Gynecol Obstet Invest. 2015;79(1):34-9.

Pregnancy rate in endometriosis patients according to the severity of the disease after using a combined approach of laparoscopy, GnRH agonist treatment and in vitro fertilization.

Sõritsa D¹, Saare M, Laisk-Podar T, Peters M, Sõritsa A, Matt K, Karro H, Salumets A.

 

Abstract

AIM:

To evaluate the effects of combined treatment approaches on endometriosis-associated infertility in different stages of endometriosis using laparoscopy, gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and in vitro fertilization (IVF).

METHODS:

This retrospective study was carried out on 179 women with surgically confirmed endometriosis. Patients were divided into subgroups: group 1 (stage I-II, n = 121) and group 2 (stage III-IV, n = 58). Patients eligible for IVF, who were found to have adenomyosis or moderate to severe endometriosis, were also given postoperative GnRHa. Pregnancy and delivery rates were cumulatively calculated during 5 years according to the severity of the disease.

RESULTS:

The overall pregnancy, delivery and miscarriage rates were 66.5, 56.4 and 15.1%, respectively, for all patients following spontaneous and assisted conception. There were no significant differences in reproductive outcomes between the study groups. The pregnancy and delivery rates were also comparable within group 1 between the patients with and without GnRHa treatment.

CONCLUSION:

Pregnancy and delivery rates at different stages of endometriosis were not affected by the different approaches used for infertility treatment, with >60 and >50% of patients having conceived and delivered a baby, respectively, in both groups. The usefulness of GnRHa treatment for endometriosis patients with minimal to mild forms is questionable and deserves further studies.

 

Pain. 2014 Dec;155(12):2680-6.

Role of nociceptor estrogen receptor GPR30 in a rat model of endometriosispain.

Alvarez P¹, Bogen O¹, Levine JD².

 

Abstract

Endometriosis, the most common cause of chronic pelvic pain, is an estrogen-dependent disease in which classic estrogen receptors (ERα, ERβ) play an important role. Although recent evidence suggests that the novel G protein-coupled estrogen receptor (GPR30) also plays a key role in the progression of endometriosis, whether it is also involved in endometriosis pain is still unknown. Here we tested the hypothesis that GPR30 expressed by nociceptors contributes to endometriosis pain. Intramuscular injection of the GPR30 agonists raloxifene or 17β-estradiol produced a fast-onset, persistent, mechanical hyperalgesia at the site of the injection. Intrathecal antisense (AS) oligodeoxynucleotides (ODN), but not mismatch (MM) ODN, targeting mRNA for GPR30 markedly inhibited its protein expression in nociceptors and attenuated the mechanical hyperalgesia induced by local raloxifene or 17β-estradiol. Pretreatment with the GPR30 antagonist G-36 also inhibited the hyperalgesia induced by raloxifene or 17β-estradiol in naive control rats. Surgical implant of autologous uterine tissue onto the gastrocnemius muscle, which induces endometriosis-like lesions, produced local mechanical hyperalgesia. Intrathecal AS, but not MM, ODN targeting GPR30 mRNA reversibly inhibited the mechanical hyperalgesia at the site of endometriotic lesions. Finally, intralesional injection of the GPR30 antagonist G-36 also inhibited the mechanical hyperalgesia at the site of ectopic uterine tissue. We conclude that local GPR30 agonists produce persistent mechanical hyperalgesia in naive female rats, whereas local GPR30 antagonists inhibit mechanical hyperalgesia in a model of endometriosis pain. Thus, GPR30 expressed by nociceptors innervating ectopic uterine lesions might play a major role in endometriosis pain.

 

 

BMC Womens Health. 2014 Oct 4;14:123

Impact of endometriosis on women’s lives: a qualitative study.

Moradi M¹, Parker M, Sneddon A, Lopez V, Ellwood D.

 

Abstract

BACKGROUND:

This study aimed to explore women’s experiences of the impact of endometriosis and whether there are differences across three age groups.

METHODS:

A qualitative descriptive design was conducted using semi-structured focus group discussions with 35 Australian women with endometriosis, in three age groups. All tape-recorded discussions were transcribed verbatim and read line by line to extract meaningful codes and categories using NVivo 9 software through a thematic analysis approach. Categories were then clustered into meaningful themes.

RESULTS:

Participants’ ages ranged from 17 to 53 years and had a history of 2 to 40 years living with endometriosis, with an average delay time to diagnosis of 8.1 years. Two main themes emerged: (1) experiences of living with endometriosis, and (2) impact of endometriosis on women’s lives, with 14 discrete categories. The results showed similarities and differences of the impact between the three age groups. The most highlighted impacts were on marital/sexual relationships, social life, and on physical and psychological aspects in all three age groups, but with different orders of priority. Education was the second most highlighted for the 16-24 years, life opportunities and employment for the 25-34 years; and financial impact for those 35 years and above.

CONCLUSIONS:

Our findings show that endometriosis impacts negatively on different aspects of women’s lives. A better understanding of these findings could help to decrease the negative impact of endometriosis by guiding service delivery and future research to meet more effectively the needs of women and teenagers with this condition.

