Gynecol Obstet Fertil. 2013 Sep;41(9):524-8.

Interest of selective progesterone receptor modulators in endometriosis.

Merviel P1Lourdel ESanguin SGagneur OCabry RNasreddine A.

 

Abstract

The SPRM (selective progesterone receptor modulators) are agonists and/or antagonists of progesterone receptor. They are responsible for anovulation, amenorrhea and a lower prostaglandin levels, which leads to an improvement in pain and regression of lesions in endometriosis. On the endometrium, a particular aspect, the progesterone receptor modulator-associated endometrial changes (PAEC), raises additional studies to verify its harmlessness. However, due to the lack of hypoestrogenism and metabolic effects with these drugs, it is very likely that the SPRM will in the near future an important place in the treatment of endometriosis.

 

 

BMJ Case Rep. 2013 Aug 26;2013:007730.

Malignant transformation of superficial peritoneal endometriosis lesion.

Marchand E1Hequet DThoury ABarranger E.

 

Abstract

A 63-year-old woman with no medical history underwent an abdominal surgery with hysterectomy and bilateral salpingo-oophorectomy for a 10 cm peritoneal cyst with increased cancer antigene-125. A large suspicious tumour of the Douglas space, with contact to the uterus and the rectal wall was described. The rest of the exploration was normal, specially the rest of the peritoneum. Histopathology revealed a malignant transformation of a superficial peritoneal endometriosis. Secondary surgery was thus completed by laparoscopy with bilateral pelvic and para-aortic lymph node dissections, omentectomy and multiple peritoneal biopsies. All staging samples were free of cancer; therefore no complementary therapy was administered. After 18 months of follow-up, consisting of clinical examination and pelvis magnetic resonance imaging every 6 months, we did not observe any recurrence. Malignant transformation of superficial peritoneal endometriosis is a rare disease and surgical management seems to be the main treatment.

 

J Assist Reprod Genet. 2013 Nov;30(11):1505-12.

HOXA-11 mediated dysregulation of matrix remodeling during implantation window in women with endometriosis.

Jana SK1Banerjee PMukherjee RChakravarty BChaudhury K.

Author information

Abstract

PURPOSE:

To investigate the Homeobox genes HOXA-10 and HOXA-11 mediated endometrial molecular defects during implantation window in endometriosis-associated infertility cases.

METHODS:

Endometrial biopsies were obtained during implantation window from 31 infertile women with endometriosis (age < 35 years) and 26 age and BMI-matched infertile women without endometriosis were included in the study for comparison purposes. Endometrial expression of HOXA-10 and HOXA-11 genes, MMP-2, -9, α(v)β(3) integrin, leukemia inhibitory factor and surface characteristics including average roughness and topology were assessed.

RESULTS:

A significantly lower expression of HOXA-10 and HOXA-11 were observed in endometriotic women compared to non-endometriotic controls. Further, a significantly higher endometrial expression of MMP-2 and -9 were observed in women with endometriosis when compared with controls. Interestingly, endometrial surface were observed to be grossly affected in terms of average roughness and topology in women with endometriosiscompared to controls.

CONCLUSIONS:

The findings suggest that aberrant expression of HOXA-10 and -11 genes adversely affects endometrial remodelling and expression of receptivity markers.

 

 

 

Genet Mol Res. 2013 Aug 2;12(3):2764-70.

GSTM1 and GSTT1 polymorphisms in endometriosis in women from Goiás, Brazil.

Frare AB1Barbosa AMCosta IRSouza SRSilva RCBordin BMRibeiro Júnior CLMoura KK.

 

Abstract

Endometriosis is a gynecologic pathology with a high prevalence and unknown etiology. Therefore, an increasing number of studies has been undertaken to search for associations between endometriosis and alterations or polymorphisms in candidate genes, including glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1). We analyzed the frequency of present/absent polymorphisms of GSTM1 and GSTT1 in 50 women diagnosed with endometriosis and in a control group of 46 women without complaints related to this pathology. The association of these polymorphisms with p53 gene codon 72 was also evaluated within each group, and a higher frequency of absence of GSTM1 (61%) and GSTT1 (45%) genes in the group of women studied, women with endometriosis and control group was found. The contributions of GSTM1 and GSTT1 polymorphisms to the proliferation of endometriosis were not statistically significant, but the analysis of pathology and the association of GSTM1 and GSTT1 gene polymorphisms with p53 codon 72 revealed statistical significance.

 

 

 

J Ultrasound Med. 2013 Sep;32(9):1635-42.

Potential role of strain elastography for detection of the extent of large-scar endometriosis.

Xie M1Zhang XZhan JRen YWang W.

Abstract

OBJECTIVES:

The purpose of this study was to evaluate the clinical value of strain elastography for detection of the lesion extent of large-scar endometriosis and compare it to conventional sonography and magnetic resonance imaging (MRI).

METHODS:

Eight patients suspected of having large-scar endometriosis underwent transabdominal sonography, strain elastography, and MRI. The mass was located and assessed for its size, imaging appearance, and, especially, widest boundary and vertical extent. After wide surgical excision and pathologic diagnosis, lesions in the central area shown on conventional sonography and the extended area shown on strain elastography underwent immunohistochemical examination.

RESULTS:

Nodules were always deep in the subcutaneous plane, in contact with the fascia or muscle. Horizontally, the mean lesion size shown on conventional sonography was mainly consistent with the size on MRI in all cases, but it was obviously smaller on sonography than on strain elastography in 7 cases. Vertically, the lesion depth was mainly consistent with the depth on MRI in 7 cases, but it was more infiltrative on strain elastography in 6 cases. The vertical and horizontal infiltration scales of the postoperative specimens were consistent with strain elastography in all cases. All 8 patients showed strong collagen type I expression in the central area of the lesions; 6 patients showed strong collagen type I expression and the other 2 showed moderate expression in the extended area.

CONCLUSIONS:

Strain elastography can elevate the diagnostic accuracy of large-scar endometriosis, the extent of which may be evaluated insufficiently by transabdominal sonography and MRI.

 

 

Eur Radiol. 2014 Jan;24(1):95-101.

Diffusion tensor imaging and tractography to evaluate sacral nerve root abnormalities in endometriosis-related pain: a pilot study.

Manganaro L1Porpora MGVinci VBernardo SLodise PSollazzo PSergi MESaldari MPace GVittori GCatalano CPantano P.

Abstract

OBJECTIVE:

To prospectively evaluate microstructural abnormalities in sacral nerve roots in women affected by chronic pelvic pain associated with endometriosis.

METHODS:

We enrolled 30 women with an ultrasound diagnosis of endometriosis and moderate-severe chronic pelvic pain; 10 age-matched healthy women comprised the control group. All subjects underwent 3 T magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI); the sacral roots were reconstructed by post-processing the DTI data with dedicated software. Mean fractional anisotropy (FA) values in the S1, S2 and S3 roots were quantified. Analysis of FA values was performed by two radiologists in order to evaluate the interobserver agreement.

RESULTS:

The sacral nerve roots in healthy subjects were clearly visualised. Most of the patients with endometriosis displayed abnormalities of S1, S2 and S3 bilaterally at tractography, including an irregular and disorganised appearance. FA values in the S1, S2 and S3 roots were significantly lower in patients than in controls (P < 0.0001, <0.05 and <0.02, respectively) for both observers. No significant difference was found between observers.

CONCLUSION:

DTI with tractography is a non-invasive means of detecting changes in the microarchitecture of the sacral nerve roots. It can qualitatively and quantitatively reveal sacral root abnormalities in patients with endometriosis-associated pain.

KEY POINTS:

  • MRI is increasingly used for endometriosisand chronic pelvic pain (CPP). • Magnetic resonance tractography can demonstrate microarchitectural abnormalities in sacral nerve roots. • Tractography shows altered microstructure of sacral roots affected by endometriosisand CPP. • S1-S3 fractional anisotropy values are lower in endometriosis than in healthy women. • Sacral nerve root alteration may explain the nature of endometriosis-related CPP.

 

 

Mol Hum Reprod. 2014 Jan;20(1):1-14.

