Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
J Clin Diagn Res. 2017 Jul;11(7):QC10-QC12.
Evaluating the Efficacy of Levonorgestrel Intrauterine System and Danazol for Relief of Postoperative Pain in Endometriosis.
Taneja A1, Kaur S2, Soni RK3, Bhanupriya4, Kaur J4, Singla L4.
Endometriosis is an oestrogen-dependent disorder, manifests during reproductive years and is associated with pain and infertility. There is considerable debate about the effectiveness of various interventions for pain relief.
To evaluate the efficacy of Levonorgestrel Intrauterine System (LNG-IUS) and Danazol in postoperative pain relief for patients with endometriosis.
MATERIALS AND METHODS:
Hundred patients with diagnosis of endometriosis, who were treated laparoscopically, entered the study to receive either danazol (600 mg once daily) or LNG-IUS (inserted during immediate post operative period) postsurgery, for pain relief. Patients were analysed for pain relief according to VAS score and recurrence of disease using ultrasonography at third and sixth months of follow up.
There were 50% patients in stage IV of endometriosis. Majority of them presented with complaint of infertility (49%) and pelvic pain (43%). It was observed that LNG-IUS was significantly more effective in relieving pain compared to danazol (65.2% vs 38.0%, p<0.05). Recurrence rate was significantly lower in LNG-IUS users compared to other group.
LNG-IUS was found to be more effective in relieving pain compared to danazol.
J Minim Invasive Gynecol. 2017 Sep 8. pii: S1553-4650(17)31124-X.
Laparoscopic Blinded Endometrial Cavity Resection for Robert’s Uterus.
Kiyak H1, Karacan T2, Wetherilt LS1, Seckin KD1, Ozyurek ES3.
To demonstrate that laparoscopic excision of the endometrial tissue of a blind endometrial cavity in a patient with a Robert’s uterus who did not consent to hysteroscopic surgery due to her virgin state and religious beliefs was an effective alternative treatment option for progressive dismenorrhea and pelvic pain.
Presentation of a rare müllerian anomaly and a step-by-step demonstration of a laparoscopic excision technique in the endometrium of a blind uterine cavity (educative video) (Canadian Task Force classification III).
Robert’s uterus is a rare müllerian anomaly characterized by the presence of a blind endometrial cavity and an asymmetric septum. Endometriosis may be encountered in 40% of patients with this anomaly. A 15-year-old virgin patient with progressive dysmenorrhea was diagnosed with a Robert’s uterus anomaly on magnetic resonance imaging. Hysteroscopic surgery was suggested to form a communication between the blind endometrial cavity and the hemiuterus; however, the patient refused to undergo any vaginal surgery due to her virgin state and religous beliefs. A decision to excise the endometrial tissue of the blind cavity laparoscopically instead of performing a hemihysterectomy was made to prevent any adverse effects on the ovarian blood supply and damage to the myometrial wall of the unicornuate uterus.
Laparoscopic resection of the blind endometrial cavity in a patient with a Robert’s uterus anomaly.
Laparoscopic resection of a blind endometrial cavity is a safe and effective surgical alternative in patients who refuse vaginal surgery.
J Minim Invasive Gynecol. 2018 Jan;25(1):139-146.
Multiple Nodule Removal by Disc Excision and Segmental Resection in Multifocal Colorectal Endometriosis.
Millochau JC1, Stochino-Loi E1, Darwish B1, Abo C1, Coget J2, Chati R2, Tuech JJ2, Roman H3.
To report postoperative outcomes after dual digestive resection for deep endometriosis infiltrating the rectum and the colon.
A retrospective study using data prospectively recorded in the CIRENDO database (Canadian Task Force classification II-2).
A university tertiary referral center.
Twenty-one patients managed for multiple colorectal deep endometriosis infiltrating nodules.
Concomitant disc excision and segmental resection of both the rectum and sigmoid colon.
MEASUREMENTS AND MAIN RESULTS:
The assessment of postoperative outcomes was performed. Rectal nodules were managed by disc excision and segmental resection in 20 patients and 1 patient, respectively. Sigmoid colon nodules were removed by short segmental resection and disc excision in 15 and 6 patients, respectively. The rectal nodule diameter was between 1 and 3 cm and over 3 cm in 33% and 67% of patients, respectively. Associated vaginal infiltration requiring vaginal excision was recorded in 76.2% of patients. The mean diameter of the rectal disc removed averaged 4.6 cm, and the mean height of the rectal suture was 5.8 cm. The length of the sigmoid colon specimen and the height of the anastomosis were 7.3 cm and 18.5 cm, respectively. The mean operative time was 290 minutes, and the mean postoperative follow-up averaged 30 months. Clavien-Dindo 3 complications occurred in 28% of patients, including 4 with rectal fistulae (19%). The pregnancy rate was 67% among patients with pregnancy intention.
Our data suggest that combining disc excision and segmental resection to remove multiple deep endometriosis nodules infiltrating the rectum and the sigmoid colon can preserve the healthy bowel located between 2 consecutive nodules. However, the rate of postoperative complications is high, particularly in patients with large low rectal nodules.
Onco Targets Ther. 2017 Aug 28;10:4225-4238.
miRNA expression profiling in formalin-fixed paraffin-embedded endometriosis and ovarian cancer samples.
Braicu OL1, Budisan L2, Buiga R2,3, Jurj A2, Achimas-Cadariu P1,4, Pop LA2, Braicu C2, Irimie A1,4, Berindan-Neagoe I2,5,6.
Endometriosis is an inflammatory pathology associated with a negative effect on life quality. Recently, this pathology was connected to ovarian cancer, in particular with endometrioid ovarian cancer. microRNAs (miRNAs) are a class of RNA transcripts ~19-22 nucleotides in length, the altered miRNA pattern being connected to pathological status. miRNAs are highly stable transcripts, and these can be assessed from formalin-fixed paraffin-embedded (FFPE) samples leading to the identification of miRNAs that could be developed as diagnostic and prognostic biomarkers, in particular those involved in malignant transformation. The aim of our study was to evaluate miRNA expression pattern in FFPE samples from endometriosis and ovarian cancer patients using PCR-array technology and also to compare the differential expression pattern in ovarian cancer versus endometriosis. For the PCR-array study, we have used nine macrodissected FFPE samples from endometriosis tissue, eight samples of ovarian cancers and five normal ovarian tissues. Quantitative real-time PCR (qRT-PCR) was used for data validation in a new patient cohort of 17 normal samples, 33 endometriosis samples and 28 ovarian cancer macrodissected FFPE samples. Considering 1.5-fold expression difference as a cut-off level and a P-value <0.05, we have identified four miRNAs being overexpressed in endometrial tissue, while in ovarian cancer 15 were differentially expressed (nine overexpressed and six downregulated). The expression level was confirmed by qRT-PCR for miR-93, miR-141, miR-155, miR-429, miR-200c, miR-205 and miR-492. Using the interpretative program Ingenuity Pathway Analysis revealed several deregulated pathways due to abnormal miRNA expression in endometriosis and ovarian cancer, which in turn is responsible for pathogenesis; this differential expression of miRNAs can be exploited as a therapeutic target. A higher number of altered miRNAs were detected in endometriosis versus ovarian cancer tissue, most of them being linked with epithelial-to-mesenchymal transition.
PLoS One. 2017 Sep 12;12(9):e0184647.
P2X3 receptor involvement in endometriosis pain via ERK signaling pathway.
Ding S1, Zhu L1, Tian Y1, Zhu T1, Huang X1, Zhang X1.
The purinergic receptor P2X ligand-gated ion channel 3 (P2X3) is crucially involved in peripheral nociceptive processes of somatic and visceral pain. Endometriosis pain is considered as a kind of inflammatory and neuropathic pain. However, whether P2X3 is involved in endometriosis pain has not been reported up to date. Here, we aimed to determine whether P2X3 expression in endometriotic lesions is involved in endometriosis pain, which is regulated by inflammatory mediators through extracellular regulated protein kinases (ERK) signalling pathway. We found that P2X3 expressions in endometriosis endometrium and endometriotic lesions were both significantly higher as compared with control endometrium (P<0.05), and both positively correlated with pain (P<0.05). The expression levels of phosphorylated -ERK (p-ERK), phosphorylated-cAMP-response element binding protein (p-CREB), and P2X3 in endometriotic stromal cells (ESCs) were all significantly increased in comparison to the initial levels after treated with interleukin (IL)-1β (P<0.05) or adenosine triphosphate (ATP) (P<0.05), respectively, and did not increase after the ESCs were pre-treated with ERK1/2 inhibitor. Additionally, P2X3 and calcitonin gene related peptide (CGRP) were co-expressed in endometriotic lesions. These obtained results suggest that P2X3 might be involved in endometriosis pain signal transduction via ERK signal pathway.
Sci Rep. 2017 Sep 12;7(1):11380.
Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry.
Sapkota Y1,2, Vivo I3,4, Steinthorsdottir V5, Fassbender A6,7, Bowdler L8, Buring JE3,9, Edwards TL10, Jones S11, O D6,7, Peterse D6,7, Rexrode KM3,9, Ridker PM3,9, Schork AJ12,13, Thorleifsson G5, Wallace LM8; iPSYCH-SSI-Broad Group, Kraft P14, Morris AP15, Nyholt DR8,16, Edwards DRV17, Nyegaard M18,19, D’Hooghe T6, Chasman DI3,9, Stefansson K5,20, Missmer SA3,4, Montgomery GW8,21.
Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10-9) in GREB1 at 2p25.1 – a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.
J Autism Dev Disord. 2017 Dec;47(12):3994-4005.
Maternal and Paternal Infertility Disorders and Treatments and Autism Spectrum Disorder: Findings from the Study to Explore Early Development.
Schieve LA1, Drews-Botsch C2, Harris S3, Newschaffer C4, Daniels J5, DiGuiseppi C6, Croen LA7, Windham GC8.
Previous studies of associations between ASD and conception using assisted reproductive technology (ART) are inconsistent and few studies have examined associations with other infertility treatments or infertility disorders. We examined associations between ASD and maternal/paternal infertility disorders and numerous maternal treatments among 1538 mother-child pairs in the Study to Explore Early Development, a population-based case-control study. ASD was associated with any female infertility diagnosis and several specific diagnoses: blocked tubes, endometriosis, uterine-factor infertility, and polycystic ovarian syndrome. Stratified analyses suggested associations were limited to/much stronger among second or later births. The findings were not explained by sociodemographic factors such as maternal age or education or multiple or preterm birth. ASD was not associated with ART or non-ART infertility treatments.
