Hum Reprod. 2013 Oct;28(10):2822-31.

NME1 suppression promotes growth, adhesion and implantation of endometrial stromal cells via Akt and MAPK/Erk1/2 signal pathways in the endometriotic milieu.

Li MQ1Shao JMeng YHMei JWang YLi HZhang LChang KKWang XQZhu XYLi DJ.

 

Abstract

STUDY QUESTION:

Is Nometastatic gene 23-H1 (NME1, also known as nm23-H1) involved in regulating the biological behavior of endometrial stromal cells (ESCs), and does it participate in the pathogenesis of endometriosis?

SUMMARY ANSWER:

NME1 suppression induces ESC dysfunction in the endometriotic milieu.

WHAT IS KNOWN ALREADY:

NME1 is a wide-spectrum tumor metastasis suppressor gene that plays an important role in suppressing the invasion and metastasis of tumor cells.

STUDY DESIGN, SIZE, DURATION:

An in vitro investigation of the effect of NME1 on the proliferation, adhesion and invasion of eutopic ESCs from patients with endometriosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Primary ESCs were prepared from 12 samples of ectopic endometrial tissue (6 peritoneal and 6 ovarian lesions), 18 samples of eutopic endometrial tissues (16 from women with ovarian and 2 from women with pelvic endometriomas) and 12 samples of normal endometrial tissue from women without endometriosis, after the tissues had been analyzed histologically. The growth, invasiveness and adhesion of ESCs were studied by the 5-bromo-2′-deoxyuridine cell proliferation assay and by the Matrigel invasion and adhesion assay. Additionally, the effects of NME1 on the activation or expression of related regulatory proteins were investigated by in-cell Western and flow cytometry assays.

MAIN RESULTS AND THE ROLE OF CHANCE:

Expression of NME1 in ESCs derived from eutopic or ectopic endometrium from women with endometriosis is lower than in ESCs from women without endometriosis. Estrogen could down-regulate NME1 expression in ESCs. Silencing NME1 in ESCs promoted the expression of proliferating cell nuclear antigen (PCNA), the anti-apoptotic molecule, survivin, and the adhesion-related molecules, integrin β1 and integrin ανβ3. Silencing NME1 also stimulated ESC proliferation, adhesion and invasion but these effects were inhibited by MAPK/Erk and/or Akt blockers.

LIMITATIONS, REASONS FOR CAUTION:

Further studies are needed to examine the regulatory mechanism of estrogen on NME1 expression of ESCs.

WIDER IMPLICATIONS OF THE FINDINGS:

Abnormally low expression of NME1 in ESCs may be involved in the pathogenesis of endometriosis by up-regulating growth, adhesion and invasion of ESCs via activating the Akt and MAPK/Erk1/2 signal pathways.

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported by National Natural Science Foundation of China (NSFC) (31270969, 31101064 and 81270677) and Program for ZhouXue of Fudan University. None of the authors has any conflict of interest to declare.

 

 

Cytojournal. 2013 Apr 24;10:7

Abdominopelvic washings: A comprehensive review.

Rodriguez EF1Monaco SEKhalbuss WAustin RMPantanowitz L.

 

Abstract

Intraperitoneal spread may occur with gynecological epithelial neoplasms, as well as with non-gynecological malignancies, which may result in serosal involvement with or without concomitant effusion. Therefore, washings in patients with abdominopelvic tumors represent important specimens for cytologic examination. They are primarily utilized for staging ovarian cancers, although their role has decreased in staging of endometrial and cervical carcinoma. Abdominopelvic washings can be positive in a variety of pathologic conditions, including benign conditions, borderline neoplastic tumors, locally invasive tumors, or distant metastases. In a subset of cases, washings can be diagnostically challenging due to the presence of co-existing benign cells (e.g., mesothelial hyperplasia, endosalpingiosis, or endometriosis), lesions in which there is only minimal atypia (e.g., serous borderline tumors) or scant atypical cells, and the rarity of specific tumor types (e.g., mesothelioma). Ancillary studies including immunocytochemistry and fluorescence in situ hybridization may be required in difficult cases to resolve the diagnosis. This article provides a comprehensive and contemporary review of abdominopelvic washings in the evaluation of gynecologic and non-gynecologic tumors, including primary peritoneal and mesothelial entities.

 

 

 

 

 

Mediators Inflamm. 2013;2013:624540.

Low-density lipoproteins oxidation and endometriosis.

Polak G1Barczyński BKwaśniewski WBednarek WWertel IDerewianka-Polak MKotarski J.

 

Abstract

The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF) and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis and 119 women with serous (n = 78) or dermoid (n = 41) ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease.

 

 

Gynecol Endocrinol. 2013 Sep;29(9):834-8.

Predictive factors for pregnancy during the first four intrauterine insemination cycles using gonadotropin.

Jeon YE1Jung JAKim HYSeo SKCho SChoi YSLee BS.

 

Abstract

PURPOSE:

Although a variety of factors have been reported as affecting pregnancy rates after intrauterine insemination (IUI), there have been conflicting results on prognostic factors. This study aimed to determine predictive factors for pregnancy in patients undergoing the first four IUI cycles.

METHODS:

A total of 348 IUI cycles using clomiphene citrate or letrozole combined with gonadotropin, or gonadotropin only were analyzed. Baseline clinical characteristics, variables related to ovulation induction and sperm parameters were compared between pregnant (n = 54) and non-pregnant groups (n = 294). Logistic regression analysis was performed to identify factors that could predict a pregnancy.

RESULTS:

The overall clinical pregnancy rate was 15.5% (54/348) per cycle and 30.0% (54/180) per couple. During the first four IUI cycles, logistic regression analysis revealed that woman who were 39 years or older (OR: 0.263, 95% CI: 0.076-0.906, p = 0.034), longer duration of infertility (OR: 0.967, 95% CI: 0.942-0.993, p = 0.012), endometriosis (versus unexplained infertility; OR: 0.177, 95% CI: 0.040-0.775, p = 0.022) and endometrial thickness below 7 mm (OR: 0.114, 95% CI: 0.015-0.862, p = 0.035) were unfavorable factors to predict clinical pregnancy.

CONCLUSIONS:

Women with old age, longer duration of infertility, the presence of endometriosis or thin endometrium in the preovulatory phase may have unfavorable outcomes during the first four IUI cycles.

 

 

Recent Pat DNA Gene Seq. 2013 Dec;7(3):169-78

Recent advances in gene therapy of endometriosis.

Shubina ANEgorova AABaranov VSKiselev AV1.

 

Abstract

Endometriosis is a gynecological disease that affects up to 10%-15% of all reproductive-age women worldwide. It is characterized by the presence of endometrial tissues outside the uterine cavity. Endometriosis is a complex disease; its pathogenesis includes altered steroid metabolism and immune system abnormalities such as inflammation, increased angiogenic activity in the peritoneal fluid and impaired recognition of ectopic endometrial cells. The development of endometriosis also depends on genetic, anatomical and environmental factors. Numerous surgical and medical approaches to treat endometriosis have been developed to date. However, complete resolution of the problem has not been achieved so far. Gene therapy holds exciting promise for the treatment of numerous disorders and current studies have indicated it can also be applied to endometriosis. The focus of this review is to summarize the pathogenetic background of the disease and to highlight current gene therapy approaches for this common gynecological disorder.

 

 

 

 

 

J Pak Med Assoc. 2013 Jan;63(1):114-6.

Thoracic endometriosis syndrome with bloody pleural effusion in a 28 year old woman.