The future for genetic studies in reproduction.

Montgomery GW1Zondervan KTNyholt DR.

 

Abstract

Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies (GWAS) have revolutionized gene discovery for common traits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases. GWAS ‘hits’ provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.

 

 

Mymensingh Med J. 2013 Jul;22(3):478-82.

Laparoscopic findings of subfertile women attended in a tertiary level care centre.

Deeba F1Alam MMIslam MRMatin AKhan RAva NN.

 

Abstract

This retrospective study was done in the Obstetrics and Gynaecology Department of Bangladesh Medical College hospital during the period of July 2003 to June 2004 in the women suffering from primary and secondary subfertility, who underwent laparoscopy. The aim of this study was to see the laparoscopic findings of internal genitalia and other pelvic structures in subfertile women. The study group comprises 55 cases of which 67.37% of primary and 32.73% were of secondary subfertility. Both the ovaries were normal looking in 41.81% cases. Endometriosis was present in 5.45% of both the ovaries. Corpus luteum was seen in 20% cases on right ovary and in 27.27% cases on left ovary. Laparoscopy shows normal looking fallopian tube in 65.45% cases in right side and 61.81% cases in the left side. Right sided tubal block was in 5.46% and 9.10 % in the left side. Both the tubes were patent in 81.6% cases.

 

 

Biomed Res Int. 2013;2013:329058.

1H NMR based targeted metabolite profiling for understanding the complex relationship connecting oxidative stress with endometriosis.

Jana SK1Dutta MJoshi MSrivastava SChakravarty BChaudhury K.

 

Abstract

Accumulating evidence indicates the active role of oxidative stress in the development of endometriosis; however, the mechanism of reactive oxygen species generation is poorly understood. Metabonomics/metabolomics is a scientific discipline that can be used to study changes in metabolite ensembles associated with disease pathophysiology. The present study focuses on the use of proton nuclear magnetic resonance spectroscopy based targeted metabolite profiling approach to explore dysregulation in metabolites expression in women with endometriosis. Further, association of oxidative stress with the metabolite ensembles, if any, is investigated. Using multivariate statistics, partial least square discriminant analysis model was generated which could classify endometriosis patients with sensitivity and specificity of 92.83% and 100%, respectively, and with a classification rate of 96.4%. In conjunction with increased glucose metabolism, citrate and succinate were found to be elevated in endometriosis patients. Higher levels of reactive oxygen species, lipid peroxidation, and advanced oxidation protein products and lower levels of total antioxidant capacity, superoxide dismutase, catalase, and glutathione were also observed. Increased glucose metabolism and defects in the mitochondrial respiratory system are suggested to be the possible sources of excessive reactive oxygen species generation in endometriosis.

 

 

Arch Esp Urol. 2013 Jul-Aug;66(6):605-8.

Endosalpingiosis of the bladder. A case report.

García Sánchez C1Ocón Revuelta EMFontillón MArgüelles Salido EMedina López RA.

Abstract

OBJECTIVE:

To describe a case of endo-salpingiosis of bladder and review of the literature.

METHOD:

A 38 years old women referred to an outpatient urology clinic with postmenstrual voiding symptoms.

RESULTS:

We studied her and ultrasound imaging detects tumor that was confirmed by cystoscopy. She is diagnosed of endosalpingiosis of the bladder after transurethral resection, and a CT shows a consistent mass next to left adnexal with high probablility of being an endometrioma.

CONCLUSIONS:

Endosalpingiosis of the bladder is a rare disease that occurs in young women with cyclic urinary symptoms. The implantation of tubular tissue in the bladder is diagnosed and treated definitively by tumor excision and anatomopathologic examination.

 

 

Patient Prefer Adherence. 2013 Aug 9;7:777-85.

Role of the levonorgestrel intrauterine system in effective contraception.

Attia AM1Ibrahim MMAbou-Setta AM.

 

Abstract

Norgestrel, a synthetic progestin chemically derived from 19-nortestosterone, is six times more potent than progesterone, with variable binding affinity to various steroid receptors. The levonorgestrel-releasing intrauterine system (LNG IUS) provides a long-acting, highly effective, and reversible form of contraception, with a pearl index of 0.18 per 100 women-years. The locally released hormone leads to endometrial concentrations that are 200-800 times those found after daily oral use and a plasma level that is lower than that with other forms of levonorgestrel-containing contraception. The contraceptive effect of the LNG IUS is achieved mainly through its local suppressive effect on the endometrium, leading to endometrial thinning, glandular atrophy, and stromal decidualization without affecting ovulation. The LNG IUS is generally well tolerated. The main side effects are related to its androgenic activity, which is usually mild and transient, resolving after the first few months. Menstrual abnormalities are also common but well tolerated, and even become desirable (eg, amenorrhea, hypomenorrhea, and oligomenorrhea) with proper counseling of the patient during the choice of the method of contraception. The satisfaction rates after 3 years of insertion are high, reaching between 77% and 94%. The local effect of the LNG IUS on the endometrium and low rates of systemic adverse effects have led to its use in other conditions rather than contraception, as for the treatment of endometrial hyperplasia, benign menorrhagia, endometriosis, adenomyosis, and uterine fibroids.

 

 

PLoS One. 2013 Aug 21;8(8):e72284.

Bladder pain syndrome/interstitial cystitis is associated with hyperthyroidism.

Chung SD1Liu SPLin CCLi HCLin HC.

Abstract

BACKGROUND:

Although the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC) is still unclear, a common theme with BPS/IC patients is comorbid disorders which are related to the autonomic nervous system that connects the nervous system to end-organs. Nevertheless, no study to date has reported the association between hyperthyroidism and BPS/IC. In this study, we examined the association of IC/BPS with having previously been diagnosed with hyperthyroidism in Taiwan.

DESIGN:

Data in this study were retrieved from the Longitudinal Health Insurance Database. Our study consisted of 736 female cases with BPS/IC and 2208 randomly selected female controls. We performed a conditional logistic regression to calculate the odds ratio (OR) for having previously been diagnosed with hyperthyroidism between cases and controls.

RESULTS:

Of the 2944 sampled subjects, there was a significant difference in the prevalence of prior hyperthyroidism between cases and controls (3.3% vs. 1.5%, p<0.001). The conditional logistic regression analysis revealed that compared to controls, the OR for prior hyperthyroidism among cases was 2.16 (95% confidence interval (CI): 1.27∼3.66). Furthermore, the OR for prior hyperthyroidism among cases was 2.01 (95% CI: 1.15∼3.53) compared to controls after adjusting for diabetes, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma.

CONCLUSIONS:

Our study results indicated an association between hyperthyroidism and BPS/IC. We suggest that clinicians treating female subjects with hyperthyroidism be alert to urinary complaints in this population.

 

 

Dev Reprod. 2013 Sep;17(3):207-13.

Effect of Pioglitazone on Production of Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES) and IVF Outcomes in Infertile Women with Endometriosis.

Kim CH1Lee YJ1Kim JB1Lee KH1Kwon SK1Ahn JW2Kim SH1Chae HD1Kang BM1.

 

Abstract

This study was performed to investigate the effect of peroxisome proliferators activated receptor-γ (PPAR-γ) ligand, pioglitazone, on production of regulated upon activation normal T-cell expressed and secreted (RANTES) and in vitro fertilization (IVF) outcome in infertile patients with endometriosis. Sixty-four infertile patients with stage III or IV endometriosis undergoing IVF were randomly allocated to the study or the control group. The long protocol of GnRH agonist (GnRH-a) was used for controlled ovarian stimulation (COS) in all patients. Patients in the study group were treated with pioglitazone at a dose of 15 mg/day orally from the starting day of GnRH-a treatment to the day of hCG injection. Blood samples were drawn for serologic assay of RANTES on the first day of GnRH-a treatment and the day of hCG injection. There were no differences between the study and control groups in patient characteristics. There were also no differences between the two groups in COS duration, and the numbers of retrieved oocytes, fertilized oocytes and embryos transferred. The clinical pregnancy rate per cycle was higher in the study group, but this difference was not statistically significant. However, embryo implantation rate was significantly higher in the study group of 12.5% compared with 8.6% in the control group (P<0.05). The serum RANTES levels after pioglitazone treatment were significantly lower than those before pioglitazone treatmen in the study group (P<0.05). Our data suggest that pioglitazone treatment can suppress RANTES production and improve the embryo implantation rate in patients with endometriosis undergoing IVF.

