Reprod Sci. 2016 Sep;23(9):1217-24.

Surgical History and the Risk of Endometriosis: A Hospital-Based Case-Control Study.

Liu X1Long Q2Guo SW3.

 

Abstract

Women tend to receive more surgical procedures than men. Our mouse study shows that surgical stress promotes the development of endometriosis. This study was undertaken to test the hypothesis that surgery increases the risk of endometriosis. We recruited 208 patients with ovarian endometrioma and 212 age-matched patients with ovarian teratoma and retrieved information on the history of any surgical procedures after menarche, grouped by laparotomy, laparoscopy, gynecologically related procedures, cesarean section, and surgeries performed on torso and extremities was recorded. We then evaluated the association, if any, between endometriosis and history of surgical procedures. Cases and controls were comparable with respect to age, marital status, education level, and occupation. Eleven (5.3%) cases had laparotomy before the index surgery while 4 (1.9%) controls did. Sixty-six (31.7%) cases had Cesarean section while 53 (25.0%) controls did. Multivariate analysis identified age, at the index surgery laparotomy, and cesarean section as 3 factors positively associated with the risk of endometriosiswhile parity was found to be negatively associated with the risk. Laparotomy was associated with increased risk of endometriosis (odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.08-12.31), while cesarean section was associated with 2-fold increase in risk (OR = 2.16, 95% CI = 1.31-3.55). Both laparotomy and cesarean section may increase the risk of endometriosis probably by activation of adrenergic signaling, thus facilitating angiogenesis and accelerating the growth of endometriotic lesions that are already in existence. This finding may have important ramifications for the perioperative management of patients with increased risk or recurrence risk of endometriosis.

 

 

J Mol Med (Berl). 2016 Jul;94(7):835-47.

Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer.

Er TK1,2Su YF3Wu CC4Chen CC5Wang J6Hsieh TH7Herreros-Villanueva M8Chen WT4Chen YT3,4Liu TC2,9Chen HS7Tsai EM10,11,12.

Abstract

Recent molecular and pathological studies suggest that endometriosis may serve as a precursor of ovarian cancer (endometriosis-associated ovarian cancer, EAOC), especially of the endometrioid and clear cell subtypes. Accordingly, this study had two cardinal aims: first, to obtain mutation profiles of EAOC from Taiwanese patients; and second, to determine whether somatic mutations present in EAOC can be detected in preneoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from ten endometriosis patients with malignant transformation. Macrodissection was performed to separate four different types of cells from FFPE sections in six patients. The four types of samples included normal endometrium, ectopic endometriotic lesion, atypical endometriosis, and carcinoma. Ultra-deep (>1000×) targeted sequencing was performed on 409 cancer-related genes to identify pathogenic mutations associated with EAOC. The most frequently mutated genes were PIK3CA (6/10) and ARID1A (5/10). Other recurrently mutated genes included ETS1, MLH1, PRKDC (3/10 each), and AMER1, ARID2, BCL11A, CREBBP, ERBB2, EXT1, FANCD2, MSH6, NF1, NOTCH1, NUMA1, PDE4DIP, PPP2R1A, RNF213, and SYNE1 (2/10 each). Importantly, in five of the six patients, identical somatic mutations were detected in atypical endometriosis and tumor lesions. In two patients, genetic alterations were also detected in ectopic endometriotic lesions, indicating the presence of genetic alterations in preneoplastic lesion. Genetic analysis in preneoplastic lesions may help to identify high-risk patients at early stage of malignant transformation and also shed new light on fundamental aspects of the molecular pathogenesis of EAOC.

KEY MESSAGES:

Molecular characterization of endometriosis-associated ovarian cancer genes by targeted NGS. Candidate genes predictive of malignant transformation were identified. Chromatin remodeling, PI3K-AKT-mTOR, Notch signaling, and Wnt/β-catenin pathway may promote cell malignant transformation.

 

 

Biol Trace Elem Res. 2016 Oct;173(2):345-53.

Selenium Plays a Protective Role in Staphylococcus aureus-Induced Endometritis in the Uterine Tissue of Rats.

Liu Y1Qiu C1Li W1Mu W1Li C1Guo M2.

 

Abstract

The essential trace element selenium (Se) modulates the functions of many regulatory proteins in signal transduction, conferring benefits in inflammatory diseases. Endometritis is a reproductive obstacle disease both in humans and animals. Staphylococcus aureus is the major pathogen that causes endometritis. The present study analyzes the protection and mechanism of Se-methylselenocysteine (MSC) and methylseleninic acid (MSA) on S. aureus-induced endometritis. An atomic fluorescence spectrophotometry study showed that the uterine Se content increased with the addition of MSC and MSA. Histopathology observation and TUNEL detection showed that Se supplementation displayed a greater defense against uterine inflammatory damage. The quantitative PCR (qPCR) and ELISA analyses showed that the expressions of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) increased with S. aureus infection and decreased with the addition of MSC and MSA. The Toll-like receptor 2 (TLR2) expression showed the same status as the inflammatory cytokines. The Western blot results showed that the increased phosphorylation of IκBα and NF-κB p65 was also reduced by the addition of MSC and MSA. The qPCR and Western blot results also showed that the transcription expressions and the protein dissociation of caspase-9, caspase-3, caspase-7, caspase-6, and poly(ADP-ribose) polymerase (PARP), which were increased by S. aureus infection, were inhibited by Se supplementation. All of the results displayed that the protection conferred by MSC was stronger than MSA. The present study indicated the Se supplementation might be a potential prevention and control measure for S. aureus-induced endometritis.

 

 

J Steroid Biochem Mol Biol. 2016 May;159:60-9.

Altered levels of acylcarnitines, phosphatidylcholines, and sphingomyelins in peritoneal fluid from ovarian endometriosis patients.

Vouk K1Ribič-Pucelj M2Adamski J3Rižner TL4.

 

Abstract

Endometriosis is a complex, polygenic, and estrogen-dependent disease that affects 6% to 10% of women of reproductive age, and 30% to 50% of women with infertility and/or pelvic pain. Surgical diagnosis of endometriosisis still the gold standard, as there are currently no diagnostic biomarkers available. Due to the invasive diagnostics, it can take up to 11 years before affected women are diagnosed and receive the appropriate treatment. We performed a targeted metabolomics study to search for potential semi-invasive biomarkers in peritoneal fluid from endometriosis patients. Our case-control study comprised 29 ovarian endometriosis patients and 36 healthy control women. The 148 metabolites included acylcarnitines, glycerophospholipids, and sphingolipids, which were quantified by electrospray ionization tandem mass spectrometry. The strength of association between the metabolites and the metabolite ratios and disease was assessed using crude and adjusted odds ratios. The best combination of biomarkers was then selected by performing step-wise logistic regression. Our analysis reveals significantly decreased concentrations of 10 metabolites, of carnitine and acylcarnitines (C0, C8:1, C6C4:1 DC, C10:1), phosphatidylcholines (PC aa C38:3, PC aa C38:4, PC aa C40:4, PC aa C40:5), and sphingomyelins (SM C16:1, SM C18:1), and 125 significantly altered metabolite ratios in patients versus control women. The best model includes two ratios: a carnitine to a phosphatidylcholine (C0/PC ae C36:0); and between two phosphatidylcholines (PC aa C30:0/PC ae C32:2). When adjusted for age, this provides sensitivity of 82.8% and specificity of 94.4%, with AUC of 0.944. Our study supports the importance of carnitine, phosphatidylcholine, and sphingomyelin metabolites in the pathophysiology of endometriosis, and confirms the potential for the combination of individual metabolite ratios to provide biomarkers for semi-invasive diagnostics.

 

 

J Minim Invasive Gynecol. 2016 May-Jun;23(4):610-3.

Incidence of Septate Uterus in Reproductive-Aged Women With and Without Endometriosis.

LaMonica R1Pinto J2Luciano D2Lyapis A2Luciano A2.

Abstract

STUDY OBJECTIVE:

To compare the incidence of a uterine septum in women with and without endometriosis and if such incidence correlates with the stage of endometriosis Although a correlation between obstructive Mullerian anomalies and endometriosis has been well established, its link with non-obstructive anomalies remains controversial. To elucidate whether there is a correlation between endometriosis and non-obstructive Mullerian anomalies, we conducted this prospective study on all patients admitted to our Reproductive Endocrinology and Infertility surgical service from February 1, 2010 through June 30, 2012. All patients underwent both hysteroscopy and laparoscopy. Surgical indications included: infertility, pain, and/or menorrhagia. The presence or absence of endometriosis and uterine anomalies were recorded immediately after each surgery and subsequently analyzed. Endometriosis was staged according to the r-ASRM Classification and treated by resection and ablation of deep and superficial lesions, respectively. Since uterine septum is the most common Mullerian anomaly, we considered only this anomaly to test the hypothesis that uterine septum may be associated with an increased incidence of endometriosis.

DESIGN:

Prospective Study. Evidence from a well-designed case-control study (Canadian Task Force classification II-2).

SETTING:

University-affiliated tertiary care center.

PATIENTS:

Reproductive aged women admitted to our service for treatment of pelvic pain, abnormal uterine bleeding, and/or infertility.

INTERVENTION:

All patients underwent both hysteroscopy and laparoscopy as part of their evaluation and treatment of pelvic pain, abnormal uterine bleeding, and/or infertility.

MEASUREMENTS AND MAIN RESULTS:

343 patients were included in the study. The diagnosis of each patient included infertility – 52, pain – 215, both – 30 and other – 46. The diagnosis of septate uterus was made at hysteroscopy when the endometrial cavity was separated by an avascular septum that obscured visualization of both cornua when the hysteroscope was advanced to the mid-uterine segment. The septum was lysed sharply from cornua to cornua restoring normal fundal configuration. In all cases, the septolysis was bloodless, confirming its avascular nature. The overall incidence of uterine septum was 33% in our patient population. In patients with a histologically confirmed diagnosis of endometriosis, the incidence of septum was 37% versus 27% in patients without endometriosis (P = .046). In patients with advanced endometriosis, Stage IV disease, the incidence of septate uterus was 41% (P = .022). The odds ratio of Stage IV endometriosis with a uterine septum was 1.94 (CI 1.09-3.44).

CONCLUSION:

The incidence of septate uterus in our population of women with infertility and/or pelvic pain ranges from 27% to 37%, being significantly higher in women with endometriosis and mores so with Stage IV disease. Our data suggests that the presence of a uterine septum may predispose to more advanced disease.

 

 

Front Pharmacol. 2016 Feb 18;7:30.

The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases.

Rižner TL1.

 

Abstract

Gynecological diseases such as endometriosis, adenomyosis and uterine fibroids, and gynecological cancers including endometrial cancer and ovarian cancer, affect a large proportion of women. These diseases are estrogen dependent, and their progression often depends on local estrogen formation. In peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3β-hydroxysteroid dehydrogenase-Δ(4)-isomerase, aromatase, and 17-ketosteroid reductase. This review introduces the sulfatase and sulfotransferase enzymes, in terms of their structures and reaction mechanisms, and the regulation and different transcripts of their genes, together with the importance of their currently known single nucleotide polymorphisms. Data on expression of sulfatase and sulfotransferases in gynecological diseases are also reviewed. There are often unchanged mRNA and protein levels in diseased tissue, with higher sulfatase activities in cancerous endometrium, ovarian cancer cell lines, and adenomyosis. This can be indicative of a disturbed balance between the sulfatase and sulfotransferases enzymes, defining the potential for sulfatase as a drug target for treatment of gynecological diseases. Finally, clinical trials with sulfatase inhibitors are discussed, where two inhibitors have already concluded phase II trials, although so far with no convincing clinical outcomes for patients with endometrial cancer and endometriosis.

 

 

Fertil Steril. 2016 Apr;105(4):844-54.

Optimal uterine anatomy and physiology necessary for normal implantation and placentation.

de Ziegler D1Pirtea P2Galliano D3Cicinelli E4Meldrum D5.

 

Abstract

The authors review aberrations of uterine anatomy and physiology affecting pregnancy outcomes with IVF. In the case of endometriosis and hydrosalpinx, pathologies outside of the uterus alter the uterine endometrium. In the case of endometriosis, Dominique de Ziegler outlines the numerous changes in gene expression and the central role of inflammation in causing progesterone resistance. With endometriosis, the absence of ovarian function inherent in deferred transfer, with or without a more lengthy suppression of ovarian function, appears to be sufficient to restore normal function of eutopic endometrium. Because laparoscopy is no longer routine in the evaluation of infertility, unrecognized endometriosis then becomes irrelevant in the context of assisted reproductive technology. With hydrosalpinx and submucus myomas, the implantation factor HOXA-10 is suppressed in the endometrium and, with myomas, even in areas of the uterus not directly affected. Daniela Galliano reviews various uterine pathologies, the most enigmatic being adenomyosis, where the endometrium also manifests many of the changes seen in endometriosis and deferred transfer with extended suppression appears to provide the best outcomes. Ettore Cicinelli’s group has extensively studied the diagnosis and treatment of endometritis, and although more definitive diagnosis and care of this covert disorder may await techniques such as sequencing of the endometrial microbiome, it undoubtedly is an important factor in implantation failure, deserving our attention and treatment.

 

 

Am Fam Physician. 2016 Mar 1;93(5):380-7.

Chronic Pelvic Pain in Women.

Speer LM1Mushkbar S1Erbele T1.

 

Abstract

Chronic pelvic pain in women is defined as persistent, noncyclic pain perceived to be in structures related to the pelvis and lasting more than six months. Often no specific etiology can be identified, and it can be conceptualized as a chronic regional pain syndrome or functional somatic pain syndrome. It is typically associated with other functional somatic pain syndromes (e.g., irritable bowel syndrome, nonspecific chronic fatigue syndrome) and mental health disorders (e.g., posttraumatic stress disorder, depression). Diagnosis is based on findings from the history and physical examination. Pelvic ultrasonography is indicated to rule out anatomic abnormalities. Referral for diagnostic evaluation of endometriosis by laparoscopy is usually indicated in severe cases. Curative treatment is elusive, and evidence-based therapies are limited. Patient engagement in a biopsychosocial approach is recommended, with treatment of any identifiable disease process such as endometriosis, interstitial cystitis/painful bladder syndrome, and comorbid depression. Potentially beneficial medications include depot medroxyprogesterone, gabapentin, nonsteroidal anti-inflammatory drugs, and gonadotropin-releasing hormone agonists with add-back hormone therapy. Pelvic floor physical therapy may be helpful. Behavioral therapy is an integral part of treatment. In select cases, neuromodulation of sacral nerves may be appropriate. Hysterectomy may be considered as a last resort if pain seems to be of uterine origin, although significant improvement occurs in only about one-half of cases. Chronic pelvic pain should be managed with a collaborative, patient-centered approach.

 

 

Taiwan J Obstet Gynecol. 2016 Feb;55(1):55-9.

Low-dose add-back therapy during postoperative GnRH agonist treatment.

Tsai HW1Wang PH2Huang BS3Twu NF2Yen MS2Chen YJ4.

Abstract

OBJECTIVE:

Low-dose add-back therapy during postoperative GnRH agonist treatment could lower the risk of add-back-induced endometriosis recurrence and reduce treatment dropout compared with a regular dose. However, the effect of low-dose add-back therapy is still unknown. The aim of this study was to determine whether low-dose add-back therapy can also effectively relieve the hypoestrogenic side effects and simultaneously maintain a therapeutic response of GnRH agonist treatment.

MATERIALS AND METHODS:

This analysis was a prospective cohort study. During postoperative GnRH agonist treatment, a total of 107 women were prescribed add-back therapy [oral combination tablet; estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg)] (Indivina; Orion, Espoo, Finland) for 20 weeks. Patients in the low dose add-back therapy group were prescribed the tablet once a day, and patients in the regular dose group were given the tablet twice a day. Hypoestrogenic side effects, such as hot flashes and insomnia, were recorded. Patients were also questioned regarding their pelvic symptoms and pain to evaluate the possibility of endometriosisrecurrence. Lumbar spine (L2-L4) bone mineral density was measured using dual X-ray absorptiometry. The dropout rates in both groups were also evaluated.

RESULTS:

The incidence of hypoestrogenic side effects was lower in the low dose group compared with the regular dose group, including hot flashes (19.2% vs. 21.8%, p = 0.741) and insomnia (15.4% vs. 18.2%, p = 0.699), although there were no significant difference between the groups. In addition, a higher number of patients in the regular dose group dropped out of treatment compared to the low dose group (14.5% and 9.6%, respectively, p = 0.435). The patients in both groups had a significant loss of mean bone mineral density during therapy (p < 0.001 and p = 0.018 for the low dose and regular dose groups, respectively).

CONCLUSION:

Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

 

 

Taiwan J Obstet Gynecol. 2016 Feb;55(1):121-4

Puerperal ileal perforation secondary to endometriosis: Case report and literature review.

Albareda J1Albi MV2Sosa G3Cano A2Macello ME4Albi Martin B5.

Abstract

OBJECTIVE:

Bowel endometriosis is an uncommon disease that can cause serious complications and may require immediate medical attention. We wish to remind about bowel perforation caused by endometriosis, its diagnostic difficulty, and the need or urgent management in late pregnancy and puerperium.

CASE REPORT:

We present a 38-year-old woman, which presented with bowel perforation requiring urgent surgery. A pathological exam disclosed deep ileal infiltrative endometriosis.

CONCLUSION:

Even though bowel endometriosis is a rare complication, it should be considered in the differential diagnosis of severe abdominal pain in late pregnancy or puerperium. A multidisciplinary management of these patients is needed.