Sevinç S1Unsal SOztürk TUysal ASamancilar OKaya SOErmete S.

 

Abstract

Thoracic endometriosis, rarely encountered, is characterized with the localization of functional endometrium tissue in pleura, lung parenchyma or tracheobronchial system. A 28 years old female patient visited our clinic with complaints of cough and shortness of breath for the last two months. Right-sided massive pleural effusion was detected in the chest radiography and thorax computed tomography. Exudative fluid was aspirated with a haemorrhagic appearance on thoracentesis. Cytology was evaluated as suspicious. “Signet ring cells” were reported in pleural biopsy. Diagnostic biopsy was performed by video-assisted thoracic surgery (VATS) on the patient whose fiber-optic bronchoscopy was normal. The histopathological diagnosis was reported as “pleural endometriosis”. Chemical pleurodesis was applied with asbestos-free chalk. The thorax HRCT (high resolution computed tomography) performed during menstruation was normal. Thoracentesis was needed 3 times for recurrent pleural effusion in the follow-ups and then parietal pleurectomy was performed. The patient is in postoperative 10th month follow-up and evaluated as normal clinically and as radiologically. Pleural endometriosis should be considered as a differential diagnosis in female patients with infertility with chest symptoms. Video-assisted thoracoscopic surgery can be useful in the diagnosis and treatment of these patients and chemical pleurodesis and parietal pleurectomy should be considered among the treatment options.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Sep;170(1):225-8.

The occurrence of endometriosis with ovarian carcinomas is not purely coincidental.

Qiu L1Wang SLang JHShen KHuang HFPan LYWu MYang JX.

 

Abstract

OBJECTIVE:

To explore the association between epithelial ovarian cancer (EOC) and common benign gynecological disorders.

STUDY DESIGN:

The medical records of 226 patients with EOC treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histological evaluations had been performed to determine the presence of coexisting pelvic endometriosis (n=17), uterine leiomyoma (n=66), adenomyosis (n=22), or endometrial polyps (n=17).

RESULTS:

Coexistence of endometriosis occurred in 35.3% and 36.4% of cases of the clear cell and endometrioid subtypes of EOC histology, respectively. Endometriosis was more likely associated with clear cell or endometrioid ovarian carcinoma, but less likely with high grade serous cancer. No differences were observed in the concurrence of uterine myoma, adenomyosis or endometrial polyps among the different subtypes of EOC.

CONCLUSIONS:

In contrast to other common benign gynecological disorders, endometriosis showed close relationships with the clear cell and endometrioid subtypes of EOC specifically.

 

 

 

 

J Hum Reprod Sci. 2013 Jan;6(1):32-4.

Role of diagnostic hystero-laparoscopy in the evaluation of infertility: A retrospective study of 300 patients.

Nayak PK1Mahapatra PCMallick JSwain SMitra SSahoo J.

 

Abstract

OBJECTIVE:

To determine the role of diagnostic hysterolaparoscopy in the evaluation of infertility in tertiary care centres.

MATERIALS AND METHODS:

This retrospective study was conducted at two tertiary care centres (the infertility clinics of Sriram Chandra Bhanj Medical College and Prachi hospital at Cuttack, Odisha) throughout the year in 2008. Women aged 20-40 years with normal hormone profile without male factor infertility were included.

RESULTS:

Out of 300 cases, 206 (69%) patients had primary infertility. While laparoscopy detected abnormalities in 34% of the cases, significant hysteroscopy findings were noted in 18% of cases. Together, diagnostic hysterolaparoscopy detected abnormalities in 26% of the infertile patients in both groups. While the most common laparoscopic abnormality was endometriosis (14%) and adnexal adhesion (12%) in primary and secondary infertile patients, respectively, hysteroscopy found intrauterine septum as the most common abnormality in both groups.

CONCLUSIONS:

Hysterolaparoscopy is an effective diagnostic tool for evaluation of certain significant and correctable tubo-peritoneal and intrauterine pathologies like peritoneal endometriosis, adnexal adhesions, and subseptate uterus, which are usually missed by other imaging modalities.

 

 

 

Ceska Gynekol. 2013 Jun;78(3):282-8.

Determination of anti-Müllerian hormone in women.

Kučera R1Topolčan ORumpíková TRumpík DDostál J.

 

Abstract

Anti-Müllerian hormone (AMH) is a glycoprotein and belongs to the TGF-β growth factors family. Our review describes the method of AMH determination in serum and follicular fluid. The reference values and changes in AMH levels during a womans life are also discussed. In addition, it is also presented the relationship between AMH, obesity, smoking and use of hormonal contraceptives. The focus of the work is the importance of the determination of AMH in clinical practice. In assisted reproduction has become its determination one of the tools to detect ovarian reserve. It helps not only predict reduced response to stimulation with gonadotropins but also the risk of the ovarian hyperstimulation syndrome. Benefits of the ovarian reserve detection using AMH serum levels are discussed in comparison with the antral follicle count (AFC) determined by ultrasound. Several clinical indications of AMH determination are mentioned in the next section. These are primarily the polycystic ovary syndrome (PCOS), which is a great challenge not only for the AMH testing, but there is an open space for further interdisciplinary cooperation. Endometriosis has no direct effect on ovarian reserve and AMH levels in serum. AMH is very sensitive tumor marker in the diagnostics and monitoring of ovarian granulosa cells tumors. Treatment of cancer disease burdens entire body, including healthy cells. Ovarian follicles are very sensitive to chemotherapy and radiation. AMH is a good predictor of ovarian reserve damage during radio- and chemotherapy.

 

 

Aust N Z J Obstet Gynaecol. 2013 Aug;53(4):389-94.

Value of diagnostic procedures in rectovaginal endometriosis.

Mangler M1Medrano NBartley JMechsner SSpeiser DSchneider AKöhler C.

 

Abstract

OBJECTIVE:

Rectovaginal endometriosis has the potential to infiltrate into the rectal wall. The recognition of infiltration prior to surgery is of utmost importance since only infiltrative disease should be treated by partial or complete rectal resection. This study compares different imaging procedures in rectovaginal endometriosis cases in an everyday clinical setting.

METHODS:

Seventy nine consecutive women diagnosed with rectovaginal endometriosis were included in this prospective study. Preoperatively, all women had a rectovaginal gynaecological examination and transvaginal sonography. Furthermore, MRI or rectal endosonography imaging procedures together with a rectosigmoidoscopy and estimation of a serum Ca125 were undertaken. Sensitivity and specificity of all diagnostic tools were compared with the intraoperative findings.

RESULTS:

The procedure with the highest accuracy was bimanual rectovaginal gynaecological examination (sensitivity: 0.92/specificity: 0.32). Rectal endosonography obtained a sensitivity of 0.44 and a specificity of 0.77. All other diagnostic procedures such as Ca125 (sensitivity: 0.42/specificity: 0.81), MRI (sensitivity: 0.41/specificity: 0.83), transvaginal sonography (sensitivity: 0.2/ specificity: 0.79) and rectosigmoidoscopy (sensitivity: 0.03/specificity: 0.92) were only of limited value.

CONCLUSION:

The diagnostic method with the highest sensitivity to detect bowel infiltration in an everyday clinical setting is the gynaecological examination. It is followed by rectal endosonography. However, none of the currently available preoperative diagnostic tools can predict infiltrative growth of rectovaginal endometriosis with any certainty. Hence, infiltrative growth still needs to be verified by operative assessment.

 

 

Clin Exp Reprod Med. 2013 Jun;40(2):55-9.

