J Minim Invasive Gynecol. 2017 Oct 31. pii: S1553-4650(17)31264-5.

Coagulation-Induced Diaphragm Fenestrations after Laparoscopic Excision of Diaphragmatic Endometriosis.

Nirgianakis K¹, Lanz S², Imboden S², Worni M³, Mueller MD².

 

Abstract

STUDY OBJECTIVE:

To present an unusual consequence of laparoscopic treatment of diaphragmatic endometriosis, to discuss the possible etiologies, and to propose proper management.

DESIGN:

A step-by-step explanation of 2 surgeries of the same patient using intraoperative video sequences (Canadian Task Force classification III).

SETTING:

University hospital.

PATIENT:

A 32-year-old woman.

INTERVENTIONS:

Two Laparoscopic surgeries.

MEASUREMENTS AND MAIN RESULTS:

Endometriosis is estimated to affect 11% of the population [1,2], with an estimated 12% of these patients having extrapelvic endometriosis [3]. When the diaphragm is involved, the disease potentially causes severe and debilitating symptoms such as catamenial chest or shoulder pain. Serious complications may involve pneumothorax and hemopneumothorax [4-6]. Diaphragmatic endometriosis is more common than realized and has been shown to occur simultaneously in 50% to 80% of cases with pelvic endometriosis [7,8]. A 32-year-old woman was admitted to our hospital with severe disabling dysmenorrhea and right shoulder pain. Despite progestin, nonsteroidal anti-inflammatory drug, and opioid treatment, pain relief remained inadequate. A laparoscopy was performed revealing diaphragmatic endometriosis, which was completely excised. A revision was necessary 14 months later because of pain recurrence in the right hemithorax and suspicion of new or persistent endometriotic lesions. The laparoscopy revealed small diaphragm fenestrations that were closed after exclusion of recurrent diaphragmatic or pleural endometriosis. No chest tube was placed, and the postoperative course was uneventful. Hormonal suppressive treatment was continued. Since the operation the patient has been pain free. Institutional Review Board/Ethics Committee ruled that approval was not required for this study (Req-2017-00415).

CONCLUSION:

The diaphragm fenestrations were possibly the result of tissue necrosis caused by thermocoagulation after excision of deep endometriotic lesions during the first surgery. Using a CO₂ laser for the vaporization of superficial lesions is favorable because of the smaller depth of penetration compared with electrocautery and better access to hard to reach areas [9,10]. Endometriotic lesions involving the entire thickness of the diaphragm should be completely excised and the defect repaired with either sutures or staples [11-13].

 

 

 

J Minim Invasive Gynecol. 2017 Oct 31. pii: S1553-4650(17)31262-1.

Patterns of Bowel Invisible Microscopic Endometriosis Reveal the Goal of Surgery: Removal of Visual Lesions Only.

Badescu A¹, Roman H², Barsan I³, Soldea V⁴, Nastasia S⁵, Aziz M⁶, Puscasiu L⁷, Stolnicu S³.

 

Abstract

STUDY OBJECTIVE:

To document the presence of bowel invisible microscopic endometriosis implants and their relationship with deep endometriosis macronodule infiltrating the bowel.

DESIGN:

A series of consecutive patients with deep endometriosis infiltrating the rectum and/or sigmoid colon (Canadian Task Force classification II-2).

SETTINGS:

A university referral center.

PATIENTS:

Ten patients managed by colorectal resection.

INTERVENTIONS:

A microscopic study of endometriotic foci of the bowel involving 3272 microsection slides was established using a unique method of step serial sections using combined transverse and longitudinal macrosection. Two-dimensional reconstruction based on slide scanning highlighted the presence and localization of the deep endometriosis macronodule in contrast with bowel invisible microscopic endometriosis microimplants.

MEASUREMENTS AND MAIN RESULTS:

The distance separating the microimplants and the nodule and their histologic characteristics. The mean length of the colorectal specimens was 91 ± 19 mm. The maximum distance between the farthest microimplants was 7.2 cm. The maximum distance from the macroscopic nodule limit to the farthest microimplant was 31 mm. Bowel invisible microscopic endometriosis microimplants presented with similar features independently of the type of spread. They had an active appearance including stroma and glands, were sometimes decidualized, and were free of fibrosis. They were found on the distal/rectal limit of the specimen in 3 patients and on both limits (distal/rectal and proximal/sigmoid colon) in 1 patient.

CONCLUSION:

Invisible microscopic endometriosis implants surround the bowel macroscopic endometriosis nodule at variable distances, suggesting that complete surgical microscopic removal may be a challenging goal. These results may help to reconsider the principles and feasibility of the surgical management of bowel endometriosis.

 

 

 

J Gynecol Obstet Hum Reprod. 2018 Jan;47(1):1-7.

Management of deep infiltrating endometriosis of the rectum: Is a systematic temporary stoma relevant?

Ledu N¹, Rubod C², Piessen G³, Roman H⁴, Collinet P².

 

Abstract

STUDY OBJECTIVE:

To assess the value of performing a protective stoma in patients operated for rectal endometriosis.

MATERIAL AND METHODS:

From June 2009 to December 2011, 47 patients were operated for rectal endometriosis by segmental or discoid resection in 4 different centers. Two groups were formed: one with protective stoma (group S), n=33 and one without protective stoma (group NS), n=14. Data were collected from the CIRENDO database.

MEASUREMENTS AND MAIN RESULTS:

Postoperative complication rate of group NS was 57% against 48% in group S (P=0.75). There was an increasing trend of the rate of anastomotic leakage in group S as compared to group NS: 21% against 3% (P=0.073). All 3 patients of group NS with an anastomotic leakage were reoperated and the group S patient had medical treatment. In a center, digestive operative time was not necessarily performed in association with a gastrointestinal surgeon. All patients in group S had a restoration of continuity in about 3 months. Two of them had dilation of anastomotic stricture and 3 others showed a transient postoperative ileus during this recovery. Quality of life was assessed by the MOS SF-36 and significantly improved in both groups thanks to the intervention.

CONCLUSION:

Temporary digestive stoma in patients operated for rectal endometriosis has to be considered because in our study, it seems reducing complications such as anastomotic leakage. This must be confirmed with studies with larger numbers.

 

 

 

Biomed Res Int. 2017;2017:8967803.

Sonographic Signs of Adenomyosis Are Prevalent in Women Undergoing Surgery for Endometriosis and May Suggest a Higher Risk of Infertility.

Eisenberg VH^1,2, Arbib N^1,2, Schiff E^1,2, Goldenberg M^1,2, Seidman DS^1,2, Soriano D^1,2.

 

Abstract

OBJECTIVES:

To determine the prevalence of ultrasound features suggestive of adenomyosis in women undergoing surgery for endometriosis compared with a control group of healthy women without endometriosis.

METHODS:

Retrospective case-control study comparing women with intractable pain or infertility, who underwent transvaginal ultrasound and subsequent laparoscopic surgery, with a control group of healthy women without a previous history of endometriosis. A diagnosis of adenomyosis on TVUS was made based on asymmetrical myometrial thickening, linear striations, myometrial cysts, hyperechoic islands, irregular endometrial-myometrial junction, parallel shadowing, and localized adenomyomas and analyzed for one sign and for three or more signs.

RESULTS:

The study and control groups included 94 and 60 women, respectively. In the study group, women were younger and had more dysmenorrhea and infertility symptoms. The presence of any sonographic feature of adenomyosis, as well as three or more signs, was found to be more prevalent in the study group, which persisted after controlling for age, for all features but linear striations. Women in the study group who had five or more sonographic features of adenomyosis had more than a threefold risk of suffering from infertility (OR = 3.19, p = 0.015, 95% CI; 1.25-8.17). There was no association with disease severity at surgery.

CONCLUSIONS:

Sonographic features of adenomyosis are more prevalent in women undergoing surgery for endometriosis compared to healthy controls. Women with more than five features had an increased risk of infertility.

 

 

 

Epigenetics. 2017;12(10):897-908.

Variability of genome-wide DNA methylation and mRNA expression profiles in reproductive and endocrine disease related tissues.

Rahmioglu N¹, Drong AW¹, Lockstone H¹, Tapmeier T², Hellner K², Saare M³, Laisk-Podar T³, Dew C², Tough E², Nicholson G¹, Peters M³, Morris AP^1,4, Lindgren CM¹, Becker CM², Zondervan KT^1,2.

 

Abstract

Genome-wide association studies in the fields of reproductive medicine and endocrinology are yielding robust genetic variants associated with disease. Integrated genomic, transcriptomic, and epigenomic molecular profiling studies are common methodologies used to understand the biologic pathways perturbed by these variants. However, molecular profiling resources do not include the tissue most relevant to many female reproductive traits, the endometrium, while the parameters influencing variability of results from its molecular profiling are unclear. We investigated the sources of DNA methylation and RNA expression profile variability in endometrium (n = 135), endometriotic disease tissue (endometriosis), and subcutaneous abdominal fat samples from 24 women, quantifying between-individual, within-tissue (cellular heterogeneity), and technical variation. DNA samples (n = 96) were analyzed using Illumina HumanMethlylation450 BeadChip arrays; RNA samples (n = 39) were analyzed using H12-expression arrays. Variance-component analyses showed that, for the top 10-50% variable DNA methylation/RNA expression sites, between-individual variation far exceeded within-tissue and technical variation. Menstrual-phase accounted for most variability in methylation/expression patterns in endometrium (P_m = 7.8 × 10^-3, P_e = 8.4 × 10^-5) but not in fat and endometriotic tissue; age was significantly associated with DNA methylation profile of endometrium (P_m = 9 × 10^-5) and endometriotic disease tissue (P_m = 2.4 × 10^-5); and smoking was significantly associated with DNA methylation in adipose tissue (P_m = 1.8 × 10^-3). Hierarchical cluster analysis showed significantly different methylation signatures between endometrium and endometriotic tissue enriched for WNT signaling, angiogenesis, cadherin signaling, and gonadotropin-releasing-hormone-receptor pathways. Differential DNA methylation/expression analyses suggested detection of a limited number of sites with large fold changes (FC > 4), but power calculations accounting for different sources of variability showed that for robust detection >500 tissue samples are required. These results enable appropriate study design for large-scale expression and methylation tissue-based profiling relevant to many reproductive and endocrine traits.

 

 

 

Fertil Steril. 2017 Dec;108(6):872-885.e1.

Pathogenesis of deep endometriosis.

Gordts S¹, Koninckx P², Brosens I³.

