was the presence of a radiological recurrence at bladder level.

RESULTS:

We included 15 patients in the RL group and 22 in the CL group. The median age was 29 years±7 years. The symptoms were similar in the 2 groups. Pre-surgical mapping of the lesions was carried out with MRI. Sixty percent of patients in the RL group vs 91% in the CL group had other associated endometriosislesions, P=0.04. The median size of the bladder lesion was 30±8mm in the RL group vs 23±7mm in the CL group, P=0.03. The median operative time was 210 vs 225min, P=0.8. We did not find any significant difference in intraoperative and early and late postoperative complications between the 2 groups. The median length of stay was 5 days vs 6 days. The proportion of relapse was 20 vs 23%, P>0.05. Clinical improvement was similar between the groups, i.e. 93 vs 86%, P=0.6 and the pregnancy rate was 93 vs 86%, P=0.6.

CONCLUSIONS:

Robot-assisted laparoscopy in the surgical treatment of bladder endometriosis as compared to traditional laparoscopy does not seem to have an adverse effect neither on the risk of recurrence nor on the occurrence of intra- and postoperative complications.

 

 

Biomed Res Int. 2016

Periostin Facilitates the Epithelial-Mesenchymal Transition of Endometrial Epithelial Cells through ILK-Akt Signaling Pathway.

Zheng QM1Lu JJ1Zhao J1Wei X1Wang L1Liu PS1.

 

Abstract

Although periostin was confirmed to facilitate the pathogenesis of endometriosis by enhancing the migration, invasion, and adhesion of human endometrial stromal cells (ESCs), its effect on the endometrial epithelial cells (EECs) is still unknown. The current study aimed to determine whether periostin enhanced the epithelial-mesenchymal transition (EMT) of EECs. EECs were isolated from 12 women with endometriosis. The migration and invasion abilities of EECs were evaluated by transwell assays. Expressions of proteins were detected by western blot. After treatment with periostin, the migration and invasion abilities of EECs were enhanced. Additionally, E-cadherin and keratin were downregulated while N-cadherin and vimentin were upregulated in EECs. Simultaneously, levels of ILK, p-Akt, slug, and Zeb1 were all upregulated in EECs. After silencing the expression of ILK in EECs, levels of p-Akt, slug, Zeb1, N-cadherin, and vimentin were downregulated while E-cadherin and keratin were upregulated. Although periostin weakened the above effects in EECs after silencing the expression of ILK, it failed to induce the EMT of EECs. Thus, periostin enhanced invasion and migration abilities of EECs and facilitated the EMT of EECs through ILK-Akt signaling pathway. Playing a pivotal role in the pathogenesis of endometriosis, periostin may be a new clinical therapy target for endometriosis.

 

 

J Clin Endocrinol Metab. 2016 Jun;101(6):2371-9.

Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis.

Miyashita M1Koga K1Izumi G1Sue F1Makabe T1Taguchi A1Nagai M1Urata Y1Takamura M1Harada M1Hirata T1Hirota Y1Wada-Hiraike O1Fujii T1Osuga Y1.

 

Abstract

CONTEXT:

Endometriosis is an estrogen-dependent, chronic inflammatory disease. Recent studies have shown that vitamin D (VD) is an effective modulator of the immune system and plays an important role in controlling many inflammatory diseases.

OBJECTIVE:

The objective of the study was to clarify the in vitro effects of 1,25-dihydroxy vitamin D3 (1,25[OH]2D3) on human endometriotic stromal cells (ESCs) and to determine the serum levels of VD in endometriosis patients.

DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES:

ESCs were isolated from ovarian endometrioma and cultured with 1,25(OH)2D3. Gene expression of IL-8, cyclooxygenase-2, microsomal prostaglandin E synthase-1, microsomal prostaglandin E synthase-2, cytosolic prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, matrix metalloproteinase (MMP)-2, and MMP-9 was examined using quantitative RT-PCR. The production of IL-8 and prostaglandin E2 was measured using an ELISA and an enzyme immunoassay. Viable cell number was assessed using a cell-counting assay, and DNA synthesis was assessed using the bromodeoxyuridine incorporation assay. Apoptosis was assessed using flow cytometry. The expression of inhibitory-κBα protein was detected using Western blotting. The serum levels of 25-hydroxyvitamin D3 and 1,25(OH)2D3 were measured by a RIA.

RESULTS:

In vitro studies showed that 1,25(OH)2D3 significantly reduced IL-1β- or TNF-α-induced inflammatory responses, such as IL-8 expression and prostaglandin activity. 1,25(OH)2D3 also reduced viable ESC numbers and DNA synthesis but did not affect apoptosis. MMP-2 and MMP-9 expressions were reduced by 1,25(OH)2D3. 1,25(OH)2D3 inhibited nuclear factor-κB activation. The serum 25-hydroxyvitamin D3 levels were significantly lower in women with severe endometriosis than in the controls and women with mild endometriosis. Serum 1,25(OH)2D3 levels were not different between groups.

CONCLUSIONS:

VD modulates inflammation and proliferation in endometriotic cells, and a lower VD status is associated with endometriosis. Taken together, VD supplementation could be a novel therapeutic strategy for managing endometriosis.

 

 

Oncotarget. 2016 May 10;7(19):27735-52

The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.

Shimada H1,2Satohisa S1Kohno T2Takahashi S2Hatakeyama T2Konno T2Tsujiwaki M3Saito T1Kojima T2.

 

Abstract

Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a novel molecular constituent of tricellular contacts that have a barrier function for the cellular sheet. LSR recruits tricellulin (TRIC), which is the first molecular component of tricellular tight junctions. Knockdown of LSR increases cell motility and invasion of certain cancer cells. However, the behavior and the roles of LSR in endometrial cancer remain unknown. In the present study, we investigated the behavior and roles of LSR in normal and endometrial cancer cells in vivo and in vitro. In endometriosis and endometrial cancer, LSR was observed not only in the subapical region but also throughout the lateral region as well as in normal endometrial epithelial cells in the secretory phase, and LSR in the cancer was reduced in correlation with the malignancy. Knockdown of LSR by the siRNA in cells of the endometrial cancer cell line Sawano, induced cell migration, invasion and proliferation, while TRIC relocalized from the tricellular region to the bicellular region at the membrane. In Sawano cells and normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced by adiponectin and the drugs for type 2 diabetes metformin and berberine were observed via distinct signaling pathways including JAK2/STAT. In Sawano cells, metformin and berberine prevented cell migration and invasion induced by downregulation of LSR by the siRNA and leptin treatment. The dissection of the mechanism in the downregulation of endometrial LSR during obesity is important in developing new diagnostic and therapy for endometrial cancer.

 

 

Reprod Sci. 2016 Oct;23(10):1282-8.

Origins and Progression of Adolescent Endometriosis.

Brosens I1Gargett CE2Guo SW3Puttemans P4Gordts S4Brosens JJ5Benagiano G6.

 

Abstract

Accumulating evidence indicates that adolescent endometriosis is common and often severe. Here we explore the possibility that seeding of naive endometrial progenitor cells into the pelvic cavity early in life, that is, at the time of neonatal uterine bleeding or soon after the menarche, results in more florid and progressive disease, characterized by highly angiogenic implants, recurrent ectopic bleeding, and endometrioma formation. We discuss the potential intergenerational risk factors associated with early-onset endometriosis and explore the molecular drivers of disease progression. Taken together, the available data suggest that an increased focus on early-life events may help to identify young women at risk of severe, progressive endometriosis.

 

 

Reprod Biomed Online. 2016 Jun;32(6):556-62.

A new approach to the management of ovarian endometrioma to prevent tissue damage and recurrence.

Benagiano G1Petraglia F2Gordts S3Brosens I4.