 

 

 

J Pediatr Adolesc Gynecol. 2017 Apr;30(2):215-222

The Effects of Gonadotropin-Releasing Hormone Agonist Combined with Add-Back Therapy on Quality of Life for Adolescents with Endometriosis: A Randomized Controlled Trial.

Sadler Gallagher J1Feldman HA2Stokes NA3Laufer MR4Hornstein MD5Gordon CM6DiVasta AD7.

Abstract

STUDY OBJECTIVE:

Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. “Add-back therapy,” the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis.

DESIGN:

Twelve-month double-blind, placebo-controlled trial.

SETTING:

Pediatric Gynecology clinic in Boston, Massachusetts.

PARTICIPANTS:

Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa.

INTERVENTIONS:

Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months.

MAIN OUTCOME MEASURES:

The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals.

RESULTS:

At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (Pbetween groups < .05) than those receiving NA alone, as well as better physical functioning (P < .05). There were no changes in depression or menopause-like symptoms in either group.

CONCLUSION:

Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Apr;199:164-8.

Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis.

Turkyilmaz E1Yildirim M2Cendek BD3Baran P4Alisik M4Dalgaci F2Yavuz AF5.

Abstract

OBJECTIVE:

The aim of the study is to evaluate alterations in intracellular and extracellular antioxidant enzymes activities and serum oxidative stress markers in patients with endometriosis.

STUDY DESIGN:

The current prospective study consisted of 31 female patients with endometriosis and 27 healthy controls. Serum total thiol, native thiol, disulphide, catalase, myeloperoxidase, and ceruloplasmin concentrations were measured. Laboratory and clinical data of all participants were recorded to compare the differences between the study and the control groups.

RESULTS:

Serum native thiol and total thiol levels in the study group were significantly lower than those in the control group [(p=0.009, p=0.03, respectively)]. Serum catalase levels are significantly higher in patients with endometriosis comparing to the control group (p=0.009).

CONCLUSIONS:

The finding that significant differences in serum total thiol, native thiol, and catalase levels observed in endometriotic patients supports that oxidative stress carries weigh in the pathophysiological aspects of endometriosis. Also significantly low levels of extracellular antioxidants and significantly high levels of intracellular antioxidants in endometriotic patients may arise from differences of free radicals in endometriosis and the activity levels of endometriosis. These non-invasive serum markers might give us an opportunity to monitor the disease’s progress during the treatment.

 

 

Praxis (Bern 1994). 2016 Mar 2;105(5):253-7.

Endometriosis Update 2016.

Imesch P1Fink D1.

 

Abstract

Endometriosis is a common gynecologic benign disease, affecting 6–10% of women of reproductive age. The disease is often associated with dysmenorrhea, dyspareunia, chronic pelvic pain and infertility. The exact mechanism of the pathogenesis of endometriosis has not yet been fully elucidated, therefore, current medical therapeutic options are more symptom-oriented than causal. The aim of the present work is to summarize the current diagnostic and therapeutic options.

 

 

Mol Med Rep. 2016 Apr;13(4):2939-48.

DNA methylation in endometriosis (Review).

Koukoura O1Sifakis S2Spandidos DA3.

 

Abstract

Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis.

 

 

 

Biol Reprod. 2016 Apr;94(4):87.

Epigenetic Modulation of Collagen 1A1: Therapeutic Implications in Fibrosis and Endometriosis.

Zheng Y1Khan Z1Zanfagnin V1Correa LF1Delaney AA1Daftary GS2.

 

Abstract

Progressive fibrosis is recalcitrant to conventional therapy and commonly complicates chronic diseases and surgical healing. We evaluate here a novel mechanism that regulates scar-tissue collagen (COL1A1/Col1a1) expression and characterizes its translational relevance as a targeted therapy for fibrosis in an endometriosisdisease model. Endometriosis is caused by displacement and implantation of uterine endometrium onto abdominal organs and spreads with progressive scarring. Transcription factor KLF11 is specifically diminished in endometriosis lesions. Loss of KLF11-mediated repression of COL1A1/Col1a1 expression resulted in increased fibrosis. To determine the biological significance of COL1A1/Col1a1 expression on fibrosis, we modulated its expression. In human endometrial-stromal fibroblasts, KLF11 recruited SIN3A/HDAC (histone deacetylase), resulting in COL1A1-promoter deacetylation and repression. This role of KLF11 was pharmacologically replicated by a histone acetyl transferase inhibitor (garcinol). In contrast, opposite effects were obtained with a HDAC inhibitor (suberoyl anilide hydroxamic acid), confirming regulatory specificity for these reciprocally active epigenetic mechanisms. Fibrosis was concordantly reversed in Klf11(-/-)animals by histone acetyl transferase inhibitor and in wild-type animals by HDAC inhibitor treatments. Aberrant lesional COL1A1 regulation is significant because fibrosis depended on lesion rather than host genotype. This is the first report demonstrating feasibility for targeted pharmacological reversal of fibrosis, an intractable phenotype of diverse chronic diseases.

 

 

Ultrasound Obstet Gynecol. 2017 Apr;49(4):515-523.

Computed tomographic colonography vs rectal water- contrast transvaginal sonography in diagnosis of rectosigmoid endometriosis: a pilot study.

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

Abstract

OBJECTIVES:

To compare the performance of computed tomographic colonography (CTC) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis, and compare precision in estimating the length of the rectosigmoid nodules and the distance between the nodules and the anal verge.

METHODS:

This prospective study included 70 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent RWC-TVS and CTC before laparoscopic excision of endometriotic nodules. The findings of RWC-TVS and CTC were compared with surgical and histological results.

RESULTS:

Of the 70 patients included in the study, 40 (57.1%) had rectosigmoid endometriosis. CTC and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.508) and similar precision in estimating the length of the endometriotic nodules (P = 0.077). CTC was more precise than RWC-TVS in estimating the distance between the rectosigmoid nodule and the anal verge (P < 0.001). The intensity of pain experienced during CTC was higher than that perceived during RWC-TVS (P < 0.001); however, intestinal distension for CTC was well-tolerated in all patients without significant adverse effects.

CONCLUSIONS:

RWC-TVS and CTC have similar accuracy in the diagnosis of rectosigmoid endometriosis and similar precision in estimating the size of the nodules; however, CTC is more precise than RWC-TVS in estimating the distance between the nodules and the anal verge, yet patients tolerate RWC-TVS better than CTC. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

 

 

Nurs Res. 2016 Mar-Apr;65(2):151-66.

Overall Adiposity, Adipose Tissue Distribution, and Endometriosis: A Systematic Review.

Backonja U1Buck Louis GMLauver DR.

Abstract

BACKGROUND:

Endometriosis has been associated with a lean body habitus. However, we do not understand whether endometriosis is also associated with other characteristics of adiposity, including adipose tissue distribution and amount of visceral adipose tissue (VAT; adipose tissue lining inner organs). Having these understandings may provide insights on how endometriosis develops-some of the physiological actions of adipose tissue differ depending on tissue amount and location and are related to proposed mechanisms of endometriosisdevelopment.

OBJECTIVES:

The aim of this study was to review the literature regarding overall adiposity, adipose tissue distribution and/or VAT, and endometriosis.

METHODS:

We reviewed and synthesized studies indexed in PubMed and/or Web of Science. We included studies that had one or more measures of overall adiposity, adipose tissue distribution, and/or VAT and women with and without endometriosis for comparison. We summarized the findings and commented on the methods used and potential sources of bias.

RESULTS:

Of 366 identified publications, 19 (5.2%) were eligible. Two additional publications were identified from reference lists. Current research included measures of overall adiposity (e.g., body figure drawings) or adipose tissue distribution (e.g., waist-to-hip ratio), but not VAT. The weight of evidence indicated that endometriosis was associated with low overall adiposity and with a preponderance of adipose tissue distributed below the waist (peripheral).

DISCUSSION:

Endometriosis may be associated with being lean or having peripherally distributed adipose tissue. Well-designed studies with various sampling frameworks and precise measures of adiposity and endometriosis are needed to confirm associations between adiposity measures and endometriosis and delineate potential etiological mechanisms underlying endometriosis.

 

 

Womens Health (Lond). 2016;12(2):175-8.

Industry is not the dark side, but an essential partner to make progress in reproductive health.

D’Hooghe T1,2,3.

 

Abstract

For the last 20 years, Thomas D’Hooghe has been coordinator of the Leuven University Fertility Center at Leuven University Hospitals, Belgium, one of the largest teaching hospitals in Europe. Since 1995, he has also been Professor of Reproductive Medicine and Biology at KU Leuven (University of Leuven) and Adjunct Professor at Yale University, USA. Since 1 October 2015, he has been the Vice President and Head of Global Medical Affairs Fertility at Merck’s headquarters in Darmstadt, Germany. He has published nearly 300 papers in internationally peer-reviewed journals and has contributed to reproductive health serving major international organizations such as the WHO, the European Society of Human Reproduction and Embryology, the Society of Reproductive Investigation and the World Endometriosis Research Foundation.

 

 

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):719-25

Short-Term Impact of Laparoscopic Cystectomy on Ovarian Reserve Tests in Bilateral and Unilateral Endometriotic and Nonendometriotic Cysts.

Salihoğlu KN1Dilbaz B1Cırık DA2Ozelci R1Ozkaya E1Mollamahmutoğlu L1.

Abstract

STUDY OBJECTIVE:

To evaluate the short-term changes in ovarian reserve markers after laparoscopic cystectomy performed for endometriotic and nonendometriotic cysts.

DESIGN:

Prospective case-control study (Canadian Task Force classification II-2).

SETTING:

The Reproductive Endocrinology Clinic of a training and research hospital.

PATIENTS:

Thirty-four women with endometrioma ≥ 4 mm (group 1) and 33 women with nonendometriotic cysts of matched size (group 2) who underwent surgery during the same period.

INTERVENTIONS:

The follicular phase follicle-stimulating hormone (FSH), estradiol (E2), and antimüllerian hormone (AMH) levels and the antral follicle count (AFC) of both groups were analyzed preoperatively and 2 months after laparoscopic cystectomy. The pre- and postoperative values were compared within the same group and between the 2 groups.

MEASUREMENT AND MAIN RESULTS:

Preoperative FSH and E2 levels were similar in both groups. However, preoperative AMH levels and AFC were significantly lower in group 1 (endometrioma) compared with group 2 (nonendometrioma; p = .004 and p = .025, respectively). In both groups there was a significant decrease in the AMH levels after surgery (3.1 ± 1.9 ng/mL to 2.5 ± 1.6 ng/mL, p < .001, and 5.7 ± 3.7 ng/mL to 4.8 ± 3.3 ng/mL, p = .04). AMH levels exhibited a significant decrease in the unilateral and bilateral endometrioma groups after cystectomy (p < .001 and p = .025, respectively). However, preoperative and postoperative changes in AMH and AFC were similar in groups 1 and 2 for both unilateral and bilateral cysts (p = .586 and p = .267).

CONCLUSION:

Preoperative AMH and AFC levels are lower in both unilateral and bilateral endometriomas compared with nonendometriotic cysts. The AMH levels decreased after cystectomy in both endometriotic and nonendometriotic cysts. However, in the short-term period the amount of change in ovarian reserve tests in both unilateral and bilateral cysts was similar for both endometrioma and nonendometriotic cysts.

 

Geburtshilfe Frauenheilkd. 2016 Feb;76(2):176-181.

Endometriosis-associated Malignancy.

Krawczyk N1Banys-Paluchowski M2Schmidt D3Ulrich U4Fehm T1.

 

Abstract

Endometriosis is a common condition in women of reproductive age. According to several epidemiological studies endometriosis may be associated with increased risk of various malignancies. However, endometriosis-associated malignancy (EAM) is defined by certain histological criteria. About 80 % of EAM have been found in the ovary, whereas 20 % are localized in extragonadal sites like intestine, rectovaginal septum, abdominal wall, pleura and others. Some authors suggest that EAM arise from atypical endometriosis as an intermediate lesion between endometriosis and cancer. Moreover, a number of genetic alterations, like loss of heterozygosity (LOH), PTEN, ARID1 A and p53 mutations have been found in both endometriosis and EAM. Endometriosis-associated ovarian cancer (EAOC) is mostly a well or intermediately differentiated tumor of endometrioid or clear cell histological sub-type. Women affected by EAOC are on average five to ten years younger than non-EAOC patients; in most of the cases EAOC is a low stage disease with favorable clinical outcome. Since EAM is a rare condition systematic data on EAM are still missing. A systematic retrospective study on endometriosis-associated malignancies (EAM study) is currently being conducted by the Endometriosis Research Foundation together with the study groups on ovarian and uterine tumors of the working group for gynecological oncology (AGO) (gyn@mlk-berlin.de).

 

 

Int J Med Sci. 2016 Feb 18;13(3):187-94.

A Prospective Randomized Experimental Study to Investigate the Eradication Rate of Endometriosis after Surgical Resection versus Aerosol Plasma Coagulation in a Rat Model.

Rothmund R1Scharpf M2Tsaousidis C1Planck C1Enderle MD3Neugebauer A3Kroeker K3Nuessle D3Fend F2Brucker S1Kraemer B1.

Abstract

PURPOSE:

To investigate the eradication rate of endometriosis after surgical resection (SR) vs. thermal ablation with aerosol plasma coagulation (AePC) in a rat model.

METHODS:

In this prospective, randomized, controlled, single-blinded animal study endometriosis was induced on the abdominal wall of 34 female Wistar rats. After 14 days endometriosis was either removed by SR or ablated by AePC. 14 days later the rats were euthanized to evaluate the eradication rate histopathologically. Intervention times were recorded.

RESULTS:

Eradication rate of endometriosis after 14 days did not significantly differ between AePC and SR (p=0.22). Intervention time per endometrial lesion was 22.1 s for AePC and 51.8 s for SR (p<0.0001).

CONCLUSIONS:

This study compares the eradication rate of the new aerosol plasma coagulation device versus standard surgical resection of endometriosis in a rat model. Despite being a thermal method, AePC showed equality towards SR regarding eradication rate but with significantly shorter intervention time.

 

 

Horm Mol Biol Clin Investig. 2016 Jan;25(1):15-28.

Is there a role for vitamin D in human reproduction?

Nandi ASinha NOng ESonmez HPoretsky L.

 

Abstract

Vitamin D is a steroid hormone with canonical roles in calcium metabolism and bone modeling. However, in recent years there has been a growing body of literature presenting associations between vitamin D levels and a variety of disease processes, including metabolic disorders such as diabetes and prediabetes and autoimmune conditions such as thyroid disease. This review focuses on the potential role of vitamin D in both male and female reproductive function. The vitamin D receptor (VDR) is expressed throughout central and peripheral organs of reproduction. VDR is often co-localized with its metabolizing enzymes, suggesting the importance of tissue specific modulation of active vitamin D levels. Both animal and human studies in males links vitamin D deficiency with hypogonadism and decreased fertility. In females, there is evidence for its role in polycystic ovary syndrome (PCOS), endometriosis, leiomyomas, in-vitro fertilization, and pregnancy outcomes. Studies evaluating the effects of replacing vitamin D have shown variable results. There remains some concern that the effects of vitamin D on reproduction are not direct, but rather secondary to the accompanying hypocalcemia or estrogen dysregulation.

 

 

Fertil Steril. 2016 Apr;105(4):873-84.

Local and systemic factors and implantation: what is the evidence?

Fox C1Morin S2Jeong JW3Scott RT Jr2Lessey BA4.

Abstract

Significant progress has been made in the understanding of embryonic competence and endometrial receptivity since the inception of assisted reproductive technology. The endometrium is a highly dynamic tissue that plays a crucial role in the establishment and maintenance of normal pregnancy. In response to steroid sex hormones, the endometrium undergoes marked changes during the menstrual cycle that are critical for acceptance of the nascent embryo. There is also a wide body of literature on systemic factors that impact assisted reproductive technology outcomes. Patient prognosis is impacted by an array of factors that tip the scales in her favor or against success. Recognizing the local and systemic factors will allow clinicians to better understand and optimize the maternal environment at the time of implantation. This review will address the current literature on endometrial and systemic factors related to impaired implantation and highlight recent advances in this area of reproductive medicine.

 

 

Medicine (Baltimore). 2016 Mar;95(9)

Length of Menstrual Cycle and Risk of Endometriosis: A Meta-Analysis of 11 Case-Control Studies.

Wei M1Cheng YBu HZhao YZhao W.

 

Abstract

Endometriosis is a complex disease that affects a large number of women worldwide and may cause pain and infertility. To systematically review published studies evaluating the relationship between menstrual cycle length and risk of endometriosis. We searched the Cochrane Library, PubMed, Web of Science, and EMBASE in databases in July 2014 using the keywords “case-control studies,” “epidemiologic determinants,” “risk factors,” “menstrual cycle,” “menstrual length,” “menstrual character,” and “endometriosis.” We included case-control studies published in English that investigated cases of surgically confirmed endometriosis and examined the relationship between endometriosis risk and menstrual cycle. Eleven articles that met the inclusion criteria included data of 3392 women with endometriosis and 5006 controls. Fixed-effects and random-effects models were used for the evaluation. For the association of risk of endometriosis and menstrual cycle length shorter than or equal to 27 days (SEQ27) or length longer than or equal to 29 days (LEQ29), the odds ratio was 1.22 (95% confidence interval [CI]: 1.05-1.43) and 0.68 (95% CI: 0.48-0.96), respectively. In conclusion, this meta-analysis suggests that menstrual cycle length SEQ27 increase the risk of endometriosis and cycle length LEQ29 decrease the risk.