 

 

J Med Assoc Thai. 2013 Aug;96(8):881-7.

Estrogen plus progestin versus estrogen after definitive surgery for endometriosis: a study of pain recurrence.

Cheewadhanaraks S1Choksuchat CWattanakumtornkul S.

Abstract

OBJECTIVE:

To compare the cumulative recurrence rate of endometriosis-associated pain in women receiving estrogen plus progestin and in those using estrogen following definitive surgery for endometriosis.

MATERIAL AND METHOD:

A prospective cohort study was conducted in a university hospital. Consecutive premenopausal women with symptomatic endometriosis received hormone therapy following definitive surgery. Before November 2008 conjugated equine estrogen 0.625 mg per day was used in all patients. After that time, all patients received conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg per day. Patients came for a follow-up visit every six months to ascertain if they had any recurrent pain.

RESULTS:

The cumulative recurrence rates of pain at months 12, 24 and 36 were 0%, 2.9% and 2.9%, respectively in the estrogen plus progestin group (n = 68) and 4.4%, 6.0% and 8.2%, respectively in the estrogen group (n = 93). No significant difference in cumulative recurrence rates of pain between the two groups was observed. It could not be demonstrated that the hormone regimen was an independent risk factor of recurrence of pain.

CONCLUSION:

There was a marginally lower recurrence rate of pain in patients receiving estrogen plus progestin than in those using estrogen. However, no statistically significant difference was demonstrated.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Oct;170(2):550-4.

Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment.

Nirgianakis K1Bersinger NAMcKinnon BKostov PImboden SMueller MD.

Abstract

OBJECTIVE:

To investigate the effect of gonadotropin-releasing hormone analogues (GnRHa) on the peritoneal fluid microenvironment in women with endometriosis.

STUDY DESIGN:

Peritoneal fluid was collected from 85 women with severe endometriosis (rAFS stage III and IV) during laparoscopic surgery during the proliferative phase. Prior to surgery clinical data were collected. The concentrations of specific markers for endometriosis in the peritoneal fluid were determined using an ELISA and a comparison between peritoneal fluid markers in women using GnRHa and no hormonal treatment was performed using a non-parametric Mann-Whitney U test.

RESULTS:

The study included peritoneal fluid from 39 patients who had been administered GnRHa (Zoladex(®)) in the three months prior to surgery and 46 from women with no hormonal treatment in this period. Concentrations of IL-8, PAPP-A, glycodelin-A and midkine were significantly reduced in the GnRHa treatment group compared to women receiving no hormonal treatment. RANTES, MCP-1, ENA-78, TNF-α, OPG, IP-10 and defensin showed no significant change between the two groups.

CONCLUSIONS:

GnRHa mediate a significant regression in the inflammatory nature of the peritoneal microenvironment in women with endometriosis.

 

 

 

Fertil Steril. 2013 Nov;100(5):1459-67.

Vascular disrupting effects of combretastatin A4 phosphate on murine endometriotic lesions.

Feng D1Menger MDLaschke MW.

Abstract

OBJECTIVE:

To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.

DESIGN:

Intravital microscopic, histologic, and immunohistochemical study.

SETTING:

University institute.

ANIMAL(S):

BALB/c mice.

INTERVENTION(S):

Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle.

MAIN OUTCOME MEASURE(S):

Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry.

RESULT(S):

All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls.

CONCLUSION(S):

This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.

 

 

Reprod Toxicol. 2013 Dec;42:116-24.

Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF.

Singh AK1Chattopadhyay RChakravarty BChaudhury K.

 

Abstract

Oxidative stress and trace elements in the oocytes environment is explored in endometriosis and impact on in vitro fertilization (IVF) outcome assessed. Follicular fluid was aspirated at the time of oocyte retrieval from endometriosis (n=200) and tubal infertility (n=140) and the analytes measured using spectroscopy and HPLC. Increased concentration of reactive oxygen species (ROS), nitric oxide (NO), lipid peroxidation (LPO), iron, lead, cadmium and reduced levels of total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), vitamins A, C, E, copper, zinc and selenium was observed compared to tubal infertility. Increased ROS and NO in endometriosis and tubal infertility associated with poor oocytes and embryo quality. Increased levels of ROS, NO, LPO, cadmium and lead were observed in women who did not become pregnant compared to women who did. Intrafollicular zinc levels were higher in women with endometriosis who subsequently became pregnant following IVF.

 

 

Orv Hetil. 2013 Sep 8;154(36):1426-34.

The impact of endometriosis on the quality of life in Hungary.

Bokor A1Koszorús EBrodszky VD’Hooghe TWERF EndoCost ConsortiumRigó J.

Abstract

in EnglishHungarianHungarian

INTRODUCTION:

Endometriosis is one of the most common gynaecological diseases affecting 70 million women worldwide.

AIM:

The aims of this study were to determinate the diagnostic delay of endometriosis, to assess the effectiveness of surgical and combined therapy and to analyse the quality of life of women suffering from this disease.

METHOD:

Of the 240 patients with endometriosis enrolled in the study, 84 patients filled in a prospective as well as a retrospective questionnaire.

RESULTS:

There was a 3.9 year delay from the onset of symptoms to the definitive diagnosis. Before therapy, 89% of the patients reported endometriosis related pain, while after therapy only 28% in the prospectively investigated months (p = 0.025). There was no significant difference between the outcome of surgical treatment alone and combined operative and medical therapy (p = 0.85). Reduced productivity at work was present in 47% of the patients and 40% of the patients reported impaired personal relationship, too. Endometriosis-associated symptoms generated 0.147 quality-adjusted life years per woman.

CONCLUSIONS:

This study is the first ever prospective survey to investigate the impact of endometriosis on the quality of life in Hungary. The results indicated a long diagnostic delay. Both surgical and combined therapies proved to be efficient. Endometriosis impaired health-related quality of life, but adequate therapy attenuated the severity of symptoms.

 

Gynecol Endocrinol. 2014 Jan;30(1):7-15.

Towards an understanding of the molecular mechanism of endometriosis: unbalancing epithelial-stromal genetic conflict.

Kobayashi H1Uekuri CShigetomi H.

Abstract

OBJECTIVES:

Despite the high incidence of endometriosis, the etiology is poorly understood. Much work has been carried out to elucidate the genetic basis of endometriosis owing to the advent of genomic analysis and new network-based analysis methods.

METHODS:

This article reviews the English literature for (epi)genome-wide profiling and association studies on the pathogenesis and pathophysiology of endometriosis.

RESULTS:

The characteristic 82 up- and 45 down-regulated unique genes in endometriosis included genes encoding cell cycle, growth factors, signal transduction, transcription factors, hormones, cytokines, chemokines and (pro)inflammation, proteases, cell adhesion and motility, stress response and detoxification, immune response, metabolism and others. There appear to be at least two types of genes: some genes (n = 50) may evolve mainly for the benefit of the endometrial growth, and the other genes (n = 55) evolve as a protective mechanism for the endometrial decidualization. The present review has shed new light on the overlapping genetic signatures between endometriosis development and decidualization process.

CONCLUSION:

In conclusion, insufficient decidualization due to unbalancing epithelial-stromal genetic conflict may result in future endometriosis.

 

 

Gynecol Endocrinol. 2013 Dec;29(12):1071-4.

Attitudes, knowledge and prescribing habits of Brazilian gynecologists regarding extended-cycle oral contraceptives.

Pompei LM1Fernandes CESteiner MLStrufaldi RMelo NR.