Curr Drug Metab. 2017;18(10):926-941.
Bacterial Toxins: A Hope Towards Angiogenic Ailments.
Khandia R1, Munjal A1, Dhama K2, Malik YS3.
Angiogenesis is an essential physiological process for growth and maintenance of the body. Especially its role becomes indispendable during the embryonic development stage but lacks in adults with some exceptions like while wound repair and menstrual cycle. It is a tightly regulated process and relies on the cascade of several molecular signaling pathways with the involvement of many effectors like vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) etc.
Related literature/ information were retrieved, analyzed and compiled from the online published resources available in Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases.
Excessive angiogenesis leads to disorders like tumor, atherosclerosis, rheumatoid arthritis, diabetic retinopathy, endometriosis, psoriasis, and adiposity. While, reduced angiogenesis also results in several ailments like cardiac ischemia, low capillary density in brain of Alzheimer’s patients and delayed wound healing. Therefore, both angio-proliferative and anti-angiogenic approaches may be of use in developing novel therapeutics. Bacterial toxins are known for modulating the process of angiogenesis by mimicking pro-angiogenic factors and/ or competing with them. Furthermore, they inactivate the receptors or keep them in ON status, hence can be used to treat angiogenic disorders. The ease in handling, cultivation and manipulating the toxins structure has enabled the use of bacteria as an ideal choice for novel therapeutic developments.
This review intends to elucidate the molecular mechanisms through which certain bacteria may alter the level of angiogenesis and consequently can work as therapeutics against angiogenic disorders.
Mol Med Rep. 2017 Nov;16(5):5881-5886.
The role of gene polymorphisms in endometriosis.
Matalliotakis M1, Zervou MI2, Matalliotaki C1, Rahmioglu N3, Koumantakis G4, Kalogiannidis I5, Prapas I6, Zondervan K3, Spandidos DA7, Matalliotakis I1, Goulielmos GN2.
Endometriosis is a benign gynecologic disorder, affecting up to 10% of women, characterized by the presence of functional endometrial tissue at ectopic positions generally within the peritoneum. It is a heritable condition influenced by multiple genetic and environmental factors, with an overall heritability estimated at approximately 50%. In this study, we investigated whether single nucleotide polymorphisms (SNPs) rs7521902, rs10859871 and rs11031006, mapping to WNT4, VEZT and FSHB genetic loci, respectively, are associated with risk for endometriosis in a Greek population. This study included 166 women with histologically confirmed endometriosis diagnosed through surgery and 150 normal controls. Genotyping of the rs7521902, rs10859871 and rs11031006 SNPs was performed with Taqman primer/probe sets. A significant association was detected with the AC genotype of rs7521902 (WNT4) in patients with stage III and IV disease only. Evidence for association with endometriosis was also found for the AC genotype of the rs10859871 of VEZT. Notably, a significant difference in the distribution of the AG genotype and the minor allele A of FSHB rs11031006 SNP was found between the endometriosis patients and controls. We found a genetic association between rs11031006 (FSHB) SNP and endometriosis. WNT4 and VEZT genes constitute the most consistently associated genes with endometriosis. In the present study, an association of rs7521902 (WNT4) and rs10859871 (VEZT) was confirmed in women with endometriosis at the genotypic but not the allelic level.
pLoS One. 2017 Sep 13;12(9):e0184399.
PreImplantation Factor in endometriosis: A potential role in inducing immune privilege for ectopic endometrium.
Sbracia M1, McKinnon B2, Scarpellini F1, Marconi D3, Rossi G3, Simmilion C2, Mueller MD2,4, Barnea ER5,6, Mueller M2,4,7.
Endometriosis is a chronic inflammatory condition characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. In addition to Sampson’s theory of retrograde menstruation, endometriosis pathogenesis is facilitated by a privileged inflammatory microenvironment, with T regulatory FoxP3+ expressing T cells (Tregs) being a significant factor. PreImplantation Factor (PIF) is a peptide essential for pregnancy recognition and development. An immune modulatory function of the synthetic PIF analog (sPIF) has been successfully confirmed in multiple animal models. We report that PIF is expressed in the epithelial ectopic cells in close proximity to FoxP3+ stromal cells. We provide evidence that PIF interacts with FoxP3+ cells and modulates cell viability, dependent on cell source and presence of inflammatory mediators. Our finding represent a novel PIF-based mechanism in endometriosis that has potential for novel therapeutics.
Hum Reprod Update. 2017 Sep 1;23(5):548-559.
The role of TGF-β in the pathophysiology of peritoneal endometriosis.
Young VJ1, Ahmad SF1, Duncan WC, Horne AW1.
Endometriosis is estimated to affect 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea and subfertility. It is currently managed surgically or medically but symptoms recur in up to 75% of cases and available medical treatments have undesirable side effects. Endometriosis is defined as the presence of endometrial tissue outside the uterus with lesions typically found on the peritoneum. The aetiology of endometriosis is uncertain but there is increasing evidence that transforming growth factor (TGF)-β plays a major role.
OBJECTIVE AND RATIONALE:
A descriptive review was undertaken of the published literature on the expression pattern of TGF-β ligands and signalling molecules in women with and without endometriosis, and on the potential roles of TGF-β signalling in the development and progression of peritoneal endometriosis. The current understanding of the TGF-β signalling pathway is summarized.
We searched the Pubmed database using the terms ‘transforming growth factor beta’ and ‘endometriosis’ for studies published between 1995 and 2016. The initial search identified 99 studies and these were used as the basic material for this review. We also extended our remit for important older publications. In addition, we searched the reference lists of studies used in this review for additional studies we judged as relevant. Studies which were included in the review focused on peritoneal endometriosis only as increasing evidence suggests that ovarian and deep endometriosis may have a differing pathophysiology. Thus, a final 95 studies were included in the review.
TGF-β1 is reported to be increased in the peritoneal fluid, serum, ectopic endometrium and peritoneum of women with endometriosis compared to women without endometriosis, and TGF-β1-null mice have reduced endometriosis lesion growth when compared to their wild-type controls. Studies in mice and women have indicated that increasing levels of TGF-β ligands are associated with decreased immune cell activity within the peritoneum, together with an increase in ectopic endometrial cell survival, attachment, invasion and proliferation, during endometriosis lesion development. TGF-β1 has been associated with changes in ectopic endometrial and peritoneal cell metabolism and the initiation of neoangiogenesis, further fuelling endometriosis lesion development.
Together these studies suggest that TGF-β1 plays a major role in the development of peritoneal endometriosis lesions and that targeting this pathway may be of therapeutic potential.
J Hum Reprod Sci. 2017 Apr-Jun;10(2):86-90.
To Study the Vitamin D Levels in Infertile Females and Correlation of Vitamin D Deficiency with AMH Levels in Comparison to Fertile Females.
Lata I1, Tiwari S2, Gupta A1, Yadav S3, Yadav S2.
Human and animal data suggest that low vitamin D (25-hydroxyvitamin D) status is associated with impaired fertility, endometriosis, and polycystic ovary syndrome. Vitamin D regulates antimullerian hormone (AMH), FSH, mRNA, and expression of genes in reproductive tissues, implicating a role in female reproduction.
To study the vitamin D levels in infertile females and to know the correlation of vitamin D deficiency (VDD) with serum AMH in infertile females compare to fertile females.
SETTINGS AND DESIGN:
This prospective study was conducted in department of Maternal and Reproductive Health in between April 2014 and April 2016.
MATERIALS AND METHODS:
After matching inclusion and exclusion criteria out of total 70 infertile females, 45 were found to have VDD. Of these 35 patients were identified as cases; in whom, the AMH levels were assessed. As control 35 fertile normal females were taken, in which vitamin D and AMH were taken. In both groups, correlation of VDD with AMH was studied.
STATISTICAL ANALYSIS USED:
To analyze the correlation between vitamin D and AMH linear regression test and for comparison of both the groups, two sample t tests were used.
The VDD was present in 64.28% of infertile females. In vitamin D deficient cases, the mean for vitamin D was 6.18 ± 2.09 and AMH was 1.94 ± 1.30. In vitamin D deficient controls, the mean for vitamin D was 4.85 ± 3.02 and AMH was 3.47 ± 2.59. On comparison, the vitamin D levels were lower in fertile than infertile females, which was significant (P = 0.04), and AMH levels were lower in cases than control group (P = 0.003).
The VDD was present in 64.28% of infertile females. No significant correlation was found in between VDD and AMH levels in both the groups.
J Reprod Immunol. 2017 Sep;123:29-34.
The role of the B lymphocytes in endometriosis: A systematic review.
Riccio LGC1, Baracat EC2, Chapron C3, Batteux F4, Abrão MS5.
The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for “endometriosis”, “B cells” and “B lymphocytes” in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells.
Fertil Steril. 2017 Nov;108(5):798-805.
Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial.
Harada T1, Kosaka S2, Elliesen J3, Yasuda M2, Ito M4, Momoeda M5.
To investigate the efficacy and safety of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen (FlexibleMIB) compared with placebo to treat endometriosis-associated pelvic pain (EAPP).
A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm.
A total of 312 patients with endometriosis.
Patients were randomized to FlexibleMIB, placebo, or dienogest. The FlexibleMIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to FlexibleMIB. Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm.
MAIN OUTCOME MEASURE(S):
Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase.
Compared with placebo, FlexibleMIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). FlexibleMIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas.
FlexibleMIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis.
Fertil Steril. 2017 Oct;108(4):679-686.
Pain cognition versus pain intensity in patients with endometriosis: toward personalized treatment.
van Aken MAW1, Oosterman JM2, van Rijn CM2, Ferdek MA3, Ruigt GSF4, Peeters BWMM5, Braat DDM6, Nap AW7.
To explore how pain intensity and pain cognition are related to health-related quality of life (HRQoL) in women with endometriosis.
Cross-sectional questionnaire-based survey.
Multidisciplinary referral center.
Women with laparoscopically and/or magnetic resonance imaging-proven endometriosis (n = 50) and healthy control women (n = 42).
For HRQoL, two questionnaires: the generic Short Form Health Survey (SF-36) and the Endometriosis Health Profile 30 (EHP-30). For pain cognition, three questionnaires: the Pain Catastrophizing Scale (PCS), the Pain Vigilance and Awareness Questionnaire (PVAQ), and the Pain Anxiety Symptoms Scale (PASS). For pain intensity, the verbal Numeric Rating Scale (NRS).