 

 

Medicine (Baltimore). 2016 Mar;95(9):e3003.

Clinicopathologic Significance of HNF-1β, AIRD1A, and PIK3CA Expression in Ovarian Clear Cell Carcinoma: A Tissue Microarray Study of 130 Cases.

Ye S1Yang JYou YCao DHuang HWu MChen JLang JShen K.

 

Abstract

Ovarian clear cell carcinoma (CCC) is a distinct histologic subtype with relatively poor survival. No prognostic or predictive molecular marker is currently available. Recent studies have shown that AT-rich interactive domain 1A (ARID1A) and phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutations are common genetic changes in ovarian CCC. Hepatocyte nuclear factor-1β (HNF-1β) expression has been proven to be highly sensitive and specific for clear cell histology. However, the correlations between these biomarkers and clinicopathologic variables and survival outcomes are controversial. The immunohistochemical analysis for HNF-1β, ARID1A, and PIK3CA was performed on a tissue microarray (TMA) consisting of 130 cases of ovarian CCC (237 tissue blocks) linked with clinical information. The immunostaining results were interpreted in a manner consistent with previous publications. The associations between biomarker expression and clinical and prognostic features were examined. All statistical analyses were conducted using 2-sided tests, and a value of P < 0.05 was considered significant. HNF-1β was expressed in 92.8% of all primary ovarian tumors, while the loss of ARID1A and PIK3CA was noted in 56.2% and 45.0%, respectively. Early-stage tumors tended to have high levels of HNF-1β immunoreactivity and expression of ARID1A (P = 0.02 and P = 0.03). Most patients (76.9%, 20/26) with concurrent endometriosis stained negative for ARID1A (P = 0.02). No relation was found between PIK3CA expression and clinical features. Low-level HNF-1β expression and loss of ARID1A were more commonly observed in patients with tumor recurrence (P = 0.02 and P < 0.001). Antibody expression was not associated with platinum-based chemotherapy response. Patients with negative ARID1A expression had worse survival outcome in terms of both overall survival (OS) and progression-free survival (PFS) (P = 0.03 and P = 0.01, respectively). On the contrary, patients with high-level HNF-1β were associated with good prognosis (P = 0.02 for OS and P = 0.01 for PFS). PIK3CA expression had no impact on survival. For univariate and multivariate analyses, only HNF-1β expression seemed to be a prognostic factor for favorable OS (P = 0.04). The loss of ARID1A was correlated with late-stage and endometriosis-associated tumors. The measurement of ARID1A expression might be a method to predict the risk of recurrence. Among the 3 biomarkers, only high-level HNF-1β expression proved to be a positive predictor for OS.

 

 

 

Am J Obstet Gynecol. 2016 Sep;215(3):

Surgery accelerates the development of endometriosis in mice.

Long Q1Liu X2Guo SW3.

Abstract

BACKGROUND:

Surgery is currently the mainstay treatment for solid tumors and many benign diseases, including endometriosis, and women tend to receive substantially more surgeries than men mainly because of gynecological and cosmetic surgeries. Despite its cosmetic, therapeutic, or even life-saving benefits, surgery is reported to increase the cancer risk and promotes cancer metastasis. Surgery activates adrenergic signaling, which in turn suppresses cell-mediated immunity and promotes angiogenesis and metastasis. Because immunity, angiogenesis, and invasiveness are all involved in the pathophysiology of endometriosis, it is unclear whether surgery may accelerate the development of endometriosis.

OBJECTIVE:

The objective of the study was to test the hypothesis that surgery activates adrenergic signaling, increases angiogenesis, and accelerates the growth of endometriotic lesions.

STUDY DESIGN:

This was a prospective, randomized experimentation. The first experiment used 42 female adult Balb/C mice, and the second used 90 female adult Balb/C mice. In experiment 1, 3 days after the induction of endometriosis, mice were randomly divided into 3 groups of approximately equal sizes, control, laparotomy, and mastectomy. In experiment 2, propranolol infusion via Alzet pumps was used to forestall the effect of sympathetic nervous system activation by surgery. In both experiments, mice were evaluated 2 weeks after surgery. Lesion size, hotplate latency, and immunohistochemistry analysis of vascular endothelial growth factor, CD31-positive microvessels, proliferating cell nuclear antigen, phosphorylated cyclic adenosine monophosphate-responsive element-binding protein, β2-adrenergic receptor (ADRB)-2, ADRB1, ADRB3, ADRA1, and ADRA2 in ectopic implants.

RESULTS:

Both mastectomy and laparotomy increased lesion weight and exacerbated hyperalgesia, increased microvessel density and elevated the immunoreactivity against ADRB2, phosphorylated cyclic adenosine monophosphate-responsive element-binding protein, vascular endothelial growth factor, and proliferating cell nuclear antigen but not ADRB1, ADRB3, ADRA1, and ADRA2, suggesting activated adrenergic signaling, increased angiogenesis, and accelerated growth of endometriotic lesions. β-Blockade completely abrogated the facilitory effect of surgery, further underscoring the critical role of β-adrenergic signaling in mediating the effect of surgery.

CONCLUSION:

Surgery activates adrenergic signaling, increases angiogenesis, and accelerates the growth of endometriotic lesions in the mouse, but such a facilitory effect of surgery can be completely abrogated by β-blockade. Whether surgery can promote the development of endometriosis in humans warrants further investigation.

 

 

Toxicol Appl Pharmacol. 2016 Apr 15;297:68-80

Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats.

Ronis MJ1Gomez-Acevedo H2Blackburn ML2Cleves MA3Singhal R4Badger TM3.

 

Abstract

There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens.

 

 

Reprod Biomed Online. 2016 May;32(5):527-31.

Knowledge of, and treatment strategies for, endometriosis among general practitioners.

van der Zanden M1Nap AW2.

 

Abstract

Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis.

 

 

F1000Res. 2016 Feb 17;5. pii: F1000 Faculty Rev-186.

Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment.

Nothnick W1Alali Z2.

 

Abstract

In this review, we focus on recent advancements in our understanding of the roles of inflammatory mediators in endometriosis pathophysiology and the potential for improved therapies based upon targeting these pathways. We review the association between endometriosis and inflammation and the initial promise of anti-tumor necrosis factor therapies based upon experimental evidence, and how and why these studies have not translated to the clinic. We then discuss emerging data on the role of inter-relationship among macrophage migration inhibitory factor, prostaglandin E 2, and estrogen receptor-beta, and the potential utility of targeting these factors in endometriosis treatment. In doing so, we highlight the strengths and discuss the current research on identification of novel, anti-inflammatory-based therapy and the necessity to expand experimental endpoints to include clinically relevant measures when assessing the efficacy of potential new therapies for endometriosis.

 

 

Fertil Steril. 2016 Jun;105(6):1584-1588

Impact of female age and nulligravidity on fecundity in an older reproductive age cohort.

Steiner AZ1Jukic AM2.

Abstract

OBJECTIVE:

To provide female age-related estimates of fecundity and incidence of infertility by history of prior pregnancy among women 30-44 years of age.

DESIGN:

Prospective, time-to-pregnancy cohort study.

SETTING:

Not applicable.

PATIENT(S):

Women, between 30 and 44 years of age, attempting to conceive for ≤3 months, and no known history of infertility, polycystic ovarian syndrome (PCOS), or endometriosis.

INTERVENTION(S):

Not applicable.

MAIN OUTCOME MEASURE(S):

Fecundability and incidence of infertility.

RESULT(S):

Compared to women aged 30-31 years, fecundability was reduced by 14% in women 34-35 years of age (fecundability ratio [FR] 0.86, 95% confidence interval [CI] 0.68-1.08), 19% in women 36-37 years of age (FR 0.81, 95% CI 0.60-1.08, 30% in women 38-39 years of age (FR 0.70, 95% CI 0.48-1.01), 53% in women 40-41 years of age (FR 0.47, 95% CI 0.28-0.78), and 59% in women 42-44 years of age (FR 0.39, 95% CI 0.16-0.93). Fecundability did not differ between women aged 30-31 years and 32-33 years. In general, fecundability and cumulative probability of pregnancy was lower for women who had never had a prior pregnancy.

CONCLUSION(S):

Women experience a significant reduction in fecundity and increase in the probability of infertility in their late thirties. At any age >30 years, women who have never conceived have a lower probability of achieving a pregnancy.

 

 

BJOG. 2016 Jul;123(8):1360-7.

Pelvic organ function before and after laparoscopic bowel resection for rectosigmoid endometriosis: a prospective, observational study.

Riiskjaer M1Greisen S1Glavind-Kristensen M1Kesmodel US2Forman A1Seyer-Hansen M1.

Abstract

OBJECTIVE:

To assess urinary, sexual, and bowel function before and after laparoscopic bowel resection for rectosigmoid endometriosis.

DESIGN:

Prospectively collected data regarding the function of the pelvic organs.

SETTING:

Tertiary endometriosis referral unit, Aarhus University Hospital.

SAMPLE:

A cohort of 128 patients who underwent laparoscopic bowel resection for endometriosis.

METHODS:

The International Consultation on Incontinence Questionnaire (ICIQ), Sexual Function-Vaginal Changes Questionnaire (SVQ), and the Low Anterior Resection Syndrome (LARS) questionnaire were answered before and after surgery. Non-invasive urodynamic testing was performed.

MAIN OUTCOME MEASURES:

Pre- and postoperative function of the pelvic organs was compared, and risk factors for improved/impaired function were identified.

RESULTS:

A total of 96.1% of the women completed the 1-year follow-up. A significant decrease (P = 0.002) in bladder filling problems (F-score) was observed 1 year after surgery, primarily caused by a significant decrease in bladder pain (P = 0.0001). No change for urodynamic parameters was observed. A significant increase in overall sexual satisfaction (P = 0.0001) and decrease in worries about sexual life (P = 0.001) was seen 1 year after surgery. Frequency of defecation was significantly increased 1 year after surgery (P = 0.0001), but the overall bowel function measured by LARS score was unchanged. Patients with anastomotic leakage had a significantly higher risk (odds ratio, OR 5.40; P = 0.002) of increased incontinence problems (I-score) 1 year after surgery.

CONCLUSION:

A significant and clinically relevant improvement in urinary and sexual function 1 year after laparoscopic bowel resection for endometriosis was found. Except for anastomotic leakage, this could be observed independent of any patient- or treatment-related factor. Apprehension about impairment of urinary and sexual function should not be a contraindication for bowel resection in endometriosis patients.

TWEETABLE ABSTRACT:

Rectal resection for endometriosis does not impair urinary and sexual function 1 year after surgery.

 

 

J Med Case Rep. 2016 Mar 9;10:56.

Levonorgestrel-releasing intrauterine system placement for severe uterine cervical stenosis after conization: two case reports.

Motegi E1Hasegawa K2Kawai S3Kiuchi K4Kosaka N5Mochizuki Y6Fukasawa I7.

Abstract

BACKGROUND:

Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully.

CASE PRESENTATION:

We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic.

CONCLUSIONS:

To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.

 

 

Abdom Radiol (NY). 2016 Sep;41(9):1699-702.

A case of polypoid endometriosis with malignant transformation.

Takeuchi M1Matsuzaki K2,3Bando Y4Nishimura M5Yoneda A4Harada M2.

Abstract

Polypoid endometriosis is a benign, rare variant of endometriosis which forms multiple polypoid nodules in the female pelvis mimicking malignant tumors; however, it may rarely cause malignant transformation. We report magnetic resonance imaging findings of a case of polypoid endometriosis with malignant transformation. Multiple high-signal intensity polypoid nodules in the cul-de-sac surrounded by low-signal intensity rim-like fibrous adhesion protruding to the posterior wall of the uterine body were demonstrated on T2-weighted images. The polypoid nodules showed weak contrast enhancement compared with that of uterine myometrium on post-contrast T1-weighted images, and slight high signal intensity on diffusion-weighted images with relatively high mean apparent diffusion coefficient. Reported cases of polypoid endometriosis showed intense contrast enhancement similar to that of uterine myometrium, and weak contrast enhancement similar to that of endometrial carcinoma may be suggestive for malignant transformation of polypoid endometriosis.

 

 

Biol Reprod. 2016 Apr;94(4):93

Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice.

Wang X1Khatri S2Broaddus R3Wang Z4Hawkins SM5.

 

Abstract

Women with endometriosis can suffer from decreased fecundity or complete infertility via abnormal oocyte function or impaired placental-uterine interactions required for normal pregnancy establishment and maintenance. Although AT-rich interactive domain 1A (SWI-like) (ARID1A) is a putative tumor suppressor in human endometrial cancers and endometriosis-associated ovarian cancers, little is known about its role in normal uterine function. To study the potential function of ARID1A in the female reproductive tract, we generated mice with a conditional knockout of Arid1a using anti-Müllerian hormone receptor 2-Cre Female Arid1a conditional knockout mice exhibited a progressive decrease in number of pups per litter, with a precipitous decline after the second litter. We observed no tumors in virgin mice, although one knockout mouse developed a uterine tumor after pregnancy. Unstimulated virgin female knockout mice showed normal oviductal, ovarian, and uterine histology. Uteri of Arid1a knockout mice showed a normal decidualization response and appropriate responses to estradiol and progesterone stimulation. In vitro studies using primary cultures of human endometrial stromal fibroblasts revealed that small interfering RNA knockdown of ARID1A did not affect decidualization in vitro. Timed pregnancy studies revealed the significant resorption of embryos at Embryonic Day 16.5 in knockout mice in the third pregnancy. In addition to evidence of implantation site hemorrhage, pregnant Arid1a knockout mice showed abnormal placental morphology. These results suggest that Arid1a supports successful pregnancy through its role in placental function.

 

Medicine (Baltimore). 2016 Mar;95(10):e2773

Increased Risk of Endometriosis in Patients With Lower Genital Tract Infection: A Nationwide Cohort Study.

Lin WC1Chang CYHsu YAChiang JHWan L.

 

Abstract

Endometriosis results from the ectopic invasion of endometrial glands and stroma in the peritoneal cavity. The exact etiology of endometriosis is still unknown. It has, however, been shown that there are higher numbers of Escherichia coli in menstrual blood, and higher endotoxin levels in menstrual fluid, as well as, in the peritoneal fluid of patients with endometriosis. In this study, we aimed to determine whether lower genital tract infections could increase the risk of endometriosis.We used the Taiwan National Health Insurance database to conduct a population-based cohort study. We included patients diagnosed with inflammatory diseases of the cervix, vagina, and vulva, and a control group comprising patients matched by age, sex, and comorbidities but without inflammatory diseases of the cervix, vagina, or vulva.A total of 79,512 patients were included in the inflammatory disease group and an equal number of control individuals were selected. The incidence of endometriosis (hazard ratio, 2.01; 95% confidence interval, 1.91-2.12; P < 0.001) was higher among patients than controls. Cox proportional hazards models showed that irrespective of comorbidities, lower genital tract infection was an independent risk factor for endometriosis.Patients with lower genital tract infections exhibit a substantially higher risk for developing endometriosis.

 

 

 

Medicine (Baltimore). 2016 Mar;95

Graves Disease Is Associated With Endometriosis: A 3-Year Population-Based Cross-Sectional Study.

Yuk JS1Park EJSeo YSKim HJKwon SYPark WI.

 

Abstract

The aim of this cross-sectional study was to compare the prevalence of thyroid diseases between women with and without endometriosis.We established the endometriosis group according to diagnosis codes, surgery codes, and gonadotropin-releasing hormone agonist codes using the Korean Health Insurance Review and Assessment Service-National Inpatients Sample (HIRA-NIS) from 2009 to 2011. Four controls were randomly matched to each endometriosis case. Thyroid disease cases were selected using the thyroid disease diagnosis code (E0X).Among the 1,843,451 women sampled, 5615 had endometriosis; 22,460 controls were matched to the endometriosiscases. After adjustment for age and sampling year, Graves disease was associated with endometriosis (odds ratio [OR]: 2.52; 95% CI: 1.30-4.88; P < 0.01), while hypothyroidism was not (OR: 1.17; 95% CI: 0.90-1.52; P = 0.25). Autoimmune hypothyroidism was also not associated with endometriosis (OR: 1.61; 95% CI: 0.88-2.94; P = 0.12).This study revealed an association between Graves disease and endometriosis.

 

 

PLoS One. 2016 Mar 10;11(3)

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

Novakovic P1Harding JC2Al-Dissi AN1Ladinig A2,3Detmer SE1.

 

Abstract

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

 

 

Radiographics. 2016 Mar-Apr;36(2):596-617.

US of the Nongravid Cervix with Multimodality Imaging Correlation: Normal Appearance, Pathologic Conditions, and Diagnostic Pitfalls.

Wildenberg JC1Yam BL1Langer JE1Jones LP1.

