Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Ned Tijdschr Geneeskd. 2014;158:A8104.
A woman with periodical bleeding from her umbilicus.
Daal SN1, van Slooten FE, van Huisseling JC.
A 33-year-old woman complained of a tumor in her umbilicus with bleeding during her menstrual periods. The diagnosis was made after surgical excision of the tumour: endometriosis of the umbilicus, also known as ‘Villar’s node’.
J Ultrasound Med. 2014 Nov;33(11):1909-15.
Decidualized endometrioma masquerading as ovarian cancer in pregnancy.
Groszmann Y1, Howitt BE2, Bromley B2, Feltmate CM2, Benacerraf BR2.
To identify the sonographic features of decidualized endometriomas in patients treated at a single institution and to determine whether sonographic findings can distinguish these lesions from malignant ovarian tumors during pregnancy.
We conducted a retrospective cohort study that included pregnant women with a histologic diagnosis of decidualized endometrioma between January 1, 2005, and December 1, 2012, and had an ovarian cyst or mass seen preoperatively on obstetrical sonography. Sonographic characteristics of these masses were retrospectively evaluated using the International Ovarian Tumor Analysis Group definitions for adnexal masses.
Seventeen patients with 22 adnexal masses were included in our study. Nine of 22 lesions (41%) were classified as unilocular solid, and 14 of 22 (64%) had solid components, of which 12 of 14 (86%) had substantial blood flow. Septations were present in 8 of 22 masses (36%). Cyst sizes varied from 30 to 120 and 32 to 270 mm at the initial and follow-up scans, respectively. Eight patients had no follow-up scans and underwent surgery within 3 weeks of diagnosis. The other 9 patients (14 masses), had follow-up scans and underwent surgery from 3 to 34 weeks after their initial scans. Eight of these masses showed no notable change in size or appearance, and 1 became smaller.
There were no characteristic sonographic features identified to distinguish decidualized endometrioma from ovarian malignancy. However, lesions showing no change in size over 4 weeks or lacking solid components and vascularity are more likely to be benign rather than malignant and may justify delaying surgery until delivery or postpartum.
Hum Reprod. 2014 Dec;29(12):2603-5.
Endometriosis of the retrocervical septum is proposed to replace the anatomically incorrect term endometriosis of the rectovaginal septum.
Batt RE1, Martin DC2, Odunsi K3.
We propose that the term retrocervical septum be added to the medical lexicon to designate the anatomic location of endometriosis of the septum that separates the vagina and posterior vaginal fornix from the rectovaginal pouch of Douglas. Use of the terms retrocervical septum and endometriosis of the retrocervical septum would correct the century-long misuse of the anatomically incorrect term, endometriosis of the rectovaginal septum.
Hum Reprod. 2015 Jan;30(1):239-48.
Association between endometriosis and the interleukin 1A (IL1A) locus.
Sapkota Y1, Low SK2, Attia J3, Gordon SD4, Henders AK4, Holliday EG3, MacGregor S4, Martin NG4, McEvoy M3, Morris AP5, Takahashi A2, Scott RJ6, Kubo M7, Zondervan KT8, Montgomery GW4, Nyholt DR4.
Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk?
We found evidence for strong association between IL1A SNPs and endometriosis risk.
WHAT IS KNOWN ALREADY:
Genetic factors contribute substantially to the complex aetiology of endometriosisand the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis.
STUDY DESIGN, SIZE, DURATION:
We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed.
MAIN RESULTS AND THE ROLE OF CHANCE:
All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with endometriosis at a nominal P < 0.05 in our independent Japanese sample. Fixed-effect meta-analysis of the eight SNPs for moderate-to-severe endometriosis produced a genome-wide significant association for rs6542095 (odds ratio = 1.21; 95% confidence interval = 1.13-1.29; P = 3.43 × 10(-8)).
LIMITATIONS, REASONS FOR CAUTION:
The meta-analysis for moderate-to-severe endometriosis included results of moderate-to-severe endometriosis cases from our European data sets and all endometriosis cases from the Japanese data sets, as disease stage information was not available for endometriosis cases in the Japanese data sets.
WIDER IMPLICATIONS OF THE FINDINGS:
SNP rs6542095 is located ∼2.3 kb downstream of the IL1A gene and ∼6.9 kb upstream of cytoskeleton-associated protein 2-like (CKAP2L) gene. The IL1A gene encodes the IL1a protein, a member of the interleukin 1 cytokine family which is involved in various immune responses and inflammatory processes. These results provide important replication in an independent Japanese sample and, for the first time, association of the IL1A locus in endometriosis patients of European ancestry. SNPs within the IL1A locus may regulate other genes, but if IL1A is the target, our results provide supporting evidence for a link between inflammatory responses and the pathogenesis of endometriosis.
Jpn Clin Med. 2014 Sep 5;5:43-5.
Functioning endometrium and endometrioma in a patient with mayer-rokitanski-kuster-hauser syndrome.
Kawano Y1, Hirakawa T1, Nishida M1, Yuge A1, Yano M1, Nasu K1, Narahara H1.
Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome is a rare disease. A 27-year-old woman was admitted for primary amenorrhea and cyclic pelvic pain. Magnetic resonance imaging (MRI) revealed bilateral Müllerian remnants with functioning endometrium and a pelvic mass considered to be an endometriotic cyst. Bilateral Müllerian remnants were removed, and right ovarian cystectomy was performed at laparoscopic surgery. Accurate evaluation before the operation and informed consent are necessary to treat patients with MRKH syndrome.
Wideochir Inne Tech Maloinwazyjne. 2014 Sep;9(3):463-7.
A pseudoneoplastic finding of deep endometriosis: laparoscopic triple segmental bowel resection.
Cosma S1, Ceccaroni M2, Benedetto C1.
Bowel endometriosis affects 3-37% of patients with endometriosis, involving more frequently the rectum and the rectosigmoid junction. Severe endometriosis with bowel involvement is often refractory to standard medical therapy. For these reasons, surgery for bowel treatment is frequently needed. We report the case of a 36-year-old woman with deep endometriosis of the pelvis, triple segmental bowel involvement (recto-sigma, ileum-cecum, transverse colon) and massive endometriotic ascites with secondary Glisson’s capsule inflammation, refractory to medical therapy. A laparoscopic triple segmental bowel resection and complete fertility sparing excision of pelvic endometriotic lesions was performed. At 48 months of follow-up, the woman was asymptomatic, with no evidence of recurrence of disease or ascites. Laparoscopic segmental bowel resection, including multiple section, is feasible in selected symptomatic patients with consequent improved quality of life, morbidity rates similar to those achieved by laparotomy and with a less detrimental effect on fertility.
J Thorac Dis. 2014 Oct;6(Suppl 4):S448-60.
Visouli AN1, Zarogoulidis K1, Kougioumtzi I1, Huang H1, Li Q1, Dryllis G1, Kioumis I1, Pitsiou G1, Machairiotis N1, Katsikogiannis N1, Papaiwannou A1, Lampaki S1, Zaric B1, Branislav P1, Porpodis K1, Zarogoulidis P1.