 

Abstract

Management of ovarian endometrioma is a matter of debate between those advocating early treatment and those believing that cysts less than 3 cm in diameter should not be submitted to surgery. To explore a new approach to its management capable of preserving future fertility, the molecular pathology of ovarian endometrioma is reviewed and mechanisms by which the endometrioma progressively affects the ovary during reproductive life are summarized. The scope of new therapeutic modalities includes restoring the progesterone receptor ratio using progestin or progesterone receptor modulators and decreasing local oestrogen production through an aromatase inhibitor. In addition, free radical production can be blocked by antioxidants and the autophagic process by increasing apoptosis. Finally, metalloproteinases and relaxin activity, as well as the inflammatory process can be controlled. Many of these pharmacological treatments lend themselves to local administration and can be applied through intracystic drug administration; in fact, the intracystic route has already been tried with recombinant interleukin-2, methotrexate and ethanol; the latter to obtain sclerotization. Specifically, it is proposed that endometrial growth in the endometrioma is suppressed by intra-cystic application of synthetic progestins, such as levonorgestrel or danazol, selective progesterone receptor modulators, such as mifepristone, ulipristal or asoprisnil, without affecting ovarian activity.

 

 

Biochem Pharmacol. 2016 Jun 1;109:91-104

Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells.

Chiappini F1Bastón JI2Vaccarezza A3Singla JJ4Pontillo C5Miret N6Farina M7Meresman G8Randi A9.

 

Abstract

Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.

 

 

 

 

Int J Gynaecol Obstet. 2016 Jul;134(1):3-7.

A systematic review of ultrasonography-guided transvaginal aspiration of recurrent ovarian endometrioma.

Gonçalves FC1Andres MP2Passman LJ3Gonçalves MO4Podgaec S5.

 

Abstract

BACKGROUND:

Ovarian endometriosis is present in 17%-44% of women with endometriosis. The main treatment is surgery, but ultrasonography-guided aspiration is a less invasive alternative.

OBJECTIVES:

To evaluate the effectiveness of this alternative treatment in recurrent ovarian endometrioma.

SEARCH STRATEGY:

Multiple databases were searched for articles published between 1994 and 2014 using the keywords “ultrasound-guided aspiration,” “ovarian,” and “endometriosis.”

SELECTION CRITERIA:

Randomized controlled trials and observational studies published in English, Portuguese, or Spanish were included.

DATA COLLECTION AND ANALYSIS:

Two researchers independently extracted and reviewed the data. The main outcome of interest was the recurrence rate.

MAIN RESULTS:

Eight studies were eligible. Ovarian endometriosis is associated with high recurrence rates after one ultrasonography-guided aspiration (28.9%-91.5%), but involves less ovarian manipulation. The results of aspiration followed by sclerotherapy are not uniform, but overall the addition of a sclerosing agent does not seem to significantly reduce the likelihood of recurrence (13.3%-75.0%). Repeated aspiration of the cysts can reduce the recurrence rate to 5.4% by the sixth aspiration.

CONCLUSIONS:

Repeated ultrasonography-guided aspiration of ovarian endometriomas can be performed for the treatment of recurrent ovarian endometriosis. Further studies comparing the efficacy of this procedure and ovarian surgery are needed.

 

 

Abdom Radiol (NY). 2016 Mar;41(3):568-81

Beyond appendicitis; radiologic review of unusual and rare pathology of the appendix.

Hines JJ1Paek GK2Lee P2Wu L3Katz DS4.

 

Abstract

Appendicitis is a very common cause of acute abdominal pathology, however, many other pathologic conditions of the appendix can be diagnosed utilizing CT. Examples of these conditions include primary appendiceal neoplasms, secondary inflammation of the appendix, stump appendicitis, endometriosis, appendicitis within a hernia, appendiceal diverticulosis and intussusception and intraluminal foreign bodies. The purpose of this article is to review appendiceal pathology outside of acute appendicitis, describe corresponding imaging findings on CT, and to illustrate various CT findings of appendiceal disease with representative cases.

 

 

Anal Chem. 2016 May 3;88(9):4613-8.

A Fast and Sensitive Method for the Detection of Leuprolide Acetate: A High-Throughput Approach for the In Vitro Evaluation of Liquid Crystal Formulations.

Báez-Santos YM1Otte A1Park K1,2.

 

Abstract

The suitability of using fluorescence spectroscopy to rapidly assay drug release by quantifying the time-dependent increase in total intrinsic protein fluorescence was assessed. Leuprolide acetate, a synthetic nonapeptide analogue of gonadotropin-releasing hormone (GnRH or LHRH), is the active pharmaceutical ingredient used to treat a wide range of sex hormone-related disorders, including advanced prostatic cancer, endometriosis, and precocious puberty. During the in vitro evaluation of drug delivery technologies for leuprolide acetate, one of the most time-consuming steps is the detection and accurate quantification of leuprolide release from formulation candidates. Thus far, the dominant means for leuprolide detection involves conventional multistep high-performance liquid chromatography (HPLC) methods, requiring sampling, dilutions, sample filtration, and chromatography, which can take up to 40 min for each sample. With the increasing demand for assay adaptation to high-throughput format, here we sought to exploit fluorescence spectroscopy as a tool to develop a novel method to rapidly assay the in vitro release of leuprolide acetate. By utilizing the intrinsic fluorescence of the tryptophan (Trp) and tyrosine (Tyr) amino acid residues present in the leuprolide nonapeptide, the in vitro release from liquid crystal formulations was accurately quantified as a function of fluorescence intensity. Here, we demonstrate that assaying leuprolide release using intrinsic protein fluorescence in a 96-well format requiring volumes as low as 100 μL is a cost-effective, rapid, and highly sensitive alternative to conventional HPLC methods. Furthermore, the high signal-to-noise ratios and robust Z’-factors of >0.8 indicate high sensitivity, precision, and feasibility for miniaturization, high-throughput format adaptation, and automation.

 

Fertil Steril. 2016 Aug;106(2):378-85.

Syndecan-4 expression is upregulated in endometriosis and contributes to an invasive phenotype.

Chelariu-Raicu A1Wilke C1Brand M1Starzinski-Powitz A2Kiesel L1Schüring AN1Götte M3.

 

Abstract

OBJECTIVE:

To study the expression and function of syndecan-4 in endometriosis.

DESIGN:

Histopathological investigation of eutopic endometrium and experimental laboratory study on a cell line derived from epithelial endometriotic cells (12Z).

SETTING:

University hospital laboratory.

PATIENT(S):

One hundred six women (62 controls/44 endometriosis) from the IVF center of Münster University Hospital aged 23-44 undergoing Pipelle biopsy and diagnostic exploratory laparoscopy.

INTERVENTION(S):

Eutopic endometrial tissue was investigated by immunohistochemistry for the expression of syndecan-4. The human endometriotic cell line 12Z was transiently transfected with syndecan-4 small interfering RNA and investigated for changes in cell behavior.

MAIN OUTCOME MEASURE(S):

Syndecan-4 expression in eutopic endometrium was evaluated immunohistochemically in endometrial glands and stroma. Scoring results were correlated with the stages of the menstrual cycle and presence or absence of endometriosis. Quantitative polymerase chain reaction was used to measure syndecan-4-dependent expression changes of MMP2, MMP3, MMP9, Rac1, and ATF2. Altered cell behavior was monitored by matrigel invasion assays and cell viability assays.

RESULT(S):

Syndecan-4 expression was significantly higher in the glands and stroma of patients with endometriosis compared with controls, whereas no menstrual cycle-dependent expression was observed. In 12Z cells, syndecan-4 depletion did not affect cell viability but resulted in a significantly reduced matrigel invasiveness and reduced expression of the small GTPase Rac1, the transcription factor ATF-2, and MMP3.