MAIN OUTCOME MEASURE(S):
Association between pain intensity and pain cognition with HRQoL in women with endometriosis, and the differences in HRQoL and pain cognition between women with endometriosis and healthy controls.
Health-related quality of life was statistically significantly impaired in women with endometriosis as compared with healthy control women. The variables of pain intensity and pain cognition were independent factors influencing the HRQoL of women with endometriosis. Patients with endometriosis had statistically significantly more negative pain cognition as compared with controls. They reported more pain anxiety and catastrophizing, and they were hypervigilant toward pain.
Pain cognition is independently associated with the HRQoL in endometriosis patients. Clinicians should be aware of this phenomenon and may consider treating pain symptoms in a multidimensional, individualized way in which the psychological aspects are taken into account. In international guidelines on management of women with endometriosis more attention should be paid to the psychological aspects of care.
Exp Ther Med. 2017 Oct;14(4):2992-2998.
Baicalein reduces endometriosis by suppressing the viability of human endometrial stromal cells through the nuclear factor-κB pathway in vitro.
The aim of the present study was to evaluate the effects of baicalein on human endometrial stromal cells in vitro. Ectopic endometrium samples were obtained from 6 female patients with ovarian endometriosiswho underwent laparoscopic surgical procedures from July to September 2015. After culturing the cells, immunocytochemistry was performed to verify the purity and homogeneity of the endometrial stromal cells, and a Cell Counting Kit-8 assay was used to evaluate cell viability. In addition, cell cycle progression was analyzed using flow cytometry, and the effects of baicalein on the expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cyclin D1 in endometrial stromal cells were evaluated using western blot analysis. The related signaling pathways were also investigated by incubating cells with inhibitors of signaling pathways, prior to adding 40 µM baicalein for 48 h, followed by analysis of cell viability using a Cell Counting Kit-8 assay. The results indicated that treatment with baicalein significantly induced a dose-dependent decrease (P<0.05) in the viability of human endometrial stromal cells, which was abolished by inhibition of the nuclear factor (NF)-κB signaling pathway. However, baicalein treatment did not induce a time-dependent decrease in viability, as cell viabilities between the 24, 48 and 72 h treatment groups did not differ significantly. The number of cells in the G0/G1 phase significantly increased following treatment with baicalein (P<0.05), while the number of cells in the S and G2/M phases significantly decreased (P<0.05). Baicalein-treated cells also exhibited significantly reduced expression of Bcl-2, PCNA and cyclin D1 compared with control cells (P<0.05). These results suggested that baicalein may suppress the viability of human endometrial stromal cells through the NF-κB signaling pathway in vitro, and may induce apoptosis and promote cell cycle arrest at the G0/G1 phase. Thus, baicalein may provide a novel treatment option for endometriosis.
Turk J Obstet Gynecol. 2017 Jun;14(2):128-132.
Comparison of libido, Female Sexual Function Index, and Arizona scores in women who underwent laparoscopic or conventional abdominal hysterectomy.
Kayataş S1, Özkaya E1, Api M1, Çıkman S1, Gürbüz A1, Eser A1.
The aim of the present study was to compare female sexual function between women who underwent conventional abdominal or laparoscopic hysterectomy.
MATERIALS AND METHODS:
Seventy-seven women who were scheduled to undergo hysterectomy without oophorectomy for benign gynecologic conditions were included in the study. The women were assigned to laparoscopic or open abdominal hysterectomy according to the surgeons preference. Women with endometriosis and symptomatic prolapsus were excluded. Female sexual function scores were obtained before and six months after the operation from each participant by using validated questionnaires.
Pre- and postoperative scores of three different quationnaires were found as comparable in the group that underwent laparoscopic hysterectomy (p>0.05). Scores were also found as comparable in the group that underwent laparotomic hysterectomy (p>0.05). Pre- and postoperative values were compared between the two groups and revealed similar results with regard to all three scores (p>0.05).
Our data showed comparable pre- and the postoperative scores for the two different hysterectomy techniques. The two groups were also found to have similar pre- and postoperative score values.
Turk J Obstet Gynecol. 2017 Jun;14(2):133-137.
Features of ovarian Brenner tumors: Experience of a single tertiary center.
Turgay B1, Koyuncu K1, Taşkın S1, Ortaç UF1.
Brenner tumors are rare neoplasms of the ovary. The aim of this study was to investigate the clinical features of Brenner tumors.
MATERIALS AND METHODS:
The clinical features of 22 patients who were treated in Ankara University Faculty of Medicine Obstetrics and Gynecology Department between 2005 and 2015 were evaluated retrospectively from hospital medical records.
The patients were aged 34 to 79 years at the time of diagnosis and the mean age was 55.1 years. Two (9.1%) patients were pre-menopausal, five (22.7%) were peri-menopausal, and 25 (68.2%) patients were postmenopausal. One patient was pregnant. Twenty of the neoplasms were benign, one was malignant, and one was both malignant and benign. There was no recurrence in the malignant cases. Six (27.2%) patients had mixed tumors consisting of Brenner tumor and another ovarian pathology. Specifically, the other component of these tumors was mucinous cystadenoma in four patients, endometriosis externa in one patient, and high-grade serous papillary cyst adenocarcinoma in one patient.
Brenner tumors are usually incidental benign pathologic findings of surgical procedures in postmenopausal women. They can be found with other ovarian pathologies such as mucinous ovarian tumors and can coexist with other female genital tumors. Further studies are needed to completely understand the clinical features of Brenner tumors.
Stem Cells. 2018 Jan;36(1):91-102.
Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models.
Ong YR1, Cousins FL1,2, Yang X1,3, Mushafi AAAA1, Breault DT4, Gargett CE1,2, Deane JA1,2.
Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium, and endothelium. We investigated the nature of bone marrow-derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing transgenic mTert-green fluorescent protein (GFP) or chicken β-actin (Ch β-actin)-GFP reporters. mTert-GFP is a telomerase marker identifying hematopoietic stem cells and subpopulations of epithelial, endothelial, and immune cells in the endometrium. Ch β-actin-GFP is a ubiquitous reporter previously used to identify bone marrow-derived cells in the endometrium. Confocal fluorescence microscopy for GFP and markers of endometrial and immune cells were used to characterize bone marrow-derived cells in the endometrium of transplant recipients. No evidence of GFP+ bone marrow-derived stroma, epithelium, or endothelium was observed in the endometrium of mTert-GFP or Ch β-actin-GFP recipients. All GFP+ cells detected in the endometrium were immune cells expressing the pan leukocyte marker CD45, including CD3+ T cells and F4/80+ macrophages. Further examination of the Ch β-actin-GFP transplant model revealed that bone marrow-derived F4/80+ macrophages immunostained weakly for CD45. These macrophages were abundant in the stroma, infiltrated the epithelial and vascular compartments, and could easily be mistaken for bone marrow-derived endometrial cells. We conclude that it is unlikely that bone marrow cells are able to transdifferentiate into endometrial stroma, epithelium, and endothelium. This result has important therapeutic implications, as the expectation that bone marrow stem cells contribute directly to endometrial regeneration is shaping strategies designed to regenerate endometrium in Asherman’s syndrome and to control aberrant endometrial growth in endometriosis. Stem Cells 2018;36:91-102.
Expert Opin Pharmacother. 2017 Oct;18(15):1569-1581.
Oral and depot progestin therapy for endometriosis: towards a personalized medicine.
Buggio L1,2, Somigliana E2,3, Barbara G1, Frattaruolo MP1,2, Vercellini P1,2.
Endometriosis is an estrogen-dependent chronic inflammatory disorder that requires a life-long management plan. Long-term adherence to treatment is pivotal to ensure an effective clinical management. In this optic, one of the cornerstone of endometriosis medical treatment is represented by progestins. Areas covered: This narrative review examines the clinical efficacy, safety and tolerability of oral and depot progestins used in the treatment of endometriosis. The material included in the current manuscript was obtained with a MEDLINE search through PubMed from inception until February 2017. Expert opinion: Progestins are effective in controlling pain symptoms in the majority of women with endometriosis, and their effect seems not inferior to that achieved with other compounds used to treat the disease, such as gonadotropin-releasing hormone agonist. Available progestins include a broad range of both oral and depot compounds, and represent, in most cases, an inexpensive treatment option. In addition, progestins do not increase significantly thrombotic risk and could be adopted in those women with metabolic or cardiovascular contraindication to estrogen-progestins. The choice between the different available compounds should be tailored for every woman with preference to the most cost-effective treatment, depending on the most complained symptom and disease location.
Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:1-4.
Androgen receptor cytosine, adenine, and guanine trinucleotide repeat polymorphism in Korean patients with endometriosis: A case-control study.
Shin JJ1, Choi YM2, Choi HY3, Chae SJ4, Hwang K5, Kim JJ6, Lee GH7, Kim JM3.
To investigate the association between the androgen receptor (AR) cytosine, adenine, and guanine (CAG) repeat polymorphisms and endometriosis.
A prospective case-control, genetic association study was performed on women with surgically proven endometriosis (n=421) and controls free of endometriosis (n=349). AR CAG repeat lengths were determined from peripheral blood samples. The difference in the frequency of each alleles were compared in patients with endometriosis and controls using Chi-square test.
No significant difference in biallelic length mean between patients and controls was observed. Alleles containing 24 CAG repeats were significantly more frequent in stage I-II (mild) endometriosis than in the control samples (19.8% and 13.3%, respectively; OR 1.60, 95% CI 1.04-2.47). Additionally, a higher frequency of both alleles with 24 or more CAG repeats was observed in individuals with mild endometriosis, in comparison with the controls (25.6% and 15.2%, respectively; OR 1.92, 95% CI 1.09-3.38).
AR gene CAG repeat polymorphisms are associated with the increased risk of mild endometriosis.
Mol Cell Endocrinol. 2017 Sep 15. pii: S0303-7207(17)30507-5.
Androgens and endometrium: New insights and new targets.
Simitsidellis I1, Saunders PTK1, Gibson DA2.
Androgens are synthesised in both the ovary and adrenals in women and play an important role in the regulation of female fertility, as well as in the aetiology of disorders such as polycystic ovarian syndrome, endometriosis and endometrial cancer. The endometrium is an androgen target tissue and the impact of AR-mediated effects has been studied using human endometrial tissue samples and rodent models. In this review we highlight recent evidence that endometrial androgen biosynthesis and intracrine action is important in preparation of a tissue microenvironment that can support implantation and establishment of pregnancy. The impact of androgens on endometrial cell proliferation, in repair of the endometrial wound at the time of menstruation and in endometrial disorders is discussed. Future directions for research focused on AR function as a therapeutic target are considered.