Catamenial pneumothorax (CP) is the most common form of thoracic endometriosis syndrome, which also includes catamenial hemothorax, catamenial hemoptysis, catamenial hemopneumothorax and endometriosislung nodules, as well as some exceptional presentations. Usually onset of lung collapse is less than 72 hours after menstruation. Most commonly occurs in women aged 30-40 years, but has been diagnosed in young girls as early as 10 years of age and post menopausal women (exclusively in women of menstrual age) most with a history of pelvic endometriosis. Diagnosis can be hinted by high recurrence rates of lung collapse in a woman of reproductive age with endometriosis. Moreover; CA-125 is elevated. Video-assisted thoracoscopy or medical thoracoscopy is used for confirmation. In our current work we will present all aspects of CP from diagnosis to treatment.
London: Royal College of Obstetricians & Gynaecologists; 2013 Feb
Fertility: Assessment and Treatment for People with Fertility Problems.
National Collaborating Centre for Women’s and Children’s Health (UK).
This guideline offers best practice advice on assisting people of reproductive age who have problems conceiving. It is estimated that infertility affects about one in seven heterosexual couples in the UK. Since the original NICE guideline on fertility was published in 2004 there has been a small increase in the prevalence of fertility problems and a greater proportion of people now seeking help for such problems. The main causes of infertility in the UK are (percentage figures indicate approximate prevalence): ovulatory disorders (25%); tubal damage (20%); factors in the male causing infertility (30%); uterine or peritoneal disorders (10%). In about 25% of cases infertility is unexplained, with no identified male or female cause. In about 40% of cases disorders are found in both the man and the woman. Uterine or endometrial factors, gamete or embryo defects, and pelvic conditions such as endometriosis may also play a role. Given the range of causes of fertility problems, the provision of appropriate investigations is critical. These investigations include semen analysis; assessment of ovulation, tubal damage and uterine abnormalities; and screening for infections such as Chlamydia trachomatisand susceptibility to rubella. Once a diagnosis has been established, treatment falls into three main types: medical treatment to restore fertility (for example the use of drugs for ovulation induction); surgical treatment to restore fertility (for example laparoscopy for ablation of endometriosis); assisted reproduction technology (ART) – any treatment that deals with means of conception other than vaginal coitus; frequently involving the handling of gametes or embryos.
Recent Pat Food Nutr Agric. 2014;6(1):16-22.
Hypothetical link between infertility and genetically modified food.
Gao M, Li B, Yuan W, Zhao L, Zhang X1.
It is speculated that genetically modified food (GMF)/genetically modified organism (GMO) is responsible for infertility development. The risk linked with a wide use of GMFs/GMOs offers the basic elements for social criticism. However, to date, it has not been justified whether the bad effects are directly resulted from products of genetic modifications or trans-genesis process. Extensive experience with the risk assessment of whole foods has been applied recently on the safety and nutritional testing of GMFs/GMOs. Investigations have tested the safety of GMFs including sub-acute, chronic, reproductive, multi-generation and carcinogenicity studies. We extrapolated the potential risks associated with GMFs/GMOs on reproduction, and analyzed the multi-aspect linked between infertility and GMFs/GMOs. It could be conjectured that GMFs/GMOs could be potential hazard on reproduction, linking to the development of infertility through influencing the endocrine metabolism, endometriosis. However, little evidence shows the impaction on embryo or reproductive related tumor due to the limited literatures, and needs further research. The article presents some related patents on GMFs/GMOs, and some methods for tracking GMOs.
Case Rep Obstet Gynecol. 2014;2014:756040.
Recurrent catamenial pneumothorax suggestive of pleural endometriosis.
Badawy SZ1, Shrestha P1.
A 42-year-old multiparous patient presented for consultation as a referral for management of recurrent catamenial pneumothorax. Evaluation by a pulmonologist failed to reveal any chest masses. She was treated for endometriosis using Danazol 800 mg daily for 6 months. Pneumothorax did not recur during treatment and during follow-up visits.
Reprod Biol Endocrinol. 2014 Oct 24;12:100.
Wisteria floribunda agglutinin-binding glycan expression is decreased in endometriomata.
Hirakawa T, Nasu K1, Kai K, Aoyagi Y, Ishii T, Uemura T, Yano M, Narahara H.
Glycosylation is one of the most common post-translational modifications of eukaryotic proteins and is known to undergo dynamic changes in a wide range of biological processes. To date, however, the glycan expression profiles in endometriosis are largely unknown. The objective of the study was to identify the panel of glycans that were aberrantly expressed in endometriosis, a hormone-dependent disease.
The glycan expression profiles in primary cultured human endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were determined by lectin microarray analysis. Distribution of Wisteria floribunda agglutinin (WFA)-binding glycans in ovarian endometriotic cysts and eutopic proliferative phase endometrium were assessed by lectin histochemistry. The expressions of N-acetylgalactosaminyl transferases that synthesize WFA-binding glycans were evaluated in ECSCs and NESCs.
We found that the levels of WFA-binding glycans were decreased in ECSCs. Lectin histochemistry revealed that WFA-binding glycans were decreased only in the stromal components of the ovarian endometriotic cysts, but not in the epithelial components, compared to the eutopic proliferative phase endometrium. The expressions of N-acetylgalactosaminyl transferases that synthesize WFA-binding glycans were downregulated in ECSCs.
Utilizing lectin microarray analysis and lectin histochemistry, we found that WFA-binding glycans were decreased in endometriosis. The synthetic enzymes of WFA-binding glycans were significantly downregulated in ECSCs. It is suggested that reduced expression of N-glycans with WFA-binding properties on ECSCs is a novel characteristics of endometriosis.
J Obstet Gynaecol Res. 2015 Feb;41(2):264-8.
Pathological assessment of follicular loss in laparoscopic endometrioma excision: effects of cyst size and surgeon’s experience.
Aytac PC1, Parlakgumus HA, Bolat FA, Cok T, Haydardedeoglu B, Kilicdag EB.
We planned to histologically demonstrate unintentional ovarian harm caused by excision of endometriomas.
One hundred and seven patients with 135 endometriomas had laparoscopic excision of endometriomas at a tertiary health-care clinic over a 6-year period. Records were obtained retrospectively and pathological specimens were reevaluated to demonstrate follicular loss. Tissue damage was scored morphologically and compared according to surgeons’ experience and endometrioma size.
Ovarian follicles were detected in 80% of endometrioma specimens near the cyst wall. Morphological scores of ovarian follicles were not affected by the surgeon’s experience or endometrioma size.
Surgical excision of endometriomas causes inevitable ovarian follicular loss. As observed in our study, this loss rate could not be traced to surgical experience or ovarian size.
Am J Reprod Immunol. 2015 Mar;73(3):221-31.
Subpopulations of macrophages within eutopic endometrium of endometriosis patients.
Takebayashi A1, Kimura F, Kishi Y, Ishida M, Takahashi A, Yamanaka A, Wu D, Zheng L, Takahashi K, Suginami H, Murakami T.
Endometriosis is recognized as a chronic inflammatory disease and is related to immune response. There have been reports that revealed the different distribution of macrophage within the eutopic endometrium of women with endometriosis. Macrophages are functionally polarized into M1 and M2 cell lineages. We studied a difference in the subpopulations of M1 and M2 macrophages within the eutopic endometrium in patients with or without endometriosis to investigate how the eutopic endometrium is stimulated immunologically.