 

Abstract

The pathophysiology of (deep) endometriosis is still unclear. As originally suggested by Cullen, change the definition “deeper than 5 mm” to “adenomyosis externa.” With the discovery of the old European literature on uterine bleeding in 5%-10% of the neonates and histologic evidence that the bleeding represents decidual shedding, it is postulated/hypothesized that endometrial stem/progenitor cells, implanted in the pelvic cavity after birth, may be at the origin of adolescent and even the occasionally premenarcheal pelvic endometriosis. Endometriosis in the adolescent is characterized by angiogenic and hemorrhagic peritoneal and ovarian lesions. The development of deep endometriosis at a later age suggests that deep infiltrating endometriosis is a delayed stage of endometriosis. Another hypothesis is that the endometriotic cell has undergone genetic or epigenetic changes and those specific changes determine the development into deep endometriosis. This is compatible with the hereditary aspects, and with the clonality of deep and cystic ovarian endometriosis. It explains the predisposition and an eventual causal effect by dioxin or radiation. Specific genetic/epigenetic changes could explain the various expressions and thus typical, cystic, and deep endometriosis become three different diseases. Subtle lesions are not a disease until epi(genetic) changes occur. A classification should reflect that deep endometriosis is a specific disease. In conclusion the pathophysiology of deep endometriosis remains debated and the mechanisms of disease progression, as well as the role of genetics and epigenetics in the process, still needs to be unraveled.

 

 

 

Reprod Biomed Online. 2018 Jan;36(1):84-87.

Comments on the ESHRE recommendations for the treatment of minimal endometriosis in infertile women.

Daniilidis A¹, Pados G².

 

Abstract

According to ESHRE recommendations for women with stage I/II endometriosis, if a decision is made to proceed to laparoscopy then operative laparoscopy (excision or ablation of the endometriotic lesions) should be performed rather than only diagnostic laparoscopy, to increase ongoing pregnancy rates. Also, for infertile women with stage I/II endometriosis doctors may consider complete surgical removal of endometriosis to improve live birth rate prior to assisted reproductive treatment. This last recommendation is not well established. Does laparoscopic treatment of minimal endometriosis increase the fertility of women with minimal endometriosis? Should we perform surgery in all cases of minimal endometriosis to improve reproductive outcomes prior to assisted reproductive treatment? The aim of this article is to present evidence on these two questions and comment on the ESHRE recommendations. Evidence is quite robust that laparoscopic destruction of minimal to mild endometriosis and associated adhesions enhances fecundity. On the other hand, to date no clear benefit has been demonstrated of performing laparoscopy for minimal endometriosis in women undergoing IVF/intracytoplasmic sperm injection, therefore it is not recommended in these cases. Further studies are needed to assess the mechanisms of endometriosis-associated infertility and how it may be overcome in cases of minimal and mild endometriosis.

 

 

 

Surg Endosc. 2017 Nov 3.

First experience with THE AUTOLAP™ SYSTEM: an image-based robotic camera steering device.

Wijsman PJM¹, Broeders IAMJ², Brenkman HJ³, Szold A⁴, Forgione A⁵, Schreuder HWR⁶, Consten ECJ², Draaisma WA², Verheijen PM², Ruurda JP³, Kaufman Y⁷.

 

Abstract

BACKGROUND:

Robotic camera holders for endoscopic surgery have been available for 20 years but market penetration is low. The current camera holders are controlled by voice, joystick, eyeball tracking, or head movements, and this type of steering has proven to be successful but excessive disturbance of surgical workflow has blocked widespread introduction. The Autolap™ system (MST, Israel) uses a radically different steering concept based on image analysis. This may improve acceptance by smooth, interactive, and fast steering. These two studies were conducted to prove safe and efficient performance of the core technology.

METHODS:

A total of 66 various laparoscopic procedures were performed with the AutoLap™ by nine experienced surgeons, in two multi-center studies; 41 cholecystectomies, 13 fundoplications including hiatal hernia repair, 4 endometriosis surgeries, 2 inguinal hernia repairs, and 6 (bilateral) salpingo-oophorectomies. The use of the AutoLap™ system was evaluated in terms of safety, image stability, setup and procedural time, accuracy of imaged-based movements, and user satisfaction.

RESULTS:

Surgical procedures were completed with the AutoLap™ system in 64 cases (97%). The mean overall setup time of the AutoLap™ system was 4 min (04:08 ± 0.10). Procedure times were not prolonged due to the use of the system when compared to literature average. The reported user satisfaction was 3.85 and 3.96 on a scale of 1 to 5 in two studies. More than 90% of the image-based movements were accurate. No system-related adverse events were recorded while using the system.

CONCLUSION:

Safe and efficient use of the core technology of the AutoLap™ system was demonstrated with high image stability and good surgeon satisfaction. The results support further clinical studies that will focus on usability, improved ergonomics and additional image-based features.

 

 

 

Adv Ther. 2017 Nov;34(11):2491-2502.

Changes in Healthcare Spending After Diagnosis of Comorbidities Among Endometriosis Patients: A Difference-in-Differences Analysis.

Epstein AJ¹, Soliman AM², Davis M³, Johnson SJ³, Snabes MC², Surrey ES⁴.

 

Abstract

INTRODUCTION:

We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities.

METHODS:

Women aged 18-49 years with endometriosis (N = 180,278) were extracted from 2006-2015 de-identified Clinformatics^® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient’s index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre-post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis.

RESULTS:

The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren’s/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p < 0.001 except for headache (p = 0.045)]. Spending decreased significantly for fatigue, cystitis/UTI, and eczema [p < 0.001 except for fatigue (p = 0.048)] and was not statistically different for the other 11 comorbidities. Difference-in-differences estimates were significantly higher for comorbidity patients for all comorbidities except eczema (p ≤ 0.003). Mean 5-year total cumulative spending was $58,191 per endometriosis patient, of which between 11% and 23% was attributable to comorbidity-related medical claims.

CONCLUSION:

For all but one of the 22 comorbidities associated with endometriosis, comorbidity onset was associated with a relative increase in total healthcare spending.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Dec;219:119-123.

Role of cytochrome P450 2C19 polymorphisms and body mass index in endometriosis: A case-control study.

Cardoso JV¹, Abrão MS², Berardo PT³, Ferrari R⁴, Nasciutti LE⁵, Machado DE⁶, Perini JA⁷.

 

Abstract

OBJECTIVE:

To investigate the contribution of CYP2C19 polymorphisms and body mass index (BMI) in the development of endometriosis.

STUDY DESIGN:

This is a case-control study that includes 356 women (187 cases and 169 controls) recruited from two hospitals in the Brazilian public health system. The genotyping analyses of the CYP2C19*2 and CYP2C19*17 polymorphisms were performed using TaqMan allelic discrimination assays, and the association of the studied polymorphisms with endometriosis was evaluated by multivariate logistic regression. Pearson correlation coefficients were used to investigate the interaction between BMI and CYP2C19 polymorphisms.

RESULTS:

The variant allele frequencies of CYP2C19*2 were significantly different between cases and controls, and after adjusting for confounding factors, the CYP2C19*2 polymorphism was more frequent in women with endometriosis, considering all cases (CYP2C19*2: OR=1.83; 95% CI=1.17-2.85) and only deeply infiltrating endometriosis (DIE) cases (CYP2C19*2: OR=2.32; 95% CI=1.42-3.77). BMI was significantly lower in endometriosis patients (26.5±4.68) than in controls (27.8±5.65, P<0.02). Among obese women (BMI 30-40), the CYP2C19*2 polymorphism had a greater association with endometriosis(CYP2C19*2: OR=3.27; 95% CI=1.55-6.89). There was a positive correlation between CYP2C19*2 and BMI 30-40 (P=0.004).

CONCLUSIONS:

The findings of our study suggest that CYP2C19*2 is positively associated with endometriosis and that BMI may have a significant interaction with CYP2C19*2 and the risk of endometriosis.

 

 

 

Gynecol Endocrinol. 2017 Nov 5:1-7.

Endometriosis and gestational diabetes mellitus risk: a systematic review and meta-analysis.

Pérez-López FR^1,2, Martínez-Domínguez SJ¹, Viñas A¹, Pérez-Tambo R¹, Lafita A¹, Lajusticia H¹, Chedraui P³; Health Outcomes and Systematic Analyses (HOUSSAY) Project.

 

Abstract

OBJECTIVE:

To perform a systematic review and meta-analysis regarding endometriosis and the risk of gestational diabetes mellitus (GDM).

METHODS:

We carried out a search of the following databases: Medline, Embase, Web of Science, Cochrane Library, Scopus, Scielo, Clinicaltrials.gov, the UK Clinical Trials Gateway, and the Australian New Zealand Clinical Trials Registry, from inception through April 28 2017, without language restrictions, in order to evaluate the effect of endometriosis over GDM risk, in women with and without endometriosis. Odds ratios (ORs) and their 95% confidence intervals (CIs) or mean differences (MDs) were calculated as effects. Methodological quality of evidence was assessed with the Newcastle-Ottawa Scale, and heterogeneity among studies with the I² statistic. Random-effects models were used for meta-analyses, and publication bias was assessed with Egger’s test.

RESULTS:

We identified 12 studies (10 cohort and two case control studies) with a total of 48,762 pregnancies, including 3,461 with endometriosis. Endometriosis had no significant effect on GDM risk (OR =1.14; 95% CI: 0.86, 1.51; p = .35, I² = 56%, Egger’s test p = .45). Secondary outcomes (gestational age at delivery, birthweight, and Neonatal Intensive Care Unit admission) were statistically similar in women with and without endometriosis.

CONCLUSIONS:

Better-designed studies are needed to confirm our results.

 

 

Am J Reprod Immunol. 2018 Jan;79(1).

Inhibition of IAP (inhibitor of apoptosis) proteins represses inflammatory status via nuclear factor-kappa B pathway in murine endometriosislesions.

Taniguchi F¹, Uegaki T¹, Nakamura K², Mon KY¹, Harada T¹, Ohbayashi T², Harada T¹.

 

Abstract

PROBLEM:

How is the role of inhibitor of apoptosis proteins (IAPs) in the development of murine endometriosis lesions?

METHOD OF STUDY:

BALB/c female mice (n = 36) were used for the murine endometriosis model. Endometriotic lesions were surgically induced in mice by transplanting mouse uterine tissue. After 4 weeks of IAP antagonist (BV6) treatment, the expression of inflammatory factors in the implants was evaluated using real-time RT-PCR. Inflammatory state, angiogenic activity, and nuclear factor-kappa B (NF-κB) activation were assessed by immunohistochemical staining.

RESULTS:

The number, size, and level of inflammatory cytokines (Vegf, Il-6, Ccl-2, Lif) gene expression in the murine endometriosis-like lesions were reduced by BV6 treatment. BV6 repressed the intensity and rate of positive cells of CD3, F4/80, and PECAM immunostaining; in addition, the expression of NF-κB p65 and phospho-NF-κB p65 was also attenuated.