 

Abstract

Extended-cycle and continuous use combined oral contraceptives (COC) have been widely investigated; however, gynecologists’ prescribing habits are largely unknown. This study evaluated the opinions and prescribing habits of Brazilian gynecologists regarding extended/continuous COC. Gynecologists caring for reproductive-age women and used to prescribing COC were recruited to an online survey. Overall, 1097 physicians were included. Of these, 93.0% stated that patients requested extended/continuous COC, with 93.9% of the physicians having already prescribed these regimens at least once. Only 67 physicians reported never having prescribed extended/continuous COC. The most common reasons for prescribing extended/continuous COC were “dysmenorrhea”, “endometriosis” and “convenience of menstrual suppression”. Physicians reported prescribing extended/continuous regimens for 20.7 ± 17.2% of their patients with an indication for COC, postgraduate degree holders being more likely to prescribe extended/continuous regimens than physicians without postgraduate degree (23.6 ± 19.1% versus 20.0 ± 16.7%; p = 0.014). In conclusion, the vast majority of gynecologists prescribe extended/continuous COC. Women often request information from their doctors on the subject. “Convenience of menstrual suppression” is a common reason given for prescribing extended/continuous COC. According to the physicians, the great majority of extended/continuous COC users are satisfied or very satisfied with the regimen prescribed.

 

 

Gynecol Endocrinol. 2013 Nov;29(11):978-81.

Factors associated with the laterality of recurrent endometriomas after conservative surgery.

Lee DY1Kim HJYoon BKChoi D.

 

Abstract

We evaluated the laterality of primary endometrioma and characteristics of patients according to the laterality of recurrent endometrioma in 140 women with recurrent endometrioma after conservative surgery. Histologically confirmed recurrent endometriomas were found on the left side in 49 patients (35.0%), the right in 44 (31.4%) and bilaterally in 47 (33.6%). The sites of primary endometrioma were not associated with those of recurrent endometrioma, and the recurrence rate in the treated ovary (59.8%) was similar to that of the intact ovary (69.0%) at the primary surgery. Proportions of stage IV endometriosis and posterior cul-de-sac obliteration were higher in patients with bilateral recurrence than in those with unilateral recurrence (p < 0.01 for all comparisons) and in patients with contralateral recurrence than in those with ipsilateral recurrence (p < 0.05 for all comparisons), but no differences were found in other characteristics of participants according to the laterality or pattern of recurrence. In conclusion, the lateral distribution of recurrent endometrioma was not associated with that of the primary lesion, and endometrioma did not recur more frequently in the treated ovary. An advanced stage and the presence of posterior cul-de-sac obliteration were factors associated with bilateral or contralateral recurrence of endometrioma.

 

Gynecol Endocrinol. 2013 Dec;29(12):1026-30.

Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis.

Niu Z1Chen QSun YFeng Y.

 

Abstract

Some studies have shown that long-term gonadotropin-releasing hormone (GnRH) agonist administration before in vitro fertilization/intracytoplasmic sperm in infertile women with endometriosis or adenomyosis significantly increases the chances of pregnancy. We were interested in whether long-term GnRH agonist pretreatment could improve pregnancy outcomes in adenomyosis patients undergoing frozen embryo transfer (FET) after preparation of the endometrium with hormone replacement therapy (HRT). Totally, 339 patients with adenomyosis were included in this retrospective study, 194 received long-term GnRH agonist plus HRT (down-regulation + HRT) and 145 received HRT. There were no differences between the groups in characteristic such as age, body mass index, duration or cause of infertility, serum CA-125 level and basal hormone levels. On the day of progesterone administration, mean endometrial thickness and serum progesterone level were significantly greater in HRT patients. Mean score and number of embryos transferred showed no differences. In down regulation + HRT group, clinical pregnancy, implantation and ongoing pregnancy rates were 51.35%, 32.56% and 48.91%, respectively, significantly higher than that of HRT group (24.83%, 16.07% and 21.38%, respectively). So, we concluded that in FET, long-term GnRH agonist pretreatment significantly improved pregnancy outcomes in patients with adenomyosis.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Nov;171(1):132-7.

Complete loss of unilateral renal function secondary to endometriosis: a report of three cases.

Arrieta Bretón S1López Carrasco AHernández Gutiérrez ARodríguez González Rde Santiago García J.

Abstract

OBJECTIVES:

To report the impact that urinary tract endometriosis may have on renal function. Ureteral endometriosis is an uncommon and silent cause of renal injury. It is therefore very important to be highly suspicious in order to be able to make an early diagnosis and thus prevent renal failure.

STUDY DESIGN:

Case reports of the management and outcome of three cases of premenopausal women with deep endometriosis affecting the ureter, associated with secondary unilateral complete loss of renal function.

RESULTS AND CONCLUSIONS:

Ureteral involvement by endometriosis is a rare and often silent disease which is capable of producing significant morbidity, as it can lead to hydronephrosis and ultimately to renal failure. Because of the lack of specific symptoms and the limitations of imaging methods, a high index of suspicion is necessary to obtain an early diagnosis. On diagnosis of deep infiltrating endometriosis, urinary tract ultrasound is a screening tool to detect ureterohydronephrosis due to ureteral obstruction. MRI is of value to map the extent of disease. Surgery is the treatment of choice to remove endometriotic lesions and relieve ureteral obstruction if the kidney is still functional, or to perform a nephrectomy if there is a complete loss of renal function.

 

 

 

Acta Obstet Gynecol Scand. 2014 Jan;93(1):20-31.

The relation between endometriosis and ovarian cancer – a review.

Heidemann LN1Hartwell DHeidemann CHJochumsen KM.

Abstract

BACKGROUND:

Endometriosis is known to harbor characteristics substantiating its possible role as a precursor of ovarian cancer.

OBJECTIVE:

To assess the quality of the literature regarding the association between endometriosis and ovarian cancer and to estimate the extent of this relation.

METHODS:

An electronic literature search was conducted in PubMed and 1112 articles dealing with the relation between endometriosis and ovarian cancer were identified. Original articles based on case-control studies, cohort studies and cross-sectional studies were included. Studies consisting of populations with self-reported endometriosis were excluded, as were articles with fewer than 20 cases of ovarian cancer. Twenty-eight studies underwent detailed quality assessments based on the checklists developed by the Scottish Intercollegiate Guidelines Network (SIGN). Meta-analyses were conducted on selected subgroups of ovarian cancer with coexisting endometriosis.

RESULTS:

None of the 28 studies was given the highest possible rating using the SIGN checklists. The risk of ovarian cancer in women with endometriosis was reported to be a standardized incidence ratio of 1.43-8.95, a rate ratio of 1.6-2.88, an odds ratio of 1.34, with a prevalence of ovarian cancer in 2.0-17.0% of women with endometriosis. Conversely, the prevalence of endometriosis in women with ovarian cancer ranged from 3.4 to 52.6%. Meta-analysis results were weakened by heterogeneity.

CONCLUSION:

There is sufficient evidence to conclude that there is an increased risk of developing clear-cell and endometrioid epithelial ovarian cancer for women with histologically verified endometriosis. Nonetheless, prospective cohort studies assessing the relation between endometriosis and ovarian cancer will increase knowledge in this field.

 

 

Fertil Steril. 2013 Dec;100(6):1642-9.

Differential expression of steroidogenic enzymes according to endometriosistype.

Colette S1Defrère SVan Kerk OVan Langendonckt ADolmans MMDonnez J.

Abstract

OBJECTIVE:

To evaluate, in peritoneal, ovarian, and rectovaginal endometriotic lesions, expression of steroidogenic enzymes involved in the activation and inactivation of estrogens: 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) and 2 (HSD17B2), estrone sulfotransferase (EST), and steroid sulfatase (STS).

SETTING:

Academic gynecology research unit.

DESIGN:

Retrospective study.

PATIENT(S):

Disease-free (n = 41) patients and patients with endometriosis (n = 79) were included for quantitative polymerase chain reaction (q-PCR) (15 disease-free, 33 endometriosis) and immunohistochemistry (26 disease-free, 46 endometriosis) studies.

INTERVENTION(S):

Q-PCR and immunohistochemistry.

MAIN OUTCOME MEASURE(S):

Evaluation of mRNA and protein expression.