CONCLUSION(S):

The upregulation of syndecan-4 in the eutopic endometrium of endometriosis patients may facilitate the pathogenetic process by promoting invasive cell growth via Rac1, MMP3, and ATF-2.

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):833-8.

Primary Vaginal Adenosarcoma With Sarcomatous Overgrowth Arising in Recurrent Endometriosis: Feasibility of Laparoscopic Treatment and Review of the Literature.

Pontrelli G1Cozzolino M2Stepniewska A1Bruni F1Pesci A3Ceccaroni M1.

 

Abstract

We report a case of a primary vaginal adenosarcoma with sarcomatous overgrowth in a postmenopausal 58-year-old woman with recurrent endometriosis. In the past 5 years she underwent several biopsies of a polypoid lesion on the vaginal cuff, and the last histologic examination of the biopsy showed an adenosarcoma with “sarcomatous overgrowth” in a background of endometriosis. There was no evidence of distant metastatic disease on the diagnostic workup, and we performed a laparoscopy to remove the pelvic mass. We reviewed the literature on the electronic databases Medline, Embase, and Science Direct on articles published in English from 1990 to 2015. We identified 5 articles in which the surgical treatment was performed via a laparotomic approach. The present case is the first in the literature to report feasibility of laparoscopic treatment for this kind of pathology with a detailed description of the surgical technique.

 

 

J Clin Diagn Res. 2016 Feb;10(2):ED14-5.

Persistent Mullerian Duct Syndrome with Ovarian Endometriosis-A Rare Case Report.

Nerune SM1Hippargi SB2Mestri NB3Mehrotra NM3.

 

Abstract

Persistent Mullerian Duct Syndrome (PMDS) is a rare form of internal male pseudohermaphroditism, characterised by presence of Mullerian duct derivatives in a genotypic and phenotypic male. It is caused by absence of anti- Mullerian hormone or defective functioning of its receptors. We report a case of 19-year-old cryptorchid male with history of orchideopexy who was clinically and radiologically diagnosed as left sided chylocele. A definitive diagnosis of PMDS with ovarian endometriosis was made on histopathological examination which is important for genetic counselling and to reduce complications like infertility and neoplastic transformation. We report this case of PMDS with ovary showing evidence of endometriosis for its rarity.

 

 

 

J Clin Diagn Res. 2016 Feb;10(2):PD12-3.

Bladder Endometriosis Mimicking TCC – A Case Report.

Gupta A1Bhatnagar A1Seth BN2Dang A3Gupta V4.

 

Abstract

Endometriosis is the ectopic presence of endometrial tissue outside the uterus. Though on its own endometriosis is not a rare lesion, the involvement of the urinary tract is rare but with the bladder being the most commonly affected organ. Endometriosis is usually seen in females between the ages of 30-40 years and may occur due to fluctuating levels of oestrogen and progesterone. Clinically the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been suggested that ultrasonography should be done either before or during menstruation as the lesion becomes more evident and a biopsy taken during this period is a strong aid in reaching a final diagnosis. We report here an unusual case of bladder endometriosis where the patient came with severe pelvic pain and an endoluminal mass seen on the ultrasonographic report. Based on these findings a differential of transitional cell carcinoma was given which was ruled out based on the cystoscopic findings.

 

 

Surg Technol Int. 2016 Apr;28:196-201.

Abdominal Wall Endometriosis Excision with Mesh Closure – Report of Two Cases.

Vaz-de-Macedo C1Gomes-da-Costa A1Mendes S1Barata S2Alho C1Jorge CC1Osório F3.

 

Abstract

Abdominal wall endometriosis (AWE) is a rare condition included in the differential diagnosis of an abdominal wall mass and/or pelvic pain in women of reproductive age. It usually occurs after pelvic surgery, most commonly caesarean section. Given the variable clinical presentation, diagnosis can be challenging if a high index of suspicion for AWE does not exist. Consequently, the correct diagnosis is often missed in the preoperative assessment. The presence of endometriosis in other locations can aid in the diagnosis, but other endometriotic lesions do not always exist. Image studies, particularly ultrasound and magnetic resonance imaging, can also be of help in the differential diagnosis. Even though new management techniques such as ultrasound-guided percutaneous cryoablation seem to be promising, surgical excision is still the mainstay of treatment. When the aponeurosis is involved, lesion excision might need to be followed by wall closure with the use of a mesh to lessen tissue tension. We present two typical cases of AWE after caesarean section, one of them recurrent, in patients with concurrent endometriosis of other locations. Total lesion excision followed by polypropylene mesh closure has been performed, with very good post-operative outcomes. We aim to raise awareness towards this diagnosis and to highlight the importance of complete lesion excision and adequate closure of the abdominal wall.

 

 

 

Medicine (Baltimore). 2016 Mar;95(13)

Acute Urinary Retention During Pregnancy–A Nationwide Population-Based Cohort Study in Taiwan.

Chen JS1Chen SCLu CLYang HYWang PHuang LCLiu FS.

 

Abstract

The aim of the study was to investigate the epidemiology and risk factors of acute urinary retention (AUR) during pregnancy. We included all cases of pregnancies with AUR reported in Taiwan’s Longitudinal Health Insurance Database from January 1, 1998, to December 31, 2011. Cases of AUR onset 1 day before delivery were excluded. The Cochrane-Armitage trend test and logistic regression analysis were used to evaluate the age distribution and types of deliveries of pregnant women. Chi-square tests and Fisher’s exact test were performed to examine the association among all covariates. The odds ratios (OR) and 95% confidence intervals (CI) were estimated. We identified 308 cases of AUR in 65,490 pregnancies. The risk of AUR during pregnancy was 0.47%. The peak incidence occurred between the 9th and 16th gestational weeks. Patients who experienced preterm delivery exhibited the highest risk for AUR (2.18%). Those with post-term delivery had the second highest risk (0.46%), and patients with a normal delivery exhibited the lowest risk (0.33%). Compared with normal delivery, preterm delivery carried a higher risk of AUR (OR: 6.33, 95% CI: 4.94-8.11). The AUR risk was higher for patients with advanced maternal age (>35 years old) than it was for those in the younger group (< 20 years old) (OR: 2.62, 95% CI: 1.18-5.81). Within the normal delivery group, higher incidences of urogenital infection, gestational diabetes mellitus, previous abortion, abnormal pelvis, disproportion, and endometriosis were noted in women with AUR than in those without AUR (all P values <0.05). Women with advanced maternal age and those who experienced preterm delivery had an increased risk for AUR. The peak incidence of AUR in normal pregnancies occurred between the 9th and 16th gestational weeks. Urogenital infection, gestational diabetes mellitus, previous abortion, abnormal pelvis, disproportion, and endometriosis were associated with AUR in women who underwent a normal delivery.

 

 

 

 

PLoS One. 2016 Apr 5;11(4):

An Exploratory Study into Objective and Reported Characteristics of Neuropathic Pain in Women with Chronic Pelvic Pain.

Whitaker LH1Reid J2Choa A2McFee S2Seretny M3Wilson J3Elton RA4Vincent K5Horne AW1.