CONCLUSION:

Inhibitor of apoptosis proteins antagonist represses the inflammation status of murine endometriosis-like lesions viaNF-κB pathway. IAPs may be a novel therapeutic target for endometriosis.

 

 

 

Biochem Biophys Res Commun. 2018 Jan 1;495(1):60-63.

Autophagy in endometriosis: Friend or foe?

Zhan L¹, Li J², Wei B³.

 

Abstract

Endometriosis is a chronic, estrogen-dependent disease and characterized by the implantation of endometrial glands and stroma deep and haphazardly into the outside the uterine cavity. It affects an estimated 10% of the female population of reproductive age and results in obvious reduction in health-related quality of life. Unfortunately, there is no a consistent theory for the etiology of endometriosis. Furthermore, the endometriosis is hard to diagnose in early stage and the treatment methods are limited. Importantly, emerging evidence has investigated that there is a close relationship between endometriosisand autophagy. However, autophagy is a friend or foe in endometriosis is puzzling, the precise mechanism underlying autophagy in endometriosis has not been fully elucidated yet. Here, we provide an integrated view on the acquired findings of the connections between endometriosis and autophagy. We also discuss which may contribute to the abnormal level of autophagy in endometriosis.

 

 

 

J Gynecol Obstet Hum Reprod. 2018 Jan;47(1):29-31.

Differed surgery in patient with colorectal endometriosis and pregnancy intention: Is it reasonable?

Touleimat S¹, Huet E², Sanguin S³, Roman H⁴.

 

Abstract

The management of patients presenting deep infiltrating endometriosis involving the rectum (DIER) and pregnancy intention is controversial. Assisted Reproduction Techniques (ART) are often proposed first, but this may lead to complications and further difficulties managing DIER. A 29-years-old woman was diagnosed with pre-occlusive DIER. However, she was offered in vitro fertilization (IVF) and underwent six unsuccessful cycles with serious complications: an ectopic pregnancy and a hemoperitoneum following arterial injury during oocyte retrieval, requiring two laparotomies in emergency. The patient’s symptoms worsened over time and colorectal resection with diverting colostomy was performed. The patient’s quality of life was then improved. In our opinion, prior ART in patients presenting DIER delays surgery and may have harmful complications. Therefore, primary surgery followed by ART may be a valuable option in some cases and should be discussed with the patients.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2018 Jan;220:1-5.

The Wnt/β-catenin signaling in endometriosis, the expression of total and active forms of β-catenin, total and inactive forms of glycogen synthase kinase-3β, WNT7a and DICKKOPF-1.

Pazhohan A¹, Amidi F¹, Akbari-Asbagh F², Seyedrezazadeh E³, Farzadi L⁴, Khodarahmin M¹, Mehdinejadiani S¹, Sobhani A⁵.

 

Abstract

OBJECTIVES:

The cyclical changes in proliferation and differentiation of endometrial cells are regulated by estrogen and progesterone via modulating Wnt/β-catenin signaling. Imbalance in the expression of estrogen and progesterone receptors causes progesterone resistance in endometriosis patients. The aim of this study was to investigate the expression of some main components of Wnt/β-catenin signaling including WNT7a, DKK-1, β-catenin, and GSK-3β in eutopic endometrium and peritoneal endometriotic lesions of endometriosis patients compared to healthy endometrium in the mid-secretory phase of menstrual cycle.

STUDY DESIGN:

This prospective study was performed, during a 12 months period from December 2015 to November 2016, on healthy women as the control group (n=14) and endometriosis patients (n=34). We used real-time polymerase chain reaction and Western blot techniques.

RESULTS:

Protein and mRNA expression of DKK-1 were significantly down-regulated in both endometriotic lesions and eutopic endometrium of endometriosis group. We also demonstrated that the expression of non-phosphorylated β-catenin (active form) and phosphorylated GSK-3β (inactive form) were up-regulated in endometriosis patients. The mRNA levels of β-catenin, GSK-3β, and WNT7a, as well as the protein levels of total β-catenin, total GSK-3β, and WNT7a in endometriosis group, were not significantly different with those in control group. The patterns of mRNA and protein expression of all interested factors in the lesions were similar to those in the eutopic endometrium of same patients.

CONCLUSIONS:

It seems that the aberrant activation of Wnt/β-catenin signaling in the secretory phase of the menstrual cycle in endometriosis has two essential elements: excessive inactivation of GSK-3β and suppression of the expression of Wnt signaling inhibitor DKK-1. Interventions in this signaling pathway may allow for the exploration of potential new targets for the control of development and progression of endometriosis.

 

 

 

 

 

Reprod Sci. 2017 Jan 1:1933719117737846.

Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression.

Cuevas M¹, Cruz ML¹, Ramirez AE¹, Flores I¹, Thompson KJ¹, Bayona M^1,2, Vernon MW³, Appleyard CB¹.

 

Abstract

PURPOSE:

We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations.

METHODS:

Endometriosis was surgically induced in female Sprague-Dawley rats by suturing uterine horn implants onto the small intestine mesentery. Two weeks later, one group of rats (endo-stress) was subjected to a 10-day swim stress protocol. Controls had no stress (endo-no stress) or sutures only and stress (sham-stress). On day 60, all rats were killed and examined for the presence of endometriotic vesicles. The size of each vesicle was measured. The uterus and colon were removed and assessed for damage, cell infiltration, and expression of nerve growth factor (NGF), its receptors (p75 and Tropomyosin receptor kinase A (Trk-A)/pTrk-A), and calcitonin gene-related peptide, a sensory fiber marker. A differential analysis of peritoneal fluid white blood cell count was performed.

RESULTS:

Stress significantly increased endometriotic vesicle size but not colonic damage and increased infiltration of mast cells. Significantly increased expression of NGF and its receptors was found in the uterus of animals with endometriosis receiving stress.

CONCLUSIONS:

Stress stimulates the development of ectopic endometrial vesicles in an animal model of endometriosis and increases inflammatory cell recruitment to the peritoneum. In addition, stress promotes nerve fiber growth in the uterus.

 

 

 

Cancer Genomics Proteomics. 2017 Nov-Dec;14(6):455-460.

The Association of Flap Endonuclease 1 Genotypes with the Susceptibility of Endometriosis.

Chou AK¹, Shen MY^2,3, Chen FY², Hsiao CL^3,4, Shih LC⁴, Chang WS⁴, Tsai CW⁴, Ying TH⁵, Wu MH⁶, Huang CY⁷, Bau DT^8,4,9.

 

Abstract

BACKGROUND/AIM:

Flap endonuclease 1 (FEN1), a protein with multiple functions in genome stability maintenance, is important in cancer prevention. The two functional germline variants of FEN1, rs174538 and rs4246215, regarding cancer susceptibility have been reported in lung, breast, liver, esophageal, gastric, colorectal cancer, glioma and leukemia, but not endometriosis. In this study, we firstly aimed at evaluating the contribution of FEN1 genotypes to endometriosis risk in a representative Taiwan population.

MATERIALS AND METHODS:

In total, 153 patients with endometriosis and 636 non-cancer healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology.

RESULTS:

The genotypes of FEN1 rs174538, but not those of rs4246215, were differently distributed between the endometriosis and control groups. In detail, the AA of FEN1 rs174538 genotypes were significantly less frequently found among endometriosis patients than among controls (odds ratio [OR]=0.43, 95% confidence interval [CI]=0.24-0.78, p=0.0125). The A allele at FEN1 rs174538 was also significantly less frequent among cases than controls (OR=0.65, 95%CI=0.50-0.86, p=0.0021). As for age of first menarche, those with first menarche at the age >12.8 carrying the FEN1 rs174538 AA genotype conferred lower OR of 0.29 (95%CI=0.11-0.78, p=0.0381) for endometriosis. Regarding the full pregnancy status, those without having had a full-term pregnancy carrying the FEN1 rs174538 AA genotype were of lower risk (ORs=0.12, 95%CI=0.03-0.53, p=0.0050).

CONCLUSION:

The FEN1 rs174538 A allele is a novel protective biomarker for endometriosis and this genotype may have interactions with age- and hormone-related factors on the development of endometriosis.

 

 

 

Br J Gen Pract. 2017 Dec;67(665):e816-e823.

Pointers to earlier diagnosis of endometriosis: a nested case-control study using primary care electronic health records.

Burton C¹, Iversen L², Bhattacharya S², Ayansina D², Saraswat L³, Sleeman D⁴.

 

Abstract

BACKGROUND:

Endometriosis is a condition with relatively non-specific symptoms, and in some cases a long time elapses from first-symptom presentation to diagnosis.

AIM:

To develop and test new composite pointers to a diagnosis of endometriosis in primary care electronic records.

DESIGN AND SETTING:

This is a nested case-control study of 366 cases using the Practice Team Information database of anonymised primary care electronic health records from Scotland. Data were analysed from 366 cases of endometriosis between 1994 and 2010, and two sets of age and GP practice matched controls: (a) 1453 randomly selected females and (b) 610 females whose records contained codes indicating consultation for gynaecological symptoms.

METHOD:

Composite pointers comprised patterns of symptoms, prescribing, or investigations, in combination or over time. Conditional logistic regression was used to examine the presence of both new and established pointers during the 3 years before diagnosis of endometriosis and to identify time of appearance.

RESULTS:

A number of composite pointers that were strongly predictive of endometriosis were observed. These included pain and menstrual symptoms occurring within the same year (odds ratio [OR] 6.5, 95% confidence interval [CI] = 3.9 to 10.6), and lower gastrointestinal symptoms occurring within 90 days of gynaecological pain (OR 6.1, 95% CI = 3.6 to 10.6). Although the association of infertility with endometriosis was only detectable in the year before diagnosis, several pain-related features were associated with endometriosis several years earlier.

CONCLUSION:

Useful composite pointers to a diagnosis of endometriosis in GP records were identified. Some of these were present several years before the diagnosis and may be valuable targets for diagnostic support systems.

 

 

 

Obstet Gynecol. 2017 Dec;130(6):1261-1268.

Opioid Prescribing Patterns, Patient Use, and Postoperative Pain After Hysterectomy for Benign Indications.

As-Sanie S¹, Till SR, Mowers EL, Lim CS, Skinner BD, Fritsch L, Tsodikov A, Dalton VK, Clauw DJ, Brummett CM.

 

Abstract

OBJECTIVE:

To quantify physician prescribing patterns and patient opioid use in the 2 weeks after hysterectomy at an academic institution and to determine whether patient factors predict postsurgical opioid use and pain recovery.