 

Abstract

The adult uterine cervix may exhibit a wide variety of pathologic conditions that include benign entities (eg, cervicitis, hyperplasia, nabothian cysts, cervical polyps, leiomyomas, endometriosis, and congenital abnormalities) as well as malignant lesions, particularly cervical carcinoma. In addition, lesions that arise in the uterine body may secondarily involve the cervix, such as endometrial carcinoma and prolapsed intracavitary masses. Many of these conditions can be identified and characterized at ultrasonography (US), which is considered the first-line imaging examination for the female pelvis. However, examination of the cervix is often cursory during pelvic US, such that cervical disease may be overlooked or misdiagnosed. Transabdominal US of the cervix may not afford sufficient spatial resolution to depict cervical disease in many patients; therefore, endovaginal US is considered the optimal technique. Use of supplemental imaging techniques, particularly the application of transducer pressure on the cervix, may be helpful. This review describes the normal appearance of the cervix at US, the appearance of cervical lesions and conditions that mimic abnormalities at US, and optimal US techniques for evaluation of the cervix. This information will help radiologists detect and diagnose cervical abnormalities more confidently at pelvic US. Online supplemental material is available for this article.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 May;200:1-5.

Soluble tumor necrosis factor-alpha receptors in the serum of endometriosispatients.

Othman ER1Hornung D2Hussein M3Abdelaal II3Sayed AA4Fetih AN3Al-Hendy A5.

Abstract

INTRODUCTION:

We examine serum levels sTNFR-I and sTNFR-II in endometriosis patients, and their role as biomarkers of endometriosis.

MATERIAL AND METHODS:

Women were diagnosed with endometriosis during laparoscopy to investigate pelvic pain and/or infertility (N=62). Control group included women with pelvic pain and/or infertility, whose laparoscopy showed no abnormalities (N=55). Serum concentrations of sTNFR-I and sTNFR-II were measured using Bioplex Protein Array system. Non-parametric statistics were used.

RESULTS:

Endometriosis patients had significantly higher levels of sTNFR-I than controls (257.46pg/ml, IQR=2.37-1048.92 versus 130.39pg/ml, IQR=0.99-361.1 respectively, P value=0.01). For TNFR-II, difference between women with (232pg/ml, IQR=0.0-624.4), and women without (132.93pg/ml, IQR=0.0-312.81) endometriosis was not significant (P value=0.05). Early stage endometriosis patients had significantly higher level of sTNFR-I (559.13, IQR=1.82-1289.86) and sTNFR-II (248.8, IQR=0-644.65) than control women (P value is 0.01 for TNFR-I and 0.04 for TNFR-II). Levels of sTNFR-I and sTNFR-II were comparable for advanced endometriosis and controls, and between early and advanced endometriosis. As a biomarker for all- stage endometriosis, sTNFR-I produces AUC of 0.62, sensitivity of 61%, and specificity of 47.3%, at a cutoff of 81.87pg/ml. For early stage disease, sTNFR-I yields AUC of 0.68, sensitivity of 60.7%, specificity of 75%, at a cutoff of 351.22pg/ml.

CONCLUSION:

sTNFR-I is significantly higher in serum of endometriosis patients than controls. As an endometriosis biomarker, sTNFR-I achieves better performance for early stage disease.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:95-99.

Prior colorectal surgery for endometriosis-associated infertility improves ICSI-IVF outcomes: results from two expert centres.

Ballester M1Roman H2Mathieu E3Touleimat S2Belghiti J3Daraï E4.

Abstract

OBJECTIVE(S):

To assess fertility outcomes after ICSI-IVF in infertile women having undergone prior complete surgical removal of colorectal endometriosis.

STUDY DESIGN:

Prospective longitudinal cohort study in two referral French centres including 60 infertile women who underwent ICSI-IVF after complete surgical removal of colorectal endometriosis, from January 2005 to May 2014. Women underwent either conservative colorectal surgery (i.e., rectal shaving or full thickness disc excision, n=18) or segmental colorectal resection (n=42). Clinical pregnancies were defined by the presence of a gestational sac on vaginal ultrasound examination from the fifth week. The overall pregnancy rate was calculated. The Kaplan-Meier method was used to estimate the cumulative pregnancy rate (CPR). Comparisons of CPR were made using the log-rank test to detect determinant factors.

RESULTS:

The median number of ICSI-IVF cycles per patient was one (range: 1-4). Of the 60 women, 36 became pregnant (i.e., overall pregnancy rate=60%). The CPR was 41.7% after one ICSI-IVF cycle, 65% after two ICSI-IVF cycles and 78.1% after three ICSI-IVF cycles. A decreased CPR was observed for women who required segmental colorectal resection compared to those who underwent rectal shaving or full thickness disc excision (p=0.04). A trend for a decreased CPR was observed for women who received a first ICSI-IVF cycle more than 18 months following surgery (p=0.07). Among the nine women with prior ICSI-IVF failure, five (55.5%) became pregnant after surgery.

CONCLUSION(S):

Colorectal surgery for endometriosis completed by ICSI-IVF is a good option for women with proven infertility, even if prior ICSI-IVF had failed.

 

 

Gynecol Endocrinol. 2016 Sep;32(9):733-736.

Serum pentraxin 3 as a possible marker for mature cystic teratomas.

Ishida C1Iwase A1,2Osuka S1Goto M1Takikawa S1Nakamura T1Kotani T1Kikkawa F1.

 

Abstract

Pentraxin 3 (PTX3) is an inflammatory mediator that is released by a wide range of tissues and cells. Elevated PTX3 levels may represent a useful diagnostic and/or prognostic marker for a number of diseases. The purpose of this study was to investigate serum PTX3 levels in benign gynecological conditions including mature cystic teratomas (MCTs), endometriomas, and uterine leiomyomas. Serum PTX3 levels of the MCT group were found to be significantly higher compared to those of the other groups, including healthy controls (p = 0.001), although carbohydrate antigen 19-9 (CA19-9) did not exhibit a significant difference. Serum PTX3 levels of the MCT, but not the endometrioma group, were also found to have significantly decreased post-operatively (mean ± standard deviation, 4.98 ± 2.10 to 3.61 ± 1.53 ng/mL). Immunohistochemical analyses demonstrated positive staining for PTX3 protein in the sebaceous glands, epidermal tissues, and hair roots of MCT specimens. PTX3 is expressed by MCTs and is associated with increased serum concentrations compared to healthy controls and patients with either endometriomas or uterine leiomyomas. We conclude that serum PTX3 levels could be used as a potential diagnostic marker for MCTs, especially helpful in differentiating them from endometriomas with elevated expression of CA19-9.

 

 

Hum Reprod. 2016 May;31(5):986-98.

Overexpression of chloride channel-3 is associated with the increased migration and invasion ability of ectopic endometrial cells from patients with endometriosis.

Guan YT1Huang YQ2Wu JB3Deng ZQ1Wang Y4Lai ZY4Wang HB3Sun XX4Zhu YL2Du MM2Zhu LY3Chen LX5Wang LW6.

Abstract

STUDY QUESTION:

Is chloride channel-3 (ClC-3) involved in regulating the biological behavior of endometrial stromal cells (ESCs)?

SUMMARY ANSWER:

ClC-3 promotes endometriotic cell migration and invasion.

WHAT IS KNOWN ALREADY:

ClC-3 plays a significant role in the migration and invasion of various kinds of cells.

STUDY DESIGN, SIZE, DURATION:

An ITALIC! in vitro investigation of the effect of ClC-3 on the migration and invasion of ectopic ESCs from patients with endometriosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The ectopic and eutopic endometrial samples from 43 female patients with endometriosis and the endometrial samples from 39 non-endometriotic female patients were collected. Primary cells from these samples were isolated and cultured. Real-time RT-PCR, immunohistochemistry and western blot were used to detect the expression of ClC-3 and matrix metalloproteinase 9 (MMP-9). Small interfering RNA (siRNA) technology was employed to knock down ClC-3 expression. The migration and invasion ability of ESCs was measured by the transwell assay with uncoated or Matrigel-coated membranes.

MAIN RESULTS AND THE ROLE OF CHANCE:

The expression of ClC-3 mRNA and proteins was significantly up-regulated in the ectopic tissues from endometriotic patients, while that in the eutopic endometrial tissues of the same patients did not significantly differ from that in non-endometriotic patients. The migration and invasion ability and MMP-9 expression was increased in the ESCs from ectopic endometrial tissues. The knockdown of ClC-3 expression by ClC-3 siRNA inhibited ESC migration and invasion and attenuated the expression of MMP-9. ClC-3 expression level was well-correlated to the clinical characteristics and symptoms of endometriosis patients, including infertility, dysmenorrhea, chronic pelvic pain, dyspareunia and diameter of endometriosis lesion.

LIMITATIONS, REASONS FOR CAUTION:

Further studies are needed to examine the regulatory mechanism of estrogen on ClC-3 expression of ESCs.

WIDER IMPLICATIONS OF THE FINDINGS:

ClC-3 is involved in the migration and invasion processes of ESCs and can regulate MMP-9 expression. Up-regulation of ClC-3 expression may contribute to endometriosis development by regulating MMP-9 expression.

 

 

Hum Reprod. 2016 May;31(5):1014-23.

Increased rate of spontaneous miscarriages in endometriosis-affected women.

Santulli P1Marcellin L2Menard S3Thubert T3Khoshnood B4Gayet V3Goffinet F5Ancel PY4Chapron C2.

Abstract

STUDY QUESTION:

Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls?

SUMMARY ANSWER:

Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls.

WHAT IS KNOWN ALREADY:

The association between endometriosis and miscarriages has long been debated without reaching a consensus.

STUDY DESIGN, SIZE, DURATION:

We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosisgroup and 466 in the control group.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification).

MAIN RESULTS AND THE ROLE OF CHANCE:

Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16).

LIMITATIONS, REASONS FOR CAUTION:

There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented.

WIDER IMPLICATIONS OF THE FINDINGS:

This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates.

STUDY FUNDING/COMPETING INTERESTS:

No external funding was used for this study. The authors have no conflicts of interest to declare.

 

 

Clin Med Insights Womens Health. 2016 Mar 7;9:7-11.

Radical Surgery for Endometriosis: Analysis of Quality of Life and Surgical Procedure.

De la Hera-Lazaro CM1Muñoz-González JL1Perez RO1Vellido-Cotelo R1Díez-Álvarez A1Muñoz-Hernando L1Alvarez-Conejo C1Jiménez-López JS1.

Abstract

OBJECTIVE:

The main aim of this study is to determine the improvement in quality of life in patients who have undergone radical surgery because of severe endometriosis.

PATIENTS AND METHODS:

This nonrandomized interventional study (quasi experimental) was carried out between January 2009 and September 2014. A total of 46 patients with diagnosis of severe endometriosis were included. Radical surgery, including hysterectomy, was performed. Acting as their own control group, the patients were asked to fill in a validated questionnaire of quality of life [Endometriosis Health Profile-5 (EHP-5)] and a visual analog scale of pain at the moment of the preoperative visit (one month prior to surgery) and six months after the surgery.

RESULTS:

Radical surgery for endometriosis was performed in 46 patients at our center over the period of six years. Among the patients, 73.9% of them had undergone previous surgery for endometriosis. In 82.6% of cases, a complete laparoscopic resection was carried out. Gastrointestinal tract resection was performed in 21.7%, and urinary tract resection was necessary in 8.7%. The mean age of the patients was 38.6 years. The rate of complications was 30.4%. Six months after the surgery, all items of the EHP-5 questionnaire had a lower score, which means an improvement in all aspects of quality of life related to endometriosis. The difference obtained between the scores before and after the surgery was statistically significant. The mean visual analog scale score before the surgery was 8.5, whereas it decreased to 1.4 after the surgery (P < 0.001).

CONCLUSION:

Performing a radical surgery is a difficult decision to make; however, it can provide optimal results in terms of improvement of quality of life and, therefore, should be considered when conservative therapy fails.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:81-85.

Treatment of endometrioma for improving fertility.

Leone Roberti Maggiore U1Gupta JK2Ferrero S3.

 

Abstract

Endometrioma is a frequent clinical manifestation of endometriosis. It is controversial how endometriomas may affect women’s fertility. This review addresses: the impact of the endometrioma per se and of its surgical treatment on ovarian physiology, on the ovarian reserve, on spontaneous conception and pregnancy outcomes, and on IVF/ICSI outcomes. Based on current evidence, although there are plausible biological detrimental effects on the ovarian cortex surrounding the endometrioma and an impairment of the normal ovarian physiology, the clinical impact of the endometrioma per se is not significantly altered. There is a negligible detrimental effect on ovarian reserve with spontaneous ovulation not being impaired. Conversely, surgical excision of an endometrioma reduces ovarian reserve as measured by AMH levels. Studies investigating the impact of the endometrioma per se and of its surgical treatment in women requiring IVF/ICSI show similar implantation rates, clinical pregnancy rates and live birth rates between women with endometrioma and controls.

 

 

 

Med Hypotheses. 2016 Apr;89:43-7.

Autonomic denervation: A new aetiological framework for clinical obstetrics and gynaecology.

Quinn MJ1.

 

Abstract

The hypothesis is that many clinical conditions in obstetrics and gynaecology result from the diverse and varying consequences of injuries to pelvic autonomic nerves. These injuries result from difficult first labours, persistent physical efforts during defaecation, and, medical and surgical techniques for evacuation of the uterus. The neuro-immunohistochemical “signatures” of these injuries are variations of the Dixon-Robertson-Brosens (DRB) lesion in preeclampsia, where there is hyperplasia of the tunica intima and media of arterioles with narrowing of the lumen of the vessel. In stage IV, nulliparous “endometriosis” (and other gynaecological conditions) there are circumferential layers of abnormal nerves around a narrowed arteriole, whereas in early-onset preeclampsia (and other obstetric conditions) there are similar histological findings in uterine arterioles but there is no sign of injured nerves. During pregnancy there is elongation of blood vessels but no elongation of injured nerves leading to relative denervation of the myometrium. These lesions are detectable in most of the “great” obstetric syndromes, and, across the spectrum of gynaecological syndromes. They provide a coherent explanation of the natural history and clinical presentations of many of these syndromes. Clinical features vary with the site, nature and extent of the injury; a minor injury may enable pregnancy though it is complicated by late-onset pre-eclampsia whereas a more extensive injury may prevent pregnancy and present with chronic pelvic pain with, or without, endometriosis.

 

 

 

Int J Gynecol Pathol. 2016 Nov;35(6):544-548.

Non-Neoplastic Conditions of the Ovaries in Grossly Normal Adnexa: A Clinicopathologic Study of 403 Completely Embedded Cases.

Seidman JD1Krishnan J.

 

Abstract

Most non-neoplastic lesions of the ovaries have not been comprehensively examined in the contemporary literature. We evaluated completely embedded ovaries from 403 unselected, consecutive patients who had grossly normal adnexa. These included prophylactic specimens in high-risk women with BRCA mutations (38 women) and women with a personal history of breast cancer or a family history of breast and/or ovarian cancer (79 women). Transitional cell (Brenner) nests were found in 9.1%; 31% of these lesions were smaller than 1 mm, and 8 were solitary nests. Cortical granulomas were found in 20.5%, fatty metaplasia in 5.3%, mucinous metaplasia of surface epithelial inclusions in 5.5%, and smooth muscle stromal metaplasia in 2%. One or more types of stromal hyperplasia were found in 24.3%. Endometriosis was found in 22% of adnexa. There were no significant differences in the findings in high-risk women compared with non-high-risk except those attributable to age differences between the groups. These findings establish baseline frequencies for non-neoplastic ovarian lesions, and suggest that transitional cell nests are so common that they can be regarded as a normal finding.

 

 

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):753-9

Assessment of Long-Term Bowel Symptoms After Segmental Resection of Deeply Infiltrating Endometriosis: A Matched Cohort Study.

Soto E1Catenacci M2Bedient C3Jelovsek JE4Falcone T5.

Abstract

STUDY OBJECTIVE:

To assess long-term bowel symptoms in women who underwent segmental bowel resection for deep-infiltrating endometriosis (DIE) compared with women who underwent resection of severe endometriosiswithout bowel resection.

DESIGN:

Cohort study with matched controls (Canadian Task Force classification II-2).

SETTING:

Cleveland Clinic.

PATIENTS:

71 patients (36 cases and 35 controls).

INTERVENTIONS:

Patients who were at least 4 years out from undergoing segmental bowel resection due to DIE were matched with patients who had undergone resection of stage III/IV endometriosis without bowel resection. The patients completed validated questionnaires, and data were analyzed using the Wilcoxon rank-sum, χ(2), and Fisher exact tests.

MEASUREMENTS AND MAIN RESULTS:

The Bristol Stool Form Scale, Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM), and St Mark’s Vaizey Fecal Incontinence Grading System were used to elicit information. The median duration of follow-up was 10.1 years (range, 4-18 years). The mean patient age and body mass index were comparable in the cases and the controls. A larger proportion of cases than controls reported new bowel symptoms (58% [21 of 36] vs 14% [5 of 35]; p = .001), as well as abdominal pain, incomplete bowel movements, and false alarms on the PAC-SYM questionnaire; however, total PAC-SYM and Vaizey Fecal Incontinence Grading System scores were similar in the 2 groups (median, 8 [interquartile range, 8-10] vs 8 [8-10]; p = .86). Similarly, the proportion of patients with normal stool consistency (Bristol Stool Form Scale score 2-6) was similar in the 2 groups (80.6% [29 of 36] vs 94.3% [33 of 35]; p = .59).

CONCLUSION:

Segmental bowel resection for DIE may be associated with a higher incidence of new bowel symptoms (possibly due to abdominal pain, incomplete bowel movements, and/or false alarms), but not with worse constipation or fecal incontinence, compared with surgery without bowel resection.

 

 

 

Reprod Sci. 2016 Sep;23(9):1217-24.

Surgical History and the Risk of Endometriosis: A Hospital-Based Case-Control Study.

Liu X1Long Q2Guo SW3.