Update on the treatment of endometriosis.

Kim SH1Chae HDKim CHKang BM.

 

Abstract

Endometriosis is defined as the presence of functional endometrial tissue outside the uterus, causing diverse progressive symptoms such as infertility, pelvic pain, and dysmenorrhea. Although endometriosis has been described since the 1800s, the mechanisms responsible for its pathogenesis and progression remain poorly understood. It is well established that endometriosis grows and regresses in an estrogen-dependent fashion and the disease can be effectively cured by definitive surgery. However, prolonged medical therapy may be needed in most of the cases since conservative surgery is usually performed especially in young women. This treatment modality is often associated with only partial relief and/or recurrence of the disease. In the present review, up-to-date findings on the treatment of endometriosis will be briefly summarized. The outcomes of surgery in patients with endometriosis will be reviewed in terms of pelvic pain relief as well as infertility treatment largely based on recent Cochrane reviews and clinical reports. The efficacy of newer drugs including aromatase inhibitor, anti-tumor necrosis factor-alpha, and dienogest will be also reviewed based on recent clinical studies.

 

 

 

Clin Exp Reprod Med. 2013 Jun;40(2):67-75.

Peroxisome proliferator-activated receptor γ agonist suppresses human telomerase reverse transcriptase expression and aromatase activity in eutopic endometrial stromal cells from endometriosis.

Chang HJ1Lee JHHwang KJKim MRYoo JH.

 

Abstract

OBJECTIVE:

To investigate the effect of peroxisome proliferator activated receptor γ (PPARγ) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis.

METHODS:

Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPARγ agonist).

RESULTS:

We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPARγ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin E2 production in the ESCs of endometriosis.

CONCLUSION:

This study suggests that PPARγ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

 

 

 

J Obstet Gynaecol Res. 2013 Nov;39(11):1518-25.

Role of osteopontin in differential diagnosis of ovarian tumors.

Moszynski R1Szubert SSzpurek DMichalak SSajdak S.

 

Abstract

AIM:

The aim of this study was to evaluate the role of the serum osteopontin (OPN) level as a biomarker for discriminating between malignant and benign ovarian tumors. Furthermore, comparisons with the diagnostic usefulness of the other tests were performed.

METHODS:

The study included 114 consecutive women with ovarian tumors (82 benign and 32 malignant) who were referred to our division.

RESULTS:

A cut-off level of 28.0 ng/mL for OPN showed a sensitivity of 71.87% and a specificity of 89.02%. The area under the receiver-operator curve (ROC) was 0.812. There were no differences in diagnostic utility between OPN and the other studied tests. OPN levels were lower in patients with endometriotic ovarian cysts than in those with other benign ovarian tumors (14.00 vs 19.50 ng/mL; P = 0.018). The difference between the median OPN level in patients with endometriotic cysts (14.0 ng/mL) and those with malignant tumors (40.85 ng/mL) was also statistically significant (P < 0.0001). The calculated OPN/CA-125 ratio was significantly different between patients with endometriotic cysts (median, 0.36; range, 0.05-2.89) and those with other benign tumors (median, 1.25; range, 0.05-5.70) (P = 0.0002). There was also a statistically significant difference in the median OPN/CA-125 ratio between patients with endometrial cysts (median, 0.36; range, 0.05-2.89) and those with malignant tumors (median, 0.12; range, 0.01-3.39) (P = 0.004).

CONCLUSION:

The diagnostic utility of OPN is similar to that of ultrasonographic evaluation and CA-125 level assessment. Thus, OPN may be useful in differential diagnosis for less experienced ultrasonographers and is especially valuable for differential diagnosis of endometriotic cysts.

 

 

Gynecol Endocrinol. 2013 Sep;29(9):859-62.

Endometriosis and IVF: are agonists really better? Analysis of 1180 cycles with the propensity score matching.

Rodriguez-Purata J1Coroleu BTur RCarrasco BRodriguez IBarri PN.

 

Abstract

OBJECTIVE:

To compare the outcomes of patients with confirmed endometriosis undergoing in vitro fertilization (IVF)-embryo transfer (ET) treated with either gonadotropin-releasing hormone agonist (GnRHa) or gonadotropin-releasing hormone antagonist (GnRHant) using the propensity score (PS) matching.

DESIGN:

Observational, retrospective analysis from January 2000 to December 2010.

SETTING:

Private tertiary fertility clinic.

PATIENT(S):

Patients with endometriosis confirmed by ultrasound or surgery (American Fertility Society; AFS grades I-IV) that underwent an IVF-ET, stimulated with standard controlled ovarian hyperstimulation (COH) and GnRHa or GnRHant.

INTERVENTION(S):

A PS was assigned to all patients, which calculates the conditional probability of receiving a certain treatment; a higher PS (1) meant a higher probability of receiving treatment with GnRHa, and a lower PS (0) meant a higher probability of receiving GnRHant. The PS was calculated with a logistic regression model adjusted specifically for age, follicle stimulating hormone, antral follicle count and previous IVF cycles. All patients were divided into three groups according to their PS.

MAIN OUTCOME MEASURE(S):

pregnancy rate (PR) per cycle.

RESULTS:

1180 patients were analyzed. Raw PR per cycle was 41.8% and 23.4%, and PR per ET was 44.3 and 27%, respectively. PR per cycle: 41.9 versus 30% in group A; in group B, 39.7% versus 36.4% and in group C, 15.4% versus 18.9%. The overall odds ratio for PR adjusted by PS was 1.10 [0.58-2.19].

CONCLUSIONS:

After matching patients by PS, PR after COH with either GnRHa or GnRHant may be equally effective.

 

 

 

 

Fertil Steril. 2013 Oct;100(4):1170-8.

Parthenolide reduces cell proliferation and prostaglandin E2 [corrected] in human endometriotic stromal cells and inhibits development of endometriosisin the murine model.

Takai E1Taniguchi FNakamura KUegaki TIwabe THarada T.

 

Erratum in

  • Fertil Steril. 2013 Dec;100(6):1788.

Abstract

OBJECTIVE:

To evaluate the effects of parthenolide on human endometriotic cells and murine endometriotic lesions.

DESIGN:

Experimental study.

SETTING:

University hospital and laboratory of animal science.

PATIENT(S) AND ANIMAL(S):

Twenty women with ovarian endometrioma and 30 mice.

INTERVENTION(S):

Ectopic endometrial tissue from the endometrioma was collected.

MAIN OUTCOME MEASURE(S):

Human endometriotic stromal cells (ESCs) were pretreated with parthenolide and exposed to tumor necrosis factor (TNF)-α. Interleukin 8 (IL-8) and COX-2 gene expressions were evaluated by real-time reverse transcription-polymerase chain reaction. Interleukin-8 protein, prostaglandin E₂ (PGE₂) level, and intranuclear p65 protein concentration were determined by ELISA. Cell proliferation was assessed by 5-bromo-2′-deoxyuridine-ELISA. Phosphorylation of signaling pathways in ESCs was evaluated by Western blotting. Gene expression and proliferative activity in murine endometriosis-like lesions were assessed by real-time reverse transcription-polymerase chain reaction and Ki67 staining, respectively.

RESULT(S):

With parthenolide pretreatment, TNF-α-induced IL-8 gene and protein expression in ESCs were diminished. Tumor necrosis factor α-induced COX-2 expression and PGE2 synthesis were also inhibited. Adding parthenolide repressed TNF-α-induced 5-bromo-2′-deoxyuridine incorporation and IκB phosphorylation in ESCs. As in vivo experiments, administering parthenolide reduced the number, surface area, and weight, the level of Vegf, Il-6, Mcp-1, and Lif gene expression, and the percentage of Ki67-positive cells in murine endometriosis-like lesions.