METHOD OF STUDY:
Thirty-six patients with endometriosis (endometriosis group) and 37 without endometriosis(non-endometriosis group) were analyzed. Paraffin-embedded endometrial specimens were used for the study. Consecutive sections were used for immunostaining of CD68 (pan-macrophage marker) and CD163 (M2 macrophage marker). Cells positive for each marker were quantified, and the ratio of M2 macrophages in pan-macrophages was calculated.
The endometriosis group had a significantly higher number of pan-macrophages than the control group in all phases (P < 0.05). The ratios of M2 macrophages in pan-macrophages were significantly lower in all phases in the endometriosis group (P < 0.05).
The macrophage population slants toward M1 in the endometrium of endometriosis patients. The endometrium appeared to be stimulated by some organelles and/or substances that induce M1 in endometriosispatients.
J Sex Med. 2015 Jan;12(1):219-27
Concurrent deep-superficial dyspareunia: prevalence, associations, and outcomes in a multidisciplinary vulvodynia program.
Yong PJ1, Sadownik L, Brotto LA.
Little is known about women with concurrent diagnoses of deep dyspareunia and superficial dyspareunia.
The aim of this study was to determine the prevalence, associations, and outcome of women with concurrent deep-superficial dyspareunia.
This is a prospective study of a multidisciplinary vulvodynia program (n = 150; mean age 28.7 ± 6.4 years). Women with superficial dyspareunia due to provoked vestibulodynia were divided into two groups: those also having deep dyspareunia (i.e., concurrent deep-superficial dyspareunia) and those with only superficial dyspareunia due to provoked vestibulodynia. Demographics, dyspareunia-related factors, other pain conditions, and psychological variables at pretreatment were tested for an association with concurrent deep-superficial dyspareunia. Outcome in both groups was assessed to 6 months posttreatment.
MAIN OUTCOME MEASURES:
Level of dyspareunia pain (0-10) and Female Sexual Distress Scale were the main outcome measures.
The prevalence of concurrent deep-superficial dyspareunia was 44% (66/150) among women with superficial dyspareunia due to provoked vestibulodynia. At pretreatment, on multiple logistic regression, concurrent deep-superficial dyspareunia was independently associated with a higher level of dyspareunia pain (odds ratio [OR] = 1.19 [1.01-1.39], P = 0.030), diagnosis of endometriosis (OR = 4.30 [1.16-15.90], P = 0.022), history of bladder problems (OR = 3.84 [1.37-10.76], P = 0.008), and more depression symptoms (OR = 1.07 [1.02-1.12], P = 0.007), with no difference in the Female Sexual Distress Scale. At 6 months posttreatment, women with concurrent deep-superficial dyspareunia improved in the level of dyspareunia pain and in the Female Sexual Distress Scale to the same degree as women with only superficial dyspareunia due to provoked vestibulodynia.
Concurrent deep-superficial dyspareunia is reported by almost half of women in a multidisciplinary vulvodynia program. In women with provoked vestibulodynia, concurrent deep-superficial dyspareunia may be related to endometriosis or interstitial cystitis, and is associated with depression and more severe dyspareunia symptoms. Standardized multidisciplinary care is effective for women with concurrent dyspareunia.
Can J Urol. 2014 Oct;21(5):7433-41.
The role of cystectomy for non-malignant bladder conditions: a review.
Chong JT1, Dolat MT, Klausner AP, Dragoescu E, Hampton LJ.
Few studies have adequately addressed the indications, efficacy, and quality-of-life for cystectomy performed for non-malignant bladder conditions. Patients with debilitating non-malignant bladder conditions who have failed all previous conservative therapies may undergo various forms of cystectomy, including partial, simple or radical cystectomy. We provide a review of the current literature and recommendations for cystectomy for various non-malignant bladder conditions.
MATERIALS AND METHODS:
A systematic review of MEDLINE was conducted to find prospective and retrospective studies using the keywords “cystectomy”, “benign”, and `non-malignant`. Articles were reviewed and triaged, background articles were added as supplements, leaving a final review of 67 papers.
Data from the final review suggests that common benign indications for cystectomy are interstitial cystitis/painful bladder syndrome (IC/PBS), neurogenic bladder, hemorrhagic/radiation cystitis, infectious diseases of the bladder and miscellaneous conditions of the bladder such as endometriosis and total refractory incontinence. The most common perioperative complications include urinary tract and wound infections. Efficacy of cystectomy in patients with IC/PBS is greater than 80%, while efficacy in patients with neurogenic bladder is greater than 90%. Finally, improved urinary quality-of-life has been demonstrated in patients with neurogenic bladder post-cystectomy.
Cystectomy for non-malignant conditions can be considered for patients who have failed previous conservative therapy. The limited data in existence suggests fertility can be adequately preserved after cystectomy in younger males. The data regarding the forms of urinary diversion suggests no significant advantage between any of the major forms of urinary diversion. Finally, while newer pharmacologics and technological advances are widely used in the treatment of various benign urological conditions, their role in preventing or treating refractory benign bladder conditions have not been fully characterized.
Asian J Endosc Surg. 2014 Nov;7(4):320-2.
Surgical excision of umbilical endometriotic lesions with laparoscopic pelvic observation is the way to treat umbilical endometriosis.
Chikazawa K1, Mitsushita J, Netsu S, Konno R.
Primary umbilical endometriosis is extremely rare, although cases secondary to previous surgery have occasionally been reported. Here, we report three cases of umbilical endometriosis: two cases with previous cesarean section and one case of primary umbilical endometriosis. The treatment of choice for umbilical endometriosis is the excision of the lesions, and we believe laparoscopic pelvic observation is a beneficial addition, as 13%-15% of umbilical endometriosis cases are accompanied by pelvic endometriosis.
Zhonghua Fu Chan Ke Za Zhi. 2014 Aug;49(8):599-603.
Significance of symptom and physical sign to diagnosis of deeply infiltrating endometriosis.
Zhang J1, Leng J2, Dai Y1, Lang J1.
To study the significance of pain symptoms and physical signs to diagnosis of deeply infiltrating endometriosis (DIE).
Totally 500 patients with laparoscopic diagnosis of endometriosis were studied retrospectively and divided into two groups depending on the existance of DIE. The pain symptoms and gynecological physical signs were recorded detail, and the correlation with diagnose of DIE were analyzed.
(1) The significance of pain symptoms: the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and OR, 95% CI of each pain symptom were: dysmenorrhae (90.5%, 37.2%, 59.6%, 79.3%, 5.66, 3.46-9.28), chronic pelvic pain (35.2%, 82.6%, 67.4%, 55.4%, 2.58, 1.70-3.91), dyspareunia (46.2%, 80.6%, 70.7%, 59.6%, 3.56, 2.39-5.32), dyschezia (51.0%, 73.7% , 66.5% , 59.5%, 2.91, 2.00- 4.24), respectively. (2) Pelvic physical examination: the sensitivity, specificity, PPV and NPV of each physical sign were: fixed uterine: 73.6%, 71.2%, 79.5%, 64.0%; fixed ovarian cyst: 94.1%, 20.3%, 63.3%, 70.0%; uterosacral ligaments nodule: 47.1%, 97.5%, 96.6%, 54.9%; uterosacral ligaments nodule with tenderness: 81.7%, 75.0%, 83.1%, 73.2%; rectovaginal septum nodule: 32.2%, 100.0%, 100.0%, 49.4%; rectovaginal septum nodule with tenderness: 32.2%, 100.0%, 100.0%, 49.4%; blue nodule in posterior vaginal forni: 14.9%, 100.0%, 100.0%, 43.7%.