 

Abstract

Women tend to receive more surgical procedures than men. Our mouse study shows that surgical stress promotes the development of endometriosis. This study was undertaken to test the hypothesis that surgery increases the risk of endometriosis. We recruited 208 patients with ovarian endometrioma and 212 age-matched patients with ovarian teratoma and retrieved information on the history of any surgical procedures after menarche, grouped by laparotomy, laparoscopy, gynecologically related procedures, cesarean section, and surgeries performed on torso and extremities was recorded. We then evaluated the association, if any, between endometriosis and history of surgical procedures. Cases and controls were comparable with respect to age, marital status, education level, and occupation. Eleven (5.3%) cases had laparotomy before the index surgery while 4 (1.9%) controls did. Sixty-six (31.7%) cases had Cesarean section while 53 (25.0%) controls did. Multivariate analysis identified age, at the index surgery laparotomy, and cesarean section as 3 factors positively associated with the risk of endometriosiswhile parity was found to be negatively associated with the risk. Laparotomy was associated with increased risk of endometriosis (odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.08-12.31), while cesarean section was associated with 2-fold increase in risk (OR = 2.16, 95% CI = 1.31-3.55). Both laparotomy and cesarean section may increase the risk of endometriosis probably by activation of adrenergic signaling, thus facilitating angiogenesis and accelerating the growth of endometriotic lesions that are already in existence. This finding may have important ramifications for the perioperative management of patients with increased risk or recurrence risk of endometriosis.

 

 

J Mol Med (Berl). 2016 Jul;94(7):835-47.

Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer.

Er TK1,2Su YF3Wu CC4Chen CC5Wang J6Hsieh TH7Herreros-Villanueva M8Chen WT4Chen YT3,4Liu TC2,9Chen HS7Tsai EM10,11,12.

Abstract

Recent molecular and pathological studies suggest that endometriosis may serve as a precursor of ovarian cancer (endometriosis-associated ovarian cancer, EAOC), especially of the endometrioid and clear cell subtypes. Accordingly, this study had two cardinal aims: first, to obtain mutation profiles of EAOC from Taiwanese patients; and second, to determine whether somatic mutations present in EAOC can be detected in preneoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from ten endometriosis patients with malignant transformation. Macrodissection was performed to separate four different types of cells from FFPE sections in six patients. The four types of samples included normal endometrium, ectopic endometriotic lesion, atypical endometriosis, and carcinoma. Ultra-deep (>1000×) targeted sequencing was performed on 409 cancer-related genes to identify pathogenic mutations associated with EAOC. The most frequently mutated genes were PIK3CA (6/10) and ARID1A (5/10). Other recurrently mutated genes included ETS1, MLH1, PRKDC (3/10 each), and AMER1, ARID2, BCL11A, CREBBP, ERBB2, EXT1, FANCD2, MSH6, NF1, NOTCH1, NUMA1, PDE4DIP, PPP2R1A, RNF213, and SYNE1 (2/10 each). Importantly, in five of the six patients, identical somatic mutations were detected in atypical endometriosis and tumor lesions. In two patients, genetic alterations were also detected in ectopic endometriotic lesions, indicating the presence of genetic alterations in preneoplastic lesion. Genetic analysis in preneoplastic lesions may help to identify high-risk patients at early stage of malignant transformation and also shed new light on fundamental aspects of the molecular pathogenesis of EAOC.

KEY MESSAGES:

Molecular characterization of endometriosis-associated ovarian cancer genes by targeted NGS. Candidate genes predictive of malignant transformation were identified. Chromatin remodeling, PI3K-AKT-mTOR, Notch signaling, and Wnt/β-catenin pathway may promote cell malignant transformation.

 

 

Biol Trace Elem Res. 2016 Oct;173(2):345-53.

Selenium Plays a Protective Role in Staphylococcus aureus-Induced Endometritis in the Uterine Tissue of Rats.

Liu Y1Qiu C1Li W1Mu W1Li C1Guo M2.

 

Abstract

The essential trace element selenium (Se) modulates the functions of many regulatory proteins in signal transduction, conferring benefits in inflammatory diseases. Endometritis is a reproductive obstacle disease both in humans and animals. Staphylococcus aureus is the major pathogen that causes endometritis. The present study analyzes the protection and mechanism of Se-methylselenocysteine (MSC) and methylseleninic acid (MSA) on S. aureus-induced endometritis. An atomic fluorescence spectrophotometry study showed that the uterine Se content increased with the addition of MSC and MSA. Histopathology observation and TUNEL detection showed that Se supplementation displayed a greater defense against uterine inflammatory damage. The quantitative PCR (qPCR) and ELISA analyses showed that the expressions of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) increased with S. aureus infection and decreased with the addition of MSC and MSA. The Toll-like receptor 2 (TLR2) expression showed the same status as the inflammatory cytokines. The Western blot results showed that the increased phosphorylation of IκBα and NF-κB p65 was also reduced by the addition of MSC and MSA. The qPCR and Western blot results also showed that the transcription expressions and the protein dissociation of caspase-9, caspase-3, caspase-7, caspase-6, and poly(ADP-ribose) polymerase (PARP), which were increased by S. aureus infection, were inhibited by Se supplementation. All of the results displayed that the protection conferred by MSC was stronger than MSA. The present study indicated the Se supplementation might be a potential prevention and control measure for S. aureus-induced endometritis.

 

 

J Steroid Biochem Mol Biol. 2016 May;159:60-9.

Altered levels of acylcarnitines, phosphatidylcholines, and sphingomyelins in peritoneal fluid from ovarian endometriosis patients.

Vouk K1Ribič-Pucelj M2Adamski J3Rižner TL4.

 

Abstract

Endometriosis is a complex, polygenic, and estrogen-dependent disease that affects 6% to 10% of women of reproductive age, and 30% to 50% of women with infertility and/or pelvic pain. Surgical diagnosis of endometriosisis still the gold standard, as there are currently no diagnostic biomarkers available. Due to the invasive diagnostics, it can take up to 11 years before affected women are diagnosed and receive the appropriate treatment. We performed a targeted metabolomics study to search for potential semi-invasive biomarkers in peritoneal fluid from endometriosis patients. Our case-control study comprised 29 ovarian endometriosis patients and 36 healthy control women. The 148 metabolites included acylcarnitines, glycerophospholipids, and sphingolipids, which were quantified by electrospray ionization tandem mass spectrometry. The strength of association between the metabolites and the metabolite ratios and disease was assessed using crude and adjusted odds ratios. The best combination of biomarkers was then selected by performing step-wise logistic regression. Our analysis reveals significantly decreased concentrations of 10 metabolites, of carnitine and acylcarnitines (C0, C8:1, C6C4:1 DC, C10:1), phosphatidylcholines (PC aa C38:3, PC aa C38:4, PC aa C40:4, PC aa C40:5), and sphingomyelins (SM C16:1, SM C18:1), and 125 significantly altered metabolite ratios in patients versus control women. The best model includes two ratios: a carnitine to a phosphatidylcholine (C0/PC ae C36:0); and between two phosphatidylcholines (PC aa C30:0/PC ae C32:2). When adjusted for age, this provides sensitivity of 82.8% and specificity of 94.4%, with AUC of 0.944. Our study supports the importance of carnitine, phosphatidylcholine, and sphingomyelin metabolites in the pathophysiology of endometriosis, and confirms the potential for the combination of individual metabolite ratios to provide biomarkers for semi-invasive diagnostics.

 

 

J Minim Invasive Gynecol. 2016 May-Jun;23(4):610-3.

Incidence of Septate Uterus in Reproductive-Aged Women With and Without Endometriosis.

LaMonica R1Pinto J2Luciano D2Lyapis A2Luciano A2.

Abstract

STUDY OBJECTIVE:

To compare the incidence of a uterine septum in women with and without endometriosis and if such incidence correlates with the stage of endometriosis Although a correlation between obstructive Mullerian anomalies and endometriosis has been well established, its link with non-obstructive anomalies remains controversial. To elucidate whether there is a correlation between endometriosis and non-obstructive Mullerian anomalies, we conducted this prospective study on all patients admitted to our Reproductive Endocrinology and Infertility surgical service from February 1, 2010 through June 30, 2012. All patients underwent both hysteroscopy and laparoscopy. Surgical indications included: infertility, pain, and/or menorrhagia. The presence or absence of endometriosis and uterine anomalies were recorded immediately after each surgery and subsequently analyzed. Endometriosis was staged according to the r-ASRM Classification and treated by resection and ablation of deep and superficial lesions, respectively. Since uterine septum is the most common Mullerian anomaly, we considered only this anomaly to test the hypothesis that uterine septum may be associated with an increased incidence of endometriosis.

DESIGN:

Prospective Study. Evidence from a well-designed case-control study (Canadian Task Force classification II-2).

SETTING:

University-affiliated tertiary care center.

PATIENTS:

Reproductive aged women admitted to our service for treatment of pelvic pain, abnormal uterine bleeding, and/or infertility.

INTERVENTION:

All patients underwent both hysteroscopy and laparoscopy as part of their evaluation and treatment of pelvic pain, abnormal uterine bleeding, and/or infertility.

MEASUREMENTS AND MAIN RESULTS:

343 patients were included in the study. The diagnosis of each patient included infertility – 52, pain – 215, both – 30 and other – 46. The diagnosis of septate uterus was made at hysteroscopy when the endometrial cavity was separated by an avascular septum that obscured visualization of both cornua when the hysteroscope was advanced to the mid-uterine segment. The septum was lysed sharply from cornua to cornua restoring normal fundal configuration. In all cases, the septolysis was bloodless, confirming its avascular nature. The overall incidence of uterine septum was 33% in our patient population. In patients with a histologically confirmed diagnosis of endometriosis, the incidence of septum was 37% versus 27% in patients without endometriosis (P = .046). In patients with advanced endometriosis, Stage IV disease, the incidence of septate uterus was 41% (P = .022). The odds ratio of Stage IV endometriosis with a uterine septum was 1.94 (CI 1.09-3.44).

CONCLUSION:

The incidence of septate uterus in our population of women with infertility and/or pelvic pain ranges from 27% to 37%, being significantly higher in women with endometriosis and mores so with Stage IV disease. Our data suggests that the presence of a uterine septum may predispose to more advanced disease.

 

 

Front Pharmacol. 2016 Feb 18;7:30.

The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases.

Rižner TL1.

 

Abstract

Gynecological diseases such as endometriosis, adenomyosis and uterine fibroids, and gynecological cancers including endometrial cancer and ovarian cancer, affect a large proportion of women. These diseases are estrogen dependent, and their progression often depends on local estrogen formation. In peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3β-hydroxysteroid dehydrogenase-Δ(4)-isomerase, aromatase, and 17-ketosteroid reductase. This review introduces the sulfatase and sulfotransferase enzymes, in terms of their structures and reaction mechanisms, and the regulation and different transcripts of their genes, together with the importance of their currently known single nucleotide polymorphisms. Data on expression of sulfatase and sulfotransferases in gynecological diseases are also reviewed. There are often unchanged mRNA and protein levels in diseased tissue, with higher sulfatase activities in cancerous endometrium, ovarian cancer cell lines, and adenomyosis. This can be indicative of a disturbed balance between the sulfatase and sulfotransferases enzymes, defining the potential for sulfatase as a drug target for treatment of gynecological diseases. Finally, clinical trials with sulfatase inhibitors are discussed, where two inhibitors have already concluded phase II trials, although so far with no convincing clinical outcomes for patients with endometrial cancer and endometriosis.

 

 

Fertil Steril. 2016 Apr;105(4):844-54.

Optimal uterine anatomy and physiology necessary for normal implantation and placentation.

de Ziegler D1Pirtea P2Galliano D3Cicinelli E4Meldrum D5.

 

Abstract

The authors review aberrations of uterine anatomy and physiology affecting pregnancy outcomes with IVF. In the case of endometriosis and hydrosalpinx, pathologies outside of the uterus alter the uterine endometrium. In the case of endometriosis, Dominique de Ziegler outlines the numerous changes in gene expression and the central role of inflammation in causing progesterone resistance. With endometriosis, the absence of ovarian function inherent in deferred transfer, with or without a more lengthy suppression of ovarian function, appears to be sufficient to restore normal function of eutopic endometrium. Because laparoscopy is no longer routine in the evaluation of infertility, unrecognized endometriosis then becomes irrelevant in the context of assisted reproductive technology. With hydrosalpinx and submucus myomas, the implantation factor HOXA-10 is suppressed in the endometrium and, with myomas, even in areas of the uterus not directly affected. Daniela Galliano reviews various uterine pathologies, the most enigmatic being adenomyosis, where the endometrium also manifests many of the changes seen in endometriosis and deferred transfer with extended suppression appears to provide the best outcomes. Ettore Cicinelli’s group has extensively studied the diagnosis and treatment of endometritis, and although more definitive diagnosis and care of this covert disorder may await techniques such as sequencing of the endometrial microbiome, it undoubtedly is an important factor in implantation failure, deserving our attention and treatment.

 

 

Am Fam Physician. 2016 Mar 1;93(5):380-7.

Chronic Pelvic Pain in Women.

Speer LM1Mushkbar S1Erbele T1.

 

Abstract

Chronic pelvic pain in women is defined as persistent, noncyclic pain perceived to be in structures related to the pelvis and lasting more than six months. Often no specific etiology can be identified, and it can be conceptualized as a chronic regional pain syndrome or functional somatic pain syndrome. It is typically associated with other functional somatic pain syndromes (e.g., irritable bowel syndrome, nonspecific chronic fatigue syndrome) and mental health disorders (e.g., posttraumatic stress disorder, depression). Diagnosis is based on findings from the history and physical examination. Pelvic ultrasonography is indicated to rule out anatomic abnormalities. Referral for diagnostic evaluation of endometriosis by laparoscopy is usually indicated in severe cases. Curative treatment is elusive, and evidence-based therapies are limited. Patient engagement in a biopsychosocial approach is recommended, with treatment of any identifiable disease process such as endometriosis, interstitial cystitis/painful bladder syndrome, and comorbid depression. Potentially beneficial medications include depot medroxyprogesterone, gabapentin, nonsteroidal anti-inflammatory drugs, and gonadotropin-releasing hormone agonists with add-back hormone therapy. Pelvic floor physical therapy may be helpful. Behavioral therapy is an integral part of treatment. In select cases, neuromodulation of sacral nerves may be appropriate. Hysterectomy may be considered as a last resort if pain seems to be of uterine origin, although significant improvement occurs in only about one-half of cases. Chronic pelvic pain should be managed with a collaborative, patient-centered approach.

 

 

Taiwan J Obstet Gynecol. 2016 Feb;55(1):55-9.

Low-dose add-back therapy during postoperative GnRH agonist treatment.

Tsai HW1Wang PH2Huang BS3Twu NF2Yen MS2Chen YJ4.

Abstract

OBJECTIVE:

Low-dose add-back therapy during postoperative GnRH agonist treatment could lower the risk of add-back-induced endometriosis recurrence and reduce treatment dropout compared with a regular dose. However, the effect of low-dose add-back therapy is still unknown. The aim of this study was to determine whether low-dose add-back therapy can also effectively relieve the hypoestrogenic side effects and simultaneously maintain a therapeutic response of GnRH agonist treatment.

MATERIALS AND METHODS:

This analysis was a prospective cohort study. During postoperative GnRH agonist treatment, a total of 107 women were prescribed add-back therapy [oral combination tablet; estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg)] (Indivina; Orion, Espoo, Finland) for 20 weeks. Patients in the low dose add-back therapy group were prescribed the tablet once a day, and patients in the regular dose group were given the tablet twice a day. Hypoestrogenic side effects, such as hot flashes and insomnia, were recorded. Patients were also questioned regarding their pelvic symptoms and pain to evaluate the possibility of endometriosisrecurrence. Lumbar spine (L2-L4) bone mineral density was measured using dual X-ray absorptiometry. The dropout rates in both groups were also evaluated.

RESULTS:

The incidence of hypoestrogenic side effects was lower in the low dose group compared with the regular dose group, including hot flashes (19.2% vs. 21.8%, p = 0.741) and insomnia (15.4% vs. 18.2%, p = 0.699), although there were no significant difference between the groups. In addition, a higher number of patients in the regular dose group dropped out of treatment compared to the low dose group (14.5% and 9.6%, respectively, p = 0.435). The patients in both groups had a significant loss of mean bone mineral density during therapy (p < 0.001 and p = 0.018 for the low dose and regular dose groups, respectively).

CONCLUSION:

Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

 

 

Taiwan J Obstet Gynecol. 2016 Feb;55(1):121-4

Puerperal ileal perforation secondary to endometriosis: Case report and literature review.

Albareda J1Albi MV2Sosa G3Cano A2Macello ME4Albi Martin B5.

Abstract

OBJECTIVE:

Bowel endometriosis is an uncommon disease that can cause serious complications and may require immediate medical attention. We wish to remind about bowel perforation caused by endometriosis, its diagnostic difficulty, and the need or urgent management in late pregnancy and puerperium.

CASE REPORT:

We present a 38-year-old woman, which presented with bowel perforation requiring urgent surgery. A pathological exam disclosed deep ileal infiltrative endometriosis.

CONCLUSION:

Even though bowel endometriosis is a rare complication, it should be considered in the differential diagnosis of severe abdominal pain in late pregnancy or puerperium. A multidisciplinary management of these patients is needed.