CONCLUSION(S):

Parthenolide repressed the development of endometriosis by suppressing the inflammatory peritoneal environment through the nuclear factor κB pathway.

 

Arch Gynecol Obstet. 2014 Jan;289(1):193-200.

Effects of amifostine on endometriosis, comparison with N-acetyl cysteine, and leuprolide as a new treatment alternative: a randomized controlled trial.

Onalan G1Gulumser CMulayim BDagdeviren AZeyneloglu H.

 

Abstract

PURPOSE:

To assess the effects of amifostine, N-acetyl cysteine (NAC), and leuprolide as a scavenger in a rat endometriosis model.

METHODS:

This is a prospective randomized animal study. Setting The Animal Laboratory of Medical University. Animals 40 rats were used for transplantation of an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. After allowing 3 weeks for growth, laparotomies were performed to check the implants. Then animals were randomized into four groups: Group I amifostine (200 mg/day loading dose after 20 mg/kg/day, p.o.); Group II NAC (200 mg/day, p.o.); Group III leuprolide acetate 1 mg/kg single dose, sc; and Group IV (controls) no medication. Three weeks later, implants were evaluated morphologically. Serum and peritoneal TNF-alpha levels were evaluated. The transmission electron microscopic examination of the peritoneal samples and ovaries was also performed.

RESULTS:

Leuprolide acetate, amifostine and NAC caused significant decreases in the mean implant areas and significant decreases in serum and peritoneal TNF-alpha levels. On comparing all groups, these reductions were higher in Group II. According to the transmission electron microscopic findings, leuprolide seems to be protecting normal structure of peritoneum best when compared to the other groups.

CONCLUSIONS:

Amifostine, NAC and leuprolide caused regression of endometriosis in this experimental rat model by a yet unsettled mechanism.

 

 

Endocr J. 2013;60(10):1155-64.

Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis.

Kajitani T1Maruyama TAsada HUchida HOda HUchida SMiyazaki KArase TOno MYoshimura Y.

 

Abstract

Nerve growth factor (NGF) has been recently proposed as one of the key factors responsible not only for promotion of nerve fiber growth but also for the onset and maintenance of pain in a variety of diseases. The aim of this study was to investigate the role of NGF in the pelvic pain associated with endometriosis. Tissue and peritoneal fluid samples were collected from 95 women with laparoscopically and histopathologically confirmed endometriosis and 59 control women without endometriosis. Expression levels of NGF mRNA and protein were examined using real-time RT-PCR and immunohistochemistry, respectively. Concentration of NGF in the peritoneal fluid (PF-NGF) was measured using ELISA. The degree of dyspareunia and dysmenorrhea was evaluated using a verbal rating scale. Real-time RT-PCR analysis revealed that NGF mRNA was significantly more abundant in the ovarian endometriomas and peritoneal endometriosis than in the normal control endometrium. Immunohistochemical analyses demonstrated that NGF was prominently expressed and preferentially localized to the glands of the ovarian endometriomas and peritoneal endometriosis, whereas it was only weakly detectable in the normal endometrium. Although PF-NGF was undetectable in some normal subjects and endometriosis patients, elevated PF-NGF in the peritoneal fluid was more frequently observed in endometriosis patients with severe pain than in those with less severe pain. Our results suggest that NGF produced locally in the peritoneal cavity may be involved in the generation of endometriosis-associated pelvic pain.

 

 

Hum Reprod Update. 2013 Nov-Dec;19(6):625-39.

The social and psychological impact of endometriosis on women’s lives: a critical narrative review.

Culley L1Law CHudson NDenny EMitchell HBaumgarten MRaine-Fenning N.

 

Abstract

BACKGROUND Endometriosis is a chronic condition affecting between 2 and 17% of women of reproductive age. Common symptoms are chronic pelvic pain, fatigue, congestive dysmenorrhoea, heavy menstrual bleeding and deep dyspareunia. Studies have demonstrated the considerable negative impact of this condition on women’s quality of life (QoL), especially in the domains of pain and psychosocial functioning. The impact of endometriosis is likely to be exacerbated by the absence of an obvious cause and the likelihood of chronic, recurring symptoms. The aims of this paper are to review the current body of knowledge on the social and psychological impact of endometriosis on women’s lives; to provide insights into women’s experience of endometriosis; to provide a critical commentary on the current state of knowledge and to make recommendations for future psycho-social research. METHODS The review draws on a method of critical narrative synthesis to discuss a heterogeneous range of both quantitative and qualitative studies from several disciplines. This included a systematic search, a structured process for selecting and collecting data and a systematic thematic analysis of results. RESULTS A total of 42 papers were included in the review; 23 used quantitative methods, 16 used qualitative methods and 3 were mixed methods studies. The majority of papers came from just four countries: UK (10), Australia (8), Brazil (6) and the USA (5). Key categories of impact identified in the thematic analysis were diagnostic delay and uncertainty; ‘QoL’ and everyday activities; intimate relationships; planning for and having children; education and work; mental health and emotional wellbeing and medical management and self-management. CONCLUSIONS Endometriosis has a significant social and psychological impact on the lives of women across several domains. Many studies have methodological limitations and there are significant gaps in the literature especially in relation to a consideration of the impact on partners and children. We recommend additional prospective and longitudinal research utilizing mixed methods approaches and endometriosis-specific instruments to explore the impact of endometriosis in more diverse populations and settings. Furthermore, there is an urgent need to develop and evaluate interventions for supporting women and partners living with this chronic and often debilitating condition.

 

 

Reprod Sci. 2014 Mar;21(3):329-39.

Effect of siRNA against β-NGF on nerve fibers of a rat model with endometriosis.

Chen Y1Li DZhang ZTakushige NKong BHWang GY.

 

Abstract

OBJECTIVE:

This study examines whether silencing specific β-nerve growth factor small interfering RNA (β-NGF siRNA) can affect the growth of ectopic endometriotic implants, generalized hyperalgesia, and nerve fiber density in endometriosis.

METHODS:

Four specific β-NGF siRNAs were detected by Western blot analysis, and the most efficient specific siRNA was transferred into rats with surgically induced endometriosis through gene transfer. The length × width × height of each ectopic transplant that survived from 2 groups were measured at pre-and postbombardment after 2 weeks. The transplants were collected 2 weeks after bombardment. Warm-water tail flick test was performed before the rats were sacrificed. The specimens were sectioned and stained immunohistochemically with antibodies against the types of nerve fibers to compare the presence of different nerve fibers in the treatment and control groups. The serums and supernatants of the peritoneal washings in the treatment and control groups were collected for enzyme-linked immunosorbent assay (ELISA) analysis. The extra rats were successfully induced with endometriosis and through gene transfer as described above. The spherical volumes of the transplants and tail flick latency post-bombardment after 4, 6, 8, and 10 weeks were measured.

RESULTS:

The spherical volumes in the treatment group were much smaller than those in the control group, and tail flick latency significantly increased in the treatment group postbombardment after 2 weeks. The ELISA analysis showed that the concentrations of β-NGF in the serums and supernatants of the peritoneal fluid decreased in the treatment group unlike in the control group. Less sympathetic and sensory innervation was observed in the treatment group postbombardment after 2 weeks. The outcomes of the spherical volumes of the transplants and tail flick latency postbombardment after 4, 6, 8, and 10 weeks showed that the sizes of the transplants did not return to their previous size and that the treatment had some effects on generalized hyperalgesia.