In the symptoms, the dysmenorrheal has the highest sensitivity and NPV for the diagnosis. And chronic pelvic pain has the highest specificity, and dysparaunia has the highest PPV for the diagnosis. In pelvic vaginal examination, fixed uterine, fixed ovarian cyst and the nodule on uretosarcal ligment and rectovaginal septum with tenderness, the blue lesion on posterior fornix have the strong significance for DIE. So record the symptom detail and careful digital vaginal examination, especially the vaginal-recto-abdominal examination could improve the diagnosis DIE obviously before procedure.
BMJ Case Rep. 2014 Oct 29;2014.
Endometriosis: a rare and interesting cause of recurrent haemorrhagic ascites.
Bignall J1, Arambage K2, Vimplis S3.
Recurrent haemorrhagic ascites as a cause of endometriosis is rare. We report the case of a 36-year-old woman presenting acutely with abdominal distension, ascites and an elevated CA-125 raising the suspicion of ovarian malignancy. Tissue biopsies retrieved during laparoscopy confirmed the diagnosis of endometriosis associated with haemorrhagic ascites. Gonadotropin-releasing hormone (GnRH) analogues were started to manage symptoms, with good effect. Subsequently, in vitro fertilisation resulted in a successful singleton pregnancy and by the second trimester, there was full resolution in symptoms. During the early puerperal period, the development of massive ascites recurred, requiring symptomatic relief through repeated ascitic drainage and GnRH analogues. Long-term follow-up is planned with the hope of continuing with medical management at least until the patient’s family is complete when the surgical option of bilateral salpingo-oophorectomy with or without hysterectomy will be discussed.
Reprod Sci. 2015 May;22(5):585-94.
17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis.
Khan KN1, Kitajima M2, Inoue T2, Fujishita A3, Nakashima M4, Masuzaki H2.
Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E2) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E2 and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E2 (10(-8) mol/L) compared to nontreated Mφ. This effect of E2 was abrogated after pretreatment of cells with ICI 182720 (10(-6) mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E2 and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E2 + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E2 and LPS on promoting proinflammatory response in pelvis and growth of endometriosis.
Int J Clin Exp Med. 2014 Sep 15;7(9):2939-40.
Perineal endometriosis: a case report.
A previously healthy 28-year-old G1P1 Asian woman presented with a 1-year history of a painful palpable lesion arising within the left perineum. Histopathology revealed multiple endometriotic foci composed of endometrial glands and moderate dense stroma, surrounded by dense fibro-elastic tissue. This patient was diagnosed as endometriosis and the endometriotic mass was excised under local anaesthesia.
Ultrasound Obstet Gynecol. 2015 Jul;46(1):109-17.
Fusion imaging for evaluation of deep infiltrating endometriosis: feasibility and preliminary results.
Millischer AE1, Salomon LJ2, Santulli P3,4,5, Borghese B3,4, Dousset B3,6, Chapron C3,4.
Magnetic resonance imaging (MRI) and ultrasound scanning complement each other in screening for and diagnosis of endometriosis. Fusion imaging, also known as real-time virtual sonography, is a new technique that uses magnetic navigation and computer software for the synchronized display of real-time ultrasound and multiplanar reconstructed MR images. Our aim was to evaluate the feasibility and ability of fusion imaging to assess the main anatomical sites of deep infiltrating endometriosis (DIE) in patients with suspected active endometriosis.
This prospective study was conducted over a 1-month period in patients referred to a trained radiologist for an ultrasound-based evaluation for endometriosis. Patients with a prior pelvic MRI examination within the past year were offered fusion imaging, in addition to the standard evaluation. All MRI examinations were performed on a 1.5-T MRI machine equipped with a body phased-array coil. The MRI protocol included acquisition of at least two fast spin-echo T2-weighted orthogonal planes. The Digital Imaging Communications in Medicine dataset acquired at the time of the MRI examination was loaded into the fusion system and displayed together with the ultrasound image on the same monitor. The sets of images were then synchronized manually using one plane and one anatomical reference point. The ability of this combined image to identify and assess the main anatomical sites of pelvic endometriosis (uterosacral ligaments, posterior vaginal fornix, rectum, ureters and bladder) was evaluated and compared with that of standard B-mode ultrasound and MRI.
Over the study period, 100 patients were referred for ultrasound examination because of endometriosis. Among them were 20 patients (median age, 35 (range, 27-49) years) who had undergone MRI examination within the past year, with a median (range) time interval between MRI and ultrasound examination of 171 (1-350) days. All 20 patients consented to undergo additional evaluation by fusion imaging. However, in three (15%) cases, fusion imaging was not technically possible because of changes since the initial MRI examination resulting from either interval surgery (n = 2; 10%) or pregnancy (n = 1; 5%). Data acquisition, matching and fusion imaging were performed in under 10 min in each of the other 17 cases. The overall ability of each technique to identify and assess the main anatomical landmarks of endometriosis was as follows: uterosacral ligaments: ultrasound, 88% (30/34); MRI, 100% (34/34); fusion imaging, 100% (34/34); posterior vaginal fornix: ultrasound, 88% (30/34); MRI, 100% (34/34); fusion imaging, 100% (34/34); rectum: ultrasound, 100% (17/17); MRI, 82.3% (14/17); fusion imaging, 100% (17/17); ureters: ultrasound, 0%; MRI, 100% (34/34); fusion imaging, 100% (34/34); and bladder: ultrasound, 100%; MRI, 100%; fusion imaging, 100%.
Fusion imaging is feasible for the assessment of endometriotic lesions. Because it combines information from both ultrasound and MRI techniques, fusion imaging allows better identification of the main anatomical sites of DIE and has the potential to improve the performance of ultrasound and MRI examination.
Pathol Int. 2014 Nov;64(11):576-80.
Clear cell carcinoma arising from a uterus-like mass.
Nakakita B1, Abiko K, Mikami Y, Kido A, Baba T, Yoshioka Y, Yamaguchi K, Matsumura N, Konishi I.
A uterus-like mass is an extrauterine mass with a cavity lined by endometrial tissue and a smooth muscle layer resembling the uterine corpus. It is a rare condition of unknown histogenesis. Herein, we describe a case of clear cell carcinoma arising from a uterus-like mass located in the retroperitoneal space. The patient, a 67-year old nulliparous woman, had been followed with the diagnosis of an ovarian endometriotic cyst for 14 years until ultrasonography and magnetic resonance imaging (MRI) demonstrated an enlargement of the cystic mass with a thickened irregular wall. Suspicion of malignant transformation prompted us to excise the lesion. At laparotomy, the uterus and right ovary appeared normal, and a mass measuring 8 cm was identified in the retroperitoneal space without any connection to the uterus. Grossly, the removed mass was composed of a cyst filled with blackish-brownish fluid and a thick wall resembling uterine myometrium. Microscopically, endometrial tissue inside the cyst, which was diffusely lined by clear cell carcinoma, was identified. Although the histogenesis of a uterus-like mass remains unclear, this case indicates that malignant tumors may occur from a uterus-like mass through the pathway similar to the carcinogenesis of endometriosis-related ovarian neoplasms.