RESULT(S):

Glandular HSD17B1, HSD17B2, and STS protein expression were demonstrated. HSD17B2 mRNA values were higher in the secretory phase of the menstrual cycle in the endometrium of disease-free women, but not in the eutopic endometrium of patients with endometriosis. HSD17B1 mRNA was equally expressed in the various tissues investigated, and EST mRNA was expressed at low levels in the different lesion types. HSD17B2 mRNA expression was decreased in ovarian and rectovaginal endometriosis compared with eutopic endometrium, while STS mRNA was increased in rectovaginal lesions compared with ovarian lesions. Ratios between pro- and antiestrogenic enzymes (STS/EST and HSD17B1/HSD17B2) were more in favor of estrogens in ovarian and rectovaginal endometriosis.

CONCLUSION(S):

In endometriosis development, local activation of estrogens appears to be important. STS and HSD17B1 inhibitors may therefore prove useful to treat the disease.

 

 

Fertil Steril. 2013 Nov;100(5):1476-85.

A tumor necrosis factor-α inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid.

Chen YJ1Wu HHLiau WTTsai CYTsai HWChao KCSung YJLi HY.

Abstract

OBJECTIVE:

To determine whether a tumor necrosis factor-α (TNF-α) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis.

DESIGN:

Experimental clinical study.

SETTING:

University hospital.

PATIENT(S):

Twelve women with chocolate cysts and 12 control women without endometriosis.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-α inhibitor.

RESULT(S):

We found that CH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-α, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-α retarded development and induced apoptosis. Important, adalimumab, a TNF-α inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF.

CONCLUSION(S):

These data collectively highlight the crucial role of TNF-α in CH-PF-induced embryotoxicity and suggest that TNF-α inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility.

 

 

Clin Imaging. 2013 Nov-Dec;37(6):1061-8.

Multislice computed tomography with colon water distension (MSCT-c) in the study of intestinal and ureteral endometriosis.

Iosca S1Lumia DBracchi EDuka EDe Bon MLekaj MUccella SGhezzi FFugazzola C.

 

Abstract

This study evaluates retrospectively the accuracy and reproducibility of multislice computed tomography with colon water distension (MSCT-c) in diagnosing bowel (BE) and ureteral (UE) endometriosis. Sixty-four patients underwent MSCT-c and videolaparoscopic surgery. Two radiologists reviewed MSCT-c examinations: sensitivity and specificity were calculated, considering histological exam as reference standard. In the BE cases, the degree of bowel wall infiltration was also assessed. Sensitivity and specificity for both readers were 100% and 97.6% for BE and 72.2% and 100% for UE; the interobserver agreement was excellent. The degree of bowel wall involvement was correctly defined in 90.9% of cases. MSCT-c is an accurate and reproducible technique but-considering the age of the patients-delivers a nonnegligible radiation dose.

 

 

Clin Chem Lab Med. 2013 Sep;51(9):1815-24.

Cancer antigen 125, human epididymis 4, kallikrein 6, osteopontin and soluble mesothelin-related peptide immunocomplexed with immunoglobulin M in epithelial ovarian cancer diagnosis.

Bandiera EZanotti LFabricio ASBucca ESquarcina ERomani CTassi RBignotti ETodeschini PTognon GRomagnolo CGion MSartori EMaggino TPecorelli SRavaggi A.

Abstract

BACKGROUND:

Human epididymis protein 4 (HE4), kallikrein 6 (KLK6), osteopontin (OPN) and soluble mesothelin-related peptide (SMRP) are new promising biomarkers that could integrate CA125 in epithelial ovarian cancer (EOC) diagnosis. The autoantibody response to tumor antigens is a potential tool for improving the diagnostic performances of biomarkers. The aim of this study was to assess the diagnostic potential of these biomarkers in the form of free markers and immunocomplexed with immunoglobulin M (IgM). Moreover, we analyzed the association between these markers and clinico-pathological characteristics of EOC patients.

METHODS:

Serum and plasma samples of 60 healthy controls, 60 ovarian benign cysts, 60 endometriosis and 60 EOCs, collected before any treatment, were tested for CICs and free antigens by immunoassays.

RESULTS:

Immunocomplexes were characterized by poor sensitivity and specificity, since they allowed the detection only of a small number of EOC patients and were increased in patients with benign gynecological pathologies. However, the markers in the form of free antigens showed good diagnostic performances. Of note, CA125 and HE4 showed high sensitivity in the detection of the malignancy and HE4 emerged as a useful biomarker in differential diagnosis between EOC and endometriosis. Finally, elevated KLK6 and OPN, were associated with advanced FIGO stage, high grade disease, suboptimally debulked tumor and ascites.

CONCLUSIONS:

This study confirms the diagnostic role of CA125, HE4, KLK6, OPN and SMRP, and for the first time showed that CA125, HE4, KLK6, OPN and SMRP immunocomplexed with IgM are not a potential tool for EOC diagnosis.

 

 

J Assist Reprod Genet. 2013 Nov;30(11):1445-50.

Live birth rates and birth outcomes by diagnosis using linked cycles from the SART CORS database.

Stern JE1Brown MBWantman EKalra SKLuke B.

Abstract

PURPOSE:

This study uses linked cycles of assisted reproductive technology (ART) to examine cumulative live birth rates, birthweight, and length of gestation by diagnostic category.

METHODS:

We studied 145,660 women with 235,985 ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System during 2004-2010. ART cycles were linked to individual women by name, date of birth, social security number, partner’s name, and sequence of ART treatments. The study population included the first four autologous oocyte cycles for women with a single diagnosis of male factor, endometriosis, ovulation disorders, diminished ovarian reserve, or unexplained infertility. Live birth rates were calculated per cycle, per cycle number (1-4), and cumulatively. Birthweight and length of gestation were calculated for singleton births.

RESULTS:

Within each diagnosis, live birth rates were highest in the first cycle and declined with successive cycles. Women with diminished ovarian reserve had the lowest live birth rate (cumulative rate of 28.3 %); the live birth rate for the other diagnoses were very similar (cumulative rates from 62.1 % to 65.7 %). Singleton birthweights and lengths of gestation did not differ substantially across diagnoses, ranging from 3,112 to 3,286 g and 265 to 270 days, respectively. These outcomes were comparable with national averages for singleton births in the United States (3,296 g and 271 days).

CONCLUSION:

Women with the diagnosis of diminished ovarian reserve had substantially lower live birth rates. However, singleton birthweights and lengths of gestation outcomes were similar across all other diagnoses.

 

 

Hum Reprod. 2013 Dec;28(12):3358-69.

Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis.

Buis CC1van Leeuwen FEMooij TMBurger CWOMEGA Project Group.

Abstract

STUDY QUESTION:

Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)?

SUMMARY ANSWER:

We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

WHAT IS KNOWN ALREADY:

There is increasing evidence of an association between endometriosis and increased risk of ovarian cancer. However, most reports were based on self-reported diagnosis of endometriosis.

STUDY DESIGN, SIZE, DURATION:

We conducted a nationwide historic cohort study among women with subfertility problems between 1980 and 1995. For this analysis we selected all cohort members with endometriosis, and a comparison group of subfertile women (male factor or idiopathic) without endometriosis(total cohort of 8904 women). Median follow-up time was 15.2 for the entire study population.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

For this analysis we selected all cohort members with (n = 3657) and without (n = 5247) evidence of endometriosis. Seventy-eight per cent of diagnoses of endometriosiswere confirmed by pathology report, and 22% was self-reported endometriosis (positive predictive value of 73%). We linked the cohort with the Dutch Pathology Database and the Netherlands Cancer Registry to assess the occurrence of ovarian cancer and BOT between January 1989 and June 2007.

MAIN RESULTS AND THE ROLE OF CHANCE:

We observed a substantially increased risk of all ovarian malignancies combined in women with endometriosis when we based the definition of endometriosis on self-report, medical records information at subfertility treatment and/or the nationwide pathology database (hazard ratio (HR) 8.2; 95% confidence interval (CI) 3.1-21.6). The HR associated with endometriosis was 12.4 (95% CI 2.8-54.2) for ovarian cancer and 5.5 (95% CI 1.5-20.2) for BOT. When we excluded information from the pathology database, HRs were 3.0 (95% CI 1.5-6.1) for all ovarian tumours, 4.3 (95% CI 1.6-11.2) for ovarian cancer and 1.9 (95% CI 0.6-5.8) for BOT. Both ovarian and extra-ovarian endometriosis carried a significantly increased risk for ovarian cancer and BOT.