 

Abstract

Chronic pelvic pain (CPP) affects 5.7-26.6% women worldwide. 55% have no obvious pathology and 40% have associated endometriosis. Neuropathic pain (NeP) is pain arising as a consequence of a lesion/disease affecting the somatosensory system. The prevalence of NeP in women with CPP is not known. The diagnosis of NeP is challenging because there is no gold-standard assessment. Questionnaires have been used in the clinical setting to diagnose NeP in other chronic pain conditions and quantitative sensory testing (QST) has been used in a research setting to identify abnormal sensory function. We aimed to determine if women with chronic pelvic pain (CPP) have a neuropathic pain (NeP) component to their painful symptoms and how this is best assessed. We performed an exploratory prospective cohort study of 72 pre-menopausal women with a diagnosis of CPP. They underwent a clinician completed questionnaire (DN4) and completed the S-LANSS and PainDETECT™ questionnaires. Additionally QST testing was performed by a clinician. They also completed a patient acceptability questionnaire. Clinical features of NeP were identified by both questionnaires and QST. Of the women who were NeP positive, 56%, 35% and 26% were identified by the S-LANSS, DN4 and PainDETECT™ respectively. When NeP was identified by questionnaire, the associated laparoscopy findings were similar irrespective of which questionnaire was used. No subject had entirely unchanged QST parameters. There were distinct loss and gain subgroups, as well as mixed alteration in function, but this was not necessarily clinically significant in all patients. 80% of patients were confident that questionnaires could diagnose NeP, and 90% found them easy to complete. Early identification of NeP in women with CPP with a simple questionnaire could facilitate targeted therapy with neuromodulators, which are cheap, readily available, and have good safety profiles. This approach could prevent unnecessary or fertility-compromising surgery and prolonged treatment with hormones.

 

 

 

J Pathog. 2016;2016:4698314.

Antibiotic Prophylaxis for Gynecologic Procedures prior to and during the Utilization of Assisted Reproductive Technologies: A Systematic Review.

Pereira N1Hutchinson AP2Lekovich JP1Hobeika E3Elias RT1.

 

Abstract

The use of assisted reproductive technologies (ART) has increased steadily. There has been a corresponding increase in the number of ART-related procedures such as hysterosalpingography (HSG), saline infusion sonography (SIS), hysteroscopy, laparoscopy, oocyte retrieval, and embryo transfer (ET). While performing these procedures, the abdomen, upper vagina, and endocervix are breached, leading to the possibility of seeding pelvic structures with microorganisms. Antibiotic prophylaxis is therefore important to prevent or treat any procedure-related infections. After careful review of the published literature, it is evident that routine antibiotic prophylaxis is generally not recommended for the majority of ART-related procedures. For transcervical procedures such as HSG, SIS, hysteroscopy, ET, and chromotubation, patients at risk for pelvic infections should be screened and treated prior to the procedure. Patients with a history of pelvic inflammatory disease (PID) or dilated fallopian tubes are at high risk for postprocedural infections and should be given antibiotic prophylaxis during procedures such as HSG, SIS, or chromotubation. Antibiotic prophylaxis is recommended prior to oocyte retrieval in patients with a history of endometriosis, PID, ruptured appendicitis, or multiple prior pelvic surgeries.

 

 

Clin Exp Obstet Gynecol. 2016;43(1):25-30.

The effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in the first SCID-mouse endometriosis-model developed in Turkey.

Yesildaglar NYildirim GYildirim OKAttar ROzkan FAkkaya HYilmaz B.

 

Abstract

OBJECTIVE:

To evaluate the effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in SCID mice.

MATERIALS AND METHODS:

Prospective, randomized, controlled, experimental study. Experimental Research Center of Yeditepe University (YUDETAM). Thirty female, non-pregnant, nulligravid severe combined immunodeficient (SCID) mice. Endometriotic cells collected from patients with endometriosis were implanted subcutaneously in 30 SCID mice. These mice were randomized into two study groups: in the first group, mice were administered melatonin (20 mg/kg/day) following induction of endometriosis for four weeks; in the second group, nothing was administered. All the mice were given a high dose of exogenous estradiol (50 µg/kg/d, twice weekly). Four weeks after inoculation, necropsies were performed and endometriotic lesions were collected. All the lesions were evaluated histopathologically and the levels of SOD and MDA were assessed in the lesions.

RESULTS:

Successful implantation was observed in the 28 mice that survived. Mean MDA level was 5.0 ± 1.7 and 8.8 ± 2.6 in the melatonin and control groups, respectively (p = 0.01); mean SOD level was 1.1 ± 0.1 and 1.0 ± 0.1 in the melatonin and control groups, respectively (p = 0.49). Mean histopathological score was lower in the melatonin group (p = 0.04).

CONCLUSIONS:

Melatonin was effective in the treatment of experimental endometriosis induced in SCID mice.

 

 

Clin Exp Obstet Gynecol. 2016;43(1):31-6.

Laparoscopic surgery improves pregnancy outcomes in women with suspected endometriosis with or without pathological confirmation.

Miller PBSavaris RFForstein DALikes CENichols CCooper LJLessey BA.

 

Abstract

PURPOSE OF THE INVESTIGATION:

To verify whether histologic confirmation of endometriosis impacts fertility outcomes.

MATERIALS AND METHODS:

Women with unexplained infertility (UI) underwent laparoscopic excision or ablation with CO2 laser or electrocautery of all suspected endometriotic lesions, followed by clinical treatment between January 2007 and December 2013; pregnancy (> 12 weeks) within 12 months of monitored cycles was the main outcome measured.

RESULTS:

Women with histological confirmation (n = 74) did not differ from those not confirmed (n = 29) with age, body mass index, gravidity, parity, ovulation induction protocol, and past duration of infertility. Pregnancy outcome was similar in both groups (39/74 vs. 15/29-p = 0.9–Chi-square) and there was no statistical difference in time to conceive/deliver (p = 0.7) between groups.

CONCLUSIONS:

There is no difference in fertility outcomes in women with UI, whether or not suspected endometriosis is confirmed pathologically.

 

 

 

 

Clin Exp Obstet Gynecol. 2016;43(1):75-81.

Expression and significance of ERβ and TrkB in endometriosis.

Yu XRen HLiu TYong MZhong H.

 

Abstract

OBJECTIVES:

To study the potential pathogenesis of endometriosis (EMs) in an area of estrogen receptors (ERs) and tyrosine kinase receptor type B (TrkB) expressions in tissues from patients with EMs.

STUDY DESIGN:

The authors examined the expressions of ERα, ERβ, TrkB, brain-derived neurotrophic factor (BDNF), and SGPL1 in tissues with EMs, using real-time PCR, western blot, and immunohistochemistry.

RESULTS:

ERα and SGPL1 were mainly expressed in eutopic endometrium than that in ectopic endometrium of patients with ovarian endometriosis (p < 0.05), while ERβ, BDNF, and TrkB were adverse, mainly detected in ectopic endometrium of the same patients with EMs (p < 0.01 and p < 0.05 ) by real-time PCR and western blot. ERβ, ERα, TrkB, and SGPL1 proteins were mainly expressed in eutopic endometrium of proliferative phase with EMs than that in eutopic endometrium of secretory phase (p < 0.05 ). TrkB, BDNF, and SGPL1 were not found in endometrium of proliferative or secretory phase in control group.

CONCLUSIONS:

ERβ expressed in cytoplasm may mediate pathogenesis of EMs.

 

 

Clin Exp Obstet Gynecol. 2016;43(1):112-3.

Increased tissue permeability and sympathetic nervous system hypofunction may be the common link between dysmenorrhea, chronic pelvic pain, Mittelschmerz, and Crohn’s disease.

Check JH.

 

Abstract

PURPOSE:

To determine if severe periovulatory diarrhea in a woman with Crohn’s disease for just one day may be related to increased permeability of the large bowel related to hormonal changes that occur at this time of menstrual cycle.

MATERIALS AND METHODS:

Dextroamphetamine sulfate was given to a woman whose Crohn’s disease was markedly improved by adalimumab but who still had one day of severe diarrhea at mid-cycle.

RESULTS:

She did not have any diarrhea or frequent defecation for the first two periovulatory times before she achieved pregnancy. Previously for two years there had not been one month where she did not have the severe periovulatory diarrhea.

CONCLUSIONS:

This case helps support the concept that the classic symptoms of Mittelschmerz in women with endometriosis may be related to periovulatory events which either cause increased permeability of an already compromised tissue, whether it be pelvic or bowel or other tissues, or these periovulatory events impair sympathetic nervous system function, which is already impaired.