Ann Coloproctol. 2014 Oct;30(5):232-6.
Müllerian adenosarcoma arising from rectal endometriosis.
A Müllerian adenosarcoma is an extremely rare tumor characterized by a stromal component of usually low-grade malignancy and by a benign glandular epithelial component. A Müllerian adenosarcoma occurs mainly in the uterus, but also in extrauterine locations. Extrauterine Müllerian adenosarcomas are thought to arise from endometriotic deposits. A 36-year-old female presented to Daegu Catholic University Medical Center with a symptom of loose stool for several months. The imaging studies revealed a rectal mass, so she underwent a laparoscopic low anterior resection. Although extemporary pathology revealed an inflammatory myofibroblastic tumor, the final histologic diagnosis was a Müllerian adenosarcoma arising from rectal endometriosis. To our knowledge, except a concomitant rectal villotubular adenoma, cases of Müllerian adenosarcomas arising the rectal wall are rare. An adenosarcoma arising from endometriosis should be considered in the differential diagnosis of a pelvic mass, even one appearing in rectal wall, because ectopic endometrial tissue exists everywhere.
Reprod Sci. 2015 Jun;22(6):679-84.
Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis.
Farahani MS1, Shahbazi S2, Moghaddam SA3, Mahdian R4.
Since the activation of KRAS results in de novo endometriosis in mice, KRAS is regarded as a crucial gene in ectopic endometrial implantation. Recently, it has been reported that 31% of women with endometriosis have KRAS let-7 complementary binding site 6 single-nucleotide polymorphism (LCS6 SNP). This study addresses the correlation between KRAS LCS6 SNP and endometriosis in a case-control study. To detect probable somatic mutation in ectopic endometrial tissue, we evaluated LCS6 SNP in cell-free DNA samples. Quantitative real-time reverse transcription-polymerase chain reaction was performed to determine the expression of KRAS transcripts in eutopic endometrial tissue. Our results suggest that the variant is not associated with the development of endometriosis in Iranian women. We observed higher levels of KRAS messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis compared to controls. Although, the KRAS LCS6 is neither constitutional nor somatic biomarker for endometriosis, increased expression ratio of KRAS mRNA indicates its role in the implantation of endometrial tissue outside the uterine cavity.
Geburtshilfe Frauenheilkd. 2014 Oct;74(10):940-946.
Endometriosis – A Chameleon: Patients’ Perception of Clinical Symptoms, Treatment Strategies and Their Impact on Symptoms.
Wimberger P1, Grübling N1, Riehn A1, Furch M1, Klengel J2, Goeckenjan M1.
Introduction: Endometriosis is a chronic disease with differing clinical presentations. Treatment strategies depend mainly on clinical presentation and patient lifestyle. In women newly diagnosed with endometriosis, it is often difficult to understand the pathophysiologic origin, the potential individual impairment due to disease and the different treatment options. Compliance with the selected treatment is therefore often not optimal. Material and Methods: In a descriptive study, data of 51 women with endometriosis (mean age 36.2 years ± 11.3) were analyzed according to the predominant clinical presentation: asymptomatic disease, disease with typical symptoms, ovarian cysts or infertility. Results: More than 50 % of patients ascribed a therapeutic benefit to surgical intervention or endocrine treatment, especially women in the subgroup with dysmenorrhea who received combined treatment. It should be noted that in the group of women facing infertility, more than half stated that they could not decide on the value of diagnostic and therapeutic reproductive medicine. Nevertheless, more than half of the women in this group became pregnant within two years after the initial diagnosis. Discussion: When deciding on the best treatment strategy for endometriosis, it is important to take account of potential pain and infertility. Women’s perception of endometriosis will vary depending on their symptoms, the time of diagnosis and their lifestyle. Offering continuous information on clinical aspects and manifestations of the disease may improve treatment outcomes. Personalized counseling is an essential part of the clinical management of the disease.
Indian J Med Res. 2014 Sep;140(3):387-91.
In vitro fertilization outcome in women with endometriosis & previous ovarian surgery.
Pop-Trajkovic S1, Kopitovic V, Popovic J, Antic V, Radovic D, Zivadinovic R.
BACKGROUND & OBJECTIVES:
Women with endometriosis often need in vitro fertilization (IVF) to concieve. There are conflicting data on the results of IVF in patients with endometriosis. This study was undertaken to elucidate the influence of endometriosis on IVF outcome to give the best counselling for infertile patient with this problem.
The outcome measures in 78 patients with surgically confirmed endometriosis were compared with 157 patients with tubal factor infertility, all of whom have undergone IVF. The groups were matched for age and follicle stimulating hormone (FSH) levels. Outcome measures included number of follicles, number of oocytes, peak oestradiol (E2) concentrations and mean number of ampoules of gonadotropins. Cumulative pregnancy, miscarriage and live birth rates were calculated in both the groups.
Higher cancelation rates, higher total gonadotropin requirements, lower peak E2 levels and lower oocyte yield were found in women with endometriosis and previous surgery compared with those with tubal factor infertility. However, no differences were found in fertilization, implantation, pregnancy, miscarriage, multiple births and delivery rates between the endometriosis and tubal factor infertility groups.
INTERPRETATION & CONCLUSIONS:
The present findings showed that women with endometriosis and previous surgery responded less well to gonadotropins during ovarian stimulation and hence the cost of treatment to achieve pregnancy was higher in this group compared with those with tubal factor infertility. However, the outcome of IVF treatment in patients with endometriosis was as good as in women with tubal factor infertility.
J Ovarian Res. 2014 Oct 2;7:86.
Clear cell adenocarcinoma of the peritoneum: a case report and literature review.
Shigeta N, Yoshino K1, Matsuzaki S, Morii E, Ueda Y, Kimura T.
Clear cell adenocarcinoma (CCC) is generally thought to originate from ovarian, endometrial, or renal tissue. A CCC of the peritoneum (CCAP) is an extremely rare medical condition and is associated with a poor prognosis. To date, only 10 cases of CCAP have been reported, of which half resulted in death or recurrence within 6 months after initial treatment because CCAP is commonly resistant to multiple drugs. In this report, we present a case of CCAP of the pouch of Douglas coexisting with an endometriosis and we offer a review of the related literature.
Gynecol Endocrinol. 2015 Mar;31(3):214-8.
Phospholipase A2 group IIA is elevated in endometriomas but not in peritoneal fluid and serum of ovarian endometriosis patients.
Kocbek V1, Bersinger NA, Brglez V, Mueller MD, Petan T, Rižner TL.