CONCLUSION:

Specific siRNA-mediated silencing of the β-NGF gene expression after gene transfer suppressed the growth of ectopic endometriotic implants resulted in a significant improvement in generalized hyperalgesia as well as reduced sympathetic and sensory nerve fiber density in the treatment group.

 

 

Reprod Sci. 2014 Mar;21(3):363-71.

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

Diamond MP1Carr BDmowski WPKoltun WO’Brien CJiang PBurke JJimenez RGarner EChwalisz K.

 

Abstract

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

 

 

World J Gastroenterol. 2013 Jul 21;19(27):4413-7.

Coincidence of active Crohn’s disease and florid endometriosis in the terminal ileum: a case report.

Kaemmerer E1Westerkamp MKasperk RNiepmann GScherer AGassler N.

 

Abstract

Crohn’s disease (CD), a variant of chronic inflammatory bowel disease, frequently affects the terminal ileum and coecal region. The clinical symptoms are often subtle and depend on the inflammatory activity of disease. In women of child-bearing age, florid intestinal endometriosis can simulate CD. Moreover, current pathophysiological concepts include intestinal endometriosis as a putative founder lesion for consecutive CD establishment. The report summarizes clinical and histomorphological data of a 35-year-old woman with the rare coincidence of florid intestinal endometriosis and CD both affecting the terminal ileum. The patient was suffering over 10 years from strong abdominal disorders including constipation, diarrhea, weight loss, and diffuse abdominal pain. In magnetic resonance imaging-Sellink, strong inflammation and intestinal obstruction of the terminal ileum were found. The laparoscopy revealed further evidence for existence of an inflammatory disease like CD, but brownish spots on the peritoneum were found indicative for endometriosis. Surgical resection of the terminal ileum and the coecal segment was performed followed by histopathological investigations. In transmural sections of the terminal ileum, histomorphological features of florid endometriosis intermingled with florid CD was found. The diagnostic findings were substantiated with a panel of immunohistological stainings. In conclusion, the findings demonstrate that florid endometriosis persists in florid CD lesions and the putative link between intestinal endometriosis and CD is more complex than previously assumed.

 

 

Neurol Int. 2013 Jun 25;5(2):28-30.

Adult mitochondrial DNA depletion syndrome with mild manifestations.

Finsterer J1G Kovacs GAhting U.

 

Abstract

Mitochondrial DNA depletion syndrome (MDS) is usually a severe disorder of infancy or childhood, due to a reduced copy number of mtDNA molecules. MDS with only mild, nonspecific clinical manifestations and onset in adulthood has not been reported. A 47-year-old Caucasian female with short stature and a history of migraine, endometriosis, Crohn’s disease, C-cell carcinoma of the thyroid gland, and a family history positive for mitochondrial disorder (2 sisters, aunt, niece), developed day-time sleepiness, exercise intolerance, and myalgias in the lower-limb muscles since age 46y. She slept 9-10 hours during the night and 2 hours after lunch daily. Clinical exam revealed sore neck muscles, bilateral ptosis, and reduced Achilles tendon reflexes exclusively. Blood tests revealed hyperlipidemia exclusively. Nerve conduction studies, needle electromyography, and cerebral and spinal magnetic resonance imaging were noninformative. Muscle biopsy revealed detached lobulated fibers with subsarcolemmal accentuation of the NADH and SDH staining. Realtime polymerase chain reaction revealed depletion of the mtDNA down to 9% of normal. MDS may be associated with a mild phenotype in adults and may not significantly progress during the first year after onset. In an adult with hypersomnia, severe tiredness, exercise intolerance, and a family history positive for mitochondrial disorder, a MDS should be considered.

 

 

Curr Pharm Des. 2014;20(11):1786-95.

Hypomethylation and activation of syncytin-1 gene in endometriotic tissue.

Zhou HLi JPodratz KCTipton TMarzolf SChen HBJiang SW1.

 

Abstract

Syncytin-1 plays a critical role in the maintenance of normal pregnancy by mediating the formation of syncytiotrophoblasts through a fosugenic action. Encoded by the human endogenous retrovirus envelope gene HERV-W, syncytin-1 trophoblast-specific expression is controlled by epigenetic mechanisms. In non-placental tissues, the syncytin-1 gene is suppressed by hypermethylation in the LTR promoter region. Hypomethylated and activated syncytin-1 gene is found in placental trophoblast lineages and malignant cells. We here demonstrate that while syncytin-1 gene remains silenced in the eutopic endometrium from endometriotic patients, syncytin-1 mRNA and protein are detected in ectopic, endometriotic lesions; particularly the endometrioid glandular endothelial cells. LINE-1 COBRA assay and immunohistochemistry using the 5-MC-specific antibody did not detect any changes in global DNA methylation in the endometriotic tissues. However, results from COBRA and bisulfite sequencing indicated that the LTR region of the syncytin-1 promoter is hypomethylated in endometriotic tissues, highlighting the significance of DNA demethylation in syncytin-1 gene activation. Analysis of DNA methyltransferase 3B (DNMT3B) mRNA levels revealed that DNMT3B3, an isoform carrying methyltransferase activity, is downregulated; whereas DNMT3B7, the isoform without enzymatic activity, is upregulated in the endometriotic tissues, pointing to positive and negative regulatory functions, respectively, of these isoforms on syncytin-1 methylation. These results have provided the first evidence supporting the involvement of epigenetic mechanisms for syncytin-1 upregulation in endometriotic tissues. Considering recent findings on the nonfusogenic activity of syncytin-1, its expression in endometriotic tissues suggests that this multifunctional protein may be implicated in the pathogenesis and/or progression of endometriosis.

 

 

Curr Pharm Des. 2014;20(11):1726-50. Review.

DNA methylation, an epigenetic mode of gene expression regulation in reproductive science.

Calicchio RDoridot LMiralles FMéhats CVaiman D1.

 

Abstract

DNA methylation is an important part of the epigenetic code governing gene expression. In human reproductive diseases, recent studies have shown the existence of deviations from the normal methylation profile at various genome loci. In this review, this type of epigenetic alterations is explored in pathological spermatogenesis, ovarian diseases, placental syndromes, such as preeclampsia and Intra- Uterine Growth Restriction, uterine diseases such as endometriosis, and putative pathophysiological effects of Assisted Reproductive Technologies. We review the notion of epigenetics, the technical methods available to analyze methylation, and the known associations between reproductive diseases and DNA methylation, focusing on human pathologies and on animal models when available. We show that imprinted genes control regions (ICRs) are a prominent and frequent target of methylation anomalies in reproductive disorders, but such alterations also affect non-imprinted genes. The mechanistic aspects of gene regulation in response to methylation anomalies are also discussed in this review when they have been investigated.

 

 

Endocr Regul. 2013 Jul;47(3):123-31.

Effect of 1α,25-dihydroxyvitamin D3 on progesterone secretion by porcine ovarian granulosa cells.

Smolikova KMlynarcikova AScsukova S.