 

 

 

Eur J Gynaecol Oncol. 2016;37(1):89-94.

Possible relevance of tumor-related genes mutation to malignant transformation of endometriosis.

Ma XHui YLin LWu YZhang XQin X.

 

Abstract

OBJECTIVE:

Despite studies have suggested that endometriosis has malignant potential, the molecular mechanism underlying the malignant transformation of endometriosis is poorly understood so far. Endometriosis-associated ovarian cancer (EAOC) or ovarian cancer arising from endometriosis (OCEM) may provide an ideal model for genetic studies. To investigate the genetic alterations during transformation of ovarian endometriosis into cancer, the authors analysed mutations of tumour-related genes (PTEN and p53) in EAOC cases (n=23, group 1), including 19 cases which were detected co-existence of endometriosis and cancer and four cases which fulfilled the histological criteria in malignant transformation of endometriosis (OCEMs), and in atypical hyperplasia ovarian endometriosis (aEMs) (n = 10, group 2), as well as in solitary ovarian endometriosis (EMs) (n = 20, group 3), simultaneously, to study the correlation of the two genes in the development and progression of the ovarian endometriosis malignancy.

MATERIALS AND METHODS:

Each paraffin block was sliced into serial ten-µm-thick sections. Extracted DNA was amplified by nested PCR. Mutations of PTEN and p53 were examined by bidirectional DNA sequencing.

RESULTS:

It was acknowledged by experiments that the PTEN and p53 mutation frequency in EAOCs were significantly higher than that in aEMs and EMs. There was significant difference to compare EAOCs with EMs (p < 0.01, p < 0.05), and converse to compare with aEMs (p > 0.05), respectively. No definite involvement between the frequency of PTEN and p53 mutations in EAOCs and age difference, histological type, clinical stage, pathological grade, and whether accompanied by metastasis (p > 0.05); however, a decreasing trend of PTEN mutation with the increased age, decreased clinical stage and pathological grade, and when accompanied by metastasis was detected. Adversely, an increasing trend of p53 mutation was represented. In EAOCs group, the authors detected eight PTEN and four p53 mutation events, respectively. Moreover, one case occurred PTEN and p53 mutation simultaneously. With 23 EAOCs, two cases which fulfilled the histological criteria in malignant transformation of endometriosis, which may be a specific entity distinct from non-endometriosis-associated ovarian cancer, the authors named them the OCEMs, occurred PTEN or p53 mutation, respectively.

CONCLUSION:

The present study suggested that the mutation and functional incapacitation of certain tumor-related genes may be involved in malignant transformation of endometriosis. PTEN mutation is the pristine event, but p53 mutation is the late.

 

 

 

J Biol Regul Homeost Agents. 2016 Jan-Mar;30(1):31-40.

The role of NADPH-derived reactive oxygen species production in the pathogenesis of endometriosis: a novel mechanistic approach.

Nassif J1Abbasi SA1Nassar A1Abu-Musa A1Eid AA2.

 

Abstract

Endometriosis is defined as endometriotic tissue growing outside the uterine cavity. It is a common gynecological disorder in women of reproductive age and is associated with chronic pelvic pain and infertility. Despite several studies and theories to explain its cause, the exact pathogenesis of endometriosis remains unclear. Retrograde menstruation is the most plausible theory, however, it is not exclusive. The disparity between the actual prevalence of retrograde menstruation and the prevalence of endometriosis suggests that other factors may determine the susceptibility to endometriosis development. Oxidative stress has been associated with endometriosis. This study aimed to explore the role of NADPH oxidase family in the production of reactive oxygen species (ROS) and to determine whether ROS induce the proliferation of endometriotic implants via mammalian target of rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected from women undergoing laparoscopy for endometriosis. The samples were stained with dihydroethidium and fluorescent images of the slides were taken to detect ROS production. After extraction of RNA from the samples and c-DNA generation, quantitative real-time PCR, protein extraction and Western blot were performed to study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and fibronectin. The results showed an increase in ROS levels and NOX 1 gene and protein expression in the endometriotic tissues compared to the normal surrounding tissue control. Also, mTOR and fibronectin, gene expression was found to be increased. Up regulation of NOX at gene and protein level leads to increased production of ROS in the endometriotic tissue, which in turn causes proliferation of the ectopic tissue via alteration of the mTOR signaling pathway. Increased fibronectin gene expression points towards tissue injury in endometriosis as compared to the normal surrounding tissue. This manuscript adds a new insight into the pathogenesis of endometriosis and serves as a background for development of new treatments for the disease-associated pain and infertility.

 

 

J Biol Regul Homeost Agents. 2016 Jan-Mar;30(1):211-7.

Ultrasound diagnosis in gynecological acute abdomen.

Wu J1Cui SH2Li HZ1Li QH1Yuan R1Zhang YP1Zhao TW3.

 

Abstract

As ultrasound diagnosis is applied more frequently in gynecological acute abdomen, we carried out this study to discuss the diagnosis of endometriosis with ultrasound imaging and analyze the efficacy of microRNA used for diagnosing endometriosis and evaluating prognosis by comparing differentially expressed microRNA in subjects with or without endometriosis. Ultrasound examination results and clinical pathological examination results of 60 cases of gynecological acute abdomen were compared. Blood samples were collected from patients with endometriosis. Of 60 cases, 38 cases recurred in 20 months after surgery and the remaining 22 cases had no recurrence in the 30-month follow-up. Additionally, blood was collected from 40 patients without endometriosis as control. Then total RNA was extracted from these blood samples to determine the difference of expression of microRNA (miR-17-5p, miR-20a, miR-199a and miR-141). Compared to healthy subjects, the endometriosispatients showed significantly increased expression of miR-199a, but the expression of miR-17-5p, miR-20a and miR-141 had an obvious decrease; the differences were statistically significant (p less than 0.01). For recurred cases, miR-199 showed a remarkably high expression and miR-17-5p and miR-20a expressed significantly low.

 

 

 

Ann Anat. 2016 Jul;206:1-6.

Altered expression of progesterone receptor isoforms A and B in human eutopic endometrium in endometriosis patients.

Wölfler MM1Küppers M2Rath W3Buck VU2Meinhold-Heerlein I3Classen-Linke I4.

 

Abstract

Recent data implicate an altered expression of progesterone receptor isoform A (PR-A) and B (PR-B) in the endometrium of endometriosis patients. This prospective exploratory study aimed to precisely determine the PR-A and PR-B expression using immunohistochemical techniques in eutopic endometrium of women with endometriosis compared with disease-free women throughout the menstrual cycle. All symptomatic patients underwent laparoscopy for the diagnosis of endometriosis and histological confirmation of the disease (EO) whereas controls were proven disease-free (CO). In CO samples (n=10) an increased expression of PR-A and PR-B during the proliferative to early secretory phase and a decreased expression of both receptor isoforms during the mid to late secretory phase was ascertained in accordance with previous studies. In patients with endometriosis(n=16) no cycle dependent pattern of PR-A and PR-B expression was identified in contrast to patients without endometriosis. Moreover, in EO samples a huge variety of inter- and intra-individual differences in PR-A and PR-B expression were detected. These data provide further evidence that dysregulation of the PR-A and PR-B expression might contribute to the pathophysiology of endometriosis.

 

 

Int J Gynecol Cancer. 2016 Jun;26(5):825-32.

BAF250a Expression in Atypical Endometriosis and Endometriosis-Associated Ovarian Cancer.

Stamp JP1Gilks CBWesseling MEshragh SCeballos KAnglesio MSKwon JSTone AHuntsman DGCarey MS.