Horm Behav. 2017 Nov;96:69-83.
Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder.
Dinsdale NL1, Crespi BJ2.
Hippocrates attributed women’s high emotionality – hysteria – to a ‘wandering womb’. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin’s associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease.
Jpn J Radiol. 2017 Dec;35(12):697-706.
The spectrum of imaging appearances of müllerian duct anomalies: focus on MR imaging.
Fukunaga T1, Fujii S2, Inoue C2, Mukuda N2, Murakami A3, Tanabe Y2, Harada T4, Ogawa T2.
Müllerian duct anomalies (MDAs) are the result of incomplete development, vertical or lateral fusion, or absorption of the müllerian ducts. The range of anomalies includes uterovaginal agenesis or hypoplasia, unicornuate uterus, uterus didelphys, bicornuate uterus, septate uterus, and arcuate uterus. Correct diagnosis and classification of these anomalies are essential because pregnancy outcomes and treatment options vary between the types of anomaly. Furthermore, early identification of MDAs helps to avoid prolonged symptomatic periods and the complications that may subsequently arise, such as infertility, endometriosis, and neoplasm. Although many of these abnormalities are initially diagnosed by ultrasound or hysterosalpingography, MR imaging is the most accurate noninvasive modality available for classification of the various anomalies because of its better anatomic assessment compared with other diagnostic modalities. Familiarity with the wide variety of MDA presentations can help in the planning of appropriate treatment.
Am J Reprod Immunol. 2017 Dec;78(6).
The extracellular signal-regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation.
Arlier S1, Murk W2, Guzeloglu-Kayisli O1, Semerci N1, Larsen K1, Tabak MS2, Arici A2, Schatz F1, Lockwood CJ1, Kayisli UA1.
The role of extracellular signal-regulated kinase (ERK)1/2-mediated angiogenesis during endometriotic nidation is unknown. We posit that ERK1/2-induced angioblast differentiation and proliferation promotes ectopic endometrial angiogenesis.
METHODS OF STUDY:
Human eutopic and ectopic endometria were immunostained for total- (T-) or phosphorylated- (P-) ERK1/2 or double-immunostained for P-ERK1/2-CD34 and PCNA-CD34. Estradiol (E2 ), cytokines, normal peritoneal fluid (NPF) or endometriotic peritoneal fluid (EPF) ±PD98059, an ERK1/2 inhibitor, treaded primary human endometrial endothelial cells (HEECs) were evaluated by T-/P-ERK1/2 immunoblotting, MTT viability and tube formation assays.
HEECs exhibited higher endothelial P-ERK1/2 immunoreactivity in ectopic vs eutopic endometria. Double-immunostained ectopic endometria displayed abundant CD34-positive angioblasts exhibiting strong P-ERK1/2 and PCNA immunoreactivity. EPF and vascular growth factor (VEGF)-A significantly increased HEEC proliferation and P-ERK1/2 levels. PD98059 reduced basal, EPF, and VEGF-induced HEEC proliferation and promoted vascular stabilization following tube formation.
Enhanced ERK1/2 activity in angioblasts by such peritoneal factors as VEGF, E2 induces proliferation to trigger ectopic endometrial angiogenesis.
J Ovarian Res. 2017 Sep 18;10(1):63.
Prognostic analysis for Chinese patients with stage I ovarian endometrioid carcinoma.
Zhao Y1,2, Wang S3, Qu YM4, Ji YT1, Shen K1, Lang JH1.
This study aimed to identify the clinical and pathological characteristics and the possible prognostic factors for Chinese patients with early-stage ovarian endometrioid carcinoma.
The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of ovarian endometrioid carcinoma at our center. In all, 78 patients had stage I ovarian endometrioid carcinoma.
In this series, the 5-year overall survival rate and 5-year disease-free survival (DFS) rates of patients with stage I ovarian endometrioid carcinoma was 98.7% and 87.2%, respectively. Univariate analysis showed the factors that influence the DFS rates include menopausal status, FIGO stage, histological grade, lymphadenectomy, cytology of ascites. Multivariate analysis showed that grade 3 and lymphadenectomy were the independent prognostic factors of DFS for Stage I ovarian endometrioid carcinoma (P = 0.0259, 0.0276 respectively). However, the coexisting endometriosis, concomitant endometrial disorders, dissection of para-aortic lymph node and more courses of thermotherapy had no influence on DFS. Besides, it was found that 19.3% of patients in this series had synchronous early stage and well-to-moderate differentiated endometrial carcinoma.
Grade 3 and lymphadenectomy were indicated as the independent factors of DFS for stage I patients with ovarian endometrioid carcinoma. The endometrial changes should be considered seriously when fertility-sparing surgery was planned.
Fertil Steril. 2017 Nov;108(5):858-867.e2.
Aberrant expression of epithelial leucine-rich repeat containing G protein-coupled receptor 5-positive cells in the eutopic endometrium in endometriosis and implications in deep-infiltrating endometriosis.
Vallvé-Juanico J1, Suárez-Salvador E2, Castellví J3, Ballesteros A4, Taylor HS5, Gil-Moreno A6, Santamaria X7.
To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5+) cells from the endometrium of women with endometriosis.
Prospective experimental study.
University hospital/fertility clinic.
Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples.
Obtaining of uterine aspirates by using a Cornier Pipelle.
MAIN OUTCOMES MEASURE(S):
Immunofluorescence in formalin-fixed paraffin-embedded tissue from mice and healthy and pathologic human endometrium using antibodies against LGR5, E-cadherin, and cytokeratin, and epithelial and stromal LGR5+ cells isolated from healthy and pathologic human eutopic endometrium by fluorescence-activated cell sorting and transcriptomic characterization by RNA high sequencing.
Immunofluorescence showed that LGR5+ cells colocalized with epithelial markers in the stroma of the endometrium only in endometriotic patients. The results from RNA high sequencing of LGR5+ cells from epithelium and stroma did not show any statistically significant differences between them. The LGR5+ versus LGR5– cells in pathologic endometrium showed 394 differentially expressed genes. The LGR5+ cells in deep-infiltrating endometriosis expressed inflammatory markers not present in the other types of the disease.
Our results revealed the presence of aberrantly located LGR5+ cells coexpressing epithelial markers in the stromal compartment of women with endometriosis. These cells have a statistically significantly different expression profile in deep-infiltrating endometriosis in comparison with other types of endometriosis, independent of the menstrual cycle phase. Further studies are needed to elucidate their role and influence in reproductive outcomes.
Acta Pharm Sin B. 2017 Sep;7(5):593-602.
Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system.
Ci L1, Huang Z1, Liu Y2, Liu Z1, Wei G2, Lu W2.
Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.
Zhongguo Zhong Yao Za Zhi. 2016 Sep;41(18):3478-3482.
Effect of Tripterygium wilfordii glycosides combined with gestrinone on endometriosis and serum cytokine expression.
Zhou XH1, Fu WJ2, Wang BD3, Fu QX4.
To study the effect of Tripterygium wilfordii glycosides and gestrinone on endometriosis and serum cytokine expression, 135 cases of endometriosis patients were divided into treatment group(n=69) and control group(n=68). The observation group was orally given with T. wilfordii glycosides, 20 mg, tid, for 4 weeks. Then, the dose decreased to 10 mg/time, tid. T. wilfordii glycosides combined with gestrinone capsule(2.5 mg) were given in the 1st and 4th day of a menstrual cycle. Later, the administration was fixed at two times every week. The course of treatment lasted for 3 months. The control group was treated with gestrinone capsule(according to the same intake method). The serum-related cytokine levels before and after treatment were determined, and the clinical efficacy was observed. The results showed the total effective rate of the observation group was 89.71%, which was obviously higher than that of the control group(74.63%), with statistically significant differences(P<0.05). After treatment, TDS showed varying degrees of decreases, with a better effect in the observation group (P<0.01). Before treatment, serum TGF-β, IL-10 and IL-4 level had no significant difference. After treatment, all of these cytokines decreased, particularly for the observation decreased(P<0.01). Before and after treatment, serum IL-17 had no obvious difference between the two groups. This study suggested that the integrated traditional Chinese medicine and western medicine has an obvious clinical efficiency in endometriosis. Its mechanism may be related to the effective regulation of cytokines.
Ceska Gynekol. 2017 Fall;82(4):308-312.
Catamenial pneumothorax – case reports and literature review.
Voláková E, Kolek V, Kufa J, Zatloukal J, Chudáček J, Szkorupa M, Pilka R.
Catamenial pneumothorax is menstrual cycle dependent and represents the most common form of thoracic endometriosis syndrome. Recurrences are very common even after surgical resection.
Case reports and literature overview.
Department of Respiratory Medicine, Department of Surgery I, Department of Obstetrics and Gynecology, University Hospital, Palacky University, Olomouc.
Two cases of catamenial pneumothorax are presented with repeated recurrences of right-sided pneumothorax even after surgical treatment. Histopathologic finding of pelvic endometriosis was shown in both patients.
Catamenial pneumothorax is usually connected with thoracic endometriosis and also includes catamenial hemothorax, recurrent catamenial hemoptysis, catamenial pleural pain as well as endometriosis lung nodules. Multidisciplinary approach including pneumologist, thoracic surgeon and gynecologist with early postoperative hormonal treatment that deals with the main chronic systemic disease may lead to improved results, mainly reduced recurrence rates of catamenial and/or endometriosis related pneumothorax.
Gynecol Endocrinol. 2017 Sep 19:1-4.
Plasma urocortin-1 as a preoperative marker of endometriosis in symptomatic women.
Maia LM1, Rocha AL1, Del Puerto HL2, Petraglia F3, Reis FM1.
Accurate noninvasive diagnostic tests for endometriosis are still missing. This study evaluated the predictive value of the neuropeptide urocortin 1 (Ucn1) to detect pelvic endometriosis in symptomatic women. We enrolled prospectively 97 consecutive women submitted to gynecologic laparoscopy for chronic or acute pelvic pain, infertility or adnexal mass. Preoperative blood samples were assayed for Ucn1 using enzyme immunoassay. Patients with endometriosis had higher plasma Ucn1 levels compared to patients with no lesions (median 59 vs. 34 pg/ml, p < .01, Dunn’s test). Elevated plasma Ucn1 levels were found among all endometriosis phenotypes (superficial peritoneal lesions, ovarian endometrioma, and deep infiltrating endometriosis, p < .05 vs. no lesions). Receiver operating characteristics curve analysis identified plasma Ucn1 > 46 pg/mL as the best cutoff point to detect endometriosis vs. no lesions, with 76% sensitivity and 88% specificity (area under the curve [AUC] 0.827, 95% confidence interval [CI] 0.695 - 0.959), but no cutoff could accurately distinguish endometriosis from other pathological conditions (AUC 0.593 [95% CI 0.474 - 0.711]). In women with chronic pelvic pain, infertility, or both symptoms, the probability of endometriosis (positive predictive value) increased consistently with the increase of plasma Ucn1 levels. The present findings suggest that high plasma Ucn1 levels increase the likelihood of endometriosis in symptomatic women.
Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:12-20.
Association between X-ray repair cross-complementing group 1(XRCC1) Arg399Gln polymorphism and endometriosis: A systematic review and meta-analysis.
Lv MQ1, Wang J2, Yu XQ3, Hong HH1, Ren WJ4, Ge P1, Zhou DX5.
X-ray repair cross-complementing group 1(XRCC1) gene is one of the DNA repair pathway genes playing a vital role in endometriosis risk. Various studies have explored the association between them, however, the results remained inconsistent. So to confirm the association between XRCC1 Arg399Gln polymorphism and the risk of endometriosis, a meta-analysis was conducted.
PubMed, Web of Science, Science Director, Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases were searched to identify the all relevant studies before Sep. 30, 2016 focusing on the association between XRCC1 Arg399Gln polymorphism and the risk of endometriosis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and analyzed by Review Manager 5.2 and Stata 12 to assess the strength of the association. Meanwhile, Begg’s test was used to check the publication bias.
The present meta-analysis identified 6 studies with 646 cases and 616 controls. The overall analysis revealed that the AA genotype exhibited a significant association with a decreased risk for endometriosis compared with GG (OR=0.43, 95%CI=0.20-0.94, P=0.03), GA (OR=0.57, 95%CI=0.35-0.95, P=0.03) and GG+GA (OR=0.54, 95%CI=0.31-0.96, P=0.04) respectively. In addition, subgroup analyses based on varied regions indicated that a total comparisons of allelic and various genetic models had statistical significances among Asians (A allele vs. G allele: OR=0.62, 95%CI=0.48-0.81, P=0.0004; AA vs. GG: OR=0.22, 95%CI=0.11-0.46, P<0.0001; AA vs. GA: OR=0.32, 95%CI=0.16-0.63, P=0.001; AA vs. GG+GA: OR=0.28, 95%CI=0.14-0.54, P=0.0002; AA+GA vs. GG: OR=0.28, 95%CI=0.14-0.54, P=0.008) but not among Middle Eastern. The Begg’s test did not reveal any obvious publication bias in the present study.
Our meta-analysis suggested that Arg399Gln in XRCC1 was associated with endometriosis risk. And especially in Asians, the A allele might be a preventive factor for this disease. Further well-designed researches with larger sample size and various regions are required to validate our conclusion.
Endocrinology. 2018 Jan 1;159(1):103-118.
Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.
Burns KA1, Thomas SY2, Hamilton KJ1, Young SL3, Cook DN2, Korach KS1.
Endometriosis is a gynecological disease that negatively affects the health of 1 in 10 women. Although more information is known about late stage disease, the early initiation of endometriosis and lesion development is poorly understood. Herein, we use a uterine tissue transfer mouse model of endometriosisto examine early disease development and its dependence on estradiol (E2) and estrogen receptor (ER) α within 72 hours of disease initiation. Using wild-type and ERα knockout mice as hosts or donors, we find substantial infiltration of neutrophils and macrophages into the peritoneal cavity. Examining cell infiltration, lesion gene expression, and peritoneal fluid, we find that E2/ERα plays a minor role in early lesion development. Immune-mediated signaling predominates E2-mediated signaling, but 48 hours after the initiation of disease, a blunted interleukin (IL)-6-mediated response is found in developing lesions lacking ERα. Our data provide evidence that the early initiation of endometriosis is predominantly dependent on the immune system, whereas E2/ERα/IL-6-mediated cross-talk plays a partial role. These findings suggest there are two phases of endometriosis-an immune-dependent phase and a hormone-dependent phase, and that targeting the innate immune system could prevent lesion attachment in this susceptible population of women.
Front Biosci (Elite Ed). 2018 Jan 1;10:92-102.
Association between ovarian endometrioma and ovarian reserve.
Kitajima M1, Khan KN2, Harada A3, Taniguchi K3, Inoue T3, Kaneuchi M3, Miura K3, Masuzaki H3.
Endometrioma is one of the main pathologies of endometriosis, though its pathogenesis still remains enigmatic. Ovarian reserve is defined as the number and quality of the follicles left in the ovary at any given time. The cause of infertility in women with endometriosis is multifactorial. Diminished ovarian reserve is major concern in women with endometriosis-associated infertility. Cystectomy for endometriomas could negatively impact on post-operative ovarian reserve. Some women had surgery for endometriomas suffer from poor ovarian response, which directly affects treatment results. In addition, endometriomas themselves may be a cause of diminished ovarian reserve. Destruction of normal histological structure in ovarian cortex may affect dormancy of primordial follicles. Therefore, determination of ovarian reserve may serve as an important role in the management of reproductive health of women with endometriosis. Although the knowledge on the physiology of follicular development and mechanism of maintenance of ovarian reserve are rapidly accumulating, results obtained by ovarian reserve testing after surgery should be carefully evaluated according to the time-points and selected test. Further investigation on this issue is warranted.
Int J Gynecol Cancer. 2018 Jan;28(1):11-18.
Significance of Ovarian Endometriosis on the Prognosis of Ovarian Clear Cell Carcinoma.
Park JY1, Kim DY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH.
The aim of this study was to evaluate the significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma (OCCC).
Patients with OCCC were divided into 2 groups according to the presence of ovarian endometriosis: group 1, no coexisting ovarian endometriosis; group 2, clear cell carcinoma arising from ovarian endometriosis or the presence of ovarian endometriosis elsewhere in the ovary. Clinicopathologic characteristics, disease-free survival (DFS), and overall survival (OS) were compared between the 2 groups.
Of 155 patients with OCCC, 77 were categorized into group 1 and 78 into group 2. Group 2 patients were younger than group 1 (median age, 48 vs 51 years; P = 0.005) and had higher incidence of early-stage disease (stage I, 77% vs 58%; P = 0.001) and lower incidence of lymph node metastasis (4% vs 17%; P = 0.008). Group 2 patients were observed to have a significantly higher 5-year DFS (P < 0.001) and OS (P = 0.001) compared with group 1. In stage I disease, group 2 had a significantly higher 5-year DFS (P = 0.004) and OS (P = 0.016) than did group 1. In the multivariate analysis, coexisting endometriosis and advanced International Federation of Obstetrics and Gynecology stage were significant factors for both DFS and OS rates.
Ovarian clear cell carcinoma with endometriosis was found more frequently in younger women and had a higher incidence of early-stage disease and a lower incidence of lymph node metastasis compared with OCCC without endometriosis. Ovarian endometriosis was associated with improved prognostic factors and a better DFS and OS even in stage I disease. Ovarian endometriosis was an independent prognostic factor for OCCC.
Sci Rep. 2017 Sep 20;7(1):11927.
Use of medroxyprogesterone acetate in women with ovarian endometriosis undergoing controlled ovarian hyperstimulation for in vitro fertilization.
Guo H1, Wang Y1, Chen Q1, Chai W1, Sun L1, Ai A1, Fu Y1, Lyu Q1, Kuang Y2.
This study investigated the use of medroxyprogesterone acetate (MPA) or a short protocol for controlled ovarian hyperstimulation (COH) in patients with advanced endometriosis who have normal ovarian function, and to compare cycle characteristics and pregnancy outcomes after frozen-thawed embryo transfer (FET). This was a retrospective case-control study of 244 patients with advanced endometriosisundering COH. The patients were allocated to three groups: the surgery group with MPA COH (62 patients, 71 IVF/ICSI cycles, 78 FET cycles); the aspiration group with MPA COH (85 patients had ovarian “chocolate” cysts (>3 cm) aspirated, 90 IVF/ICSI cycles, 76 FET cycles); and the short protocol group (97 patients, 101 IVF/ICSI cycles, 51 FET cycles). The results showed that higher rates of mature oocyte, D3 high quality embryo, hMG dose were observed in the two study groups using MPA compared with the short protocol. The number of >10-14 mm follicles on the trigger day, D3 top-quality embryos, viable embryos, rates of cancellation, fertilization, implantation, pregnancy outcomes were similar among the three groups. The oocytes, embryos, and pregnancy outcomes were not influenced by endometrioma surgery or presence of endometrioma. MPA COH could be effective for women with ovarian advanced endometriosis who had normal ovarian function.
Arch Womens Ment Health. 2018 Feb;21(1):1-13.
Behavioral, cognitive, and emotional coping strategies of women with endometriosis: a critical narrative review.
Zarbo C1, Brugnera A2, Frigerio L3, Malandrino C3, Rabboni M4, Bondi E4, Compare A2.
Endometriosis is a disabling and long-term medical condition affecting quality of life and mental health. Behavioral, cognitive, and emotional coping strategies, emotional intelligence, and metacognition could in part explain the link between the disease and impaired psychological and life functioning. This critical narrative review aimed at examining the state of the art of the relationships between endometriosis and these factors. According to PRISMA principles, we performed a systematic search for quantitative and qualitative studies on multiple electronic databases as regards coping strategies, emotional intelligence, and metacognition in women with endometriosis. Studies were subjected to interpretative and critical narrative synthesis. A total of 9 papers were included in the review. Three main categories were identified in thematic analysis and resumed in the manuscript. Findings suggested that (a) pain is considered the major stressor; (b) they usually use both adaptive and maladaptive coping strategies; (c) women with endometriosis and related chronic pain seem to repress emotions more likely than healthy ones; (d) suppressing own emotions, pain catastrophizing, and having a passive coping style are related to higher self-reported pain; and (e) emotional and avoidance coping styles are associated to poor mental status, while positive coping strategies focusing on the problem or on emotions, detached and rational styles are associated to better mental health. Few studies with mixed results and some methodological flaws have focused on coping strategies in women with endometriosis. No studies focusing on metacognition or emotional intelligence were found. Methodological biases, suggestions for future research, and implications for clinical practice were discussed.
Chin Med J (Engl). 2017 Oct 5;130(19):2339-2345.
Evaluation of Circulating Endometrial Cells as a Biomarker for Endometriosis.