LIMITATIONS, REASONS FOR CAUTION:

We did not have information on oral contraceptive use and parity for 23.4 and 3.4%, of women in the analytic cohort, respectively. Furthermore, a limitation of our study, and also of other studies, is that the date of diagnosis of endometriosis is usually made long after the onset of the disease. Also, the number of cases in the cohort is small (n = 34), resulting in wide CIs.

WIDER IMPLICATIONS OF THE FINDINGS:

The fact that endometriosis was assessed before diagnosis of ovarian malignancy and the high degree of medical confirmation in our study likely contribute to the validity of our estimate of a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis. The risk of ovarian malignancies associated with endometriosis was much higher in analyses including information on endometriosisfrom the nationwide pathology database, implying that risk estimates from studies using self-reported information on endometriosis may be too low due to non-differential misclassification bias.

 

 

J Clin Endocrinol Metab. 2013 Nov;98(11):E1802-6.

Endometrial Intracrinology–generation of an estrogen-dominated microenvironment in the secretory phase of women.

Gibson DA1McInnes KJCritchley HOSaunders PT.

Abstract

CONTEXT:

The human endometrium is a complex multicellular tissue subject to cyclical fluctuations in ovarian-derived steroid hormones. Fertile cycles are characterized by differentiation (decidualization) of endometrial stromal cells (ESC).

OBJECTIVE:

To determine the impact of human stromal cell decidualization on biosynthesis and secretion of estrogens.

DESIGN:

Primary cell culture was used. Cells were decidualized in vitro. Some cultures were treated with an aromatase inhibitor.

SETTING:

A University Research Institute.

PATIENTS:

Primary ESC were derived from women with normal menstrual cycles (n = 12). None of the women were receiving hormonal therapy or suffering from endometriosis.

MAIN OUTCOME MEASUREMENTS:

Expression of mRNA and protein encoded by the aromatase (CYP19A1) and 3-β-hydroxysteroid dehydrogenase (HSD3B1) genes was assessed. Aromatase activity was measured using a tritiated water assay; steroid metabolism was determined using thin layer chromatography. Estrone (E1) and estradiol (E2) in cell culture media were measured by ELISA.

RESULTS:

Decidualization induced a two-fold increase in aromatase mRNA. Aromatase protein was only detected in decidualized ESC. 3-β-Hydroxysteroid dehydrogenase protein was present in ESC both before and after decidualization; concentrations appeared unchanged. The existence of functional aromatase in decidualized ESC was confirmed; E1 and E2 were secreted into culture media in decidualized ESC and concentrations were reduced when cells were incubated with an aromatase inhibitor. Decidualization resulted in reduced metabolism of E2 and an increase in the ratio of E2:E1.

CONCLUSIONS:

Decidualization is characterized by an increase in aromatase expression/activity favoring the generation of an E2-dominated estrogen microenvironment within the endometrial stroma.

 

 

Acta Obstet Gynecol Scand. 2013 Dec;92(12):1375-82.

Quality of life in patients with endometriosis and the effect of pertubation with lidocaine – a randomized controlled trial.

Wickström K1Bruse CSjösten ASpira JEdelstam G.

Abstract

OBJECTIVE:

Pertubation with lidocaine has been shown to reduce pain (on a VAS-scale) in women with endometriosis. A clinical study was performed to evaluate the effect of lidocaine pertubations on quality of life.

DESIGN:

Double-blind, randomized and controlled trial.

SETTING:

Three outpatient units in Stockholm, Sweden.

POPULATION:

Eligible patients had endometriosis with dysmenorrhoic pain >VAS 50 mm.

METHODS:

The patients were randomized to pre-ovulatory pertubations with lidocaine (n = 24) or placebo (n = 18) during three consecutive menstrual cycles. The procedure comprised passing the solution through the uterus and the Fallopian tubes via an intracervical balloon catheter. The effect was evaluated with the validated Endometriosis Health Profile-30 questionnaire before and after treatments.

MAIN OUTCOME MEASURES:

Changes in scores at six and 12 months from baseline were compared between the groups with the Mann-Whitney U-test.

RESULTS:

After 6 months there was a significant difference between the lidocaine (n = 19) and the placebo (n = 16) groups for the dimension social support (median -18.8 vs. -6.3, p = 0.034), whereas there were no significant differences for the other dimensions after 6 or 12 months. The mean changes in the lidocaine group were above the minimal important difference levels in eight of 12 measurements of quality of life dimensions compared with two of 12 in the placebo group.

CONCLUSIONS:

This clinical trial indicates that pertubations with lidocaine might improve the social support dimension of quality of life in patients with endometriosis.

 

 

Zhonghua Fu Chan Ke Za Zhi. 2013 May;48(5):338-43.

A meta-analysis of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues with add-back therapy.

[Article in Chinese]

Niu ZR1Yue XJKong QYWang YFYao YQ.

Abstract

OBJECTIVE:

To evaluate the role and efficacy of preventing bone mineral loss in patients with endometriosistreated by gonadotrophin-releasing hormone analogues (GnRH-a) combined with add-back therapy.

METHODS:

Prospective, randomized controlled studies of the use of GnRHa with add-back therapy in treatment of endometriosis were enrolled in this study from Medline, Embase, Cochrane library, China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM) and Data Base of Wanfang.After quality assessment and data extraction, meta-analysis were conducted in the change of BMD, reproductive hormone (E2) and visual pain score(VAS) by Stata 11.0 software.

RESULTS:

A total of 785 patients from 13 randomized controlled trail (RCT) studies enrolled in this study after exclude no following up, poor quality and repeat published studies.377 patients were in group of GnRH-a with add-back treatment and 408 patients were in group of GnRna alone.The findinds were showed in meta-analysis: (1) there was a significant difference in percentage change of bone mineral density (BMD) between two groups, the add-back therapy was more effective in prevention of bone loss which was (SMD = 0.223, 95%CI:0.003 to 0.443, P = 0.047). (2) There was no significant difference in the level of reproductive hormone between two groups (SMD = -0.053, 95% CI:-0.479 to 0.373, P = 0.807). (3) There was also no significant difference in the visual pain score between the two groups (SMD = -0.157, 95% CI: -0.474 to 0.160, P = 0.332).

CONCLUSIONS:

GnRH-a with add-back therapy have been shown to be more effective in preventing loss of BMD than GnRH-a treatment alone.However, the long term effect of preventing BMD should be studied.

 

 

Eur J Radiol. 2013 Dec;82(12):2183-8.

Correlation between MRI and double-balloon urethrography findings in the diagnosis of female periurethral lesions.

Portnoy O1Kitrey NEshed IApter SAmitai MMGolomb J.

 

Abstract

This study aims to evaluate the correlation of MRI findings with double-balloon urethrography (DBU) in diagnosing female urethral diverticula and other periurethral lesions. In this retrospective study, females with clinically suspected periurethral lesions who underwent both MRI and DBU between 2008 and 2012 were evaluated. MRI was performed on a 1.5 Tesla unit using a pelvic phased array coil. Protocol included small FOV pelvic images, multiplanar T2-w, T1-w with and without contrast injection. DBU was performed by a dedicated catheter. Images were evaluated in consensus by two readers. Diverticula were evaluated by, size, number, complexity, location and connection to urethra, and other periurethral lesions were evaluated by size, location and connection. Supplement clinical and surgical data were retrieved from medical records and telephone interviews. Seventeen females (mean age 44 years, range 20-69) were included in the study. Diverticula were diagnosed by both modalities (9 cases), by neither (6 cases, 88% correlation) by MRI alone (1 case) and by DBU alone (1 case). Among diverticula, correlation of number, complexity, location and demonstration of connection to urethra was 89%, 67%, 67%, and 56%, respectively. Alternative diagnosis solely by MRI included vaginal wall cysts (3 cases), endometriosis (1 case) and ectopic ureter (1 case). No periurethral lesion was found by either modality in 2 cases. The correlation between MRI and DBU in diagnosing female periurethral lesions is very good for anatomical delineation of diverticula. MRI, which does not involve radiation, may also indicate alternative diagnoses that can contribute to proper patient management.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Nov;171(1):146-9.