 

Abstract

BACKGROUND AND OBJECTIVE:

Atypical endometriosis (AE) is thought to be a precursor lesion to the ovarian cancer subtypes associated with endometriosis, namely, endometrioid and clear cell carcinomas. ARID1A encodes a nuclear protein (BAF250a) governing chromatin remodeling, and mutations in ARID1A have been found in 30% to 50% of clear cell and endometrioid ovarian cancers. As BAF250a expression loss by immunohistochemistry (IHC) has been documented in the endometriosis precursor lesions closely associated with these ovarian cancers subtypes, our goal was to further study the association between BAF250a expression in cases of AE with and without an associated cancer.

METHODS:

Three separate databases were screened for suspected cases of AE. Based on a detailed review of the pathology reports, we selected cases likely to contain AE for slide review. After slide review, tissue blocks were recalled to perform IHC for BAF250a in the associated cancer, AE, or typical endometriosis when present.

RESULTS:

There were 35 cases of endometriosis-associated cancer and 8 cases of AE not associated with cancer. Atypical endometriosis was found on pathology review in 23 endometriosis-associated cancer cases (66%). In the 35 cancer cases, BAF250a IHC showed loss of expression in 14 cases. Atypical endometriosis was present in 10 of these cases, 6 of which showed BAF250a loss (60%). BAF250a loss was not observed in the 8 cases of AE not associated with cancer or in the contiguous AE of 13 cases, whereby BAF250a expression was retained in the associated cancer.

CONCLUSIONS:

BAF250a loss in AE is consistently associated with the development of BAF250a-negative endometriosis-associated cancers and appears to be an early event in most of these cases. This research provides additional evidence that in the absence of cancer, BAF250a expression should be evaluated as a biomarker of cancer risk in patients diagnosed with AE.

 

 

Arch Gynecol Obstet. 2016 Jul;294(1):201-7.

Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis.

Zheng Q1Mao H1Xu Y1Zhao J1Wei X1Liu P2.

 

Abstract

PURPOSE:

To investigate whether postoperative GnRH agonist (GnRH-a) treatment can prevent endometriosisrecurrence.

METHODS:

This meta-analysis searched PubMed, Embase and Cochrane Library for relevant studies published online before June 2015. Seven randomized controlled trials including 328 patients with postoperative GnRH-a treatment and 394 patients in control group were included in the meta-analysis. In the meta-analysis, the recurrence rate of GnRH-a group compared with control group was evaluated with odds ratio (OR) and its 95 % confidence interval (CI). Heterogeneity, small study effect and publication bias were, respectively, assessed using Higgins I (2), sensitivity analysis and funnel plot.

RESULTS:

Postoperative GnRH-a treatment for endometriosis (pooled OR = 0.71; 95 % CI 0.52-0.96) was superior to expectant or placebo treatment in prevention of the recurrence. The recurrence rate decreased significantly in patients who received 6 months GnRH-a treatment (pooled OR = 0.59, 95 % CI 0.38-0.90), whereas no significant difference of recurrence rate existed between patients with 3 months post-surgical GnRH-a therapy and the control group (pooled OR = 0.87, 95 % CI 0.56-1.34). No significant heterogeneity and small study effect were found in the meta-analysis. However, publication bias did existed in the present meta-analysis.

CONCLUSIONS:

Longer-term (6 months) postoperative administration of GnRH-a can decrease the recurrence risk of endometriosis, whereas 3 months duration of GnRH-a therapy makes no significant difference in preventing the recurrence of endometriosis. Therefore, instead of a 3 month therapy, the duration of the postoperative administration should be longer enough (6 months) to prevent the recurrence of endometriosis.

 

 

Fertil Steril. 2016 Jun;105(6):1381-93.

Complete evaluation of anatomy and morphology of the infertile patient in a single visit; the modern infertility pelvic ultrasound examination.

Groszmann YS1Benacerraf BR2.

 

Abstract

The comprehensive “one-stop shop” ultrasound evaluation of an infertile woman, performed around cycle days 5 to 9, will reveal abundant information about the anatomy and morphology of the pelvic organs and thereby avoid costly radiation and iodinated contrast exposure. We propose a two-dimensional and three-dimensional ultrasound to examine the appearance and shape of the endometrium, endometrial cavity, myometrium, and junctional zone, to assess for müllerian duct anomalies fibroids, adenomyosis, and polyps. We then evaluate the adnexa with grayscale ultrasound and Doppler, looking for ovarian masses or cysts, and signs of tubal disease. The cul-de-sac is imaged to look for masses, endometriosis, and free fluid. We then push gently on the uterus and ovaries to assess mobility. Lack of free movement of the organs would suggest adhesions or endometriosis. The sonohysterogram then allows for more detailed evaluation of the endometrial cavity, endometrial lining, and any intracavitary lesions. Tubal patency is then assessed during the sonohysterogram in real time by introducing air and saline or contrast and imaging the tubes (HyCoSy). With this single comprehensive ultrasound examination, patients can obtain a reliable, time-efficient, minimally invasive infertility evaluation in their own clinician’s office at significantly less cost and without radiation.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Jun;201:46-50.

Fertility outcome after laparoscopic treatment of advanced endometriosis in two groups of infertile patients with and without ovarian endometrioma.

Shervin A1Mohazzab A2Aminlou M3Kamali K4Padmehr R3Shadjoo K3Jaberi-Pour P3Akbari E5.

 

Abstract

OBJECTIVE:

To evaluate the result of laparoscopic endometrioma excision in fertility outcome of advanced endometriosis patients.

STUDY DESIGN:

The study was designated as historical cohort, in a private referral center of advance laparoscopy. 111 infertile patients, diagnosed as endometriosis, were divided in two groups: DIE (deep infiltrative endometriosis) and endometrioma (case group), and patients with only DIE (without endometrioma ((control group). All patients underwent global laparoscopic resection of DIE lesion (both groups) and laparoscopic excisional cystectomy of endometrioma (case groups). Patients were followed for fertility outcomes and data were analyzed by Kaplan-Meier test and COX regression using SPSS software.

RESULTS:

After adjusting covariates, the Kaplan-Meier analysis of cumulative pregnancy rates (CPR) did not show any statistical significance between cases (35.6%) and controls (39.5%) (Log-rank P-value=0.959). The COX regression analysis of covariates showed there is no significant relationship between cystectomy and fertility outcome. It showed statistical significance effect of age (hazard ratio [HR]=0.772), years of infertility (HR=0.224), and previous endometrioma surgery (HR=0.180), on fertility chance.

CONCLUSION:

In advanced endometriosis with DIE and infertility, fine excision and stripping of the endometrioma along with radical resection of DIE improves fecundity without any significant adverse effect in comparison with patients with intact ovaries.

 

 

 

PLoS Genet. 2016 Apr 7;12(4):e1005893.

Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.

Nakaoka H1Gurumurthy A1Hayano T1Ahmadloo S1Omer WH1Yoshihara K2Yamamoto A3Kurose K3Enomoto T2Akira S3Hosomichi K1,4Inoue I1.

 

Abstract

Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage.

 

 

Case Rep Obstet Gynecol. 2016;2016:2713943.

Cystic Endometriosis in a Huge Degenerated Subserous Leiomyoma Mimicking Bilateral Multicystic Endometriomas in an Infertile Woman with Diminished Ovarian Reserve: A Rare Endometriotic Implantation.

Hatirnaz S1Colak S2Reis A3.