Chen Y1, Zhu HL1, Tang ZW2, Neoh KH2, Ouyang DF3, Cui H1, Cheng HY1, Ma RQ1, Ye X1, Han RP2, Chang XH1.
Circulating endometrial cells (CECs) have been reported to be present in the peripheral blood of women with endometriosis (EM), providing clear and specific evidence of the presence of ectopic lesions. In this study, we established a method with a high detection rate of CECs, assessed the diagnostic value of CECs for EM and compared with serum CA125, and proposed a hypothesis for the pathogenesis of EM from the new perspective of CECs.
The participants were enrolled prospectively from October 2015 to July 2016. The peripheral blood samples were collected from 59 participants, and the blood cells were isolated for immunofluorescence staining via microfluidic chips. The cells that were positive for vimentin/cytokeratin and estrogen/progesterone receptor and negative for CD45 were identified as CECs. The serum CA125 level was tested with electrochemiluminescence immunoassay.
The detection rate of CECs reached 89.5% (17/19) in the EM group, which was significantly higher than that of the control group (15.0% [6/40], P < 0.001) and was independent of menstrual cycle phases. Furthermore, a positive CEC assay detected 4/5 cases of Stage I-II EM. In contrast, a positive CA125 test had limited value in detecting EM (13/19, 68.4%) and detected only one case of Stage I-II EM.
CECs are promising biomarkers for EM with great potential for a noninvasive diagnostic assay.
Endocrinology. 2017 Oct 1;158(10):3605-3619.
Progressive Fibrosis: A Progesterone- and KLF11-Mediated Sexually Dimorphic Female Response.
Shenoy CC1, Khan Z1, Zheng Y1, Jones TL1, Khazaie K2, Daftary GS1.
Progressive scarring is ubiquitous postoperatively and in an array of chronic systemic diseases. Recent studies indicate that such scarring has a high female propensity; females are also almost exclusively affected by endometriosis, a common sex steroid-dependent fibrotic disease. Endometriosis-related fibrosis is regulated epigenetically through transcription factor Krüppel-like factor 11 (KLF11). In response to surgical induction of endometriosis, Klf11-/- female mice develop significant fibrosis in contrast to wild-type mice. We therefore hypothesized that female fibrotic predilection was mediated by differential sex steroid regulation of KLF11/collagen 1a1 signaling and investigated the fibrotic response in wild-type and Klf11-/- male and female animals using a sterile peritonitis model. Fibrosis selectively developed in Klf11-/- females. Fibrosis in these animals was almost completely abrogated by ovariectomy. Ovariectomized animals were selectively supplemented with estradiol, medroxyprogesterone acetate (MPA), or dihydrotestosterone; fibrosis was only observed in mice exposed to MPA. Fibrosis therefore selectively developed in Klf11-/- female mice in response to physiological or pharmacological progesterone. The fibrotic response in these animals was also mitigated in response to antiprogestin therapy. Profibrotic gene expression was activated in a primary human peritoneal cell line in response to KLF11 short hairpin RNA and MPA but not estradiol. KLF11/collagen 1a1 signaling previously shown to be linked to fibrosis was thus selectively dysregulated in MPA-treated cells. Our in vivo and in vitro findings in an animal model and human cells, respectively, suggest that progressive fibrotic scarring is a sexually dimorphic response irrespective of etiology; moreover, it is responsive to novel, individualized therapeutic intervention.
F1000Res. 2017 Sep 5;6:1645.
Dysmenorrhea and related disorders.
Bernardi M1, Lazzeri L1, Perelli F2, Reis FM3, Petraglia F2.
Dysmenorrhea is a common symptom secondary to various gynecological disorders, but it is also represented in most women as a primary form of disease. Pain associated with dysmenorrhea is caused by hypersecretion of prostaglandins and an increased uterine contractility. The primary dysmenorrhea is quite frequent in young women and remains with a good prognosis, even though it is associated with low quality of life. The secondary forms of dysmenorrhea are associated with endometriosis and adenomyosis and may represent the key symptom. The diagnosis is suspected on the basis of the clinical history and the physical examination and can be confirmed by ultrasound, which is very useful to exclude some secondary causes of dysmenorrhea, such as endometriosis and adenomyosis. The treatment options include non-steroidal anti-inflammatory drugs alone or combined with oral contraceptives or progestins.
Metab Brain Dis. 2017 Dec;32(6):2165.
Erratum to: Treadmill exercise alters ecstasy- induced long- term potentiation disruption in the hippocampus of male rats.
Sajadi A1, Amiri I2,3, Gharebaghi A1, Komaki A1, Asadbegi M1, Shahidi S1, Mehdizadeh M4, Asl SS5,6.
In the original publication of the article, author name Masoumeh Asadbegi was incorrectly written as Masoumeh Asadbeigi. The authors regret the oversight.
BMC Womens Health. 2017 Sep 26;17(1):89.
Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial.
Waiyaput W1, Pumipichet S2, Weerakiet S3, Rattanasiri S4, Sophonsritsuk A5.
Simvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis.
A prospective, randomized, controlled study was conducted at the Reproductive Endocrinology Unit of the Department of Obstetrics and Gynecology at the Faculty of Medicine Ramathibodi Hospital. Forty women (mean age: 18-45 years) scheduled for laparoscopic surgery who had been diagnosed with endometriosis were recruited and randomly assigned to either a treatment group (20 mg/d of orally administered simvastatin for 2 weeks before surgery) or an untreated control group. Serum was collected before and after treatment and protein levels of MCP-1 were determined. MCP-1 and CD68 transcript levels were also quantified using real-time PCR on endometriotic cyst tissues.
MCP-1 gene expression on endometriotic cyst was not significantly different between the simvastatin-treated and untreated groups (P = 0.99). CD68 expression was higher in the treatment group compared to the control group, but this was not statistically significant (P = 0.055). Serum MCP-1 levels following simvastatin treatment were higher than in samples obtained before treatment (297.89 ± 70.77 and 255.51 ± 63.79 pg/ml, respectively) (P = 0.01).
Treatment with 20 mg/d of simvastatin for 2 weeks did not reduce the expression of either the chemokine MCP-1 gene or macrophage-specific genes. Cumulatively, this suggests that simvastatin is not ideal for treating endometriosis because a higher dose of simvastatin (40-100 mg/d) would be needed to achieve the target outcome, which would significantly increase the risk of myopathy in patients.
BJOG. 2018 Jan;125(1):64-72.
Impact of endometriosis on risk of further gynaecological surgery and cancer: a national cohort study.
Saraswat L1, Ayansina D2, Cooper KG1, Bhattacharya S3, Horne AW4, Bhattacharya S5.
To evaluate the long-term risk of further gynaecological surgery and cancer in women with endometriosis.
281 937 women with nearly 5 million person years (4 923 628) of follow up from 1981 to 2010.
In this national population-based study we compared 17 834 women with a new surgical diagnosis of endometriosis with 83 303 women with no evidence of endometriosis at laparoscopy, 162 966 women who underwent laparoscopic sterilisation, and 17 834 age-matched women from the general population. Cox proportional hazards regression was used to calculate crude and adjusted hazard ratios with 95% confidence intervals.
MAIN OUTCOME MEASURES:
Risk of further gynaecological surgery, number and type of repeat surgery and time to repeat surgery from the diagnosis of endometriosis. Cancer outcomes included subsequent risk of all cancer, gynaecological and non-gynaecological cancers.
Women with endometriosis had a significantly higher risk of further surgery when compared with women with no evidence of endometriosis at laparoscopy [hazard ratio (HR) 1.69, 95% (confidence interval) CI 1.65-1.73], women who had undergone laparoscopic sterilisation (HR 3.30, 95% CI 3.23-3.37) and age-matched women from the general population (HR 5.95, 95% CI 5.71-6.20). They also have an increased risk of ovarian cancer when compared with general population counterparts (HR 1.77, 95% CI 1.08-2.89) or those with laparoscopic sterilisation (HR 1.75, 95% CI 1.2-2.45).
Women with surgically diagnosed endometriosis face an increased risk of multiple surgery. They have a higher chance of developing ovarian cancer in comparison with the general population and women with laparoscopic sterilisation.
Women with endometriosis face an increased risk of recurrent surgery and developing ovarian cancer.
Gynecol Endocrinol. 2018 Jan;34(1):10-14.
Conservative treatment of deep infiltrating endometriosis: review of existing options.
Szubert M1, Ziętara M2, Suzin J1.
Endometriosis with its estimated incidence rate of ∼7-10% of women of reproductive age is a disease with the wide spectrum of symptoms depending on form and localization of endometrial foci. One clinical form of endometriosis is deep infiltrating endometriosis (DIE), most difficult to manage and generating a lot of direct and indirect treatment costs. We search the literature from PubMed database to establish the role of conservative treatment of DIE. Randomised controlled trials are lacking but in experts opinion hormonal treatment should be the first-line treatment in DIE. After evaluation of pain or other symptoms, second-line therapy with GnRH analogs or danazol should be offered or minimally invasive surgery. Consensus is not made whether surgery is the best therapeutic treatment for affected patients. Strong depending on surgeon’s experience conservative surgery should be offered if the total excision of DIE foci is possible, which is essential for a successful outcome. If available treatment options do not release pain associated with DIE, experimental treatment in clinical trials should be discussed with patients.
Cien Saude Colet. 2017 Sep;22(9):3023-3032.
The experience of illness of women with endometriosis: narratives about institutional violence.
This paper conjures up the centrality of the relational category of gender to shed a light on women’s life narratives with a chronic disease named endometriosis. It aims to discuss the meaning of the illness experience of women with endometriosis in the interface with institutional violence. Based on Bertaux reference, in the Narratives of Life method, twenty women participated in this research. They were invited from two virtual spaces of discussion and gatherings about living with endometriosis. Interviews were conducted in person in the States of Rio de Janeiro, São Paulo and Minas Gerais circuit. Authors sustained the theoretical approach and addressed the experience of chronic illness as a sociocultural phenomenon, metaphorical readings of the problem and criticism of institutional violence. The results identify situations of gender/institutional violence perpetrated in various women care settings. They are expressed through the trivialization of women’s discourses; user-physician tensions, where the supposed lay knowledge appears as an insult to official biomedical knowledge and, mainly, the difficult access to services, leading women to a care pilgrimage and to submit themselves to care types not necessarily based on best practices.
Eur J Contracept Reprod Health Care. 2017 Oct;22(5):334-343.
Incidence, treatment and recurrence of endometriosis in a UK-based population analysis using data from The Health Improvement Network and the Hospital Episode Statistics database.