Long-term follow-up after ureteral reimplantation in patients with severe deep infiltrating endometriosis.

Schonman R1Dotan ZWeintraub AYGoldenberg MSeidman DSSchiff ESoriano D.

Abstract

OBJECTIVE:

To investigate the intraoperative features and long-term postoperative results of patients with ureteral endometriosis who underwent ureteral reimplantation.

STUDY DESIGN:

In this retrospective study, we reviewed records of all patients with ureteral endometriosistreated by ureteral reimplantation. Pre-, intra- and post-operative information was collected.

RESULTS:

Of patients operated for endometriosis, seven were diagnosed with severe ureteral endometriosis and underwent ureteral reimplantation. Psoas hitch was the preferred technique for the ureteral reimplantation. During a mean postoperative follow up of 42.3 ± 20.0 months, all but one patient reported significant symptomatic improvement. None of the patients needed additional medical or surgical treatment and no recurrence was noted.

CONCLUSION:

Ureteral reimplantation performed by a multidisciplinary surgical team is a suitable technique in selected cases, gives good long-term results and has no need for repeated surgical treatment.

 

 

 

Biosci Biotechnol Biochem. 2013;77(9):1879-81.

Effects of Lactobacillus gasseri OLL2809 on the induced endometriosis in rats.

Uchida M1Kobayashi O.

 

Abstract

We have reported an inhibitory effect of Lactobacillus gasseri OLL2809 (OLL2809) on the growth of mouse endometrial tissue in the abdominal cavity. The present study aimed to investigate the efficacy of Lactobacillus gasseri OLL2809 (OLL2809) on pre-existing endometriosis implanted on the abdominal wall in diestrus Wistar-Imamichi female rats. One week after implantation, the volume of the endometrial tissue was measured after laparotomy. OLL2809 and dienogest were administered for 4 weeks. OLL2809 significantly enhanced the decrease in the volume (p<0.01) as compared with control. Complete healing was observed in two of nine rats, but in none of the control group. Dienogest did not show significant efficacy. These findings suggest that OLL2809 is useful not only in therapy of pre-existing endometriosis but also in the prevention of the growth of endometrial tissue.

 

 

Pathology. 2013 Oct;45(6):559-66.

Immunophenotypic analysis of ovarian endometrioid adenocarcinoma: correlation with KRAS mutation and the presence of endometriosis.

Stewart CJ1Walsh MDBudgeon CACrook MLBuchanan DB.

Abstract

AIMS:

The relationship between endometriosis and ovarian endometrioid adenocarcinoma (OEC) is well recognised but it is unclear whether endometriosis positive and negative OECs develop via similar pathogenetic mechanisms.

MATERIALS:

Sixty-seven low grade OECs (35 associated with endometriosis) were stained immunohistochemically for β-catenin, cyclin D1, BAF250a, PTEN, p53, WT1 and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6. The results were correlated with KRAS mutation analysis and the presence of concurrent endometriosis.

RESULTS:

Abnormal β-catenin, cyclin D1, BAF250a, PTEN, p53 and MMR protein expression was identified in 61.2%, 50.7%, 19.4%, 23.9%, 9.0%, and 6.0% of cases, respectively; these changes were equally common in endometriosis positive and negative tumours. WT1 expression was restricted to endometriosis negative EOC (8/32, 25%) and four WT1 positive cases showed sertoliform/spindle cell histological patterns. Abnormal β-catenin expression correlated with cyclin D1 overexpression but was inversely related to KRAS mutation. Immunophenotypic abnormalities were present in four of 17 histologically benign endometriotic lesions.

CONCLUSIONS:

Most immunophenotypic alterations were equally common in endometriosis associated and independent OECs but only the latter were associated with abnormal WT1 expression. The inverse relationship between abnormal β-catenin expression and KRAS mutation merits further study. Histologically benign endometriotic epithelium may show immunophenotypic abnormalities similar to those present in associated carcinomas.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Oct;170(2):419-22.

Expression of integrin β3 and osteopontin in the eutopic endometrium of adenomyosis during the implantation window.

Xiao Y1Li TXia EYang XSun XZhou Y.

Abstract

OBJECTIVE:

To investigate the expression of integrin β3 and osteopontin (OPN) in the eutopic endometrium of adenomyosis and to characterize possible endometrial defects in adenomyosis.

STUDY DESIGN:

Twenty-eight adenomyosis patients and 27 control fertile women were involved in this study. Endometrial samples were collected during the implantation window. Integrin β3 subunits and OPN in the adenomyosis and control endometria were assessed by immunohistochemical staining and quantitative real-time polymerase chain reaction. A one-tailed t-test and a non-parametric Mann-Whitney U-test were used to test significance.

RESULTS:

The mRNA and immunostaining intensity of integrin β3 and OPN were significantly lower in the adenomyosis patients than in the controls.

CONCLUSIONS:

Abnormal expression of integrin β3 and OPN in the endometrium of adenomyosis may contribute to infertility in some patients.

 

 

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013 Jul;42(4):461-3.

Research advances on the role of mast cells in pelvic pain of endometriosis.

Zhu L1Zhang X.

 

Abstract

Endometriosis (EMs) is a common gynecologic disease that affects women’s physical and mental health seriously. The pathogenesis is still unknown and the mechanism of endometriosis-associated pain remains unclear. Mast cells (MC) are known to be multifunctional players in the immune system. Recent studies have shown that nerve fibers in EMs lesions can release neural peptides such as nerve growth factor and substance P to induce MC degranulating and releasing histamine, proteases, cytokines, chemokines etc., which contributes to the development of pain and hyperalgesia in patients with endometriosis.

 

 

Reprod Sci. 2014 Apr;21(4):526-31.

Is a positive family history of endometriosis a risk factor for endometrioma recurrence after laparoscopic surgery?

Campo S1Campo VGambadauro P.

 

Abstract

A total of 148 patients were followed up for an average of 30.1 ± 17 months following to laparoscopic excision of ovarian endometriomas by a single surgical team. Bivariate and multivariate analyses were used to investigate the association between endometrioma recurrence and several factors, age, body mass index, family history, cyst diameter, number and location, adhesions or peritoneal implants, occurrence of spillage, postoperative treatment with gonadotropin-releasing hormone agonist, or pregnancies. The overall recurrence rate of the endometriomas was 18.2%. At bivariate analysis, recurrence rate was significantly higher in patients with a positive family history of endometriosis (40% vs 14.8%). Recurrence was also more frequent, albeit nonsignificantly, in patients with a history of dysmenorrhea, intraoperative spillage, and postoperative hormonal suppression. At multivariate analysis with logistic regression, a positive family history of endometriosis was the only variable independently associated with endometrioma recurrence following laparoscopic removal (odds ratio 3.245; 95% confidence interval: 1.090-9.661).

 

 

Eur Radiol. 2014 Feb;24(2):335-43.

Diagnostic confidence analysis in the magnetic resonance imaging of ovarian and deep endometriosis: comparison with surgical results.

Saba L1Sulcis RMelis GBIbba GAlcazar JLPiga MGuerriero S.

Abstract

OBJECTIVE:

To assess the diagnostic confidence of multiple readers in the magnetic resonance imaging (MRI) diagnosis of endometriosis.

METHODS:

Sixty-five patients (mean age 33; range 19-45 years) who had undergone MRI were retrospectively evaluated. Five regions were analysed and the presence of endometriosis was scored on a five-point scale in order to assess the diagnostic confidence. Statistical analysis included receiver operating characteristic (ROC) curve analysis, the Cohen weighted test and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LR+) and negative likelihood ratio (LR-).