 

Abstract

Uterine leiomyomas are the most common pelvic tumor in women. Leiomyoma can show atypical locations and degenerations and may not be easily differentiated from adnexal masses. Uterine leiomyoma can undergo cystic degeneration and is said to be found in 4% of all types of degenerations. The commonest type of degeneration is hyaline seen in 60% of patients. Usually uterine leiomyoma does not present as clinical and radiological diagnostic challenge. However, when leiomyoma undergoes massive cystic degeneration they may become clinical and radiological diagnostic dilemmas. The MRI showed a huge cystic mass protruding up to the pelvis not differentiated from bilateral endometriomas and accompanying subserous myomas. Surgery revealed that the mass is not bilateral endometriomas but a huge pedunculated leiomyoma with cystic degeneration and cystic endometriosis. Endometriosis is a troubling gynecologic condition occurring in 10% to 15% of women of reproductive age and is associated with fertility problems. As a peritoneal disease, the locations of endometriotic lesions are predominantly the ovaries (96.4%), followed by the soft tissue (2.8%), gastrointestinal tract (0.3%), and urinary tract (0.2%) and other rare locations. The presented case is multiple sized cystic endometriosis (endometriomas) located in a huge pedunculated subserous leiomyoma in an infertile woman having a history of laparoscopic bilateral endometrioma surgery. Conclusion. To our knowledge, this is the first reported case for endometriotic cysts (endometriomas) located in a huge cystic degenerated leiomyoma. PubMed search revealed no report concerning endometriotic implantation in the leiomyomas.

 

 

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):787-92

Lymph Node Involvement in Deep Infiltrating Intestinal Endometriosis: Does It Really Mean Anything?

Rossini R1Monsellato D2Bertolaccini L2Pesci A3Zamboni G3Ceccaroni M4Ruffo G2.

 

Abstract

STUDY OBJECTIVE:

To review our data for any correlation between the severity of endometriosis and lymph node involvement.

DESIGN:

Observational study with control (Canadian Task Force classification III).

SETTING:

Public medical center.

PATIENTS:

All women who underwent laparoscopic segmental rectal resection for endometriosis at our institution (Sacro Cuore Negrar Hospital) between 2000 and 2010.

INTERVENTIONS:

We retrospectively included 140 cases of colorectal surgery for intestinal endometriosisperformed between 2004 and 2010 in our institution. Based on histopathological analysis of specimens, we divided our population into 2 groups: 70 patients with lymph node involvement and 70 patients without lymph node involvement.

MEASUREMENTS AND MAIN RESULTS:

No statistical correlation was found between the positivity of lymph nodes and the rate of intestinal stenosis, the histopathological specimen infiltration rate and depth and the intestinal recurrence rate. Only a poor correlation was found with preoperative CA-125 serous levels.

CONCLUSION:

The presence of lymph nodes involvement in intestinal resection specimens does not modify the natural history of the disease. The reason of its presence still has to be determined.

 

 

Fertil Steril. 2016 Jul;106(1):164-171.

Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database.

Senapati S1Sammel MD2Morse C3Barnhart KT4.

 

Abstract

OBJECTIVE:

To assess the impact of endometriosis, alone or in combination with other infertility diagnoses, on IVF outcomes.

DESIGN:

Population-based retrospective cohort study of cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.

SETTING:

Not applicable.

PATIENT(S):

A total of 347,185 autologous fresh and frozen assisted reproductive technology cycles from the period 2008-2010.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Oocyte yield, implantation rate, live birth rate.

RESULT(S):

Although cycles of patients with endometriosis constituted 11% of the study sample, the majority (64%) reported a concomitant diagnosis, with male factor (42%), tubal factor (29%), and diminished ovarian reserve (22%) being the most common. Endometriosis, when isolated or with concomitant diagnoses, was associated with lower oocyte yield compared with those with unexplained infertility, tubal factor, and all other infertility diagnoses combined. Women with isolated endometriosis had similar or higher live birth rates compared with those in other diagnostic groups. However, women with endometriosis with concomitant diagnoses had lower implantation rates and live birth rates compared with unexplained infertility, tubal factor, and all other diagnostic groups.

CONCLUSION(S):

Endometriosis is associated with lower oocyte yield, lower implantation rates, and lower pregnancy rates after IVF. However, the association of endometriosis and IVF outcomes is confounded by other infertility diagnoses. Endometriosis, when associated with other alterations in the reproductive tract, has the lowest chance of live birth. In contrast, for the minority of women who have endometriosis in isolation, the live birth rate is similar or slightly higher compared with other infertility diagnoses.

 

 

Ultrasound Obstet Gynecol. 2017 Apr;49(4):524-532.

Magnetic resonance enema vs rectal water-contrast transvaginal sonography in diagnosis of rectosigmoid endometriosis.

Leone Roberti Maggiore U1,2Biscaldi E3Vellone VG4Venturini PL1,2Ferrero S1,2.

 

Abstract

OBJECTIVE:

To compare the accuracy of magnetic resonance enema (MR-e) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis.

METHODS:

This prospective study included 286 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent MR-e and RWC-TVS before laparoscopic excision of endometriotic lesions. The findings of MR-e and RWC-TVS were compared with surgical and histological results.

RESULTS:

Of the 286 patients included in the study, 151 (52.8%) had rectosigmoid endometriosis. MR-e and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.063). In the diagnosis of rectosigmoid endometriosis with MR-e, the sensitivity was 95.4% (95% CI, 90.7-99.1%), specificity was 97.8% (95% CI, 93.6-99.5%), positive predictive value (PPV) was 98.0% (95% CI, 94.1-99.6%), negative predictive value (NPV) was 95.0% (95% CI, 89.9-97.9%), positive likelihood ratio (LR+) was 42.91 (95% CI, 14.01-131.46) and negative likelihood ratio (LR-) was 0.05 (95% CI, 0.02-0.10). For diagnosis with RWC-TVS, sensitivity was 92.7% (95% CI, 87.3-96.3%), specificity was 97.0% (95% CI, 92.6-99.2%), PPV was 97.2% (95% CI, 93.0-99.2%), NPV was 92.3% (95% CI, 86.6-96.1%), LR+ was 31.29 (95% CI, 11.90-82.25) and LR- was 0.08 (95% CI, 0.04-0.13). MR-e and RWC-TVS underestimated the size of the endometriotic nodules; for both imaging techniques the underestimation was greater for nodules with a diameter ≥ 30 mm. There was no significant difference in the mean intensity of pain experienced by the patients during the two examinations.

CONCLUSIONS:

RWC-TVS should be the first-line investigation in patients with clinical suspicion of rectosigmoid endometriosis and physicians should be trained in performing this examination. Considering that MR-e is more expensive than RWC-TVS, it should be used only when the findings of RWC-TVS are unclear. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

 

 

Reprod Biol Endocrinol. 2016 Apr 9;14:17

Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis.

Sun Q1Ding D2Liu X2,3Guo SW4,5.

 

Abstract

BACKGROUND:

Growing evidence indicates that endometriosis is an epigenetic disease. Encouragingly, histone deacetylases (HDACs) and DNA methyltransferases have been shown to be promising targets by numerous in vitro studies. However, only a few studies have shown promising effects of HDAC inhibition in preclinical studies in endometriosis. While lysine-specific demethylase 1 (LSD1) is recently found to be aberrantly expressed in endometriosis, and that the treatment of endometriotic stromal cells with tranylcypromine (TC), an LSD1 inhibitor, significantly reduced cellular proliferation, cell cycle progression, and invasiveness, the in vivo effect of TC treatment is currently lacking. This study sought to evaluate the effect of TC in a mouse model of endometriosis.

METHODS:

Forty-seven female C57BL/6 mice were used in this experimentation. All mice, except those randomly selected to form Sham surgery (M) and specificity control (S) groups, received an endometriosis-inducing surgery. Group S was set up mainly to ensure that the reduced generalized hyperalgesia in mice treated with TC is not due to any possible analgesic effect of TC, but rather resulting from the treatment effect specific to endometriosis. Two weeks after the surgery, mice that received surgery were further divided randomly into 3 groups: 1) untreated group (U); 2) low-dose TC group (L); 3) high-dose TC group (H). Group S received the same treatment as in group H. Two weeks after treatment, all mice were sacrificed and their ectopic endometrial tissues were harvested and analyzed by immunohistochemistry analysis. Hotplate test was administrated to all mice before the induction, treatment and sacrifice. Lesion size, hotplate latency, immunoreactivity against markers of proliferation, angiogenesis, H3K4 methylation, and of epithelial-mesenchymal transition (EMT).