Our previous gene expression analysis identified phospholipase A2 group IIA (PLA2G2A) as a potential biomarker of ovarian endometriosis. The aim of this study was to evaluate PLA2G2A mRNA and protein levels in tissue samples (endometriomas and normal endometrium) and in serum and peritoneal fluid of ovarian endometriosis patients and control women. One-hundred and sixteen women were included in this study: the case group included 70 ovarian endometriosis patients, and the control group included 38 healthy women and 8 patients with benign ovarian cysts. We observed 41.6-fold greater PLA2G2A mRNA levels in endometrioma tissue, compared to normal endometrium tissue. Using Western blotting, PLA2G2A was detected in all samples of endometriomas, but not in normal endometrium, and immunohistochemistry showed PLA2G2A-specific staining in epithelial cells of endometrioma paraffin sections. However, there were no significant differences in PLA2G2A levels between cases and controls according to ELISA of peritoneal fluid (6.0 ± 4.4 ng/ml, 6.6 ± 4.3 ng/ml; p = 0.5240) and serum (2.9 ± 2.1 ng/ml, 3.1 ± 2.2 ng/ml; p = 0.7989). Our data indicate that PLA2G2A is implicated in the pathophysiology of ovarian endometriosis, but that it cannot be used as a diagnostic biomarker.
BMC Cancer. 2014 Nov 3;14:799.
MicroRNA-21 is a candidate driver gene for 17q23-25 amplification in ovarian clear cell carcinoma.
Hirata Y, Murai N, Yanaihara N1, Saito M, Saito M, Urashima M, Murakami Y, Matsufuji S, Okamoto A.
Epithelial ovarian cancer (EOC) is the most common cause of gynecological malignancy-related mortality. Ovarian clear cell carcinoma (CCC) has unique clinical characteristics and behaviors that differ from other histological types of EOC, including a frequent association with endometriosis and a highly chemoresistant nature, resulting in poor prognosis. However, factors underlying its malignant behavior are still poorly understood. Aberrant expression of microRNAs has been shown to be involved in oncogenesis, and microRNA-21 (miR-21) is frequently overexpressed in many types of cancers. The aim of this study was to investigate the role of miR-21 in 17q23-25 amplification associated with CCC oncogenesis.
We identified 17q23-25 copy number aberrations among 28 primary CCC tumors by using a comparative genomic hybridization method. Next, we measured expression levels of the candidate target genes, miR-21 and PPM1D, for 17q23-25 amplification by real-time RT-PCR analysis and compared those data with copy number status and clinicopathological features. In addition, immunohistochemical analysis of PTEN (a potential target of miR-21) was performed using the same primary CCC cases. We investigated the biological significance of miR-21 overexpression in CCC using a loss-of-function antisense approach.
17q23-25 amplification with both miR-21 overexpression and PTEN protein loss was detected in 4/28 CCC cases (14.2%). The patients with 17q23-25 amplification had significantly shorter progression-free and overall survival than those without 17q23-25 amplification (log-rank test: p = 0.0496; p = 0.0469, respectively). A significant correlation was observed between miR-21 overexpression and endometriosis. Both PTEN mRNA and PTEN protein expression were increased by miR-21 knockdown in CCC cells. We also confirmed that miR-21 directly bound to the 3′-untranslated region of PTEN mRNA using a dual-luciferase reporter assay.
MiR-21 is a possible driver gene other than PPM1D for 17q23-25 amplification in CCC. Aberrant expression of miR-21 by chromosomal amplification might play an important role in CCC carcinogenesis through the regulation of the PTEN tumor suppressor gene.
J Transl Med. 2014 Nov 4;12:306.
GnRH agonists induce endometrial epithelial cell apoptosis via GRP78 down-regulation.
Weng H1,2, Liu F3, Hu S4, Li L5, Wang Y6.
Endometriosis is a benign chronic gynecological disease that affects women of reproductive age, characterized by the presence of functional endometrial tissues outside the uterine cavity. GnRH agonists exhibit anti-proliferative and apoptosis-enhancing activities and have long been used for the treatment of endometriosis. There is a critical need to identify the signaling modules involving GnRH agonist therapy for the treatment of endometriosis. In this study, we compared the proteomic profiles of endometriosis in patients before and after GnRH agonist therapy to identify proteins that might provide further information concerning the mechanisms underlying the functions of GnRH agonists.
A total of 55 protein spots with different abundances were observed using Difference Gel Electrophoresis (DIGE), and 26 of these proteins were assigned clear identities through Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectroscopy (MALDI-TOF/TOF MS).
We validated four of these proteins through Western blotting and immunohistochemistry using human endometrial tissue. We also characterized the effect of Leuprolide acetate (LA) on the apoptosis of eutopic endometrial epithelial cells. LA treatment significantly promoted the apoptosis of eutopic endometrial epithelial cells and inhibited the expression of the anti-apoptotic factor GRP78. GRP78 knockdown enhanced LA-induced cell apoptosis, whereas, the overexpression of GRP78 in eutopic endometrial epithelial cells suppresses LA-induced apoptosis.
These results suggest that GnRH agonists induce endometrial epithelial cell apoptosis via GRP78 down-regulation. This study might provide an important molecular framework for further evaluation of GnRH agonist therapy.
Arch Gynecol Obstet. 2015 May;291(5):1103-11.
Comparison of efficacy of bromocriptine and cabergoline to GnRH agonist in a rat endometriosis model.
Ercan CM1, Kayaalp O, Cengiz M, Keskin U, Yumusak N, Aydogan U, Ide T, Ergun A.
To determine the effect of dopamine agonists in a surgically induced endometriosis model on rats.
In this prospective randomized experimental study, surgical induction of endometriosis was performed by autotransplantation technique on 52 adult female Wistar-Albino rats. Endometriosis formation was confirmed by a second-look laparotomy (n:48) 1 month later. Four study groups were randomly generated according to their treatment regimens: group 1 (leuprolide acetate, n = 12), group 2 (bromocriptine, n = 12), group 3 (cabergoline, n = 12) and group 4 (control, n = 12). Endometriotic implants were excised for histopathological examination after treatment at the setting of laparotomy. The mean surface areas and histopathological glandular tissue (GT) and stromal tissue (ST) scores of endometriotic implants were studied and compared among groups.
After 30 days of treatment, the mean surface area of the endometriotic implants of leuprolide acetate, bromocriptine and cabergoline groups was significantly decreased. The regression of endometriotic foci size in comparison to control was highest in group 1, followed by group 2, then group 3. In the histopathological evaluation both the ST and GT scores of group 1, 2 and 3 were significantly decreased in comparison to controls without a statistically significant difference between the groups.
Dopamine agonists are as effective as GnRH agonists in the regression of experimental endometriotic implants in rats. Further trials are needed to elucidate the pathways affected by dopamine agonists.
J Cell Physiol. 2015 Jun;230(6):1270-5
A tissue specific magnetic resonance contrast agent, Gd-AMH, for diagnosis of stromal endometriosis lesions: a phase I study.
The anti-mullerian hormone (AMH) is a homodimeric glycoprotein member of the transforming growth factor β (TGF-β) superfamily, is secreted by Sertoli cells in the embryonic testes and is responsible of the regression of the mullerian duct. The physiological functions of this protein remain largely unknown, and its expression in human tissues has yet to be completely determined. Firstly, we analyzed AMH expression in human tissues by immunohistochemistry. AMH was distributed in many organs, although with different tissue and cell localization and various expression levels; we also demonstrated strong AMH expression in endometriosis tissues. Secondly, we demonstrated the ability of an anti-AMH antibody, labeled with gadiolinium, to be directly detected by magnetic resonance in small endometriosis lesions (5 mm in diameter) in vivo in a mouse model. In conclusion, our data suggest that based on its expression pattern, AMH may serve to maintain physiological cellular homeostasis in different human tissues and organs. Moreover, it is strongly expressed in endometriosislesions as a selective tissue specific contrast agent for in vivo detection of stromal endometriosis lesions. The potential significance of these findings could be further validated in a clinical setting.