Cea Soriano L1,2, López-Garcia E3, Schulze-Rath R4, Garcia Rodríguez LA1.
This retrospective study used medical records from The Health Improvement Network (THIN) and Hospital Episode Statistics (HES) database to evaluate endometriosis (incidence, treatment and need for recurrent invasive procedures) in the general UK population.
MATERIALS AND METHODS:
Women aged 12-54 years between January 2000 and December 2010, with a Read code for endometriosis, were identified in THIN. Cases were validated by manual review of free-text comments in medical records and responses to physician questionnaires. False-negative cases were identified among women with Read codes for hysterectomy or dysmenorrhea. Prescriptions of medical therapies for endometriosis were identified in THIN. Cases of single and recurrent invasive procedures were identified in women with medical records in both THIN and HES.
Overall, 5087 women had a Read code for endometriosis, corresponding to an incidence of 1.02 (95% confidence interval [CI]: 0.99-1.05) per 1000 person-years. After case validation, the estimate was 1.46 (95% CI: 1.43-1.50) per 1000 person-years. Medical therapy was prescribed to 55.5% of women with endometriosis in the first year after diagnosis. In total, 48.3% of women received invasive treatment during the study period; approximately one-fifth of these women required further invasive treatment, mainly in the 3 years after the index procedure.
Using Read codes as the only method to identify women with endometriosisunderestimates incidence. Over half of women with recorded endometriosis are prescribed medical therapy in the first year after diagnosis. Women with diagnosed endometriosis are at risk of requiring recurrent invasive procedures.
Reprod Sci. 2017 Jan 1:1933719117732161.
Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain.
Ding S1, Zhu T1, Tian Y1, Xu P1, Chen Z1, Huang X1, Zhang X1.
Brain-derived neurotrophic factor (BDNF) is a regulator for the formation and maintenance of chronic pain in various chronic disorders and has been shown to increase in the serum of women with endometriosis. However, BDNF expression in the peritoneal fluid (PF) and ectopic lesions and its role in endometriosispain remain unclear. Thus, this study aims to determine the BDNF concentrations in serum and PFs and BDNF expression levels in ectopic lesions and endometriotic stromal cells (ESCs) of women with endometriosis (n = 60). The obtained results were then compared with those of women without endometriosis (n = 38). Brain-derived neurotrophic factor concentrations in serum and PF, as well as the BDNF expression levels in ectopic lesions and endometriotic cells, were evaluated through enzyme-linked immunosorbent assay, immunohistochemical staining, quantitative real-time polymerase chain reaction, and Western blot analysis. As a result, BDNF concentrations in serum and PF were significantly higher in women with endometriosis with pain (2284.3 ± 51.5 pg/mL, n = 23; 58.8 ± 6.4 pg/mL, n = 16) than in women with endometriosis without pain (1999.8 ± 61.1 pg/mL, n = 37; 31.7 ± 2.9 pg/mL, n = 25; P < .01). Moreover, BDNF messenger RNA (mRNA) expression levels in ectopic lesions (8.97 ± 1.44, n = 29) were significantly higher than eutopic (0.97 ± 0.14, n = 16; P < .01) and control endometrium (1.23 ± 0.19, n = 18; P < .01) and were correlated with endometriosis pain ( P < .05). Furthermore, increased BDNF mRNA and protein expression levels in ESCs induced by estradiol or interleukin 1β were removed using a phosphorylated extracellular-regulated protein kinase 1/2 inhibitor. These results suggest that BDNF may play an important role in the pathogenesis of endometriosis pain.
J Am Soc Mass Spectrom. 2017 Sep 27.
A Comparison of Tissue Spray and Lipid Extract Direct Injection Electrospray Ionization Mass Spectrometry for the Differentiation of Eutopic and Ectopic Endometrial Tissues.
Chagovets V1, Wang Z1,2, Kononikhin A1,3, Starodubtseva N1,3, Borisova A1, Salimova D1, Popov I1,3, Kozachenko A1, Chingin K2, Chen H4, Frankevich V5, Adamyan L1, Sukhikh G1.
Recent research revealed that tissue spray mass spectrometry enables rapid molecular profiling of biological tissues, which is of great importance for the search of disease biomarkers as well as for online surgery control. However, the payback for the high speed of analysis in tissue spray analysis is the generally lower chemical sensitivity compared with the traditional approach based on the offline chemical extraction and electrospray ionization mass spectrometry detection. In this study, high resolution mass spectrometry analysis of endometrium tissues of different localizations obtained using direct tissue spray mass spectrometry in positive ion mode is compared with the results of electrospray ionization analysis of lipid extracts. Identified features in both cases belong to three lipid classes: phosphatidylcholines, phosphoethanolamines, and sphingomyelins. Lipids coverage is validated by hydrophilic interaction liquid chromatography with mass spectrometry of lipid extracts. Multivariate analysis of data from both methods reveals satisfactory differentiation of eutopic and ectopic endometrium tissues. Overall, our results indicate that the chemical information provided by tissue spray ionization is sufficient to allow differentiation of endometrial tissues by localization with similar reliability but higher speed than in the traditional approach relying on offline extraction. Graphical Abstract ᅟ.
Yonago Acta Med. 2017 Sep 15;60(3):182-185.
Efficacy of Norethisterone in Patients with Ovarian Endometrioma.
Taniguchi F1, Enatsu A2, Ikebuchi A1, Yamane E1, Moriyama M1, Murakami J1, Harada T1, Harada T1.
Endometriosis is a chronic inflammatory disorder associated with pelvic pain and infertility. Because surgical and medical therapies control symptoms, but it is hard to cure completely endometriosis, long term of pharmacologic management is necessary. Norethisterone (NET), one of progestins, has safety profile and advantage that allow long-term use. In this preliminary report, we showed the efficacy of NET in 6 patients with endometriosis. The size of ovarian endometrioma was decreased after treatment with NET for 6 months, and all patients were relieved from dysmenorrhea pain within 6 months, suggesting that NET would be a suitable medication to treat endometriosis.
Exp Ther Med. 2017 Sep;14(3):2317-2322.
Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis.
De Andrade VT1, Nácul AP2, Dos Santos BR1, Lecke SB1,3, Spritzer PM1,4, Morsch DM1.
Current data are inconsistent regarding the association between interleukin-6 (IL-6), a marker of acute phase inflammation, and pelvic endometriosis. The aim of the present study was to assess IL-6 levels in serum and peritoneal fluid (PF), as well as IL-6 gene expression in adipose tissue (AT) and endometrial samples in pelvic endometriosis. A total of 30 patients with endometriosis and 18 women with a normal pelvis were enrolled in this case-control study. IL-6 levels in PF and serum were determined using a human enzyme-linked immunosorbent assay and IL-6 gene expression was evaluated using reverse transcription-quantitative polymerase chain reaction. It was observed that IL-6 levels in the PF were higher in patients with endometriosis than in the control group (P=0.047) and patients with stage III/IV endometriosis exhibited higher IL-6 levels in the PF than those with stage I/II endometriosis and the control group (P<0.001). Furthermore, a strong correlation between PF IL-6 levels and the revised American Society for Reproductive Medicine score for endometriosis severity was identified (r=0.77; P<0.001). IL-6 gene expression did not differ significantly between endometriosis and control groups in endometrial samples or in AT of both groups. The results of the current study suggest that there may be an association between IL-6 and the presence and severity of pelvic endometriosis. The source of this higher IL-6 seems not to be specifically related to regional AT.
Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:99-105.
Pro-inflammatory M1/Th1 type immune network and increased expression of TSG-6 in the eutopic endometrium from women with endometriosis.
Matteo M1, Cicinelli E2, Neri M3, Carrubba R4, Carpagnano FA4, Romeo F4, Scutiero G4, Greco P5, Garlanda C6, Vendemiale G7, Levi Setti PE8, Serviddio G7.
The study aimed to explore the type 1 and type 2 cytokines expression in the endometrium from women affected by endometriosis compared to controls. The expression of TSG-6, a multifunctional protein involved in several inflammatory disease, was also evaluated. Study Design SETTING: Experimental clinical study.
10 patients affected by endometriosis and 11 controls.
Patients underwent to an ultrasound transvaginal examination and a diagnostic hysteroscopy in order to exclude any uterine abnormality. All patients underwent endometrial biopsy using a Novak’s curette.
MAIN OUTCOME MEASURES:
The endometrial expression of type 1 (IL- 1 β TNF-α, IL-8) and type 2 (IL-10) cytokines, and of TSG-6 was evaluated by immunohistochemistry and by real time PCR. The expression of TSG-6 was confirmed by western blot.
Results of PCR analysis and of immunohistochemistry revealed an increased expression of IL-1β, TNF-α, IL-8 and of TSG-6 in the endometrium of endometriosic patients. IL-10 expression did not show any difference.
An increased expression of pro-inflammatory type 1 cytokines was demonstrated in the endometrium from endometriosic patients, suggesting an endometrial environment harmful for implantation due to the prevalence of Th1 related immunity. An increased expression of TSG-6 was also demonstrated for the first time. Our findings concur to better define the inflammatory imbalance and the abnormal endometrial receptivity, reported in literature, of the eutopic endometrium of women affected by endometriosis.
J Gynecol Obstet Hum Reprod. 2017 Nov;46(9):691-692.
Combined laparoscopic and cystoscopic approach in large deep infiltrating endometriosis of the bladder.
Millochau JC1, Stochino-Loi E2, Defortescu G3, Darwish B1, Roman H4.
Resection of endometriosis nodules infiltrating the bladder is routinely performed by laparoscopy. However, laparoscopic resection may lead to inadvertent loss of healthy bladder tissue. Conversely, when bladder nodules are treated by cystoscopy alone, resection may be incomplete. A combined laparoscopic-cystoscopic approach allows safe and controlled resection. The video reports the procedure performed in a 33 year-old primipara who presented with a 40mm bladder nodule. The laparoscopic step is carried out by the gynecologist, who separates the bladder from the uterus and opens the vesico-vaginal space. Concomitantly, the urologist identifies and circumscribes the nodule’s limits by cystoscopy. Then, the gynecologist identifies the circular incision previously performed, and completes the resection. The bladder defect is sutured. Early and mid-term postoperative outcomes were uneventful. In patients with large nodules of the bladder, combined laparoscopic-cystoscopic approach allows complete resection of endometriosis lesion, preserves healthy bladder tissue and avoids inadvertent injury of ureters.
Ann Dermatol. 2017 Oct;29(5):621-625.
Primary Cutaneous Endometriosis of Umbilicus.