 

 

 

J Pediatr Adolesc Gynecol. 2017 Apr;30(2):215-222

The Effects of Gonadotropin-Releasing Hormone Agonist Combined with Add-Back Therapy on Quality of Life for Adolescents with Endometriosis: A Randomized Controlled Trial.

Sadler Gallagher J1Feldman HA2Stokes NA3Laufer MR4Hornstein MD5Gordon CM6DiVasta AD7.

Abstract

STUDY OBJECTIVE:

Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. “Add-back therapy,” the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis.

DESIGN:

Twelve-month double-blind, placebo-controlled trial.

SETTING:

Pediatric Gynecology clinic in Boston, Massachusetts.

PARTICIPANTS:

Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa.

INTERVENTIONS:

Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months.

MAIN OUTCOME MEASURES:

The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals.

RESULTS:

At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (Pbetween groups < .05) than those receiving NA alone, as well as better physical functioning (P < .05). There were no changes in depression or menopause-like symptoms in either group.

CONCLUSION:

Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Apr;199:164-8.

Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis.

Turkyilmaz E1Yildirim M2Cendek BD3Baran P4Alisik M4Dalgaci F2Yavuz AF5.

Abstract

OBJECTIVE:

The aim of the study is to evaluate alterations in intracellular and extracellular antioxidant enzymes activities and serum oxidative stress markers in patients with endometriosis.

STUDY DESIGN:

The current prospective study consisted of 31 female patients with endometriosis and 27 healthy controls. Serum total thiol, native thiol, disulphide, catalase, myeloperoxidase, and ceruloplasmin concentrations were measured. Laboratory and clinical data of all participants were recorded to compare the differences between the study and the control groups.

RESULTS:

Serum native thiol and total thiol levels in the study group were significantly lower than those in the control group [(p=0.009, p=0.03, respectively)]. Serum catalase levels are significantly higher in patients with endometriosis comparing to the control group (p=0.009).

CONCLUSIONS:

The finding that significant differences in serum total thiol, native thiol, and catalase levels observed in endometriotic patients supports that oxidative stress carries weigh in the pathophysiological aspects of endometriosis. Also significantly low levels of extracellular antioxidants and significantly high levels of intracellular antioxidants in endometriotic patients may arise from differences of free radicals in endometriosis and the activity levels of endometriosis. These non-invasive serum markers might give us an opportunity to monitor the disease’s progress during the treatment.

 

 

Praxis (Bern 1994). 2016 Mar 2;105(5):253-7.

Endometriosis Update 2016.

Imesch P1Fink D1.

 

Abstract

Endometriosis is a common gynecologic benign disease, affecting 6–10% of women of reproductive age. The disease is often associated with dysmenorrhea, dyspareunia, chronic pelvic pain and infertility. The exact mechanism of the pathogenesis of endometriosis has not yet been fully elucidated, therefore, current medical therapeutic options are more symptom-oriented than causal. The aim of the present work is to summarize the current diagnostic and therapeutic options.

 

 

Mol Med Rep. 2016 Apr;13(4):2939-48.

DNA methylation in endometriosis (Review).

Koukoura O1Sifakis S2Spandidos DA3.

 

Abstract

Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis.

 

 

 

Biol Reprod. 2016 Apr;94(4):87.

Epigenetic Modulation of Collagen 1A1: Therapeutic Implications in Fibrosis and Endometriosis.

Zheng Y1Khan Z1Zanfagnin V1Correa LF1Delaney AA1Daftary GS2.

 

Abstract

Progressive fibrosis is recalcitrant to conventional therapy and commonly complicates chronic diseases and surgical healing. We evaluate here a novel mechanism that regulates scar-tissue collagen (COL1A1/Col1a1) expression and characterizes its translational relevance as a targeted therapy for fibrosis in an endometriosisdisease model. Endometriosis is caused by displacement and implantation of uterine endometrium onto abdominal organs and spreads with progressive scarring. Transcription factor KLF11 is specifically diminished in endometriosis lesions. Loss of KLF11-mediated repression of COL1A1/Col1a1 expression resulted in increased fibrosis. To determine the biological significance of COL1A1/Col1a1 expression on fibrosis, we modulated its expression. In human endometrial-stromal fibroblasts, KLF11 recruited SIN3A/HDAC (histone deacetylase), resulting in COL1A1-promoter deacetylation and repression. This role of KLF11 was pharmacologically replicated by a histone acetyl transferase inhibitor (garcinol). In contrast, opposite effects were obtained with a HDAC inhibitor (suberoyl anilide hydroxamic acid), confirming regulatory specificity for these reciprocally active epigenetic mechanisms. Fibrosis was concordantly reversed in Klf11(-/-)animals by histone acetyl transferase inhibitor and in wild-type animals by HDAC inhibitor treatments. Aberrant lesional COL1A1 regulation is significant because fibrosis depended on lesion rather than host genotype. This is the first report demonstrating feasibility for targeted pharmacological reversal of fibrosis, an intractable phenotype of diverse chronic diseases.

 

 

Ultrasound Obstet Gynecol. 2017 Apr;49(4):515-523.

Computed tomographic colonography vs rectal water- contrast transvaginal sonography in diagnosis of rectosigmoid endometriosis: a pilot study.

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

Abstract

OBJECTIVES:

To compare the performance of computed tomographic colonography (CTC) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis, and compare precision in estimating the length of the rectosigmoid nodules and the distance between the nodules and the anal verge.

METHODS:

This prospective study included 70 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent RWC-TVS and CTC before laparoscopic excision of endometriotic nodules. The findings of RWC-TVS and CTC were compared with surgical and histological results.

RESULTS:

Of the 70 patients included in the study, 40 (57.1%) had rectosigmoid endometriosis. CTC and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.508) and similar precision in estimating the length of the endometriotic nodules (P = 0.077). CTC was more precise than RWC-TVS in estimating the distance between the rectosigmoid nodule and the anal verge (P < 0.001). The intensity of pain experienced during CTC was higher than that perceived during RWC-TVS (P < 0.001); however, intestinal distension for CTC was well-tolerated in all patients without significant adverse effects.

CONCLUSIONS:

RWC-TVS and CTC have similar accuracy in the diagnosis of rectosigmoid endometriosis and similar precision in estimating the size of the nodules; however, CTC is more precise than RWC-TVS in estimating the distance between the nodules and the anal verge, yet patients tolerate RWC-TVS better than CTC. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

 

 

Nurs Res. 2016 Mar-Apr;65(2):151-66.

Overall Adiposity, Adipose Tissue Distribution, and Endometriosis: A Systematic Review.

Backonja U1Buck Louis GMLauver DR.

Abstract

BACKGROUND:

Endometriosis has been associated with a lean body habitus. However, we do not understand whether endometriosis is also associated with other characteristics of adiposity, including adipose tissue distribution and amount of visceral adipose tissue (VAT; adipose tissue lining inner organs). Having these understandings may provide insights on how endometriosis develops-some of the physiological actions of adipose tissue differ depending on tissue amount and location and are related to proposed mechanisms of endometriosisdevelopment.

OBJECTIVES:

The aim of this study was to review the literature regarding overall adiposity, adipose tissue distribution and/or VAT, and endometriosis.

METHODS:

We reviewed and synthesized studies indexed in PubMed and/or Web of Science. We included studies that had one or more measures of overall adiposity, adipose tissue distribution, and/or VAT and women with and without endometriosis for comparison. We summarized the findings and commented on the methods used and potential sources of bias.

RESULTS:

Of 366 identified publications, 19 (5.2%) were eligible. Two additional publications were identified from reference lists. Current research included measures of overall adiposity (e.g., body figure drawings) or adipose tissue distribution (e.g., waist-to-hip ratio), but not VAT. The weight of evidence indicated that endometriosis was associated with low overall adiposity and with a preponderance of adipose tissue distributed below the waist (peripheral).

DISCUSSION:

Endometriosis may be associated with being lean or having peripherally distributed adipose tissue. Well-designed studies with various sampling frameworks and precise measures of adiposity and endometriosis are needed to confirm associations between adiposity measures and endometriosis and delineate potential etiological mechanisms underlying endometriosis.

 

 

Womens Health (Lond). 2016;12(2):175-8.

Industry is not the dark side, but an essential partner to make progress in reproductive health.

D’Hooghe T1,2,3.

 

Abstract

For the last 20 years, Thomas D’Hooghe has been coordinator of the Leuven University Fertility Center at Leuven University Hospitals, Belgium, one of the largest teaching hospitals in Europe. Since 1995, he has also been Professor of Reproductive Medicine and Biology at KU Leuven (University of Leuven) and Adjunct Professor at Yale University, USA. Since 1 October 2015, he has been the Vice President and Head of Global Medical Affairs Fertility at Merck’s headquarters in Darmstadt, Germany. He has published nearly 300 papers in internationally peer-reviewed journals and has contributed to reproductive health serving major international organizations such as the WHO, the European Society of Human Reproduction and Embryology, the Society of Reproductive Investigation and the World Endometriosis Research Foundation.

 

 

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):719-25

Short-Term Impact of Laparoscopic Cystectomy on Ovarian Reserve Tests in Bilateral and Unilateral Endometriotic and Nonendometriotic Cysts.

Salihoğlu KN1Dilbaz B1Cırık DA2Ozelci R1Ozkaya E1Mollamahmutoğlu L1.

Abstract

STUDY OBJECTIVE:

To evaluate the short-term changes in ovarian reserve markers after laparoscopic cystectomy performed for endometriotic and nonendometriotic cysts.

DESIGN:

Prospective case-control study (Canadian Task Force classification II-2).

SETTING:

The Reproductive Endocrinology Clinic of a training and research hospital.

PATIENTS:

Thirty-four women with endometrioma ≥ 4 mm (group 1) and 33 women with nonendometriotic cysts of matched size (group 2) who underwent surgery during the same period.

INTERVENTIONS:

The follicular phase follicle-stimulating hormone (FSH), estradiol (E2), and antimüllerian hormone (AMH) levels and the antral follicle count (AFC) of both groups were analyzed preoperatively and 2 months after laparoscopic cystectomy. The pre- and postoperative values were compared within the same group and between the 2 groups.

MEASUREMENT AND MAIN RESULTS:

Preoperative FSH and E2 levels were similar in both groups. However, preoperative AMH levels and AFC were significantly lower in group 1 (endometrioma) compared with group 2 (nonendometrioma; p = .004 and p = .025, respectively). In both groups there was a significant decrease in the AMH levels after surgery (3.1 ± 1.9 ng/mL to 2.5 ± 1.6 ng/mL, p < .001, and 5.7 ± 3.7 ng/mL to 4.8 ± 3.3 ng/mL, p = .04). AMH levels exhibited a significant decrease in the unilateral and bilateral endometrioma groups after cystectomy (p < .001 and p = .025, respectively). However, preoperative and postoperative changes in AMH and AFC were similar in groups 1 and 2 for both unilateral and bilateral cysts (p = .586 and p = .267).

CONCLUSION:

Preoperative AMH and AFC levels are lower in both unilateral and bilateral endometriomas compared with nonendometriotic cysts. The AMH levels decreased after cystectomy in both endometriotic and nonendometriotic cysts. However, in the short-term period the amount of change in ovarian reserve tests in both unilateral and bilateral cysts was similar for both endometrioma and nonendometriotic cysts.

 

Geburtshilfe Frauenheilkd. 2016 Feb;76(2):176-181.

Endometriosis-associated Malignancy.

Krawczyk N1Banys-Paluchowski M2Schmidt D3Ulrich U4Fehm T1.

 

Abstract

Endometriosis is a common condition in women of reproductive age. According to several epidemiological studies endometriosis may be associated with increased risk of various malignancies. However, endometriosis-associated malignancy (EAM) is defined by certain histological criteria. About 80 % of EAM have been found in the ovary, whereas 20 % are localized in extragonadal sites like intestine, rectovaginal septum, abdominal wall, pleura and others. Some authors suggest that EAM arise from atypical endometriosis as an intermediate lesion between endometriosis and cancer. Moreover, a number of genetic alterations, like loss of heterozygosity (LOH), PTEN, ARID1 A and p53 mutations have been found in both endometriosis and EAM. Endometriosis-associated ovarian cancer (EAOC) is mostly a well or intermediately differentiated tumor of endometrioid or clear cell histological sub-type. Women affected by EAOC are on average five to ten years younger than non-EAOC patients; in most of the cases EAOC is a low stage disease with favorable clinical outcome. Since EAM is a rare condition systematic data on EAM are still missing. A systematic retrospective study on endometriosis-associated malignancies (EAM study) is currently being conducted by the Endometriosis Research Foundation together with the study groups on ovarian and uterine tumors of the working group for gynecological oncology (AGO) (gyn@mlk-berlin.de).

 

 

Int J Med Sci. 2016 Feb 18;13(3):187-94.

A Prospective Randomized Experimental Study to Investigate the Eradication Rate of Endometriosis after Surgical Resection versus Aerosol Plasma Coagulation in a Rat Model.

Rothmund R1Scharpf M2Tsaousidis C1Planck C1Enderle MD3Neugebauer A3Kroeker K3Nuessle D3Fend F2Brucker S1Kraemer B1.

Abstract

PURPOSE:

To investigate the eradication rate of endometriosis after surgical resection (SR) vs. thermal ablation with aerosol plasma coagulation (AePC) in a rat model.

METHODS:

In this prospective, randomized, controlled, single-blinded animal study endometriosis was induced on the abdominal wall of 34 female Wistar rats. After 14 days endometriosis was either removed by SR or ablated by AePC. 14 days later the rats were euthanized to evaluate the eradication rate histopathologically. Intervention times were recorded.

RESULTS:

Eradication rate of endometriosis after 14 days did not significantly differ between AePC and SR (p=0.22). Intervention time per endometrial lesion was 22.1 s for AePC and 51.8 s for SR (p<0.0001).

CONCLUSIONS:

This study compares the eradication rate of the new aerosol plasma coagulation device versus standard surgical resection of endometriosis in a rat model. Despite being a thermal method, AePC showed equality towards SR regarding eradication rate but with significantly shorter intervention time.

 

 

Horm Mol Biol Clin Investig. 2016 Jan;25(1):15-28.

Is there a role for vitamin D in human reproduction?

Nandi ASinha NOng ESonmez HPoretsky L.

 

Abstract

Vitamin D is a steroid hormone with canonical roles in calcium metabolism and bone modeling. However, in recent years there has been a growing body of literature presenting associations between vitamin D levels and a variety of disease processes, including metabolic disorders such as diabetes and prediabetes and autoimmune conditions such as thyroid disease. This review focuses on the potential role of vitamin D in both male and female reproductive function. The vitamin D receptor (VDR) is expressed throughout central and peripheral organs of reproduction. VDR is often co-localized with its metabolizing enzymes, suggesting the importance of tissue specific modulation of active vitamin D levels. Both animal and human studies in males links vitamin D deficiency with hypogonadism and decreased fertility. In females, there is evidence for its role in polycystic ovary syndrome (PCOS), endometriosis, leiomyomas, in-vitro fertilization, and pregnancy outcomes. Studies evaluating the effects of replacing vitamin D have shown variable results. There remains some concern that the effects of vitamin D on reproduction are not direct, but rather secondary to the accompanying hypocalcemia or estrogen dysregulation.

 

 

Fertil Steril. 2016 Apr;105(4):873-84.

Local and systemic factors and implantation: what is the evidence?

Fox C1Morin S2Jeong JW3Scott RT Jr2Lessey BA4.

Abstract

Significant progress has been made in the understanding of embryonic competence and endometrial receptivity since the inception of assisted reproductive technology. The endometrium is a highly dynamic tissue that plays a crucial role in the establishment and maintenance of normal pregnancy. In response to steroid sex hormones, the endometrium undergoes marked changes during the menstrual cycle that are critical for acceptance of the nascent embryo. There is also a wide body of literature on systemic factors that impact assisted reproductive technology outcomes. Patient prognosis is impacted by an array of factors that tip the scales in her favor or against success. Recognizing the local and systemic factors will allow clinicians to better understand and optimize the maternal environment at the time of implantation. This review will address the current literature on endometrial and systemic factors related to impaired implantation and highlight recent advances in this area of reproductive medicine.

 

 

Medicine (Baltimore). 2016 Mar;95(9)

Length of Menstrual Cycle and Risk of Endometriosis: A Meta-Analysis of 11 Case-Control Studies.

Wei M1Cheng YBu HZhao YZhao W.

 

Abstract

Endometriosis is a complex disease that affects a large number of women worldwide and may cause pain and infertility. To systematically review published studies evaluating the relationship between menstrual cycle length and risk of endometriosis. We searched the Cochrane Library, PubMed, Web of Science, and EMBASE in databases in July 2014 using the keywords “case-control studies,” “epidemiologic determinants,” “risk factors,” “menstrual cycle,” “menstrual length,” “menstrual character,” and “endometriosis.” We included case-control studies published in English that investigated cases of surgically confirmed endometriosis and examined the relationship between endometriosis risk and menstrual cycle. Eleven articles that met the inclusion criteria included data of 3392 women with endometriosis and 5006 controls. Fixed-effects and random-effects models were used for the evaluation. For the association of risk of endometriosis and menstrual cycle length shorter than or equal to 27 days (SEQ27) or length longer than or equal to 29 days (LEQ29), the odds ratio was 1.22 (95% confidence interval [CI]: 1.05-1.43) and 0.68 (95% CI: 0.48-0.96), respectively. In conclusion, this meta-analysis suggests that menstrual cycle length SEQ27 increase the risk of endometriosis and cycle length LEQ29 decrease the risk.