J Menopausal Med. 2013 Dec;19(3):151-3.
Endometriosis in a postmenopausal woman on hormonal replacement therapy.
Jeon DS1, Kim TH1, Lee HH1, Byun DW2.
Endometriosis is a benign disease and an estrogen-dependent disease. Postmenopausal endometriosis is rare, because the absence of estrogenic hormone production. We report a case of endometriosis presenting in a postmenopausal woman with no history of endometriosis before hormone replacement therapy.
J Menopausal Med. 2014 Apr;20(1):32-4.
Endosalpingiosis in postmenopausal elderly women.
Park J1, Kim TH1, Lee HH1, Chung SH1, Jeon DS1.
In gynecology, endosalpingiosis is a benign condition in which the fallopian tube-like epithelium is found outside the fallopian tube. The thirty-four point five percent of endosalpingiosis cases have concurrent endometriosis and 40% of the endosalpingiosis group are in postmenopausal states. In contrast with endometriosis, there are no significant links between infertility, chronic pelvic pain and endosalpingiosis. The symptoms of endosalpingiosis are not yet settled. Endosalpingiosis is almost always an incidental finding; it is commonly found through microscopic examinations, and is then confirmed by pathologists for excision and biopsy. Therefore, the clinical differential diagnosis of an intramural mass is more important for clinicians when discussing further surgery with the patients. We report case of woman who has endosalpingiosis and is presented with vaginal bleeding. We first suspect the disease during physical examination. Under the impression of pelvic mass, laboratory tests and radiological images of contrast enhanced chest computer tomography are taken. Images show multisepted cystic masses in left adnexa. To rule out the pelvic mass, we executed exploratory laparotomy. Pathologic results show endosalpingiosis near the ovary section. But the endosalpingiosis, is not generally considered a pathology, and thus, no treatment is necessary.
Minerva Ginecol. 2014 Dec;66(6):575-87.
Fertility before and after surgery for deep infiltrating endometriosis with and without bowel involvement: a literature review.
Cohen J1, Thomin A, Mathieu D’Argent E, Laas E, Canlorbe G, Zilberman S, Belghiti J, Thomassin-Naggara I, Bazot M, Ballester M, Daraï E.
Endometriosis affects from 10% to 15% of women of childbearing age and 20% of these women have deep infiltrating endometriosis (DIE). The goal of this review was to assess the impact of various locations of DIE on spontaneous fertility and the benefit of surgery and Medically Assisted Reproduction (MAR) (in vitro fertilization and intrauterine insemination) on fertility outcomes.
MEDLINE search for articles on fertility in women with DIE published between 1990 and April 2013 using the following terms: “deep infiltrative endometriosis”, “colorectal”, “bowel”, “rectovaginal”, “uterosacral”, “vaginal”, “bladder” and “fertility” or “infertility”. Twenty-nine articles reporting fertility outcomes in 2730 women with DIE were analysed.
Among the women with DIE and no bowel involvement (N.=1295), no preoperative data on spontaneous pregnancy rate (PR) were available. The postoperative spontaneous PR rate in these women was 50.5% (95% Confidence Interval [CI] =46.8-54.1) and overall PR (spontaneous pregnancies and after MAR) was 68.3% (95% CI=64.9-71.7). No evaluation of fertility outcome according to locations of DIE was feasible. For women with DIE with bowel involvement without surgical management (N.=115), PR after MAR was 29%; 95% CI=20.7-37.4). For those with bowel involvement who were surgically managed (N.=1320), postoperative spontaneous PR was 28.6% (95% CI=25-32.3) and overall postoperative PR was 46.9% (95% CI=42.9-50.9).
For women with DIE without bowel involvement, surgery alone offers a high spontaneous PR. For those with bowel involvement, the low spontaneous and relatively high overall PR suggests the potential benefit of combining surgery and MAR.
Gynecol Endocrinol. 2015 Mar;31(3):219-24.
A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model.
Ozcan Cenksoy P1, Oktem M, Erdem O, Karakaya C, Cenksoy C, Erdem A, Guner H, Karabacak O.
The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.
Hum Reprod. 2015 Jan;30(1):49-60.
Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased.
Santulli P1, Chouzenoux S2, Fiorese M3, Marcellin L4, Lemarechal H5, Millischer AE3, Batteux F2, Borderie D6, Chapron C7.
Are protein oxidative stress markers [thiols, advanced oxidation protein products (AOPP), protein carbonyls and nitrates/nitrites] in perioperative peritoneal fluid higher in women with histologically proven endometriosis when compared with endometriosis-free controls?
Protein oxidative stress markers are significantly increased in peritoneal fluids from women with deep infiltrating endometriosis with intestinal involvement when compared with endometriosis-free controls.
WHAT IS KNOWN ALREADY:
Endometriosis is a common gynaecologic condition characterized by an important inflammatory process. Various source of evidence support the role of oxidative stress in the development of endometriosis.
STUDY DESIGN, SIZE, DURATION:
We conducted a prospective laboratory study in a tertiary-care university hospital between January 2011 and December 2012, and included 235 non-pregnant women, younger than 42 year old, undergoing surgery for a benign gynaecological condition.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
After complete surgical exploration of the abdomino-pelvic cavity, 150 women with histologically proven endometriosis and 85 endometriosis-free controls women were enrolled. Women with endometriosis were staged according to a surgical classification in three different phenotypes of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deeply infiltrating endometriosis (DIE). Perioperative peritoneal fluids samples were obtained from all study participants. Thiols, AOPP, protein carbonyls and nitrates/nitrites were assayed in all peritoneal samples.
MAIN RESULTS AND THE ROLE OF CHANCE:
Concentrations of peritoneal AOPP were significantly higher in endometriosis patients than in the control group (median, 128.9 µmol/l; range, 0.3-1180.1 versus median, 77.8 µmol/l; range, 0.8-616.1; P < 0.001). In a similar manner concentrations of peritoneal nitrates/nitrites were higher in endometriosis patients than in the control group (median, 24.8 µmol/l; range, 1.6-681.6 versus median, 18.5 µmol/l; range, 1.6-184.5; P < 0.05). According to the surgical classification, peritoneal fluids protein AOPP and nitrates/nitrites were significantly increased only in DIE samples when compared with controls (P < 0.001 and P < 0.05; respectively), whereas the others forms of endometriosis (SUP and OMA) showed non-statistically significant increases. We found positive correlations between peritoneal fluids AOPP concentrations, nitrites/nitrates levels and the total number of intestinal DIE lesions (r = 0.464; P < 0.001 and r = 0.366; P = 0.007; respectively).
LIMITATIONS, REASONS FOR CAUTION:
Inclusion of only surgical patients may constitute a possible selection bias. In fact, our control group involved women who underwent surgery for benign gynaecological conditions. This specificity of our control group may lead to biases stemming from the fact that some of these conditions, such as fibroids, ovarian cysts or tubal infertility, might be associated with altered peritoneal proteins oxidative stress markers.