 

Abstract

The essential role of vitamin D (VD) in bone metabolism and mineral homeostasis is well established knowledge. Research indicates that classical and non-classical pathways of VD affect also cell proliferation and differentiation, the immune system, infection, and cancer. VD receptor (VDR) and VD metabolizing enzymes have been detected in female reproductive tissues, such as ovary, uterus and placenta. The presence of VD metabolites was demonstrated in follicular fluid (FF) in women undergoing in vitro fertilization and embryo transfer (IVF-ET). The recent studies show that VD regulates the expression of a large number of genes in reproductive tissues implicating a role for VD in female reproduction and pregnancy outcomes. There is increasing human and animal data suggesting that VD status may be associated with impaired fertility, endometriosis, polycystic ovary syndrome (PCOS), and ovarian cancer. The presence of VDR in both animal and human ovarian tissue has raised the question of a possible direct role for 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] in the regulation of steroid hormone synthesis and secretion. Our recent data have demonstrated that 1α,25(OH)2D3 may affect in vitro insulin- and follicle-stimulating hormone (FSH)-induced progesterone secretion by porcine ovarian granulosa cells. The molecular mechanisms of this action should be further investigated.

 

 

 

J Pediatr Adolesc Gynecol. 2013 Aug;26(4):224-7.

Surgical pearls: laparoscopic removal of uterine remnants in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

Will MA1Marsh CASmorgick NSmith YRQuint EH.

 

Abstract

BACKGROUND:

Females with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome may require surgical removal of uterine remnant(s) which can be accomplished with a laparoscopic approach, described in this case series.

CASES:

Nine females with MRKH and pelvic pain were treated with laparoscopic resection of uterine remnants without major complication. The following management recommendations are offered: (1) preoperative evaluation for urinary tract anomalies and postoperative cystoscopy; (2) medial traction of the remnant to allow adequate exposure of the pelvic sidewall; (3) awareness of possible anomalous vascular supply to uterine remnant; (4) individualized management of associated endometriosis; (5) careful use of surgical terminology, avoiding use of the word hysterectomy.

SUMMARY AND CONCLUSION:

Laparoscopic removal of uterine remnant(s) is safe and effective.

 

 

Environ Res. 2013 Oct;126:91-7.

Phthalates and risk of endometriosis.

Upson K1Sathyanarayana SDe Roos AJThompson MLScholes DDills RHolt VL.

 

Abstract

BACKGROUND:

Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood.

OBJECTIVE:

To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women.

METHODS:

We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year.

RESULTS:

The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1-0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ∑DEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant.

CONCLUSIONS:

Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women.

 

 

Fertil Steril. 2013 Nov;100(5):1332-6.

Deep endometriosis and bladder and detrusor functions in women without urinary symptoms: a pilot study through an unexplored world.

Serati M1Cattoni EBraga AUccella SCromi AGhezzi F.

 

Abstract

OBJECTIVE:

To evaluate the impact of deep endometriosis (DE) on bladder function, focusing on detrusor pattern, in patients without preoperative urinary symptoms.

DESIGN:

Prospective study.

SETTING:

Academic research center.

PATIENT(S):

A total of 25 asymptomatic patients: 12 patients with DE (group 1) and 13 patients with ovarian endometriosis (group 2, control group).

INTERVENTION(S):

Preoperative urodynamic evaluation.

MAIN OUTCOME MEASURE(S):

The impact of DE on urodynamic parameters.

RESULT(S):

For the first time, a urodynamic diagnosis of detrusor overactivity was correlated with the presence of deep infiltrating endometriosis (group 1, 91.7% [11/12] vs. group 2, 7.7% [1/13]). All involuntary detrusor contractions were detected only during the filling phase. All cystometry parameters were found to be altered in group 1 and statistically different between the two groups. No pressure/flow study parameter significantly differed between the two groups, besides maximal detrusor pressure (46 cmH2O [33-79] vs. 29 cmH2O [15-40]), which was significantly higher in group 1. Therefore, all detrusor-related parameters are statistically different between the two groups. Postvoid residual does not reach a statistically significant difference.

CONCLUSION(S):

DE could significantly impair detrusor functions. A preoperative urodynamic evaluation allows the attainment of important functional information, even in asymptomatic patients.

 

 

Reprod Toxicol. 2013 Dec;42:41-8.

Trace elements and endometriosis: the ENDO study.

Pollack AZ1Louis GMChen ZPeterson CMSundaram RCroughan MSSun LHediger MLStanford JBVarner MWPalmer CDSteuerwald AJParsons PJ.

 

Abstract

There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.

 

 

Proteomics Clin Appl. 2014 Feb;8(1-2):86-98.

Understanding the pathogenesis of endometriosis through proteomics: recent advances and future prospects.

Siva AB1Srivastava PShivaji S.

 

Abstract

Endometriosis is a complex gynecological disease, characterized by the presence and growth of endometrial tissue outside the uterus, resulting in pelvic pain and infertility. It occurs in 10% of women in their reproductive age. The viable endometrial cells enter the peritoneal cavity by retrograde menstruation, implant, and cause lesions ectopically; depending on their ability to survive, attach, grow, and invade. These “normal” endometrial cells turn “endometriotic” apparently because of inherent abnormalities present in them. Information on these molecular abnormalities is now being sought through proteomic approaches. Recent proteome-based comparisons between the eutopic endometrium from normal women and patients with endometriosis have revealed several proteins (many of which are shown to have a role in several cancers), of which a few have been validated as potential players in the etiology of endometriosis. After an initial in-flow of information from these proteome studies of eutopic endometrium, focus now needs to be expanded to the changes in the various protein PTMs and their upstream effectors present in these tissues. Early diagnosis of endometriosis through noninvasive means is the need of the hour as well-which would require the use of the presently existing immunoassays, along with the advancing MS-based proteomics. In this review, we aim to discuss these future thrust areas of human endometriosis proteomics and also present the proteomic advances made so far in understanding the molecular basis of endometriosis.

 

 

Int J Gynecol Pathol. 2013 Sep;32(5):454-8.

The presence of mucosal iron in the fallopian tube supports the “incessant menstruation hypothesis” for ovarian carcinoma.

Seidman JD1.

 

Abstract

The incessant ovulation hypothesis for the etiology of ovarian carcinoma has been accepted for decades, but recent evidence strongly implicates the fallopian tube mucosa as the source of most high-grade “ovarian serous carcinomas.” Menstrual reflux through the tubes, a normal phenomenon, is a putative source of tubal mucosal exposure to carcinogens. We searched for histologic evidence of deposition of iron, a well-recognized carcinogen, in the fallopian tubes in 196 women with advanced-stage high-grade pelvic serous carcinomas in comparison with 370 controls. Tubal hemosiderin and/or pseudoxanthoma cells were found in 20% of the serous carcinoma cases, and an iron stain was positive in 30% of a sample of pigment-negative cases. Controls displayed pigment in 5% (P<0.001). In both cases and controls, pigment was significantly more frequently present in women with endometriosis as compared with those without. We conclude that tubal mucosal iron is present in a significant proportion of women with advanced-stage high-grade pelvic serous carcinoma. As a carcinogen, iron may play a role in the pathogenesis of these tumors. As compared with the incessant ovulation hypothesis, the recently proposed “incessant menstruation hypothesis” may be a better explanation of the well-recognized association of ovarian carcinoma with the length of the reproductive life uninterrupted by pregnancy.

 

 

BMJ Case Rep. 2013 Jul 29;2013.

Perineal scar endometriosis: a comparison of two cases.

Jain D1.