RESULTS:

TC treatment significantly and substantially reduced the lesion size and improved generalized hyperalgesia in a dose-dependent fashion in mice with induced endometriosis. In addition, TC treatment resulted in reduced immunoreactivity to biomarkers of proliferation, angiogenesis, and H3K4 methylation, leading to arrested EMT and lesion growth.

CONCLUSION:

In light of our previously reported reduced cellular proliferation, cell cycle progression and invasiveness resulting from the LSD1 inhibition in in vitro studies, our data strongly suggest that LSD1 is a promising therapeutic target for endometriosis.

 

 

Gan To Kagaku Ryoho. 2016 Mar;43(3):286-9.

Paradigm Shift in Ovarian Tumor Pathology from the View of Genomic Abnormalities.

Mikami Y1.

 

Abstract

A decade of accumulated evidence has led to significant progress and a paradigm shift in ovarian tumor pathology. Now, ovarian carcinoma is widely recognized as a heterogeneous group of neoplasms with regard to histogenesis and underlying molecular mechanisms. Ovarian carcinoma is, therefore, divided into 2 clinicopathologic groups: type 1 and type 2 tumors. Type 1 tumors arise in association with benign neoplastic conditions (adenoma-carcinoma sequence). They include endometriosis-related ovarian neoplasias, such as clear cell carcinoma and low-grade endometrioid carcinoma, which are derived from atypical endometriosis or adenofibroma, as well as mucinous carcinoma and low-grade serous carcinoma, which are commonly associated with mucinous and serous borderline tumors, respectively. In contrast, type 2 tumors, which arise de novo directly from the normal epithelium, include high-grade serous and endometrioid carcinoma, carcinosarcoma, and undifferentiated carcinoma. Notably, the hypothesis that most high-grade serous ovarian carcinoma is not of ovarian origin and, rather, is associated with serous tubal intraepithelial carcinoma (STIC), which is mostly found on the fimbrial end of the fallopian tube in up to 70% of cases of high-grade serous carcinoma, is universally accepted. Understanding ovarian carcinoma molecular pathogenesis should aid in developing effective therapeutic strategies for these particular tumors.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:77-80.

Postoperative hormonal therapy after surgical excision of deep endometriosis.

Somigliana E1Busnelli A2Benaglia L3Viganò P4Leonardi M3Paffoni A3Vercellini P2.

 

Abstract

The clinical management of women with deep peritoneal endometriosis remains controversial. The debate focuses mainly on the precise role of hormonal medical treatment and surgery and on the most suitable surgical technique to be used. In particular, considering the risks of second-line surgery, prevention of recurrences after first-line surgery is a priority in this context. Post-surgical medical therapy has been advocated to improve the effectiveness of surgery and prevent recurrences. However, adjuvant therapy, i.e. a short course of 3-6 months of hormonal therapy after surgery, has been proven to be of limited or no benefit for endometriosis in general and for deep peritoneal endometriosis in particular. On the other hand, two cohort studies suggest a beneficial effect of prolonged hormonal therapy after surgery for deep endometriosis. Even if this evidence is too weak to confidently advocate systematic administration of prolonged medical therapy after surgery, we argue in favour of this approach because of the strong association of deep endometriosis with other disease forms. In fact, women operated on for deep endometriosis may also face recurrences of endometriomas, superficial peritoneal lesions and pelvic pain in general. The demonstrated high effectiveness of prolonged postoperative therapy for the prevention of endometriomas’ formation and dysmenorrhea recurrence should thus receive utmost consideration in the decision-making process.

 

 

Reprod Biomed Online. 2016 Jun;32(6):626-34.

Adverse pregnancy and neo-natal outcomes after assisted reproductive treatment in patients with pelvic endometriosis: a case-control study.

Jacques M1Freour T2Barriere P2Ploteau S3.

 

Abstract

To assess the impact of endometriosis on obstetric outcomes and to determine whether the severity, location and surgical treatment of the disease before the pregnancy had an impact on the prevalence of these disorders, a monocentric, case-control study was performed. In total, 113 pregnancies obtained by assisted reproductive treatment among patients with endometriosis were matched with control selected among assisted reproductive treatment pregnancies due to male infertility. The main result measures were pregnancy outcome at the obstetrical and neo-natal levels. The incidence of first trimester bleeding, pre-eclampsia, premature delivery threat, pelvic pain and Caesarean section was significantly higher (P < 0.05) in women with endometriosis. Except for gestational diabetes and intrauterine growth restriction (IUGR), the severity, location of lesions and surgical treatment of endometriosis did not have an impact on either pregnancy outcome or risk of obstetric complications. The IUGR is mainly due to deep locations and the revised American Fertility Society (rAFS) stages III-IV. Newborns with a mother suffering from endometriosis are at greater risk of being premature, smaller for their gestational age and more frequently hospitalized than the control group. Deep location of endometriosis is associated with more prematurity, hospitalization and smaller birthweight than ovarian locations.

 

 

J Pain Res. 2016 Mar 24;9:157-65.

Is acupuncture effective in the treatment of pain in endometriosis?

Lund I1Lundeberg T2.

Abstract

INTRODUCTION:

Endometriosis is a multifactorial, estrogen-dependent, inflammatory gynecological condition – often with long-lasting visceral pelvic pain of different origin, and infertility among women. Current management options for patients’ are often inadequate, with side effects for many for whom acupuncture techniques could be an alternative. Earlier studies have discussed the efficacy of acupuncture, but not its methodological aspects.

OBJECTIVES:

To summarize the documented clinical effects of acupuncture on rated visceral pelvic endometriosis-related pain, and associated variables among individuals, within and between studied groups, and to discuss the methodological treatment aspects.

METHODS:

Published full text clinical studies, case reports, and observational studies with abstracts written in English were searched by using the keywords “Acupuncture and Endometriosis” in databases such as PubMed, Web of Science, and CINAHL. The reporting guidelines, Standards for Reporting Interventions in Clinical Trials of Acupuncture was used for the methodological report.

RESULTS:

Three studies were found including 99 women, 13-40 years old, with diagnosed endometriosis. The studies were different in research design, needle stimulation techniques, and evaluation instruments. Methodological similarities were seven to12 needle insertions per subject/session, and 15-25 minutes of needle retention time. The needles were placed in lower back/pelvic-abdominal area, in the shank, feet, and hands. Treatment numbers varied from nine to 16 and patients received one to two treatments per week. Similarity in reported treatment effects in the quoted studies, irrespective of research design or treatment technique, was reported decrease of rated pain intensity.

DISCUSSION:

Meta-analysis is the standard procedure for the evaluation of evidence of treatment effects, ie, on a group level, usually without analysis of the individual responses even with obvious spread in the results leading to lack of guidance for treatment of the individual patient. By conceptualizing pain as subjective, the individual aspect should serve as the basis for the analysis to allow clinical recommendations. From a physiological and a western medical perspective, acupuncture can be regarded as a type of sensory stimulation that induces changes in the function of the central nervous system that partly can explain the decrease of perceived pain in response to acupuncture treatment irrespective of the technique.

CONCLUSION:

Endometriosis is often painful, although with various origin, where standard treatments may be insufficient or involve side effects. Based on the reported studies, acupuncture could be tried as a complement as it is an overall safe treatment. In the future, studies designed for evaluating effectiveness between treatment strategies rather than efficacy design would be preferred as the analyses of treatment effects in the individual patients.

 

 

 

 

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