WIDER IMPLICATIONS OF THE FINDINGS:
We demonstrate the existence of a significantly increased protein oxidative stress status in peritoneal fluid from women with endometriosis especially in cases of DIE with intestinal involvement. This study opens the way to future more mechanistics studies to determine the exact role of protein oxidative stress in the pathogenesis of endometriosis. Even if an association does not establish proof of cause and effect, these intrinsic biochemical characteristics of endometriosis may lead to the evaluation of therapeutic approaches targeting oxidative imbalance.
Hum Reprod. 2015 Jan;30(1):149-58.
Inhibitor of apoptosis proteins (IAPs) may be effective therapeutic targets for treating endometriosis.
Uegaki T1, Taniguchi F2, Nakamura K3, Osaki M4, Okada F4, Yamamoto O5, Harada T1.
What is the role of the inhibitor of apoptosis proteins (IAPs) in human endometriotic tissues and a mouse model of endometriosis?
Four IAP proteins were expressed in endometriotic tissue indicating IAPs may be a key factor in the pathogenesis and progression of endometriosis.
WHAT IS KNOWN ALREADY:
Overexpression of IAPs protects against a number of proapoptotic stimuli. IAPs (c-IAP1, c-IAP2, XIAP and Survivin) are expressed in human ectopic endometrial stromal cells (ESCs) from ovarian endometriomas.
STUDY DESIGN, SIZE, DURATION:
Forty-eight women with or without ovarian endometrioma are included in this study. BALB/c mice (n = 24) were used for the mouse endometriosis model. Mice with surgically induced endometriosis were treated with an IAP antagonist (BV6) for 4 weeks.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Human ectopic endometrial tissues from chocolate cysts and eutopic endometrial tissue were collected. ESCs were enzymatically isolated from these tissues. ESC proliferation was examined by 5-bromo-2′-deoxyuridine-enzyme-linked immunosorbent assay. IAPs expression in tissue derived from eutopic endometria and chocolate cysts was evaluated using real-time RT-PCR and immunohistochemistry. A homologous mouse endometriosis model was established by transplanting donor mouse uterine tissue into the abdominal cavities of recipient mice. After treating the mice with BV6 (i.p. 10 mg/ml), the extent of endometriosis-like lesions in mice was measured and proliferative activity assessed by Ki67 staining. All experiments were repeated a minimum of three times.
MAIN RESULTS AND THE ROLE OF CHANCE:
IAP (c-IAP1, c-IAP2, XIAP and Survivin) mRNA and protein in human ectopic endometrial tissues were expressed at higher levels than in eutopic endometrial tissues (P < 0.05). All four IAPs proteins were expressed in mouse endometriosis-like implants. BV6 inhibited BrdU incorporation of human ESCs (P < 0.05 versus control). BV6 also decreased the total number, weight, surface area and Ki67 positive cells in the endometriosis-like lesions in the mice (P < 0.05 versus control).
LIMITATIONS, REASONS FOR CAUTION:
Endometriotic lesions were surgically induced in mice by transplanting mouse uterine tissue only, not human pathological endometriotic tissue. Furthermore, the effects of BV6 on human ESCs and mouse endometriosis-like lesions may differ between the species.
WIDER IMPLICATIONS OF THE FINDINGS:
Our data support the hypothesis that IAPs are involved in the development of endometriosis, and therefore an inhibitor of IAPs has potential as a novel treatment for endometriosis.
Reproduction. 2015 Feb;149(2):155-62.
Alteration in the intrafollicular thiol-redox system in infertile women with endometriosis.
Choi YS1, Cho S1, Seo SK1, Park JH1, Kim SH2, Lee BS3.
The aim of this study was to compare intrafollicular biomarkers of thiol-redox system and chronic inflammation in infertile patients with and without endometriosis, and examine correlations between biomarkers and IVF outcomes. The study included 65 patients receiving IVF: 31 patients with endometriosis vs 34 patients without endometriosis. Follicular fluid (FF) was obtained from a single-dominant follicle during oocyte retrieval and stored at -70 °C. Malondialdehyde, superoxide dismutase, glutathione (GSH), glutathione peroxidase 3 (GPX3), thioredoxin (TRX), TRX-binding protein 2 (TBP2), and peroxiredoxin-4 levels were measured in the FF samples by ELISAs as biomarkers of oxidative stress. The inflammatory cytokines interleukin 1 beta (IL1β), IL6, IL8, and tumor-necrosis factor alpha (TNFα) were also measured by ELISAs. GSH levels were significantly lower in the endometriosis group compared with the controls. TBP2 levels were significantly higher in the endometriosisgroup. IL6, IL8, and TNFα levels were significantly higher in the endometriosis group. The levels of all of the inflammatory cytokines positively correlated with the levels of TRX. GSH levels positively correlated with the number of high-quality embryos. GPX3 and TRX levels negatively correlated with the percentage of mature oocytes. TNFα levels negatively correlated with the cumulative embryo score per embryo. Logistic regression analysis revealed that the number of high-quality embryos was an independent factor predicting clinical pregnancy. In conclusion, there may be an imbalance in the thiol-redox system and increased levels of inflammatory cytokines in the intrafollicular microenvironment of infertile patients with endometriosis, which may affect the qualities of the oocyte and embryo.
Reprod Health. 2014 Nov 7;11(1):76.
Assisted reproductive technologies (ARTs): evaluation of evidence to support public policy development.
Nardelli AA1, Stafinski T, Motan T, Klein K, Menon D.
Over the years, IVF/ICSI protocols have continued to evolve with efforts to improve outcomes. As a result, treatment success may be related to certain procedural factors, including number of embryos transferred and stage at which they are transferred. This review aims to assess the safety and effectiveness of IVF/ICSI in comparison to spontaneous conception and less invasive ARTs and the impact of procedure-related factors on the outcomes of IVF/ICSI in order to support the development of local clinical and policy guidance. Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of literature examining the impact of procedural characteristics on the safety or effectiveness of IVF/ICSI from 2007 to date was performed. 33 systematic reviews and 3 primary studies evaluating the impact of procedural differences, IVF/ICSI in comparison to less invasive ARTs, and ARTs in comparison to spontaneous conception were found. IVF was shown to offer significant benefits over no treatment and IUI in achieving pregnancy and live birth among couples with endometriosis or unexplained infertility. Frozen and blastocyst-stage embryo transfers were as effective as fresh and cleavage-stage embryo transfers, respectively. In comparison to single embryo transfer, double embryo transfer significantly increased pregnancy, live birth and multiple pregnancy/birth rates. IVF/ICSI was associated with more complications during pregnancy and delivery, and in infants compared to naturally conceived pregnancies, particularly when multiple embryo transfer was used. Frozen embryo transfer had fewer adverse events during pregnancy and delivery than fresh embryo transfer, and was at least as safe in terms of infant outcomes. The potential complications of IVF/ICSI may be minimized through procedural choices, but such choices often impact effectiveness. Thus, in developing clinical and policy guidance around IVF/ICSI, the risk-benefit trade-offs patients and providers are willing to accept must be carefully considered.
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