 

Abstract

Perineal scar endometriosis is a devastating illness with grave consequences. An early diagnosis is imperative as a delayed diagnosis results in extension of the disease process causing increasing damage to adjoining structures like the anal sphincter and rectum. A late recognition of the disease also prolongs the agony of the patient owing to its being a very painful condition. Two cases are presented of parous women in their early thirties who had episiotomy scars preceding the development of endometriosis. The cases were treated by a perineal incision and removal of suspicious structures. However, a recurrent endometrioma was formed in one case, which had to be excised again. In the other case, symptoms of recurrence had begun, which subsided after a dose of GnRh analogue (leuprolide acetate 3.75 mg). Both patients are on follow-up and are fine until now.

 

 

Int J Womens Health. 2013 Jul 16;5:421-4.

Effectiveness of the cyclic administration of dienogest in a case of pathological disappearance of intestinal endometriosis.

Tamura R1Tsuneki IYanase T.

 

Abstract

We have reported good control of atypical genital bleeding when using a cyclic administration of dienogest (repeated 4-week cycles, each consisting of the administration of 2 mg/day of dienogest for 3 weeks, followed by 1 week of drug withdrawal) in patients with endometriosis. Herein, we report the effectiveness of the long-term cyclic administration (22 months) of dienogest in a case of pathological disappearance of intestinal endometriosisdiagnosed by endoscopy and histology of the lower gastrointestinal tract. There is no recurrent sign after 16 months of the treatment being stopped. Atypical genital bleeding during treatment was 3-5 days a month in each cycle. Compliance was good, so we could continue the therapy. The long-term cyclic administration of dienogest in patients with intestinal endometriosis may have significant merit.

 

 

 

Australas J Ultrasound Med. 2013 Aug;16(3):118-123.

The ‘sliding sign’ in conjunction with sonovaginography: is this the optimal approach for the diagnosis of Pouch of Douglas obliteration and posterior compartment deep infiltrating endometriosis?

Menakaya U1Reid S1Infante F1Condous G2.

 

Abstract

Introduction: Endometriosis is a chronic peritoneal disease that may progress as a deep infiltrating lesion involving the posterior compartment of the pelvis. Efforts to improve pre-operative knowledge of the location and extent of these lesions have resulted in the development of Transvaginal ultrasound (TVS) as the first-line imaging modality for extra-ovarian endometriosis. However, various techniques of TVS have been described in the literature for this purpose. Methods: In this review we will detail the evolution of TVS as the primary imaging modality in the pre-operative diagnosis of posterior compartment deep infiltrating endometriosis (DIE). We will also discuss the potential of an emerging new real-time diagnostic ultrasound-based technique known as the ‘sliding sign’ in combination with office gel sonovaginography for the pre-operative diagnosis of Pouch of Douglas obliteration and posterior compartment DIE. Conclusion: Implementation of the new real-time dynamic, reproducible and simple ‘sliding sign’ in conjunction with SVG has the potential to challenge the current concept that traditional laparoscopy is the ‘gold standard’ modality for the diagnosis of women with posterior compartment DIE.

 

 

Reprod Sci. 2014 Mar;21(3):395-400.

Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells.

Xue Q1Xu YYang HZhang LShang JZeng CYin PBulun SE.

 

Abstract

Steroidogenic factor 1 (SF-1), a transcriptional factor essential for estrogen biosynthesis, is undetectable in endometrial stromal cells and aberrantly expressed in endometriotic stromal cells.

OBJECTIVE:

We tried to gain further insight into the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells.

DESIGN:

We had previously identified a novel CpG island in SF-1, which is located in the downstream intron 1 region. Here, we evaluated the methylation status of this CpG island.

PATIENTS:

We obtained the eutopic endometrium from disease-free participants (n = 8) and the walls of cystic endometriosis lesions of the ovaries from another group of participants (n = 8). None of the patients had received any preoperative hormonal therapy.

INTERVENTIONS:

Stromal cells were isolated from these 2 types of tissues and subjected to DNA bisulfite treatment and sequence analysis.

RESULTS:

The SF-1 messenger RNA (mRNA) levels in endometriotic stromal cells were significantly higher than those in endometrial stromal cells. Bisulfite sequencing showed strikingly increased methylation of a 1-kbp region around the previously identified CpG island in endometriotic cells compared with endometrial cells (P < .001). A strong correlation between SF-1 mRNA levels and percentage methylation of the intron 1 region of the SF-1 gene was observed in endometriotic cells (Spearman correlation coefficient, .96; P < .001).

CONCLUSIONS:

Methylation of the intron 1 region of the SF-1 gene is associated with its expression in endometriotic cells. This CpG island therefore plays an important role in regulating SF-1 expression.

 

 

Reprod Sci. 2014 Mar;21(3):305-18.

Endometriosis is characterized by a distinct pattern of histone 3 and histone 4 lysine modifications.

Monteiro JB1Colón-Díaz MGarcía MGutierrez SColón MSeto ELaboy JFlores I.

 

Abstract

BACKGROUND:

The histone modification patterns in endometriosis have not been fully characterized. This gap in knowledge results in a poor understanding of the epigenetic mechanisms (and potential therapeutic targets) at play. We aimed to (1) assess global acetylation status of histone 3 (H3) and histone 4 (H4), (2) measure levels of H3 and H4 lysine (K) acetylation and methylation, and (3) to identify histone acetylation patterns in promoter regions of candidate genes in tissues from patients and controls.

METHODS:

Global and K-specific acetylation/methylation levels of histones were measured in 24 lesions, 15 endometrium from patients, and 26 endometrium from controls. Chromatin immunoprecipitation (ChIP)-polymerase chain reaction was used to determine the histone acetylation status of the promoter regions of candidate genes in tissues.

RESULTS:

The lesions were globally hypoacetylated at H3 (but not H4) compared to eutopic endometrium from controls. Lesions had significantly lower levels of H3K9ac and H4K16ac compared to eutopic endometrium from patients and controls. Tissues from patients were hypermethylated at H3K4, H3K9, and H3K27 compared to endometrium from controls. The ChIP analysis showed hypoacetylation of H3/H4 within promoter regions of candidate genes known to be downregulated in endometriosis (e.g., HOXA10, ESR1, CDH1, and p21 (WAF1/Cip1) ) in lesions versus control endometrium. The stereoidogenic factor 1 (SF1) promoter region was enriched for acetylated H3 and H4 in lesions versus control tissues, correlating with its reported high expression in lesions.

CONCLUSIONS:

This study describes the histone code of lesions and endometrium from patients with endometriosis and provides support for a possible role of histone modification in modulation of gene expression in endometriosis.

 

 

Hum Reprod. 2013 Oct;28(10):2686-94

Comparison of patient- and physician-based descriptions of symptoms of endometriosis: a qualitative study.

Fauconnier A1Staraci SHuchon CRoman HPanel PDescamps P.

 

Abstract

STUDY QUESTION:

How do fully-comprehensive patient-centred descriptions of the symptoms of endometriosiscompare with the physicians’ description of the symptoms?

SUMMARY ANSWER:

The description of the painful symptoms due to endometriosis is based on numerous distinct parameters. The way these are used to describe symptoms and the way they are interpreted varies significantly between patients and clinicians. The descriptions of severe pelvic pain and dysmenorrhoea and dyspareunia by the clinicians were incomplete compared with those of the patients.

WHAT IS KNOWN ALREADY:

Painful symptoms due to endometriosis were found to be of little use to predict the location and severity of the disease. Currently there are few data on the patients’ description of symptoms and no questionnaire is available to derive data from patients.