METHODS:

We conducted a prospective quality initiative study by recruiting all English-speaking patients undergoing hysterectomy for benign, nonobstetric indications at a university hospital between August 2015 and December 2015, excluding those with major medical morbidities or substance abuse. Before hysterectomy, patients completed the Fibromyalgia Survey, a validated measure of centralized pain. After hysterectomy, opioid use (converted to oral morphine equivalents) and pain scores (0-10 numeric rating scale) were collected by a daily diary and a structured telephone interview 14 days after surgery. Primary outcomes were total opioid prescribed and consumed in the 2 weeks after hysterectomy. Secondary outcomes included daily opioid use and daily pain severity for 14 days after hysterectomy.

RESULTS:

Of 103 eligible patients, 102 (99%) agreed to participate, including 44 (43.1%) laparoscopic, 42 (41.2%) vaginal, and 16 (15.7%) abdominal hysterectomies. Telephone surveys were completed on 89 (87%) participants; diaries were returned from 60 (59%) participants. Diary nonresponders had different baseline characteristics than nonresponders. Median amount of opioid prescribed was 200 oral morphine equivalents (interquartile range 150-250). Patients reported using approximately half of the opioids prescribed with a median excess of 110 morphine equivalents (interquartile range 40-150). The best fit model of total opioid consumption identified preoperative Fibromyalgia Survey Score, overall body pain, preoperative opioid use, prior endometriosis, abdominal hysterectomy (compared with laparoscopic), and uterine weight as significant predictors. Highest tertile of Fibromyalgia Survey Score was associated with greater daily opioid consumption (13.9 [95% CI 3.0-24.8] greater oral morphine equivalents at baseline, P=.02).

CONCLUSION:

Gynecologists at a large academic medical center prescribe twice the amount of opioids than the average patient uses after hysterectomy. A personalized approach to prescribing opioids for postoperative pain should be considered.

 

 

 

 

Int J Mol Sci. 2017 Nov 6;18(11). pii: E2345.

Discovering the Deregulated Molecular Functions Involved in Malignant Transformation of Endometriosis to Endometriosis-Associated Ovarian Carcinoma Using a Data-Driven, Function-Based Analysis.

Chang CM^1,2, Yang YP^3,4, Chuang JH^5,6, Chuang CM^7,8, Lin TW^9,10, Wang PH^11,12,13, Yu MH¹⁴, Chang CC¹⁵.

 

Abstract

The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC.

 

 

 

Stem Cell Res Ther. 2017 Nov 7;8(1):251.

miR-200c suppresses endometriosis by targeting MALAT1 in vitro and in vivo.

Liang Z¹, Chen Y¹, Zhao Y¹, Xu C¹, Zhang A¹, Zhang Q¹, Wang D¹, He J², Hua W³, Duan P⁴.

 

Abstract

BACKGROUND:

Endometriosis is a common, benign, and estrogen-dependent disease characterized by pelvic pain and infertility. To date, the pathogenesis of endometriosis remains unclear. Recent studies have demonstrated that noncoding RNAs, including microRNAs and long noncoding RNAs, play important roles in the development of endometriosis.

METHODS:

Expression profiling of miRNAs in endometrial tissue was characterized using microarrays. The most differentially expressed miRNAs were confirmed using quantitative reverse transcriptase-polymerase chain reaction analysis in additional ectopic endometrial (n = 27) and normal endometrial (n = 12) tissues. For in-vitro functional studies, 5-ethynyl-2′-deoxyuridine incorporation assay, Transwell assay, and dual-luciferase reporter assay were used to measure the proliferation, migration, and luciferase activity of miR-200c and the predicted targets of miR-200c in primary endometrial stromal cells (HESCs) derived from human endometrial biopsies, respectively. For in-vivo therapeutic interventions, polymeric nanoparticles of polyethylenimine-polyethylene glycol-arginine-glycine-aspartic acid were used for delivery of miR-200c mimic and inhibitor to determine the therapeutic effect of miR-200c in a rat model of endometriosis.

RESULTS:

Exogenous overexpression of miR-200c inhibited the proliferation and migration of HESCs, which were mainly regulated by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). In contrast, inhibition of miR-200c promoted the proliferation and migration of HESCs, while the simultaneous silencing of MALAT1 expression exerted the opposite effects. We demonstrated that expression of MALAT1 in ectopic endometrial specimens was negatively correlated with that of miR-200c and that MALAT1 knockdown increased the level of miR-200c in HESCs. Moreover, the transfection of endometrial stromal cells with the miR-200c mimic or MALAT1 siRNAs decreased the protein levels of mesenchymal markers ZEB1, ZEB2, and N-cadherin and increased the protein levels of the epithelial marker E-cadherin. Furthermore, using a rat endometriosis model, we showed that local delivery of the miR-200c mimic significantly inhibited the growth of ectopic endometriotic lesions.

CONCLUSIONS:

The MALAT1/miR-200c sponge may be a potential therapeutic target for endometriosis.

 

 

 

Sao Paulo Med J. 2017 Nov 6:0.

Malignant transformation of abdominal wall endometriosis to clear cell carcinoma: case report.

Gentile JKA¹, Migliore R¹, Kistenmacker FJN¹, Oliveira MM², Garcia RB³, Bin FC⁴, Souza PMSB³, Assef JC⁴.

 

Abstract

BACKGROUND:

Malignant transformation of endometriosis in the abdominal wall is a rare and still poorly understood event. Less than 30 cases have been reported in the worldwide literature. Most cases of solid tumors are report in a previous abdominal scar with malignant transformation of a focus of endometriosis. Presence of lymph node metastases in nearby chains is frequent and is associated with poor prognosis.

CASE REPORT:

We report a case of a 42-year-old woman with a history of abdominal surgery (Pfannenstiel) to resect abdominal wall endometriosis. Physical examination revealed a solid mass of approximately 10 cm x 6 cm in the anterior wall of the abdomen. Computed tomography (CT) of the abdomen and pelvis showed a heterogeneous, predominantly hypoattenuating expansive formation measuring 10.6 cm x 4.7 cm x 8.3 cm. The patient underwent exploratory incisional laparotomy, block resection of the abdominal mass and lymphadenectomy of the external and inguinal iliac chains. The abdominal wall was reconstructed using a semi-absorbable tissue-separating screen to reconstitute the defect caused by resection of the tumor. Histological evaluation revealed infiltration by malignant epithelioid neoplasia, thus confirming the immunohistochemical profile of adenocarcinoma with clear cell components. Lymphadenectomy showed metastatic involvement of an external iliac chain lymph node.

CONCLUSION:

Resection of the mass along with the abdominal wall, with wall margins, is the most effective treatment. Reconstruction is a challenge for surgeons. The patient has been followed up postoperatively for eight months, without any evidence of disease to date.

 

 

 

Acta Clin Croat. 2017 Mar;56(1):162-5.

ABDOMINAL WALL ENDOMETRIOSIS ELEVEN YEARS AFTER CESAREAN SECTION: CASE REPORT.

Djaković I, Vuković A, Bolanča I, Vraneš HS, Kuna K.

 

Abstract

Endometriosis is a common chronic disease characterized by growth of the endometrial gland and stroma outside the uterus. Symptoms affect physical, mental and social well-being. Extrapelvic location of endometriosis is very rare. Abdominal wall endometriosis occurs in 0.03%-2% of women with a previous cesarean section or other abdominopelvic operation. The leading symptoms are abdominal nodular mass, pain and cyclic symptomatology. The number of cesarean sections is increasing and so is the incidence of abdominal wall endometriosis as a potential complication of the procedure. There are cases of malignant transformation of abdominal wall endometriosis. Therefore, it is important to recognize this condition and treat it surgically. We report a case of a 37-year-old woman with abdominal wall endometriosis 11 years after cesarean section. She had low abdominal pain related to menstrual cycle, which intensified at the end of menstrual bleeding. A nodule painful to palpation was found in the medial part of previous Pfannenstiel incision. Ultrasound guided biopsy was performed and the diagnosis of endometriosisconfirmed. Surgery is the treatment of choice for abdominal wall endometriosis. Excision with histologically proven free surgical margins of 1 cm is mandatory to prevent recurrence. A wide spectrum of mimicking conditions is the main reason for late diagnosis and treatment of abdominal wall endometriosis. In our case, the symptoms lasted for eight years and had intensified in the last six months prior to surgery.

 

 

 

Mol Hum Reprod. 2017 Dec 1;23(12):842-854.

Naringenin induces mitochondria-mediated apoptosis and endoplasmic reticulum stress by regulating MAPK and AKT signal transduction pathways in endometriosis cells.

Park S¹, Lim W², Bazer FW³, Song G¹.

 

Abstract

STUDY QUESTION:

Does the flavonoid naringenin inhibit proliferation of human endometriosis cells?

SUMMARY ANSWER:

Naringenin suppresses proliferation and increases apoptosis via depolarization of mitochondrial membrane potential and generation of reactive oxygen species (ROS) in human endometriosis cells.

WHAT IS KNOWN ALREADY:

For management of endometriosis, hormonal therapy is commonly used to decrease production of estrogens by the ovaries, but that has limitations including undesirable side effects with long-term therapies. To overcome these limitations, it is important to discover novel compounds which have no adverse effects, but inhibit expression of target molecules involved in the pathogenesis of endometriosis.

STUDY DESIGN SIZE, DURATION:

Well-established endometriosis cell lines (VK2/E6E7 and End1/E6E7) were purchased from the American Type Culture Collection. Effects of naringenin on VK2/E6E7 and End1/E6E7 cells were assessed in diverse assays in a dose- and time-dependent manner.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Effects of naringenin on viability, apoptosis (Annexin V expression, propidium iodide staining, TUNEL and invasion assays), mitochondria-mediated apoptosis, production of ROS and endoplasmic reticulum (ER) stress proteins of VK2/E6E7 and End1/E6E7 cells were determined. Signal transduction pathways in VK2/E6E7 and End1/E6E7 cells in response to naringenin were determined by western blot analyses.

MAIN RESULTS AND THE ROLE OF CHANCE:

In the present study, we demonstrated that naringenin suppressed proliferation and increased apoptosis through depolarization of mitochondrial membrane potential and inducing pro-apoptotic proteins, Bax and Bak, in both endometriosis cell lines. In addition, naringenin increased ROS, ER stress, through activation of eIF2α and IRE1α, GADD153 and GRP78 proteins in a dose-dependent manner. Furthermore, the induction of apoptosis by naringenin involved activation of MAPK and inactivation of PI3K pathways in VK2/E6E7 and End1/E6E7 cells.

LIMITATIONS REASONS FOR CAUTION:

Lack of in vivo animal studies is a major limitation of this research. Effectiveness of naringenin to induce apoptosis of human endometriosis cells requires further investigation.