 

 

Arch Gynecol Obstet. 2015 Apr;291(4):877-81

Adenomyosis and accompanying gynecological pathologies.

Genc M¹, Genc B, Cengiz H.

 

Abstract

OBJECTIVE:

The aim of the present study is to determine the potential risk factors for adenomyosis and to investigate its relationship with accompanying gynecological pathologies and clinical characteristics.

MATERIALS AND METHOD:

This study is a retrospective analysis of 945 patients who underwent hysterectomy between May 2005 and January 2013 at the Sifa University Medical Faculty Hospital, Clinic of Obstetrics and Gynecology. The study included 327 patients with adenomyosis and 618 patients without adenomyosis by histopathological examination of the uterus.

RESULTS:

There was a significant positive correlation between development of adenomyosis and presence of leiomyoma (p < 0.0001), history of previous abortion (p < 0.0001), history of previous pregnancy (p = 0.0002), and normal body mass index (p < 0.0001). However, no significant relationship existed between development of adenomyosis and smoking (p > 0.4300), normal delivery (p = 0.9600), cesarean delivery (p = 0.5705), endometrial hyperplasia (p = 0.1721), or ovarian endometriosis (p = 0.8595).

CONCLUSION:

Women who are multiparous have leiomyoma, a previous history of abortion, and a normal body mass index are at increased risk for development of adenomyosis. Adenomyosis might be one cause of unexplained recurrent spontaneous abortion during pregnancy.

 

 

Minerva Med. 2015 Jun;106(3):123-31.

Pelvic endometriosis in women under 25: a specific management?

Hanssens S¹, Rubod C, Kerdraon O, Vinatier D, Lucot JP, Duhamel A, Collinet P.

 

Abstract

AIM:

The aim of this study was to describe the characteristics of women under 25 years with pelvic endometriosis and assess their potential for recurrence and fertility after surgery.

METHODS:

In a comparative retrospective study, 108 patients aged less than 25 years who underwent surgery for pelvic endometriosis were included: 49 in the DIE group (deep infiltrating endometriosis) and 59 in the SE group (superficial endometriosis). The main outcome measures were complications, recurrence and fertility. This study received the favorable opinion of the CEROG No 2012-GYN-04-02.

RESULTS:

The diagnosis was made at 21.6 ± 2.8 years, mainly considering clinical signs (78.4%), and on average 4.3 ± 3.7 years after the onset of symptoms; 16.1% of patients had to be reoperated (N.=5/31) due to a recurrence of their endometriosis. There were more recurrent pain (50% vs. 21.7%, P=0.005) and endometriosis (35.7 vs. 19.6%, P=0.08) in the DIE group. 75% (N.=33/44) patients desired pregnancy after surgery and 50% of them became pregnant, with one third thanks to assisted reproductive technology.

CONCLUSION:

In young women, endometriosis is often more severe. The early treatment does not improve the rate of recurrence and fertility, but can reduce pain and thus improve the quality of life.

 

 

 

 

 

 

Thromb Res. 2014 Dec;134(6):1193-7.

Comparison of the hemostatic effects of a levonorgestrel-releasing intrauterine system and leuprolide acetate in women with endometriosis: a randomized clinical trial.

Yamaguti EM¹, Brito MB², Ferriani RA³, Garcia AA⁴, Rosa-e-Silva JC³, Vieira CS⁵.

 

Abstract

INTRODUCTION:

The hemostatic and inflammatory systems may activate each other. Endometriosis is a chronic inflammatory disease affecting 10% of women. The objective of this study was to compare the hemostatic effects of two treatments widely prescribed to women with endometriosis: the levonorgestrel intrauterine system (LNG-IUS) and the gonadotropin-releasing hormone analog (GnRHa) leuprolide acetate.

MATERIALS AND METHODS:

In this randomized open-label controlled trial, 44 women with endometriosis were randomly allocated to one of two groups: 22 women were assigned to use LNG-IUS and 22 to use GnRHa. The assessed variables were D-dimers, fibrinogen, prothrombin time, activated partial thromboplastin time, coagulation factors (F) II, V, VII, VIII, IX, X, and XI, antithrombin (AT), protein C, free protein S, tissue plasminogen activator (t-PA), α2-antiplasmin, thrombin-antithrombin complex, and prothrombin fragment 1+2. All variables were assessed before treatment and six months after treatment onset.

RESULTS:

In the LNG-IUS group, FVIII decreased 10% after six months of use. In the GnRHa group, there was a 6% increase in AT, 29% reduction in D-dimers, and 19% increase in t-PA. The LNG-IUS users exhibited a significantly greater reduction of FVIII than the GnRHa users (LNG-IUS: -6.4 ± 14.3% vs. GnRHa: 4.2 ± 12.3%, p=0.02). The women in the GnRHa group exhibited a greater increase of AT than the LNG-IUS users (LNG-IUS: -0.7 ± 9.5% vs. GnRHa: 6.5 ± 10.1%, p=0.02).