STUDY DESIGN, SIZE, DURATION:

Descriptions of painful symptoms by patients and by physicians were obtained by qualitative, interview-based study and analysed using Colaizzi’s method. The patients planned to be operated on for painful endometriosis were volunteers for preoperative interview. They were recruited by purposeful sampling to represent different types of endometriosis [i.e. superficial endometriosis, ovarian endometriosis or deeply infiltrating endometriosis (DIE)], the women were selected so that at least five sites of endometriosis were included in the study. The clinicians were experts in endometriosis management.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Forty-one patients were recruited, in four reference centres. Among them, 33 had DIE in various locations, including intestinal endometriosis (n = 12) or bladder endometriosis (n = 5), 14 had ovarian endometriosis (including three without associated DIE) and 5 had only superficial endometriosis. The nine experts were French-speaking gynaecological surgeons practicing in university teaching hospitals (seven), a general hospital (one) or a private centre (one).

MAIN RESULTS AND THE ROLE OF CHANCE:

In total, 47 themes were identified of which 30 were perceived by both patients and clinicians, 12 by patients only and 5 by clinicians only. Themes fall into five general categories: (i) severe pelvic pain and dysmenorrhoea, (ii) dyspareunia, (iii) gastro-intestinal symptoms, (iv) bladder symptoms, (v) other symptoms. Patients’ and clinicians’ descriptions of symptoms were in agreement for general categories, but the clinicians’ comprehensive description was incomplete, in particular concerning the severe pelvic pain and dysmenorrhoea’s themes and the dyspareunia theme. Patients did not report any clear-cut distinction between pelvic pain and dysmenorrhoea and expressed a dimension of suffering and impaired quality of life inherent to painful symptoms.

LIMITATIONS, REASONS FOR CAUTION:

Most of the patients in the study had already had treatment for endometriosis, including ongoing hormonal treatment. Furthermore, all but a few patients had documented endometriotic lesions and no specific investigations to eliminate additional causes of functional pelvic pain were done. Finally due to the qualitative design of the study the result must be regarded as inferences.

WIDER IMPLICATIONS OF THE FINDINGS:

The present study provides a first person viewpoint of the painful experience of endometriosis by the patients in a subjective, phenomenological perspective, and points out the differences of perceptions between the physicians and the patients. The considerable variability in patients’ descriptions suggests several distinct mechanisms are involved in explaining the pain related to endometriosis. The discordance between clinicians and patients might also reflect this kind of problem with the wording of the items. In future, if the goal is to properly understand the pain experienced by women with endometriosis, assessment tools using the words and phrases used in narratives of pain would potentially be very useful.

STUDY FUNDING/COMPETING INTEREST(S):

Funded by IPSEN, Boulogne-Billancourt, France. None of the authors has any conflict of interest to declare.

 

 

Hum Reprod. 2013 Oct;28(10):2643-51.

Time-lapse parameters as predictors of blastocyst development and pregnancy outcome in embryos from good prognosis patients: a prospective cohort study.

Kirkegaard K1Kesmodel USHindkjær JJIngerslev HJ.

 

Abstract

STUDY QUESTION:

Do early time-lapse parameters predict which embryos will develop to high-quality blastocysts and does timing of development differ between embryos that implant and those that do not.

SUMMARY ANSWER:

Development to high-quality blastocysts could be predicted within the first 48 h of culture, whereas time-lapse parameters could not predict pregnancy.

WHAT IS KNOWN ALREADY:

Historical cohort studies on embryos from unselected groups of patients have suggested several putative kinetic markers of viability. Before well-designed randomized studies can be conducted, relevant selection models based on solid data must be developed. So far conclusions from the previous studies are ambiguous.

STUDY DESIGN, SIZE, DURATION:

A prospective cohort study conducted from February 2011 to June 2012. A total of 571 ICSI embryos from 92 patients were included in the blastocyst development analysis and 84 single embryo transfers were included in the pregnancy outcome analysis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Embryos from women aged <38 years, with no endometriosis and ≥ 8 oocytes retrieved. University affiliated clinic. Embryos were cultured in a time-lapse incubator till Day 6. Logistic regression analysis was performed with variables selected based on indication.

MAIN RESULTS AND THE ROLE OF CHANCE:

Duration of the first cytokinesis, duration of the 3-cell stage and direct cleavage to 3-cells predicted development to high-quality blastocyst. We found no difference in timing between implanted and non-implanted embryos.

LIMITATIONS, REASONS FOR CAUTION:

A larger study might detect differences in timing between implanted and non-implanted embryos. The cohort consisted of good prognosis patients only and may not be representative of the entire IVF population.

WIDER IMPLICATIONS OF THE FINDINGS:

Our results in context with the lack of consistency in previous studies and the presumed influences of different external factors indicate that a universal algorithm for optimal timing of development might not be feasible. The apparent negative significance of division patterns that differ from the expected may imply that time-lapse will facilitate de-selection of embryos.

STUDY FUNDING/COMPETING INTEREST(S):

Funding for the present study was provided by Aarhus University, the Lippert Foundation, the Toyota Foundation, the Aase og Einar Danielsen foundation and by an unrestricted grant from MSD and Ferring. The authors declare no conflict of interest.

 

 

J Steroid Biochem Mol Biol. 2013 Nov;138:421-6.

Puerarin suppresses proliferation of endometriotic stromal cells in part via differential recruitment of nuclear receptor coregulators to estrogen receptor-α.

Ji M1Liu YYang SZhai DZhang DBai LWang ZYu JYu CCai Z.

 

Abstract

BACKGROUND AND OBJECTIVES:

Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17β-estradiol and producing an anti-estrogenic effect. In our early clinical practice to treat endometriosis, a better therapeutic effect was achieved if the formula of traditional Chinese medicine included Radix puerariae. This study was to investigate whether puerarin could suppress the proliferation of endometriotic stromal cells (ESCs) and to further elucidate the potential mechanism.

METHODS AND RESULTS:

The ESCs were successfully established. The effects of puerarin on the proliferation of ESCs, cell cycle and apoptosis were determined by Cell Counting Kit-8 assay and flow cytometry. The mRNA and protein levels of cyclin D1 and cdc25A were detected by real-time PCR and Western blot analysis. Coimmunoprecipitation was applied to examine the recruitment of nuclear receptor coregulators to the estrogen receptor-α. We found that puerarin can suppress estrogen-stimulated proliferation partly through down-regulating the transcription of cyclin D1 and cdc25A by promoting the recruitment of corepressors to estrogen receptor-α as well as limiting that of coactivators in ESCs.

CONCLUSIONS:

Our data suggest that puerarin could suppress the proliferation of ESCs and could be a potential therapeutic agent for the treatment of endometriosis.

 

 

Placenta. 2013 Oct;34(10):863-72.

Expression and function of galectins in the endometrium and at the human feto-maternal interface.

Jeschke U1Hutter SHeublein SVrekoussis TAndergassen UUnverdorben LPapadakis GMakrigiannakis A.

 

Abstract

Galectins are classified as lectins that share structural similarities and bind β-galactosides via a conserved carbohydrate recognition domain. So far 16 out of 19 identified galectins were shown to be present in humans and numerous studies revealed galectins as pivotal modulators of cell death, differentiation and growth. Galectins were highlighted to interact with both the adaptive and innate immune response. In the field of reproductive medicine and placenta research different roles for galectins have been proposed. Several galectins, being abundantly present at the human feto-maternal interphase and endometrium, were hypothesized to significantly contribute to endometrial receptivity and pregnancy physiology. Hence, this review outlines selected aspects of galectin action within endometrial function and at the feto-maternal interphase. Further current knowledge on galectins in reproductive and pregnancy disorders like endometriosis, abortion or preeclampsia is summarized.

 

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