WIDER IMPLICATIONS OF THE FINDINGS:

Our results suggest that naringenin is a promising therapeutic compound for treatment of endometriosis in women.

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.). The authors declare that there are no conflicts of interest.

 

 

 

J Obstet Gynaecol Res. 2017 Nov 9.

Structural arrangement of vesicouterine fistula revisited: An immunohistochemical study documenting the presence of the endometrium.

Jóźwik M¹, Jóźwik M², Kozłowski R³, Sulkowski S⁴, Semczuk A⁵, Jóźwik M^6,7.

 

Abstract

Previous research has described a woman of reproductive age who presented with a vesicouterine fistula (VUF) of 20 months’ duration. The VUF was lined with a metaplastic glandular epithelium containing both estrogen receptors (ER) and progesterone receptors (PR) in abundance. The aim of the present investigation was to evaluate the histology of the VUF canal when exposure to urine of the cellular elements within the fistula was of much shorter duration. A 41-year-old woman who developed a VUF during her third cesarean section was treated with transvesical fistula excision, electrocoagulation, and subsequent attempted hormonal treatment. Later, the patient underwent open surgery fistula repair. Postoperative specimens were subjected to anatomopathological examination together with immunohistochemical staining for ER and PR using monoclonal anti-human antibodies. Herein, we present for the first time detailed microscopic evidence that, at two separate timepoints, the fistulous tract was lined with the endometrium, which covered approximately 80% of the length of the VUF canal. In its intermediate segment, the urothelium formed an additional layer on the surface of the endometrium. At both timepoints, in the columnar epithelial and stromal endometrial cells lining the fistula, both ER and PR were present in abundance. In conclusion, VUF in subjects of reproductive age fulfill criteria for endometriosis. This study provides a rationale for the conservative treatment of VUF consistent with the hormonal treatment of endometriosis.

 

 

 

J Assist Reprod Genet. 2017 Nov 9.

Polymorphisms of mitochondrial DNA control region are associated to endometriosis.

Andres MP¹, Cardena MMSG², Fridman C², Podgaec S^3,4.

 

Abstract

PURPOSE:

Polymorphisms in the control region of mitochondrial DNA (mtDNA) can affect generation of reactive oxygen species and impact in the pathogenesis of endometriosis. This study investigated the association of mtDNA polymorphisms with endometriosis.

METHODS:

Patients were divided in two groups: endometriosis (n = 90) and control (n = 92). Inclusion criteria were as follows: women between 18 and 50 years, with histological diagnosis and surgical staging of endometriosis (endometriosis group) or undergoing gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, with no evidence of endometriosis (control group). DNA extraction was performed from peripheral blood. Sanger sequencing of mtDNA control region was performed, and polymorphisms were determined comparing the sequences obtained with the Cambridge Reference Sequence.

RESULTS:

The frequency of polymorphisms T16217C (14.4 and 5.4% of endometriosis and control group, respectively; p = 0.049) and G499A (13.3 vs. 4.3%; p = 0.038) was higher in the endometriosis group, while T146C (32.6 vs. 18.9%; p = 0.042) and 573.2C (5.6 vs. 29.3%; p < 0.001) were lower. No difference was observed in haplogroups between groups.

CONCLUSION:

mtDNA polymorphisms T16217C and G499A were associated with endometriosis, while T416C and 573.2C were shown to be associated with an absence of disease.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2018 Jan;220:12-17. doi: 10.1016/j.ejogrb.2017.10.031. Epub 2017 Oct 31.

Fertility outcomes after laparoscopic partial bladder resection for deep endometriosis: Retrospective analysis from two expert centres and review of the literature.

Nyangoh Timoh K¹, Ballester M², Bendifallah S³, Fauconnier A⁴, Darai E².

 

Abstract

OBJECTIVE:

To evaluate fertility outcomes after laparoscopic partial bladder resection in women with bladder endometriosis and to review the literature.

STUDY DESIGN:

A retrospective study conducted at two tertiary referral centres -Tenon University Hospital and Poissy University Hospital (Canadian Task Force Classification Level II-2)-from July 2006 to November 2015. Patients with bladder endometriosis who underwent either laparoscopic partial bladder resection (PBR) alone for those without posterior endometriotic lesions (PBR group) or both laparoscopic PBR and associated posterior deep infiltrating endometriosis (DIE) resection (PBR-PDIE group) were included. Pregnancy and live birth rates according to prior infertility, and associated posterior DIE resection were analysed.

RESULTS:

Thirty-four patients were included; 15 in the PBR group and 19 in the PBR-PDIE group. The median age (range) was 31 years (25-37), Seventeen patients (50%) had prior infertility. The median follow-up after bladder resection was 60.6 months (12-116). Overall, of the 25 (73.5%) patients who wished to conceive, 17 (68%) achieved pregnancies resulting in a live birth rate of 76.4%. Among the 17 patients with prior infertility, nine (52.9%) conceived. Overall, eight patients (53.3%) in the PBR group conceived and nine (47.3%) in the PBR-PDIE group (difference not significant).

CONCLUSION:

The present study demonstrates that laparoscopic PBR results in a high pregnancy rate in patients with prior infertility as well as in those with associated posterior DIE suggesting that surgery could be an acceptable alternative to first-line assisted reproductive technology.

 

 

 

J Minim Invasive Gynecol. 2017 Nov 8. pii: S1553-4650(17)31269-4.

The Role of Magnetic Resonance Imaging-Diffusion Tensor Imaging in Predicting Pain Related to Endometriosis: A Preliminary Study.

Porpora MG¹, Vinci V², De Vito C³, Migliara G³, Anastasi E⁴, Ticino A⁵, Resta S⁵, Catalano C², Benedetti Panici P⁵, Manganaro L².

 

Abstract

OBJECTIVES:

To evaluate the sacral nerve root features by the means of magnetic resonance imaging-diffusion tensor imaging (MRI-DTI) tractography in women with endometriosis and/or adenomyosis, and to analyze the correlations among DTI abnormalities, pain symptoms, and endometriotic lesions found at surgery.

DESIGN:

A cross-sectional, observational study (Canadian Task Force classification II-2).

SETTING:

University hospital.

PATIENTS:

Women (n = 76) with clinical suspicion of endometriosis.

INTERVENTIONS:

Before surgery, dysmenorrhea, deep dyspareunia, and noncyclic pelvic pain (NCPP) were assessed using a 10-point visual analog scale. MRI enabled a 3-dimensional reconstruction of S1, S2, and S3. Fractional anisotropy was calculated for each root. Laparoscopic treatment of endometriosiswas performed in 56 patients.

MEASUREMENTS AND MAIN RESULTS:

Our findings revealed correlations among sacral root reconstruction by MRI-DTI, pain symptoms, and laparoscopic findings. DTI of sacral roots revealed a regular and homogeneous appearance in 17 patients (25.8%) and abnormalities in microstructure reconstruction, with fiber irregularities and disorganization and loss of the simple unidirectional course, in 44 patients (66.7%). At laparoscopy, ovarian endometriomas were found in 82.1% of the patients, and deeply infiltrating endometriosis (DIE) were found in 57.1%. Endometriosis was staged according to the revised American Society for Reproductive Medicine classification. Pathological DTI findings were significantly associated with the severity of dysmenorrhea and NCPP, pain duration, presence of tubo-ovarian and cul-de-sac adhesions, and DIE.

CONCLUSION:

The presence of pathological DTI findings of the sacral nerve roots correlates with the type of pain, adhesions, and DIE. At present, DTI can be useful for providing a better understanding of pain; however, DTI could become a useful tool in therapeutic planning for patients with endometriosis.

 

 

 

Presse Med. 2017 Dec;46(12 Pt 1):1184-1191.

[Fertility and deep infiltrating endometriosis].

 

Cohen J¹, Mathieu d’Argent E², Selleret L², Antoine JM², Chabbert-Buffet N³, Bendifallah S², Ballester M³, Darai E³.

 

Abstract

Deep infiltrating endometriosis is the most severe form of the disease, defined by infiltration beneath the peritoneum greater than 5mm. It affects several anatomical locations including the bladder, the vesico-uterine cul-de-sac, the torus uterinum, the uterosacral ligament, rectovaginal septum and the colon-rectum. Deep infiltrating endometriosis is associated with infertility. Surgery performed for deep infiltrating endometriosis in the context of pain offers good pregnancy rates either spontaneously or after assisted reproductive technologies. The results are less favorable when digestive tract is involved. IVF performed in the context of deep infiltrating endometriosis allows very satisfactory results and does not entail risks of aggravation of the pathology. There is currently no clear evidence to support either IVF or surgery to manage infertility associated with deep infiltrating endometriosis, but patients should be informed, although a risk of severe complication exists, that surgery is the only way to increase the chances of spontaneous fertility.

 

 

 

 

 

 

Presse Med. 2017 Dec;46(12 Pt 1):1212-1217.

Surgical management of deep infiltrating endometriosis with bowel involvement and urinary tract involvement.

 

Bendifallah S¹, Ballester M², Darai E².

 

Abstract

Endometriosis is a benign pathology that affects 3% of the general population and about 10% of women of reproductive age. Three anatomoclinical entities are described: peritoneal, ovarian (endometrioma) and deep endometriosis characterized by the infiltration of anatomical structures or organs beyond the peritoneum. Laparoscopic surgery should be performed, as this is associated with a reduction in postoperative complications, length of hospitalization and convalescence. Several surgical techniques allow the removal of deep endometriosis with colorectal involvement: rectal shaving, anterior discoid resection, segmental resection. Deep endometriosis surgery with colorectal involvement is a source of postoperative complications: anastomotic fistula, rectovaginal fistula, intestinal occlusion, digestive haemorrhage, urinary fistula, deep pelvic abscess. Involvement of the urinary tract by endometriosisaffects approximately 1% of patients with endometriosis.

 

 

 

Presse Med. 2017 Dec;46(12 Pt 1):1192-1198.

[IVF and endometriosis, oocyte donation and fertility preservation].

 

d’Argent EM¹, Antoine JM².

 

Abstract

Endometriosis is a common condition, causing pain and infertility. In infertile woman with superficial peritoneal endometriosis and patent tubes, laparoscopy is recommended, followed by ovarian stimulation alone or in combination with intrauterine inseminations. In case of ovarian or deep endometriosis, the indications of surgery and assisted reproductive technologies remain to be defined precisely. In vitro fertilization is generally proposed after the failure of up to three inseminations, directly for ovarian or deep endometriosis, or in case of an associated factor of infertility, mainly male. Before ovarian stimulation in view to in vitro fertilization, a pretreatment by GnRH agonist for 2 to 6 months or combined contraceptive for 6 to 8 weeks would improve the pregnancy rate. Egg donation is effective in patients with advanced ovarian failure or lack of ovarian response to stimulation. Fertility preservation, especially by oocytes vitrified, must be proposed preventively to women with endometriosis at risk of ovarian failure, without close wish to be pregnant.