RESULTS:

The areas under the curve (AUC) in the detection of ovarian endometrioma were 0.942, 0.893 and 0.883 for readers 1, 2 and 3, respectively; in the uterosacral ligament (USL) AUCs were 0.907, 0.804 and 0.842; in the vaginal fornix (VF) 0.819, 0.733 and 0.69; in the anterior compartment 0.916, 0.833 and 0.873; and in the rectum/sigma/pouch of Douglas (RSD) 0.936, 0.856 and 0.834.

CONCLUSIONS:

Diagnostic confidence of the observers is different according to the region of the nodules of endometriosis and it can be challenging in the VF and for the less experience readers also in the AC and RSD. Moreover the degree of uncertain diagnosis for the less expert readers may reach up to one third of the examinations.

KEY POINTS:

  • Magnetic resonance imaging (MRI) is increasingly used to assess endometriosis• The diagnostic confidence of observers varies according to the location of endometriosis• The diagnosis is more difficult to establish by MRI in some anatomical locations • Specific training should be given concerning those locations that cause difficulty.

 

 

Am J Reprod Immunol. 2013 Dec;70(6):485-96.

Death receptor 6 is epigenetically silenced by histone deacetylation in endometriosis and promotes the pathogenesis of endometriosis.

Kai K1Nasu KKawano YAoyagi YTsukamoto YHijiya NAbe WOkamoto MMoriyama MNarahara H.

Abstract

PROBLEM:

The purpose of this study is to evaluate the involvement of death receptor (DR) 6 in the pathogenesis of endometriosis.

METHODS OF STUDY:

Endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and the eutopic endometrial tissues, respectively. The effect of valproic acid (VPA) on the DR6 expression in ECSCs was examined. The roles of DR6 in NESC proliferation and apoptosis were investigated with DR6 siRNA transfection. The distribution of DR6 protein in ovarian endometriotic tissues and normal proliferative-phase endometrium was examined by immunohistochemistry. The expression of DR6 mRNA and protein in ECSCs and NESCs was also examined.

RESULTS:

Death receptor 6 expression was attenuated in ECSCs and in endometriotic tissues, and its expression was upregulated by VPA stimulation. VPA treatment resulted in an accumulation of acetylated histone H4 in the promoter region of the DR6 gene. DR6 knockdown directed the stimulation of cell proliferation and the resistance to apoptosis in NESCs.

CONCLUSION:

The present findings suggested that DR6 is involved in the pathogenesis of endometriosis by creating the proliferative and anti-apoptotic characteristics of endometriosis. The results also suggest that histone deacetylase inhibitors are promising agents for the treatment of endometriosis.

 

 

Zhonghua Yi Xue Za Zhi. 2013 May 7;93(17):1327-9.

Pelvic retroperitoneal tumors: clinical analysis of 16 cases.

Li XW1Zhao YWang YWang JLZhao YY.

Abstract

OBJECTIVE:

To explore the diagnostic rationales for pelvic retroperitoneal tumors and summarize their therapeutic regimens.

METHODS:

A total of 16 retroperitoneal tumor patients were recruited. And their general information, previous medical history, physical examinations, auxiliary tests, surgical findings and postoperative pathological results were analyzed.

RESULTS:

Two cases were diagnosed through preoperative magnetic resonance imaging (MRI) while others found intraoperatively. Complete tumor resection was performed in all except for one case. Postoperative pathological examinations revealed 10 benign cases. And there was one case of pelvic endometriosis (mild cytologic atypia). Five cases were malignant. The operation duration was 1.45-8.5 hours and peri-operative bleeding volume 50-5000 ml. Among them, 12 patients had heavy adhesion in pelvic cavity, 7 cases underwent operations collaboratively with related departments because of surgical difficulties and vascular injury and bladder rupture occurred in 1 case. During the follow-ups, one case was lost, two patients died from disease recurrence and another one had a postoperative relapse at Month 4. The other 12 cases recovered well and had no recurrence.

CONCLUSION:

Surgery remains a key for retroperitoneal tumors. With a low diagnostic rate, they are often found surprisingly intraoperatively. Because of surgical difficulties and frequent complications, multi-departmental collaboration is necessary. Preoperative correct diagnosis and adequate preoperative preparation are essential. And MRI is an effective auxiliary examination.

 

 

Acta Obstet Gynecol Scand. 2013 Nov;92(11):1331-4.

Hypermethylation of HOXA10 gene in mid-luteal endometrium from women with ovarian endometriomas.

Fambrini M1Sorbi FBussani CCioni RSisti GAndersson KL.

 

Abstract

A decrease in HOXA10 gene expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility. Promoter hypermethylation of HOXA10 is thought to be the leading mechanism for epigenetic gene regulation in patients with endometriosis. In our series we documented significantly higher HOXA10 promoter methylation levels in women with ovarian endometriomas than in healthy controls during the mid-luteal phase. Development of epigenetic-based strategies for non-surgical treatment of infertility related to ovarian endometriomas could be an attractive field of research in the coming years.

 

 

Chin J Physiol. 2013 Oct 31;56(5):263-8.

The joint effect of hOGG1 genotype and smoking habit on endometriosis in Taiwan.

Tsai CW1Ho CYShih LCYing THHsieh YHChen YCChang WSHuang CYPan SBShui HAChen CPWang PSBau DT.

 

Abstract

This study has two aims: [1] to evaluate the association between hOGG1 genotypic polymorphism and endometriosis risk, and [2] to investigate the joint effects of hOGG1 genotype and smoking habit on endometriosis susceptibility in Taiwan. For this purpose, the well-known polymorphic variants of hOGG1, codon 326, was genotyped and analyzed of its association with the risk of endometriosis. In total, 153 patients with endometriosis and 636 non-endometriosis healthy controls were recruited and genotyped. The methodology for genotyping is polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Pearson’s Chi-square test was performed to compare the distributions of the genotypes between case and control groups. The results showed that the hOGG1 codon 326 genotypes were not differently distributed between the endometriosisand non-endometriosis control groups in both genotypic (P = 0.6212) and allelic (P = 0.4006) frequency analysis. We have further analyzed the genotypic-smoking joint effects on endometriosis risk and found an obvious interaction between hOGG1 codon 326 genotypes and smoking status. The hOGG1 codon 326 genotypes were increased in endometriosis risk only in the smoker groups (P = 0.0061), but not in the non-chewer group (P = 0.0648). Our results provide the evidence that the hOGG1 codon 326 genotype may have a joint effect with smoking on the development of endometriosis.

 

 

Aust N Z J Obstet Gynaecol. 2014 Feb;54(1):13-9.

Establishment of lipiodol as a fertility treatment – prospective study of the complete innovative treatment data set.

Court KA1Dare AJWeston-Webb MHadden WESim RGJohnson NP.

Abstract

BACKGROUND:

Our randomised controlled trial (RCT) found that a hysterosalpingogram (HSG) with the oil-soluble contrast medium (OSCM) lipiodol improves pregnancy rates amongst couples with unexplained and endometriosis-related infertility. These results were supported by the findings of our observational study of the first 100 women to undergo the procedure after it was offered as an innovative treatment in New Zealand from September 2003.

AIM:

To further assess the safety and efficacy of lipiodol procedures and present together the complete data set of the procedures performed in our RCT and those performed as innovative procedures (n = 296) prior to it being offered as a standard fertility treatment.

METHODS:

Women with infertility underwent a therapeutic lipiodol procedure by HSG technique with fluoroscopy X-ray screening. Primary outcomes were clinical pregnancy within six months of the procedure and live birth.

RESULTS:

The overall pregnancy rate for the 296 women was 40.2%. The live birth/ongoing pregnancy rate was 31.4%. The pregnancy rates for women under the age of 40 with endometriosis and unexplained infertility were 51.1 and 31.4%, respectively.

CONCLUSION:

Lipiodol can now be considered a standard treatment for both unexplained and endometriosis-related infertility. The precise mechanism behind the fertility-enhancing effect of lipiodol has yet to be elucidated. This study supports a mechanism of effect on the endometrium with possible enhanced receptivity of the endometrium to embryo implantation.

 

 

 

 

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