Cutaneous endometriosis is defined by the presence of endometrial glands and/or stroma in skin and represents less than 1% of all ectopic endometrium. Cutaneous endometriosis is classified as primary and secondary. Primary cutaneous endometriosis appears without a prior surgical history and secondary cutaneous endometriosis mostly occurs at surgical scar tissue after abdominal operations. The most widely accepted pathogenesis of secondary endometriosis is the iatrogenic implantation of endometrial cells after surgery, such as laparoscopic procedures. However, the pathogenesis of primary endometriosisis still unknown. Umbilical endometriosis is composed only 0.4% to 4.0% of all endometriosis, however, umbilicus is the most common site of primary cutaneous endometriosis. A 38-year-old women presented with solitary 2.5×2.0-cm-sized purple to brown colored painful nodule on the umbilicus since 2 years ago. The patient had no history of surgical procedures. The skin lesion became swollen with spontaneous bleeding during menstruation. The skin lesion was diagnosed as a keloid at private hospital and has been treated with lesional injection of steroid for several times but there was no improvement. Imaging studies showed an enhancing umbilical mass without connection to internal organs. Biopsy specimen showed the several dilated glandular structures in dermis. They were surrounded by endometrial-type stroma and perivascular infiltration of lymphocytes. The patient was diagnosed as primary cutaneous endometriosisand skin lesion was removed by complete wide excision without recurrence. We report an interesting and rare case of primary umbilical endometriosis mistaken for a keloid and review the literatures.
JBRA Assist Reprod. 2017 Dec 1;21(4):313-320.
Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis.
Schmitz CR1, Oehninger S2, Genro VK3, Chandra N2, Lattanzio F4, Yu L2, Cunha-Filho JS1,3.
The aim of this study was to compare the endometrial expression of milk fat globule-EGF factor 8 (MFG-E8), its receptor integrin αvβ3, and leukemia inhibitory factor (LIF) in patients with endometriosis and infertility and in healthy fertile patients during the window of implantation.
Five patients with peritoneal endometriosis and infertility (case group) and four healthy fertile patients (control group) were recruited. All patients were either diagnosed with or ruled out for endometriosis by laparoscopic surgery; the case group underwent surgery for infertility investigation and the control group for tubal ligation. Endometrial biopsies were performed in all patients during the window of implantation (LH+8 to LH+10), and then the samples were analyzed by immunochemistry for MFG-E8, integrin αvβ3, and LIF.
In patients with endometriosis and infertility, expression of MFG-E8 was significantly increased in the glandular epithelium when compared to healthy fertile patients (p<0.001). Moreover, LIF expression was lower in patients with endometriosis and infertility (p<0.05). Nevertheless, we found no difference in integrin αvβ3 expression between the groups (p=0.084).
This study showed for the first time that MFG-E8 expression is impaired in the endometrium of patients with endometriosis and infertility during the window of implantation. Moreover, LIF is also diminished in the endometrium of these patients as shown before.
J Obstet Gynaecol. 2017 Oct 3:1-4.
Severe ureteral endometriosis: frequency and risk factors.
Raimondo D1, Mabrouk M1,2, Zannoni L1, Arena A1, Zanello M1, Benfenati A1, Moro E1, Paradisi R1, Seracchioli R1.
Ureteral endometriosis (UE) can be classified as severe when there is obstruction to urinary flow (ureteral compression (UC)). In this retrospective study on 205 patients, we evaluated intraoperatively the frequency of severe ureteral endometriosis (UE) in women with UE and, secondarily, risk factors associated with UC. We documented intraoperatively ureteral UC in 124 (60.5%) patients with UE. A significantly lower body mass index (BMI) was observed in women with UC than in women without UC (p = .02). A significant association was found between UC and parametrial endometriosis (p = .001). In multivariable analysis, these variables remained significantly associated with UC. Ureteral compression is common in patients with UE, especially in women with parametrial infiltration and a low BMI.
Reprod Sci. 2017 Jan 1:1933719117732164.
HOXB4 Immunoreactivity in Endometrial Tissues From Women With or Without Endometriosis.
AlKusayer GM1,2, Pon JR3, Peng B1, Klausen C1, Lisonkova S1, Kinloch M3, Yong P1, Muhammad EMS4, Leung PCK1, Bedaiwy MA1.
Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC). HOXB4 localization and immunoreactivity was assessed using immunohistochemistry and histoscore analysis. Data were analyzed with and without stratification by menstrual cycle phase. HOXB4 protein was present in the nuclei of endometrial glandular epithelial cells but not in stromal cells. HOXB4 immunoreactivity was reduced in DIE samples compared to all other groups. A smaller reduction in HOXB4 immunoreactivity was observed in SE samples compared to EC samples. HOXB4 immunoreactivity was significantly greater in proliferative compared to secretory phase samples in the EC group but not in EE, Eoma, or DIE groups. Among only proliferative phase samples, HOXB4 immunoreactivity was reduced in EE, Eoma, and DIE groups compared to EC. Based on these data, we suggest that an impaired capacity of eutopic and ectopic endometrial tissue to upregulate levels of HOXB4 during the proliferative phase may play a role in the pathogenesis of endometriosis and that further downregulation of HOXB4 may enhance ectopic implant invasiveness.
J Gynecol Obstet Hum Reprod. 2017 Nov;46(9):681-686.
Pregnancy outcomes after controlled ovarian hyperstimulation in women with endometriosis-associated infertility: GnRH-agonist versus GnRH-antagonist.
Kolanska K1, Cohen J2, Bendifallah S3, Selleret L3, Antoine JM3, Chabbert-Buffet N1, Darai E1, d’Argent EM3.
BACKGROUND OR OBJECTIVE:
Endometriosis is common in women referred for infertility. In vitro fertilization provides good results but the choice of the best-controlled ovarian hyperstimulation protocol remains a subject of debate. The objective of this retrospective study was to compare pregnancy outcomes in women with endometriosis-associated infertility after COH with a long agonist protocol or a six-week oral contraception-antagonist protocol.
MATERIAL AND METHODS:
Retrospective analysis of a prospective database identified 284 COH cycles – 165 with GnRH-agonist protocol (GnRH-agonist group) and 119 with GnRH-antagonist protocol (GnRH-antagonist group) – in 218 women, with endometriosis from January 2013 to October 2015.
No difference in the epidemiological characteristics was found between the groups. Per started cycle, pregnancy and live-birth rates after fresh embryo transfer were higher with the GnRH-agonist protocol (25% vs. 13%, P=0.02 and 18% vs. 8%, P=0.04, respectively). Considering analysis per cycle with embryo transfer, the pregnancy rate was similar in both groups while the live-birth rate was higher in the GnRH-agonist group (29% vs. 17%, P=0.053 and 22% vs. 10%, P=0.02, respectively). No difference was observed between the groups with freeze-thaw embryo transfer. Subgroup analysis (endometrioma alone, deep infiltrating endometriosis with and without endometrioma, endometriosis with and without adenomyosis) revealed no difference between the groups for either pregnancy or live-birth rates.
A GnRH-agonist protocol appears to result in higher pregnancy and live-birth rates after fresh embryo transfer in women with endometriosis-associated infertility, suggesting that a GnRH-antagonist protocol might negatively impact endometrial receptivity.
Reproduction. 2017 Dec;154(6):815-825.
The crosstalk between endometrial stromal cells and macrophages impairs cytotoxicity of NK cells in endometriosis by secreting IL-10 and TGF-β.
Yang HL1,2, Zhou WJ1,2,3, Chang KK1, Mei J4, Huang LQ5, Wang MY1, Meng Y1, Ha SY1, Li DJ1,2,3, Li MQ6,2,3.
The dysfunction of NK cells in women with endometriosis (EMS) contributes to the immune escape of menstrual endometrial fragments refluxed into the peritoneal cavity. The reciprocal communications between endometrial stromal cells (ESCs) and lymphocytes facilitate the development of EMS. However, the mechanism of these communications on cytotoxicity of natural killer (NK) cells in endometriotic milieus is still largely unknown. To imitate the local immune microenvironment, the co-culture systems of ESCs from patients with EMS and monocyte-derived macrophages or of ESCs, macrophages and NK cells were constructed. The cytokine levels in the co-culture unit were evaluated by ELISA. The expression of functional molecules in NK cells was detected by flow cytometry (FCM). The NK cell behaviors in vitrowere analyzed by cell counting kit-8 and cytotoxic activation assays. After incubation with ESCs and macrophages, the expression of CD16, NKG2D, perforin and IFN-γ, viability and cytotoxicity of NK cells were significantly downregulated. The secretion of interleukin (IL)-1β, IL-10 and transforming growth factor (TGF)-β in the co-culture system of ESCs and macrophages was increased. Exposure with anti-IL-10 receptor β neutralizing antibody (αhIL-10Rβ) or αTGF-β could partly reverse these effects of ESCs and macrophages on NK cells in vitro These results suggest that the interaction between macrophages and ESCs downregulates cytotoxicity of NK cells possibly by stimulating the secretion of IL-10 and TGF-β, and may further trigger the immune escape of ectopic fragments and promote the occurrence and the development of EMS.
J Ovarian Res. 2017 Oct 3;10(1):67.
Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.
Ren T1, Wang S2, Sun J3, Qu JM4, Xiang Y1, Shen K1, Lang JH5.
Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored.
We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months.
Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients.
EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.
Iran J Pathol. 2016 Fall;11(5):478-482.
Bilateral Ovarian Clear Cell Carcinoma Arising in 17 Year Longstanding History of Bilateral Ovarian Endometriosis.
Win TT1, Nik Mahmood NMZ2, Ma SO2, Ismail M3.
Clear cell carcinoma of ovary is uncommon ovarian tumour that arises from surface epithelium of ovary. It has well-known association with ovarian endometriosis. We report here the first case of bilateral clear cell carcinoma of ovaries in a 40-year-old woman with a 17-year history of bilateral ovarian endometriosis. In addition, during the longstanding duration of the endometriosis, the patient was treated with hormonal therapy, including oestrogen. It represents the first report of such bilateral involvement in the background of ovarian endometriosis. This should prompt clinicians to be aware that prolonged hormonal treatment of endometriosis may precipitate bilateral malignancy of the ovary.
Int J Gynecol Cancer. 2017 Nov;27(9):1804-1812.
Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status.
Schnack TH1, Høgdall E, Thomsen LN, Høgdall C.
Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status.
Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant.
Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis(hazard ratio, 2.56 [95% confidence interval, 1.29-5.02], in the multivariate analysis.
Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant
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