 

 

 

Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4509-4515.

Reactive oxygen species downregulate ARID1A expression via its promoter methylation during the pathogenesis of endometriosis.

Xie H¹, Chen P, Huang HW, Liu LP, Zhao F.

 

Abstract

OBJECTIVE:

Oxidative stress caused by reactive oxygen species (ROS) plays an important role in the pathogenesis of endometriosis. The gene AT-rich interactive domain 1A (ARID1A), is frequently down regulated and inactivated in endometriosis. This report is focused on the molecular mechanism of the correlation between oxidative stress and ARID1A gene expression in endometrial cell oxidative damage model.

PATIENTS AND METHODS:

In this study, the ARID1A gene expression level and its promoter methylation level were detected in 30 endometriosis and normal tissues. The primary endometrial cell was co-cultured with H2O2. Then, MDA and Gpx level were used to test the ROS level, RT-PCR was employed to detect the expression level of ARID1A. At last, the ARID1A gene promoter methylation level was detected by methylation-specific PCR (MSP). Finally, the expression level of DNMT1 was detected by both RT-PCR and Western blot.

RESULTS:

The expression level of ARID1A gene was down regulated in endometriosis compared with normal tissues. The low expression level of ARID1A gene was associated with its promoter hyper-methylation. In H2O2 simulated endometrial cells, ARID1A gene expression level was decreased. Finally, ROS regulated ARID1A gene expression by changing the methylation level of ARID1A gene promoter. Finally, both the mRNA level and protein level of DNMT1 increased in H2O2 simulated endometrial cells.

CONCLUSIONS:

In endometriosis, the down-regulated ofARID1A gene was highly correlated with its promoter hyper-methylation. ROS decreased the expression level of ARID1A gene via regulating methylation of its promoter which contributing to the understanding of the pathogenesis of endometriosis. The possible mechanism of ARID1A gene promoter hyper-methylation is ROS up-regulated DNMT1gene expression.

 

 

 

J Int Med Res. 2017 Sep 26:300060517728208.

Rectovaginal fistula following surgery for deep infiltrating endometriosis: Does lesion size matter?

Zheng Y^1,2,3, Zhang N¹, Lu W⁴, Zhang L⁵, Gu S¹, Zhang Y¹, Yi X^1,2,3, Hua K^1,2,3.

 

Abstract

Objective This study was performed to identify risk factors for postoperative rectovaginal fistula (PRF) in patients with deep infiltrating endometriosis (DIE). Methods Data were retrospectively obtained from the medical records of 104 patients with DIE, and statistical analysis was used to detect risk factors for PRF. Results Five of 104 (4.8%) patients developed PRF from 5 to 16 days postoperatively. The operative procedures included 84 (80.8%) superficial excisions, 6 (5.8%) full-thickness disc excisions, and 14 (13.5%) bowel resections. Most lesions were located in the cul-de-sac, and the mean lesion size was 2.6 cm (range, 0.5-7.0 cm). The univariate analysis showed that lesion location, larger lesion size, and surgical technique were statistically significant risk factors for PRF. Conclusion Surgical procedures should be very carefully executed in patients with DIE lesions of ≥4 cm.

 

 

 

Presse Med. 2017 Dec;46(12 Pt 1):1199-1211.

Medical treatment of endometriosis: Hormonal treatment of pain, impact on evolution and future perspectives.

 

Geoffron S¹, Legendre G², Daraï E³, Chabbert-Buffet N⁴.

 

Abstract

CONTEXT:

Endometriosis is a chronic painful disease, for which hormone therapy is usually offered as a first line option to women not willing to conceive.

OBJECTIVES:

To analyse and synthesize the literature, from 2006 onwards, on pain control, and disease evolution in oemn using combined hormonal contraceptives, progestins and GnRH analogs. Data on other current and future treatment perspectives is included as well.

SOURCES:

Medline (Pubmed), the Cochrane Library, and endometriosis treatment recommendations published by European Society of Human Reproduction and Embryology (ESHRE), National Institute for health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), Royal College of Obstetricians and Gynaecologists (RCOG) and Société des Obstétriciens et Gynécologues du Canada (SOGC).

STUDY SELECTION:

Meta-analysis and clinical trials are included.

RESULTS:

Study quality is heterogeneous in general. Hormone therapy inconstantly allows pain relief and prevention of endometrioma and rectovaginal wall nodules recurrence. Available molecules and routes of administration as well as risk benefit balance are evaluated. Data on future perspectives are limited to date and do not allow use in routine.

CONCLUSION:

Hormonal treatment of endometriosis relies on combined hormonal contraceptives (using different routes of administration), progestins and particularly the levonorgestrel-releasing IUS, and GnRH analogs as a last option, in combination with an add-back therapy. Promising alternatives are currently under preclinical and clinical evaluation.

 

 

 

J Gynecol Obstet Hum Reprod. 2017 Nov 10. pii: S2468-7847(17)30227-1.

A self-administered questionnaire to measure the painful symptoms of endometriosis: Results of a modified DELPHI survey of patients and physicians.

Fauconnier A¹, Staraci S², Daraï E³, Descamps P⁴, Nisolle M⁵, Panel P⁶, Roman H⁷, Boulkedid R⁸.

 

Abstract

PURPOSE:

To develop a questionnaire based on patients’ verbal descriptors, to measure the painful symptoms of endometriosis.

METHODS:

We performed a two-round modified DELPHI procedure mixing endometriosis patients and physicians to select a set of statements to describe the painful symptoms of endometriosis. Each panelist rated each statement based on diagnosis validity and clarity. The clinicians were experts in endometriosismanagement selected from various geographic regions in France. Patients were women with surgically confirmed endometriosis who volunteered from a patient association and from the recruitment of the participating physicians. The first round questions were derived from words and phrases in narratives of pain by endometriosis patients.

RESULTS:

Overall, 76 experts were invited, and of these 56 (74%), comprising 33 patients and 23 gynecologists, responded to the first round questionnaire, and 40 (71.4%) to the second round. Among the 48 statements assessed in the first-round questionnaire, 11 were selected after completion of the two round DELPHI procedure. After discussion and rewording of some items, a total of 21 questions were selected during a final face-to-face meeting. The content of the final questionnaire is organized according to four dimensions: (i) spontaneous pelvic pain and dysmenorrhea, (ii) dyspareunia, (iii) painful bowel symptoms, (iv) and other symptoms. We also provide an English (UK) version produced using several steps of translation and back-translation.

CONCLUSIONS:

The questionnaire has content validity to measure the subjective experiences of patients with painful endometriosis and can provide a solid basis on which to develop an efficient patient-centered outcome to measure the painful symptoms in therapeutic or in diagnostic studies of endometriosis.

 

 

 

Cancer Epidemiol Biomarkers Prev. 2018 Jan;27(1):96-102.

Lifestyle and Reproductive Factors and Ovarian Cancer Risk by p53 and MAPK Expression.

Harris HR^1,2, Rice MS^3,4, Shafrir AL⁵, Poole EM⁴, Gupta M⁶, Hecht JL⁶, Terry KL^2,7, Tworoger SS^4,7,8.

 

Abstract

Background: One model of ovarian cancer development model divides tumors into two types. Type I tumors are characterized by KRAS and BRAF mutations, which can activate mitogen-activated protein kinase (MAPK). Type II tumors are characterized by tubal precursor lesions with p53 mutations. We evaluated the association between lifestyle and reproductive factors and risk of ovarian cancer defined by p53 and MAPK expression.Methods: Epithelial ovarian cancer cases (n = 274) and controls (n = 1,907) were identified from the Nurses’ Health Study and Nurses’ Health Study II prospective cohorts, and the population-based New England Case-Control study. Reproductive and lifestyle exposures were assessed by questionnaire/interview. We performed immunohistochemical assays for p53 and MAPK expression. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using polytomous logistic regression.Results: Parity was associated with a decreased risk of p53 wild-type tumors (OR = 0.31; 95% CI, 0.18-0.55), but not p53-mutant tumors (OR = 0.92; 95% CI, 0.54-1.59)(P_{heterogeneity} < 0.01). Family history of breast or ovarian cancer was associated with risk of MAPK-negative (OR = 2.06; 95% CI, 1.39-3.06), but not MAPK-positive tumors (OR = 0.74; 95% CI, 0.43-1.27; P_{heterogeneity}< 0.01). In cross-classified analyses, family history of breast or ovarian cancer was most strongly associated with p53-mutant/MAPK-negative tumors (OR = 2.33; 95% CI, 1.44-3.75). Differences by MAPK expression were also observed for estrogen plus progesterone hormone therapy use (P_{heterogeneity} = 0.03).Conclusions:These findings provide evidence that parity, family history, and estrogen plus progesterone hormone therapy use may be differentially associated with tumor subtypes defined by p53 and MAPK expression.Impact: In future studies, other immunohistochemical markers or gene expression profiles that more clearly define these subtypes should be considered. Cancer Epidemiol Biomarkers Prev; 27(1); 96-102. ©2017 AACR.

 

 

 

Histochem Cell Biol. 2017 Nov 13.

Prostaglandin E2 receptor EP1 in healthy and diseased human endometrium.

Zhu J^1,2, Mayr D³, Kuhn C¹, Mahner S¹, Jeschke U⁴, von Schönfeldt V⁵.

 

Abstract

Prostaglandin E2 (PGE2) is well described to be associated with both endometrial functions and disorders. The primary aim of this study was to explore the underlying mechanisms that affect the growth and function of endometrial epithelium and stroma by assessing the staining intensity of PGE2 receptors (EP) in healthy endometrium across the menstrual cycle and in pathological endometrium, such as ovarian endometriosis and endometrial cancer. We retrospectively analyzed the EPs staining intensity in human nonpregnant endometrium throughout the menstrual cycle by immunohistochemistry and further focused on EP1 (n = 42). The variation of EP1 was compared among healthy endometrium, ovarian endometriosis (n = 14), and endometrial cancer (n = 140) crosswise. EP1 presented cyclical changes with increased intensity in both epithelium and stroma during the proliferative phase. EP1 staining in the epithelium was increased in endometriotic tissue compared to healthy endometrium and tumor tissue, while in the stroma, the staining in the tumor was lower than that in both normal tissue and endometriosis. No significant differences in EP1 intensity were detected for histological, stage, grading, metastatic and recurrent subtypes in endometrial cancer. EP1 was also correlated with neither progression-free survival nor overall survival of patients with cancer. EP1 staining in progesterone receptor B (PRB)-positive tumor was stronger compared to PRB-negative tumor. EP1 may play a role in human endometrial physiology and pathology. Further studies on the effect of EP1 on human endometrium are needed.