 

 

Medicine (Baltimore). 2016 Mar;95(9):e3003.

Clinicopathologic Significance of HNF-1β, AIRD1A, and PIK3CA Expression in Ovarian Clear Cell Carcinoma: A Tissue Microarray Study of 130 Cases.

Ye S1Yang JYou YCao DHuang HWu MChen JLang JShen K.

 

Abstract

Ovarian clear cell carcinoma (CCC) is a distinct histologic subtype with relatively poor survival. No prognostic or predictive molecular marker is currently available. Recent studies have shown that AT-rich interactive domain 1A (ARID1A) and phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutations are common genetic changes in ovarian CCC. Hepatocyte nuclear factor-1β (HNF-1β) expression has been proven to be highly sensitive and specific for clear cell histology. However, the correlations between these biomarkers and clinicopathologic variables and survival outcomes are controversial. The immunohistochemical analysis for HNF-1β, ARID1A, and PIK3CA was performed on a tissue microarray (TMA) consisting of 130 cases of ovarian CCC (237 tissue blocks) linked with clinical information. The immunostaining results were interpreted in a manner consistent with previous publications. The associations between biomarker expression and clinical and prognostic features were examined. All statistical analyses were conducted using 2-sided tests, and a value of P < 0.05 was considered significant. HNF-1β was expressed in 92.8% of all primary ovarian tumors, while the loss of ARID1A and PIK3CA was noted in 56.2% and 45.0%, respectively. Early-stage tumors tended to have high levels of HNF-1β immunoreactivity and expression of ARID1A (P = 0.02 and P = 0.03). Most patients (76.9%, 20/26) with concurrent endometriosis stained negative for ARID1A (P = 0.02). No relation was found between PIK3CA expression and clinical features. Low-level HNF-1β expression and loss of ARID1A were more commonly observed in patients with tumor recurrence (P = 0.02 and P < 0.001). Antibody expression was not associated with platinum-based chemotherapy response. Patients with negative ARID1A expression had worse survival outcome in terms of both overall survival (OS) and progression-free survival (PFS) (P = 0.03 and P = 0.01, respectively). On the contrary, patients with high-level HNF-1β were associated with good prognosis (P = 0.02 for OS and P = 0.01 for PFS). PIK3CA expression had no impact on survival. For univariate and multivariate analyses, only HNF-1β expression seemed to be a prognostic factor for favorable OS (P = 0.04). The loss of ARID1A was correlated with late-stage and endometriosis-associated tumors. The measurement of ARID1A expression might be a method to predict the risk of recurrence. Among the 3 biomarkers, only high-level HNF-1β expression proved to be a positive predictor for OS.

 

 

 

Am J Obstet Gynecol. 2016 Sep;215(3):

Surgery accelerates the development of endometriosis in mice.

Long Q1Liu X2Guo SW3.

Abstract

BACKGROUND:

Surgery is currently the mainstay treatment for solid tumors and many benign diseases, including endometriosis, and women tend to receive substantially more surgeries than men mainly because of gynecological and cosmetic surgeries. Despite its cosmetic, therapeutic, or even life-saving benefits, surgery is reported to increase the cancer risk and promotes cancer metastasis. Surgery activates adrenergic signaling, which in turn suppresses cell-mediated immunity and promotes angiogenesis and metastasis. Because immunity, angiogenesis, and invasiveness are all involved in the pathophysiology of endometriosis, it is unclear whether surgery may accelerate the development of endometriosis.

OBJECTIVE:

The objective of the study was to test the hypothesis that surgery activates adrenergic signaling, increases angiogenesis, and accelerates the growth of endometriotic lesions.

STUDY DESIGN:

This was a prospective, randomized experimentation. The first experiment used 42 female adult Balb/C mice, and the second used 90 female adult Balb/C mice. In experiment 1, 3 days after the induction of endometriosis, mice were randomly divided into 3 groups of approximately equal sizes, control, laparotomy, and mastectomy. In experiment 2, propranolol infusion via Alzet pumps was used to forestall the effect of sympathetic nervous system activation by surgery. In both experiments, mice were evaluated 2 weeks after surgery. Lesion size, hotplate latency, and immunohistochemistry analysis of vascular endothelial growth factor, CD31-positive microvessels, proliferating cell nuclear antigen, phosphorylated cyclic adenosine monophosphate-responsive element-binding protein, β2-adrenergic receptor (ADRB)-2, ADRB1, ADRB3, ADRA1, and ADRA2 in ectopic implants.

RESULTS:

Both mastectomy and laparotomy increased lesion weight and exacerbated hyperalgesia, increased microvessel density and elevated the immunoreactivity against ADRB2, phosphorylated cyclic adenosine monophosphate-responsive element-binding protein, vascular endothelial growth factor, and proliferating cell nuclear antigen but not ADRB1, ADRB3, ADRA1, and ADRA2, suggesting activated adrenergic signaling, increased angiogenesis, and accelerated growth of endometriotic lesions. β-Blockade completely abrogated the facilitory effect of surgery, further underscoring the critical role of β-adrenergic signaling in mediating the effect of surgery.

CONCLUSION:

Surgery activates adrenergic signaling, increases angiogenesis, and accelerates the growth of endometriotic lesions in the mouse, but such a facilitory effect of surgery can be completely abrogated by β-blockade. Whether surgery can promote the development of endometriosis in humans warrants further investigation.

 

 

Toxicol Appl Pharmacol. 2016 Apr 15;297:68-80

Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats.

Ronis MJ1Gomez-Acevedo H2Blackburn ML2Cleves MA3Singhal R4Badger TM3.

 

Abstract

There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens.

 

 

Reprod Biomed Online. 2016 May;32(5):527-31.

Knowledge of, and treatment strategies for, endometriosis among general practitioners.

van der Zanden M1Nap AW2.

 

Abstract

Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis.

 

 

F1000Res. 2016 Feb 17;5. pii: F1000 Faculty Rev-186.

Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment.

Nothnick W1Alali Z2.

 

Abstract

In this review, we focus on recent advancements in our understanding of the roles of inflammatory mediators in endometriosis pathophysiology and the potential for improved therapies based upon targeting these pathways. We review the association between endometriosis and inflammation and the initial promise of anti-tumor necrosis factor therapies based upon experimental evidence, and how and why these studies have not translated to the clinic. We then discuss emerging data on the role of inter-relationship among macrophage migration inhibitory factor, prostaglandin E 2, and estrogen receptor-beta, and the potential utility of targeting these factors in endometriosis treatment. In doing so, we highlight the strengths and discuss the current research on identification of novel, anti-inflammatory-based therapy and the necessity to expand experimental endpoints to include clinically relevant measures when assessing the efficacy of potential new therapies for endometriosis.

 

 

Fertil Steril. 2016 Jun;105(6):1584-1588

Impact of female age and nulligravidity on fecundity in an older reproductive age cohort.

Steiner AZ1Jukic AM2.

Abstract

OBJECTIVE:

To provide female age-related estimates of fecundity and incidence of infertility by history of prior pregnancy among women 30-44 years of age.

DESIGN:

Prospective, time-to-pregnancy cohort study.

SETTING:

Not applicable.

PATIENT(S):

Women, between 30 and 44 years of age, attempting to conceive for ≤3 months, and no known history of infertility, polycystic ovarian syndrome (PCOS), or endometriosis.

INTERVENTION(S):

Not applicable.

MAIN OUTCOME MEASURE(S):

Fecundability and incidence of infertility.

RESULT(S):

Compared to women aged 30-31 years, fecundability was reduced by 14% in women 34-35 years of age (fecundability ratio [FR] 0.86, 95% confidence interval [CI] 0.68-1.08), 19% in women 36-37 years of age (FR 0.81, 95% CI 0.60-1.08, 30% in women 38-39 years of age (FR 0.70, 95% CI 0.48-1.01), 53% in women 40-41 years of age (FR 0.47, 95% CI 0.28-0.78), and 59% in women 42-44 years of age (FR 0.39, 95% CI 0.16-0.93). Fecundability did not differ between women aged 30-31 years and 32-33 years. In general, fecundability and cumulative probability of pregnancy was lower for women who had never had a prior pregnancy.

CONCLUSION(S):

Women experience a significant reduction in fecundity and increase in the probability of infertility in their late thirties. At any age >30 years, women who have never conceived have a lower probability of achieving a pregnancy.

 

 

BJOG. 2016 Jul;123(8):1360-7.

Pelvic organ function before and after laparoscopic bowel resection for rectosigmoid endometriosis: a prospective, observational study.

Riiskjaer M1Greisen S1Glavind-Kristensen M1Kesmodel US2Forman A1Seyer-Hansen M1.

Abstract

OBJECTIVE:

To assess urinary, sexual, and bowel function before and after laparoscopic bowel resection for rectosigmoid endometriosis.

DESIGN:

Prospectively collected data regarding the function of the pelvic organs.

SETTING:

Tertiary endometriosis referral unit, Aarhus University Hospital.

SAMPLE:

A cohort of 128 patients who underwent laparoscopic bowel resection for endometriosis.

METHODS:

The International Consultation on Incontinence Questionnaire (ICIQ), Sexual Function-Vaginal Changes Questionnaire (SVQ), and the Low Anterior Resection Syndrome (LARS) questionnaire were answered before and after surgery. Non-invasive urodynamic testing was performed.

MAIN OUTCOME MEASURES:

Pre- and postoperative function of the pelvic organs was compared, and risk factors for improved/impaired function were identified.

RESULTS:

A total of 96.1% of the women completed the 1-year follow-up. A significant decrease (P = 0.002) in bladder filling problems (F-score) was observed 1 year after surgery, primarily caused by a significant decrease in bladder pain (P = 0.0001). No change for urodynamic parameters was observed. A significant increase in overall sexual satisfaction (P = 0.0001) and decrease in worries about sexual life (P = 0.001) was seen 1 year after surgery. Frequency of defecation was significantly increased 1 year after surgery (P = 0.0001), but the overall bowel function measured by LARS score was unchanged. Patients with anastomotic leakage had a significantly higher risk (odds ratio, OR 5.40; P = 0.002) of increased incontinence problems (I-score) 1 year after surgery.

CONCLUSION:

A significant and clinically relevant improvement in urinary and sexual function 1 year after laparoscopic bowel resection for endometriosis was found. Except for anastomotic leakage, this could be observed independent of any patient- or treatment-related factor. Apprehension about impairment of urinary and sexual function should not be a contraindication for bowel resection in endometriosis patients.

TWEETABLE ABSTRACT:

Rectal resection for endometriosis does not impair urinary and sexual function 1 year after surgery.

 

 

J Med Case Rep. 2016 Mar 9;10:56.

Levonorgestrel-releasing intrauterine system placement for severe uterine cervical stenosis after conization: two case reports.

Motegi E1Hasegawa K2Kawai S3Kiuchi K4Kosaka N5Mochizuki Y6Fukasawa I7.

Abstract

BACKGROUND:

Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully.

CASE PRESENTATION:

We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic.

CONCLUSIONS:

To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.

 

 

Abdom Radiol (NY). 2016 Sep;41(9):1699-702.

A case of polypoid endometriosis with malignant transformation.

Takeuchi M1Matsuzaki K2,3Bando Y4Nishimura M5Yoneda A4Harada M2.

Abstract

Polypoid endometriosis is a benign, rare variant of endometriosis which forms multiple polypoid nodules in the female pelvis mimicking malignant tumors; however, it may rarely cause malignant transformation. We report magnetic resonance imaging findings of a case of polypoid endometriosis with malignant transformation. Multiple high-signal intensity polypoid nodules in the cul-de-sac surrounded by low-signal intensity rim-like fibrous adhesion protruding to the posterior wall of the uterine body were demonstrated on T2-weighted images. The polypoid nodules showed weak contrast enhancement compared with that of uterine myometrium on post-contrast T1-weighted images, and slight high signal intensity on diffusion-weighted images with relatively high mean apparent diffusion coefficient. Reported cases of polypoid endometriosis showed intense contrast enhancement similar to that of uterine myometrium, and weak contrast enhancement similar to that of endometrial carcinoma may be suggestive for malignant transformation of polypoid endometriosis.

 

 

Biol Reprod. 2016 Apr;94(4):93

Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice.

Wang X1Khatri S2Broaddus R3Wang Z4Hawkins SM5.

 

Abstract

Women with endometriosis can suffer from decreased fecundity or complete infertility via abnormal oocyte function or impaired placental-uterine interactions required for normal pregnancy establishment and maintenance. Although AT-rich interactive domain 1A (SWI-like) (ARID1A) is a putative tumor suppressor in human endometrial cancers and endometriosis-associated ovarian cancers, little is known about its role in normal uterine function. To study the potential function of ARID1A in the female reproductive tract, we generated mice with a conditional knockout of Arid1a using anti-Müllerian hormone receptor 2-Cre Female Arid1a conditional knockout mice exhibited a progressive decrease in number of pups per litter, with a precipitous decline after the second litter. We observed no tumors in virgin mice, although one knockout mouse developed a uterine tumor after pregnancy. Unstimulated virgin female knockout mice showed normal oviductal, ovarian, and uterine histology. Uteri of Arid1a knockout mice showed a normal decidualization response and appropriate responses to estradiol and progesterone stimulation. In vitro studies using primary cultures of human endometrial stromal fibroblasts revealed that small interfering RNA knockdown of ARID1A did not affect decidualization in vitro. Timed pregnancy studies revealed the significant resorption of embryos at Embryonic Day 16.5 in knockout mice in the third pregnancy. In addition to evidence of implantation site hemorrhage, pregnant Arid1a knockout mice showed abnormal placental morphology. These results suggest that Arid1a supports successful pregnancy through its role in placental function.

 

Medicine (Baltimore). 2016 Mar;95(10):e2773

Increased Risk of Endometriosis in Patients With Lower Genital Tract Infection: A Nationwide Cohort Study.

Lin WC1Chang CYHsu YAChiang JHWan L.

 

Abstract

Endometriosis results from the ectopic invasion of endometrial glands and stroma in the peritoneal cavity. The exact etiology of endometriosis is still unknown. It has, however, been shown that there are higher numbers of Escherichia coli in menstrual blood, and higher endotoxin levels in menstrual fluid, as well as, in the peritoneal fluid of patients with endometriosis. In this study, we aimed to determine whether lower genital tract infections could increase the risk of endometriosis.We used the Taiwan National Health Insurance database to conduct a population-based cohort study. We included patients diagnosed with inflammatory diseases of the cervix, vagina, and vulva, and a control group comprising patients matched by age, sex, and comorbidities but without inflammatory diseases of the cervix, vagina, or vulva.A total of 79,512 patients were included in the inflammatory disease group and an equal number of control individuals were selected. The incidence of endometriosis (hazard ratio, 2.01; 95% confidence interval, 1.91-2.12; P < 0.001) was higher among patients than controls. Cox proportional hazards models showed that irrespective of comorbidities, lower genital tract infection was an independent risk factor for endometriosis.Patients with lower genital tract infections exhibit a substantially higher risk for developing endometriosis.

 

 

 

Medicine (Baltimore). 2016 Mar;95

Graves Disease Is Associated With Endometriosis: A 3-Year Population-Based Cross-Sectional Study.

Yuk JS1Park EJSeo YSKim HJKwon SYPark WI.

 

Abstract

The aim of this cross-sectional study was to compare the prevalence of thyroid diseases between women with and without endometriosis.We established the endometriosis group according to diagnosis codes, surgery codes, and gonadotropin-releasing hormone agonist codes using the Korean Health Insurance Review and Assessment Service-National Inpatients Sample (HIRA-NIS) from 2009 to 2011. Four controls were randomly matched to each endometriosis case. Thyroid disease cases were selected using the thyroid disease diagnosis code (E0X).Among the 1,843,451 women sampled, 5615 had endometriosis; 22,460 controls were matched to the endometriosiscases. After adjustment for age and sampling year, Graves disease was associated with endometriosis (odds ratio [OR]: 2.52; 95% CI: 1.30-4.88; P < 0.01), while hypothyroidism was not (OR: 1.17; 95% CI: 0.90-1.52; P = 0.25). Autoimmune hypothyroidism was also not associated with endometriosis (OR: 1.61; 95% CI: 0.88-2.94; P = 0.12).This study revealed an association between Graves disease and endometriosis.

 

 

PLoS One. 2016 Mar 10;11(3)

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

Novakovic P1Harding JC2Al-Dissi AN1Ladinig A2,3Detmer SE1.

 

Abstract

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

 

 

Radiographics. 2016 Mar-Apr;36(2):596-617.

US of the Nongravid Cervix with Multimodality Imaging Correlation: Normal Appearance, Pathologic Conditions, and Diagnostic Pitfalls.

Wildenberg JC1Yam BL1Langer JE1Jones LP1.

 

Abstract

The adult uterine cervix may exhibit a wide variety of pathologic conditions that include benign entities (eg, cervicitis, hyperplasia, nabothian cysts, cervical polyps, leiomyomas, endometriosis, and congenital abnormalities) as well as malignant lesions, particularly cervical carcinoma. In addition, lesions that arise in the uterine body may secondarily involve the cervix, such as endometrial carcinoma and prolapsed intracavitary masses. Many of these conditions can be identified and characterized at ultrasonography (US), which is considered the first-line imaging examination for the female pelvis. However, examination of the cervix is often cursory during pelvic US, such that cervical disease may be overlooked or misdiagnosed. Transabdominal US of the cervix may not afford sufficient spatial resolution to depict cervical disease in many patients; therefore, endovaginal US is considered the optimal technique. Use of supplemental imaging techniques, particularly the application of transducer pressure on the cervix, may be helpful. This review describes the normal appearance of the cervix at US, the appearance of cervical lesions and conditions that mimic abnormalities at US, and optimal US techniques for evaluation of the cervix. This information will help radiologists detect and diagnose cervical abnormalities more confidently at pelvic US. Online supplemental material is available for this article.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 May;200:1-5.