 

 

 

J BUON. 2017 Sep-Oct;22(5):1314-1321.

Expression and significance of ARID1A mRNA in endometriosis- associated ovarian cancer.

Wang Q¹, Wang L, L Y, Ding X, Liu A.

 

Abstract

PURPOSE:

To investigate the expression and relevant clinical and pathological significance of AT-rich interactive domaincontaining protein 1A (ARID1A) mRNA in endometriosis-associated ovarian cancer.

METHODS:

The clinical and pathological data of 63 patients with ovarian clear cell carcinoma (OCCC) and of 43 patients with ovarian endometrioid adenocarcinoma (OEAC) were collected. The expression of ARID1A-encoded protein, baf250a, in ovarian cancer tissues was detected using immunohistochemistry. The ARID1A mRNA expression was detected via RNAscope hybridization in situ, and its correlation with the clinical and pathological features of patients was analyzed.

RESULTS:

The age at the onset of OEAC patients accompanied with endometriosis (CM-EAC) was lower than that of those not accompanied with endometriosis (NCM-EAC) (p<0.001). For patients with OCCC, the lymph node metastasis (LNM) rate of CM-CCC patients was significantly lower compared to NCM-CCC (p=0.02) and FIGO stage was earlier (stage I and II) (p=0.013). The expression of baf250a in OCCC group was significantly lower than that in the EAC group (p=0.033). In the OCCC group, baf250a was significantly related to early FIGO staging (stage I and II) (p=0.026), while its expression was not significantly associated with FIGO staging of EAC, age, tumor size, occurrence site and LND. The mRNA expression of ARID1A was positively correlated with the expression of baf250a (in OCCC group, rp=0.936, p<0.01; in OEAC group, rp=0.325, p=0.035). Analysis of prognosis showed that baf250a was an important prognostic factor rather than an independent prognostic factor, affecting the overall survival (OS) of patients with OCCC, while patients with low ARID1A mRNA expression had a longer-term OS.

CONCLUSION:

The decreased gene and protein expression levels of ARID1A are related to the occurrence and development of endometriosis-associated ovarian cancer, especially OCCC. The detection of ARID1A mRNA expression may be used to predict the OS of OCCC.

 

 

 

Biol Reprod. 2017 Jan 1;97(6):873-882..

Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling.

Shi LB¹, Zhou F¹, Zhu HY¹, Huang D¹, Jin XY¹, Li C¹, Dai Y¹, Pan YB¹, Zhang SY¹.

 

Abstract

To elucidate whether the endometriotic cells of endometriomas synthesize transforming growth factor beta1 (TGF-beta1) and understand how it affects surrounding ovarian tissue. We collected biopsies of the cystic walls from 42 endometriomas and 29 mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cystic walls. Then we detected TGFB1 mRNA synthesis in endometriomas, and tested TGF-beta1 fibrotic effect in vitro. Moreover, we verified the expression of Smad2/3 signaling components in the endometriotic cystic wall in order to understand whether TGF-beta1/Smad signaling is involved in fibrosis formation of the tissue surrounding endometriomas. The cystic walls from endometriomas demonstrated severe adhesion to ovarian tissue and obvious fibrosis compared with the mature teratomas, which was proven by the increased mRNA expression of fibrotic markers. Additionally, TGFB1 was obviously expressed in the endometriotic cystic wall, and total TGFB1 protein was significantly higher in the cystic walls of endometriomas than mature teratomas. Interestingly, TGFB1 mRNA was confirmed to be specifically synthesized in the endometriotic loci through fluorescence in situ hybridization. Cultured endometriomas derived stromal cells showed obvious fibrosis after exposed to TGF-beta1. Furthermore, components of the TGF-beta1/Smad pathway such as Smad2, Smad3, Smad4, and their phosphorylated forms were also expressed in the same location as TGF-beta1, TGF-beta receptor1, and fibrotic factors expressed in the endometriotic cystic walls. In summary, endometriotic cells of endometriomas synthesize TGF-beta1 leading to fibrosis and adhesion to ovarian tissues, and TGF-beta1/Smad signaling pathway is involved in this pathological process.

 

 

 

Reprod Sci. 2017 Jan 1:1933719117741374.

Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression.

Torres-Reverón A^1,2,3, Rivera LL^2,3, Flores I^1,4, Appleyard CB^1,5.

 

Abstract

Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger area enclosure) or no enrichment (endo-NE: 2 rats per cage) starting on postnatal day 21. After 8 weeks, sham surgery or surgical endometriosis was induced by suturing uterine horn tissue next to the intestinal mesentery, then allowed to progress for 60 days during which EE or NE continued. At the time of killing, we measured anxiety behaviors, collected endometriotic vesicles and uterus, and processed for quantitative real-time polymerase chain reaction for corticotropin-releasing hormone (CRH), urocortin-1, CRH receptors type 1 and type 2, and glucocorticoid receptor (GR). Endometriosis did not affect anxiety-like behaviors, yet rats in enriched conditions showed lower basal anxiety behaviors than the nonenriched group. Importantly, the endo-EE group showed a 28% reduction in the number of endometriosis vesicles and the vesicles were significantly smaller compared to the endo-NE group. Endometriosis increased CRH and GR only in the vesicles of endo-NE, and this increase was dampened in the endo-EE. However, urocortin 1 was increased in the vesicles of the endo-EE group, suggesting different pathways of activation of CRH receptors in this group. Our results suggest that the use of multimodal complementary therapies that reduce stress in endometriosis could be an effective and safe treatment alternative, with minimal side effects.

 

 

 

PLoS One. 2017 Nov 15;12(11):e0186520.

Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosisthrough the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway.

Cao Y¹, Ye Q², Zhuang M¹, Xie S³, Zhong R³, Cui J⁴, Zhou J³, Zhu Y³, Zhang T¹, Cao L³.

 

Abstract

OBJECTIVE:

This study aimed to investigate the link between the inhibitory effect of ginsenoside Rg3 on the ectopic endometrium growth and the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, a mechanism known to inhibit angiogenesis and induce ectopic endometrial cell apoptosis.

MATERIALS AND METHODS:

A model of endometriosis was established by allotransplantation in rats. The rats were randomly divided into 5 groups: the ginsenoside Rg3 low-dose group (group A,5mg/kgBW/d of ginsenoside Rg3), the ginsenoside Rg3 high-dose group (group B, 10mg/kgBW/d of ginsenoside Rg3), the gestrinone group (group C, 0.5mg/kgBW/d of gestrinone), the control group (groupD, 10ml/kg BW/d of 0.5%CMC-Na) and the ovariectomized group (group E, 10ml/kgBW/d of 0.5%CMC-Na). Rats were executed after 21 days of continuous administration. The ectopic endometrium volume was measured and the inhibitory rate was calculated. The levels of serum estradiol (E2) and progesterone (P) were detected by Electro-Chemiluminescence Immunoassay (ECLI). The protein expressionof VEGF, VEGFR-2, p-Akt, and p-mTOR inthe ectopic endometrium wastested by immunohistochemistry(IHC) and Western Blotting. The mRNA expression levels of VEGF, VEGFR-2, Akt, and mTOR were tested by Real-Time Polymerase Chain Reaction (PCR). The apoptosis rate of the ectopic endometrial cells was detected by Terminal Deoxynucleotidyl Transferase-mediated Digoxigenin-dUTP Nick-End Labeling Assay(TUNEL).

MAIN RESULTS:

Tissue measurements revealed a dose-dependent inhibition effect of ginsenoside Rg3 on the growth of the ectopic endometrium in treated rats compared to controls. Immunohistochemical and Western Blotting assays confirmed that the expression of VEGF, p-Akt, and p-mTOR was down-regulated in ginsenoside Rg3 -treated lesions. Real-time PCR results also showed that the mRNA expression levels of VEGF, Akt, and mTOR in the ectopic endometrium were reduced.

CONCLUSIONS:

The present study demonstrates, for the first time, that ginsenoside Rg3 suppresses angiogenesis in developing endometrial lesions. The ginsenoside Rg3 inhibitory effect on the growth of the ectopic endometrium in EMs rats might occur through the blocking of the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, thus halting angiogenesis and promoting the apoptosis of ectopic endometrial cells.

 

 

 

Exp Biol Med (Maywood). 2018 Jan;243(1):50-56.

Increased serum levels of mBDNF in women with minimal and mild endometriosis have no predictive power for the disease.

Perricos A¹, Ashjaei K¹, Husslein H¹, Proestling K¹, Kuessel L¹, Obwegeser R¹, Wenzl R¹, Yotova I¹.

 

Abstract

The objective of our pilot clinical, prospective study was to determine the serum levels of mature brain-derived neurotrophic factor, in of women with endometriosis and controls and explore whether mature brain-derived neurotrophic factor is a potential biomarker for the disease. The patients were selected from the Endometriosis Marker Austria prospective cohort study conducted at the tertiary referral certified Endometriosis Center of the Medical University of Vienna. All women underwent laparoscopic surgery because there was a suspicion of endometriosis, or the women had pelvic pain, adnexal cysts, unexplained infertility, or uterine fibroids. Our main outcome parameter was total levels of mature brain-derived neurotrophic factor in serum, measured using ELISA. Our results show that serum levels of mature brain-derived neurotrophic factor are significantly higher in women with endometriosis compared to women without endometriosis. The mean serum protein levels are significantly higher in women with rAFS stage I and II endometriosis, whereas no difference was found in women with stage III and IV endometriosis and controls. Postoperative follow-up at 6-10 weeks revealed that surgical intervention leads to equilibration of the levels of secreted mature brain-derived neurotrophic factor between women with and without endometriosis. The difference between serum mature brain-derived neurotrophic factor levels of women with endometriosis compared to women without endometriosis is independent of menstrual cycle phase and overall self-reported pelvic pain. ROC-curve analysis showed that, the mature brain-derived neurotrophic factor is not a useful biomarker for endometriosis. In conclusion, although women with stage I and II endometriosis have increased levels of mature brain-derived neurotrophic factor in serum compared to controls, the difference is not predictive for the disease. Impact statement Endometriosis is a disease that can have a significant impact on the quality of life of affected women. The gold standard for diagnosis to this day remains visualization through laparoscopic surgery with histological verification. Current studies are attempting to find a biomarker with high sensitivity and specificity, which would bypass the surgery-associated risks and would significantly reduce costs. In an attempt to elucidate whether mature serum BDNF can serve as diagnostic marker for the disease, we compared the levels of the protein in women with endometriosis to endometriosis-free controls. While our results showed that serum concentrations of the mature protein were significantly higher in women with endometriosis, we did not find this marker to have the sensitivity or specificity needed in order to allow a reliable diagnosis.