Soluble tumor necrosis factor-alpha receptors in the serum of endometriosispatients.

Othman ER1Hornung D2Hussein M3Abdelaal II3Sayed AA4Fetih AN3Al-Hendy A5.

Abstract

INTRODUCTION:

We examine serum levels sTNFR-I and sTNFR-II in endometriosis patients, and their role as biomarkers of endometriosis.

MATERIAL AND METHODS:

Women were diagnosed with endometriosis during laparoscopy to investigate pelvic pain and/or infertility (N=62). Control group included women with pelvic pain and/or infertility, whose laparoscopy showed no abnormalities (N=55). Serum concentrations of sTNFR-I and sTNFR-II were measured using Bioplex Protein Array system. Non-parametric statistics were used.

RESULTS:

Endometriosis patients had significantly higher levels of sTNFR-I than controls (257.46pg/ml, IQR=2.37-1048.92 versus 130.39pg/ml, IQR=0.99-361.1 respectively, P value=0.01). For TNFR-II, difference between women with (232pg/ml, IQR=0.0-624.4), and women without (132.93pg/ml, IQR=0.0-312.81) endometriosis was not significant (P value=0.05). Early stage endometriosis patients had significantly higher level of sTNFR-I (559.13, IQR=1.82-1289.86) and sTNFR-II (248.8, IQR=0-644.65) than control women (P value is 0.01 for TNFR-I and 0.04 for TNFR-II). Levels of sTNFR-I and sTNFR-II were comparable for advanced endometriosis and controls, and between early and advanced endometriosis. As a biomarker for all- stage endometriosis, sTNFR-I produces AUC of 0.62, sensitivity of 61%, and specificity of 47.3%, at a cutoff of 81.87pg/ml. For early stage disease, sTNFR-I yields AUC of 0.68, sensitivity of 60.7%, specificity of 75%, at a cutoff of 351.22pg/ml.

CONCLUSION:

sTNFR-I is significantly higher in serum of endometriosis patients than controls. As an endometriosis biomarker, sTNFR-I achieves better performance for early stage disease.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:95-99.

Prior colorectal surgery for endometriosis-associated infertility improves ICSI-IVF outcomes: results from two expert centres.

Ballester M1Roman H2Mathieu E3Touleimat S2Belghiti J3Daraï E4.

Abstract

OBJECTIVE(S):

To assess fertility outcomes after ICSI-IVF in infertile women having undergone prior complete surgical removal of colorectal endometriosis.

STUDY DESIGN:

Prospective longitudinal cohort study in two referral French centres including 60 infertile women who underwent ICSI-IVF after complete surgical removal of colorectal endometriosis, from January 2005 to May 2014. Women underwent either conservative colorectal surgery (i.e., rectal shaving or full thickness disc excision, n=18) or segmental colorectal resection (n=42). Clinical pregnancies were defined by the presence of a gestational sac on vaginal ultrasound examination from the fifth week. The overall pregnancy rate was calculated. The Kaplan-Meier method was used to estimate the cumulative pregnancy rate (CPR). Comparisons of CPR were made using the log-rank test to detect determinant factors.

RESULTS:

The median number of ICSI-IVF cycles per patient was one (range: 1-4). Of the 60 women, 36 became pregnant (i.e., overall pregnancy rate=60%). The CPR was 41.7% after one ICSI-IVF cycle, 65% after two ICSI-IVF cycles and 78.1% after three ICSI-IVF cycles. A decreased CPR was observed for women who required segmental colorectal resection compared to those who underwent rectal shaving or full thickness disc excision (p=0.04). A trend for a decreased CPR was observed for women who received a first ICSI-IVF cycle more than 18 months following surgery (p=0.07). Among the nine women with prior ICSI-IVF failure, five (55.5%) became pregnant after surgery.

CONCLUSION(S):

Colorectal surgery for endometriosis completed by ICSI-IVF is a good option for women with proven infertility, even if prior ICSI-IVF had failed.

 

 

Gynecol Endocrinol. 2016 Sep;32(9):733-736.

Serum pentraxin 3 as a possible marker for mature cystic teratomas.

Ishida C1Iwase A1,2Osuka S1Goto M1Takikawa S1Nakamura T1Kotani T1Kikkawa F1.

 

Abstract

Pentraxin 3 (PTX3) is an inflammatory mediator that is released by a wide range of tissues and cells. Elevated PTX3 levels may represent a useful diagnostic and/or prognostic marker for a number of diseases. The purpose of this study was to investigate serum PTX3 levels in benign gynecological conditions including mature cystic teratomas (MCTs), endometriomas, and uterine leiomyomas. Serum PTX3 levels of the MCT group were found to be significantly higher compared to those of the other groups, including healthy controls (p = 0.001), although carbohydrate antigen 19-9 (CA19-9) did not exhibit a significant difference. Serum PTX3 levels of the MCT, but not the endometrioma group, were also found to have significantly decreased post-operatively (mean ± standard deviation, 4.98 ± 2.10 to 3.61 ± 1.53 ng/mL). Immunohistochemical analyses demonstrated positive staining for PTX3 protein in the sebaceous glands, epidermal tissues, and hair roots of MCT specimens. PTX3 is expressed by MCTs and is associated with increased serum concentrations compared to healthy controls and patients with either endometriomas or uterine leiomyomas. We conclude that serum PTX3 levels could be used as a potential diagnostic marker for MCTs, especially helpful in differentiating them from endometriomas with elevated expression of CA19-9.

 

 

Hum Reprod. 2016 May;31(5):986-98.

Overexpression of chloride channel-3 is associated with the increased migration and invasion ability of ectopic endometrial cells from patients with endometriosis.

Guan YT1Huang YQ2Wu JB3Deng ZQ1Wang Y4Lai ZY4Wang HB3Sun XX4Zhu YL2Du MM2Zhu LY3Chen LX5Wang LW6.

Abstract

STUDY QUESTION:

Is chloride channel-3 (ClC-3) involved in regulating the biological behavior of endometrial stromal cells (ESCs)?

SUMMARY ANSWER:

ClC-3 promotes endometriotic cell migration and invasion.

WHAT IS KNOWN ALREADY:

ClC-3 plays a significant role in the migration and invasion of various kinds of cells.

STUDY DESIGN, SIZE, DURATION:

An ITALIC! in vitro investigation of the effect of ClC-3 on the migration and invasion of ectopic ESCs from patients with endometriosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The ectopic and eutopic endometrial samples from 43 female patients with endometriosis and the endometrial samples from 39 non-endometriotic female patients were collected. Primary cells from these samples were isolated and cultured. Real-time RT-PCR, immunohistochemistry and western blot were used to detect the expression of ClC-3 and matrix metalloproteinase 9 (MMP-9). Small interfering RNA (siRNA) technology was employed to knock down ClC-3 expression. The migration and invasion ability of ESCs was measured by the transwell assay with uncoated or Matrigel-coated membranes.

MAIN RESULTS AND THE ROLE OF CHANCE:

The expression of ClC-3 mRNA and proteins was significantly up-regulated in the ectopic tissues from endometriotic patients, while that in the eutopic endometrial tissues of the same patients did not significantly differ from that in non-endometriotic patients. The migration and invasion ability and MMP-9 expression was increased in the ESCs from ectopic endometrial tissues. The knockdown of ClC-3 expression by ClC-3 siRNA inhibited ESC migration and invasion and attenuated the expression of MMP-9. ClC-3 expression level was well-correlated to the clinical characteristics and symptoms of endometriosis patients, including infertility, dysmenorrhea, chronic pelvic pain, dyspareunia and diameter of endometriosis lesion.

LIMITATIONS, REASONS FOR CAUTION:

Further studies are needed to examine the regulatory mechanism of estrogen on ClC-3 expression of ESCs.

WIDER IMPLICATIONS OF THE FINDINGS:

ClC-3 is involved in the migration and invasion processes of ESCs and can regulate MMP-9 expression. Up-regulation of ClC-3 expression may contribute to endometriosis development by regulating MMP-9 expression.

 

 

Hum Reprod. 2016 May;31(5):1014-23.

Increased rate of spontaneous miscarriages in endometriosis-affected women.

Santulli P1Marcellin L2Menard S3Thubert T3Khoshnood B4Gayet V3Goffinet F5Ancel PY4Chapron C2.

Abstract

STUDY QUESTION:

Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls?

SUMMARY ANSWER:

Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls.

WHAT IS KNOWN ALREADY:

The association between endometriosis and miscarriages has long been debated without reaching a consensus.

STUDY DESIGN, SIZE, DURATION:

We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosisgroup and 466 in the control group.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification).

MAIN RESULTS AND THE ROLE OF CHANCE:

Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16).

LIMITATIONS, REASONS FOR CAUTION:

There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented.

WIDER IMPLICATIONS OF THE FINDINGS:

This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates.

STUDY FUNDING/COMPETING INTERESTS:

No external funding was used for this study. The authors have no conflicts of interest to declare.

 

 

Clin Med Insights Womens Health. 2016 Mar 7;9:7-11.

Radical Surgery for Endometriosis: Analysis of Quality of Life and Surgical Procedure.

De la Hera-Lazaro CM1Muñoz-González JL1Perez RO1Vellido-Cotelo R1Díez-Álvarez A1Muñoz-Hernando L1Alvarez-Conejo C1Jiménez-López JS1.

Abstract

OBJECTIVE:

The main aim of this study is to determine the improvement in quality of life in patients who have undergone radical surgery because of severe endometriosis.

PATIENTS AND METHODS:

This nonrandomized interventional study (quasi experimental) was carried out between January 2009 and September 2014. A total of 46 patients with diagnosis of severe endometriosis were included. Radical surgery, including hysterectomy, was performed. Acting as their own control group, the patients were asked to fill in a validated questionnaire of quality of life [Endometriosis Health Profile-5 (EHP-5)] and a visual analog scale of pain at the moment of the preoperative visit (one month prior to surgery) and six months after the surgery.

RESULTS:

Radical surgery for endometriosis was performed in 46 patients at our center over the period of six years. Among the patients, 73.9% of them had undergone previous surgery for endometriosis. In 82.6% of cases, a complete laparoscopic resection was carried out. Gastrointestinal tract resection was performed in 21.7%, and urinary tract resection was necessary in 8.7%. The mean age of the patients was 38.6 years. The rate of complications was 30.4%. Six months after the surgery, all items of the EHP-5 questionnaire had a lower score, which means an improvement in all aspects of quality of life related to endometriosis. The difference obtained between the scores before and after the surgery was statistically significant. The mean visual analog scale score before the surgery was 8.5, whereas it decreased to 1.4 after the surgery (P < 0.001).

CONCLUSION:

Performing a radical surgery is a difficult decision to make; however, it can provide optimal results in terms of improvement of quality of life and, therefore, should be considered when conservative therapy fails.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:81-85.

Treatment of endometrioma for improving fertility.

Leone Roberti Maggiore U1Gupta JK2Ferrero S3.

 

Abstract

Endometrioma is a frequent clinical manifestation of endometriosis. It is controversial how endometriomas may affect women’s fertility. This review addresses: the impact of the endometrioma per se and of its surgical treatment on ovarian physiology, on the ovarian reserve, on spontaneous conception and pregnancy outcomes, and on IVF/ICSI outcomes. Based on current evidence, although there are plausible biological detrimental effects on the ovarian cortex surrounding the endometrioma and an impairment of the normal ovarian physiology, the clinical impact of the endometrioma per se is not significantly altered. There is a negligible detrimental effect on ovarian reserve with spontaneous ovulation not being impaired. Conversely, surgical excision of an endometrioma reduces ovarian reserve as measured by AMH levels. Studies investigating the impact of the endometrioma per se and of its surgical treatment in women requiring IVF/ICSI show similar implantation rates, clinical pregnancy rates and live birth rates between women with endometrioma and controls.

 

 

 

Med Hypotheses. 2016 Apr;89:43-7.

Autonomic denervation: A new aetiological framework for clinical obstetrics and gynaecology.

Quinn MJ1.

 

Abstract

The hypothesis is that many clinical conditions in obstetrics and gynaecology result from the diverse and varying consequences of injuries to pelvic autonomic nerves. These injuries result from difficult first labours, persistent physical efforts during defaecation, and, medical and surgical techniques for evacuation of the uterus. The neuro-immunohistochemical “signatures” of these injuries are variations of the Dixon-Robertson-Brosens (DRB) lesion in preeclampsia, where there is hyperplasia of the tunica intima and media of arterioles with narrowing of the lumen of the vessel. In stage IV, nulliparous “endometriosis” (and other gynaecological conditions) there are circumferential layers of abnormal nerves around a narrowed arteriole, whereas in early-onset preeclampsia (and other obstetric conditions) there are similar histological findings in uterine arterioles but there is no sign of injured nerves. During pregnancy there is elongation of blood vessels but no elongation of injured nerves leading to relative denervation of the myometrium. These lesions are detectable in most of the “great” obstetric syndromes, and, across the spectrum of gynaecological syndromes. They provide a coherent explanation of the natural history and clinical presentations of many of these syndromes. Clinical features vary with the site, nature and extent of the injury; a minor injury may enable pregnancy though it is complicated by late-onset pre-eclampsia whereas a more extensive injury may prevent pregnancy and present with chronic pelvic pain with, or without, endometriosis.

 

 

 

Int J Gynecol Pathol. 2016 Nov;35(6):544-548.

Non-Neoplastic Conditions of the Ovaries in Grossly Normal Adnexa: A Clinicopathologic Study of 403 Completely Embedded Cases.

Seidman JD1Krishnan J.

 

Abstract

Most non-neoplastic lesions of the ovaries have not been comprehensively examined in the contemporary literature. We evaluated completely embedded ovaries from 403 unselected, consecutive patients who had grossly normal adnexa. These included prophylactic specimens in high-risk women with BRCA mutations (38 women) and women with a personal history of breast cancer or a family history of breast and/or ovarian cancer (79 women). Transitional cell (Brenner) nests were found in 9.1%; 31% of these lesions were smaller than 1 mm, and 8 were solitary nests. Cortical granulomas were found in 20.5%, fatty metaplasia in 5.3%, mucinous metaplasia of surface epithelial inclusions in 5.5%, and smooth muscle stromal metaplasia in 2%. One or more types of stromal hyperplasia were found in 24.3%. Endometriosis was found in 22% of adnexa. There were no significant differences in the findings in high-risk women compared with non-high-risk except those attributable to age differences between the groups. These findings establish baseline frequencies for non-neoplastic ovarian lesions, and suggest that transitional cell nests are so common that they can be regarded as a normal finding.

 

 

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):753-9

Assessment of Long-Term Bowel Symptoms After Segmental Resection of Deeply Infiltrating Endometriosis: A Matched Cohort Study.

Soto E1Catenacci M2Bedient C3Jelovsek JE4Falcone T5.

Abstract

STUDY OBJECTIVE:

To assess long-term bowel symptoms in women who underwent segmental bowel resection for deep-infiltrating endometriosis (DIE) compared with women who underwent resection of severe endometriosiswithout bowel resection.

DESIGN:

Cohort study with matched controls (Canadian Task Force classification II-2).

SETTING:

Cleveland Clinic.

PATIENTS:

71 patients (36 cases and 35 controls).

INTERVENTIONS:

Patients who were at least 4 years out from undergoing segmental bowel resection due to DIE were matched with patients who had undergone resection of stage III/IV endometriosis without bowel resection. The patients completed validated questionnaires, and data were analyzed using the Wilcoxon rank-sum, χ(2), and Fisher exact tests.

MEASUREMENTS AND MAIN RESULTS:

The Bristol Stool Form Scale, Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM), and St Mark’s Vaizey Fecal Incontinence Grading System were used to elicit information. The median duration of follow-up was 10.1 years (range, 4-18 years). The mean patient age and body mass index were comparable in the cases and the controls. A larger proportion of cases than controls reported new bowel symptoms (58% [21 of 36] vs 14% [5 of 35]; p = .001), as well as abdominal pain, incomplete bowel movements, and false alarms on the PAC-SYM questionnaire; however, total PAC-SYM and Vaizey Fecal Incontinence Grading System scores were similar in the 2 groups (median, 8 [interquartile range, 8-10] vs 8 [8-10]; p = .86). Similarly, the proportion of patients with normal stool consistency (Bristol Stool Form Scale score 2-6) was similar in the 2 groups (80.6% [29 of 36] vs 94.3% [33 of 35]; p = .59).

CONCLUSION:

Segmental bowel resection for DIE may be associated with a higher incidence of new bowel symptoms (possibly due to abdominal pain, incomplete bowel movements, and/or false alarms), but not with worse constipation or fecal incontinence, compared with surgery without bowel resection.

 

 

 

 

Lascia un commento

Cerca

Utilizzando il sito, accetti l'utilizzo dei cookie da parte nostra. maggiori informazioni

Questo sito utilizza i cookie per fornire la migliore esperienza di navigazione possibile. Continuando a utilizzare questo sito senza modificare le impostazioni dei cookie o cliccando su "Accetta" permetti il loro utilizzo.

Chiudi