 

 

 

Reprod Sci. 2017 Jan 1:1933719117741373.

Relative Morphokinetics Assessed by Time-Lapse Imaging Are Altered in Embryos From Patients With Endometriosis.

Freis A¹, Dietrich JE¹, Binder M², Holschbach V¹, Strowitzki T¹, Germeyer A¹.

 

Abstract

INTRODUCTION:

Time-lapse technology allows almost continuous noninvasive assessment of embryonic development. It was shown previously that relative kinetics defining cleavage synchronicity are better predictors of blastocyst quality than absolute time points. This study aims to compare relative kinetics in embryos from patients with and without endometriosis.

METHODS:

Time-lapse data were collected retrospectively from 596 patients undergoing infertility treatment for in vitro fertilization from January 2011 to July 2016. Four hundred twenty-eight patients with confounding comorbidities (ie, polycystic ovary syndrome, pathological spermiogram in the included cycle, numerical/structural genetic abnormalities, preimplantation genetic screening performed) or incomplete data sets were excluded. Of the 168 included patients, 72 (42.9%) had endometriosis. Indications for in vitro fertilization of controls were tubal factor, unexplained infertility, or prolonged infertility. Relative kinetics were calculated as defined previously: cleavage synchronicity (CS)2-8=((t3-t2) + (t5-t4))/(t8-t2), CS4-8=(t8-t5)/(t8-t4), CS2-4=(t4-t3)/(t4-t2), DNA replication time ratio (DR)=(t3-t2)/(t5-t3). In women with more than one embryo, the median time was analyzed.

RESULTS:

Median age, body mass index, smoking status, and AMH levels were similar in both groups. Embryos from patients with endometriosis showed poorer relative kinetics. The relative time CS2-8 was decreased in embryos from patients with endometriosis (0.7 [0.0-0.93] vs 0.8 [0.0-0.94], P < .05) and CS4-8 was increased (0.4 [0.0-1.0] vs 0.3 [0.0-1.0], P < .05). The less powerful diagnostic relative kinetic parameters (CS2-4 and DR) were not significantly different.

CONCLUSIONS:

Embryos from patients with endometriosis presented with altered relative kinetics suggesting poorer embryo quality. These findings support recently published data demonstrating reduced oocyte quality in patients with endometriosis which is one possible explanation for their poor response to fertility treatment.

 

 

 

Acta Obstet Gynecol Scand. 2018 Feb;97(2):158-167.

Long-term evaluation of painful symptoms and fertility after surgery for large rectovaginal endometriosis nodule: a retrospective study.

Bourdel N¹, Comptour A¹, Bouchet P¹, Gremeau AS¹, Pouly JL¹, Slim K², Pereira B³, Canis M¹.

 

Abstract

INTRODUCTION:

Optimal surgical treatment of rectovaginal endometriosis remains a controversial topic. The objective of this study was to evaluate long-term postoperative outcomes after rectal shaving or colorectal resection for rectovaginal endometriosis.

MATERIAL AND METHODS:

195 patients underwent surgery (172 managed by shaving, 23 by colorectal resection) between January 2000 and June 2013 for rectovaginal endometriosis (>2 cm) involving at least the serosa of the rectum. Primary outcome measures were pain and fertility. Secondary outcome measures were complications, recurrence rates and quality of life.

RESULTS:

Mean follow-up was 60 ± 42 months in the shaving group and 67 ± 47 months in the resection group. The mean VAS score for pelvic pain between the pre and postoperative period decreased from 5.5 ± 3.5 (shaving group) and 7.3 ± 2.9 (resection group) to 2.3 ± 2.4 (p < 0.001) and 2.0 ± 1.8 (p < 0.001), respectively. For dysmenorrhea, the mean baseline VAS score fell postoperatively from 7.7 ± 2.8 (shaving group) and 8.2 ± 2.6 (resection group) to 3.3 ± 2.9 (p < 0.001) and 2.7 ± 2.7 (p < 0.001), respectively. Pregnancy rates were 73% for shaving and 69% for resection. Major complications occurred in 4% of patients in the shaving group and in 26% in the resection group (p = 0.001). Thirteen patients (7.6%) from the shaving group and none from the resection group were reoperated for suspicion of endometriosisrecurrence (p = 0.37). Postoperative quality of life scores revealed no differences between the two groups.

CONCLUSION:

Our study demonstrates that rectal shaving, when feasible for rectovaginal nodule (>2 cm) infiltrating the digestive serosa, has equal impact on pain and pregnancy rates compared with colorectal resection at long-term follow-up, with low complication and favorable pregnancy rates.

 

 

 

BMC Womens Health. 2017 Nov 16;17(1):112.

A preliminary evaluation of influence of body mass index on in vitro fertilization outcome in non-obese endometriosis patients.

Garalejic E^1,2, Arsic B¹, Radakovic J¹, Bojovic Jovic D¹, Lekic D¹, Macanovic B¹, Soldatovic I^2,3, Perovic M^4,5.

 

Abstract

BACKGROUND/AIMS:

Obese and overweight women experience a lower probability for pregnancy after IVF. However, despite the increasing prevalence of obesity, the large majority of infertile women are non-obese. One of the most common indications for IVF is endometriosis. Thought-provoking inverse correlation has been established between BMI and endometriosis. Lower BMI is a risk factor for development of endometriosis and a predictive factor for severe endometriosis. Since severe endometriosis carries lower reproductive chances, even after IVF, we preliminary tested a hypothesis that higher BMI among non-obese endometriosis patients improves IVF outcomes.

METHODS:

Preliminary retrospective observational cross-sectional study was performed in women with endometriosis as a sole infertility cause who underwent IVF. During analyzed period we performed 2782 IVF procedures. In order to achieve highly homogenous study sample and to eliminate almost all confound factors that could lead to bias, we implemented strict study criteria. The number of eligible subjects was 156 and they were divided into underweight, normal weight and overweight groups. Primary outcomes were number of retrieved oocytes, good quality oocytes, embryos, and the rates of biochemical, clinical and ongoing pregnancies. For group comparisons, we used parametric test, analysis of variance, and non-parametric tests (Kruskal-Wallis test, Chi-square test). Logistic regression and General linear model was used to assess correlation between BMI and dependent variables (outcome and stimulation duration) when adjusted for age.

RESULTS:

Endometriosis as a single infertility factor among IVF couples had prevalence of 5.61%. Underweight women accounted for 10.26%, normal weight 71.15% and overweight 18.59% of study population. Significant differences were not found in number of retrieved oocytes (p = 0.880), good quality oocytes (p = 0.476), obtained embryos (p = 0.706), and biochemical (p = 0.298), clinical (p = 0.770) and ongoing (p = 0.822) pregnancy rates between study groups.

CONCLUSION:

Although preliminary results do not support our hypothesis, increase in BMI did not adversely affect the outcome of IVF in non-obese endometriosis patients, which is in contrast to literature data as regards general population of infertile women undergoing IVF. Prospective studies with large number of patients with endometriosis or prospective case-control studies should address these issues and provide more comprehensive counseling of infertile endometriosis patients regarding achievement of optimal BMI prior to IVF with the intention of achievement higher pregnancy rates.

 

 

 

Biomed Res Int. 2017;2017:5981217.

Magnetic Resonance Colonography May Predict the Need for Bowel Resection in Colorectal Endometriosis.

Scardapane A¹, Lorusso F², Francavilla M¹, Bettocchi S³, Fascilla FD³, Angelelli G¹, Scioscia M⁴.

 

Abstract

PURPOSE:

To define if MRI findings in patients with deep pelvic endometriosis (DPE) may be predictive for the need of bowel resection.

MATERIAL AND METHODS:

A retrospective survey of 196 pelvic MRIs of women who received laparoscopic procedures for DPE was carried out. A pelvic MRI was performed in all patients: it consisted in T2w-TSE sequences in axial, sagittal, and coronal planes and T1w and THRIVE sequences in the axial plane; the exam was completed by MR-Colonography. Intestinal lesions were measured in short and long axis and the degree of stenosis was established. A multivariate logistic regression was used to identify the predictors of intestinal resection.

RESULTS:

57/196 patients received an intestinal resection. Multivariate logistic regression demonstrated a predictive value of short axis (Odds-Ratio = 2.29, p = 0.011) and stenosis (Odds-Ratio = 1.20, p = 0.003). ROC analysis showed that a cut-off value of 11 mm for the short axis and 30% for the stenosis may correctly classify, respectively, 96,94% (sensitivity 92,9% and specificity 98,56%) and 97,96% (sensitivity 94,74% and specificity 99,3%) of the cases.

CONCLUSION:

The presence of an endometriotic rectal nodule > 11 mm in short axis causing a stenosis > 30% in pelvic MRI reliably predicts the need of a rectal resection.

 

 

 

J Womens Health (Larchmt). 2017 Nov 17.

Impact of Pelvic Pain and Endometriosis on Patient-Reported Outcomes and Experiences of Benign Hysterectomy: A Study from the Swedish National Register for Gynecological Surgery.

Grundström H^1,2, Alehagen S², Berterö C², Kjølhede P^3,4.

 

Abstract

BACKGROUND:

The study objective was to analyze and compare patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) after hysterectomy in women with and without a preoperative complaint of pelvic pain associated with and without a confirmed diagnosis of endometriosis.

METHODS:

Retrospective nationwide register study. Data on 28,776 hysterectomies performed on benign indication between 2004 and 2016 were retrieved from the Swedish National Register for Gynecological Surgery. Multivariable logistic regression models were used to compare the PREMs and PROMs items. The results are presented as adjusted odds ratios (aORs) and 95% confidence intervals (CI).

RESULTS:

Regardless of the occurrence of pelvic pain preoperatively and a diagnosis of endometriosis, 1 year after surgery, the women were satisfied or very satisfied (>90%) with the hysterectomy, and their medical condition was improved or much improved (>95%). The women with a preoperative complaint of pelvic pain and endometriosis more often reported excessively short hospital stays (aOR 1.45, 95% CI 1.17-1.79), more severe complications after discharge (aOR 2.02, 95% CI 1.59-2.66) at the 8-week follow-up and at the 1-year follow-up (aOR 2.31, 95% CI 1.57-3.39), and more dissatisfaction with the operation (aOR 1.83, 95% CI 1.35-2.48) than preoperative pelvic pain-free women without endometriosis at the 1-year follow-up.

CONCLUSIONS:

The majority of the women were satisfied after their hysterectomy. The women with pelvic pain and endometriosis were at a higher risk of being dissatisfied. Pelvic pain per se seemed to be the main factor affecting the rating in the PREMs and PROMs, and the endometriosis was a significant contributing factor.