CONCLUSION:

Both hormonal treatments for endometriosis exhibited no association with a procoagulant profile.

 

 

J Proteomics. 2015 Jan 15;113:194-205.

Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals.

Williams KE¹, Miroshnychenko O², Johansen EB², Niles RK², Sundaram R³, Kannan K⁴, Albertolle M², Zhou Y⁵, Prasad N¹, Drake PM², Giudice LC⁶, Hall SC¹, Witkowska HE¹, Buck Louis GM³, Fisher SJ⁷.

 

Abstract

Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6-11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC-MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n=30) from women ± disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC-MS/MS for protein identification and quantification. Three proteins-matrix metalloproteinase-9, neutrophil elastase, and FAM49B-were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels.

BIOLOGICAL SIGNIFICANCE:

Endometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without endometriosis. These findings suggested proteinase imbalances at sites that were distant from the endometriotic lesions. Additionally, FAM49B and neutrophil elastase levels were associated with higher levels of a subset of environmental chemicals that were quantified in the same samples, suggesting other possible associations. Thus, this work generated hypotheses that will be tested in further studies.

 

 

Colorectal Dis. 2015 Feb;17(2):104-10.

Gracilis muscle interposition for rectovaginal and anovaginal fistula repair: a systematic literature review.

Hotouras A¹, Ribas Y², Zakeri S³, Murphy J¹, Bhan C³, Chan CL¹.

 

Abstract

BACKGROUND:

Repair of rectovaginal fistula (RVF) is associated with high recurrence. For this reason gracilis muscle interposition is increasingly being used.

AIM:

To evaluate the efficacy of this procedure for RVF repair.

METHOD/SEARCH STRATEGY:

A search of PubMed and Medline databases was performed in November 2013 using the text terms and MESH headings ‘rectovaginal fistula/fistulation’, and ‘gracilis muscle’, spanning 1980-2013. The search strategy was restricted to articles written in English with available abstracts. Sample size, aetiology of RVF, previous repair attempts, follow-up period, healing rates and complications were recorded and analysed.

RESULTS:

Seventeen studies involving 106 patients were analysed. The cause of RVF included inflammatory bowel disease (n = 37 [34.9%]: Crohn’s disease [34], ulcerative colitis [3]), pelvic surgery (37 [34.9%]), obstetric injury (9 [8.5%]), malignancy (7 [6.6%]), trauma (5 [4.7%]), miscellaneous (idiopathic, endometriosis, radiation: 11 [10.4%]). Patients had undergone a median number of two previous unsuccessful repairs. At a median follow-up of 21 months, healing had occurred in 33-100% (median 100%) with the largest studies reporting rates between 60% and 90%. Thirteen studies did not report any complications, with the remainder reporting only minor morbidity.

CONCLUSION:

Gracilis interposition appears to have a reasonable success rate for RVF repair with acceptable morbidity. It may be considered as one of the first-line treatment options for recurrent RVF.

 

 

Onco Targets Ther. 2014 Sep 23;7:1647-52.

The target therapy of ovarian clear cell carcinoma.

Jin Y¹, Li Y¹, Pan L¹.

 

Abstract

Clear cell adenocarcinoma (CCC) of the ovary accounts for 10% of epithelial ovarian cancer and is a distinct entity from other epithelial ovarian carcinomas. It arises from the endometriosis. CCC has specific biological and clinical behavior. Compared with other histological types, CCC shows a chemoresistant phenotype, which leads to poorer prognosis. Thus, development of new target-based therapies remains an unmet need for these patients. Mutations in the gene ARID1A have been found to occur in high frequency in CCC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex and considered as a bona fide tumor suppressor. Upregulation of the PIK3/AKT/mTOR pathway, particularly through mutations of PIK3CA and inactivation of PTEN, is involved in tumorigenesis of CCC. Targeting angiogenesis, the Met protooncogene pathway, and HER2 are also discussed in this review.

 

Lik Sprava. 2014 Mar-Apr;(3-4):78-82.

Effectiveness of medical rehabilitation of women of reproductive age with fatigue syndrome.

Udovika NO, Romanenko IIu, Lieonov OO.

 

Abstract

Efficacy Erbisol in combination with Lymphomyosot and Echinacea compositum C in medical rehabilitation of women of reproductive age with fatigue syndrome and chronic gynecological pathology was studied. It was found that this complex of medications promotes faster and more effective reduction of the level of circulating immune complexes in the serum, achievement of persistent clinical remission of disease and liquidation of fatigue syndrome manifestations, what improves the quality of life of patients.

 

 

Pol J Vet Sci. 2014;17(3):547-54.

Endometrosis–significance for horse reproduction, pathogenesis, diagnosis, and proposed therapeutic methods.

Buczkowska J, Kozdrowski R, Nowak M, Raś A, Mrowiec J.

 

Abstract

Equine endometrosis is a multifactorial disease considered to be a one of the most important causes of equine infertility, especially in older mares. This article reviews the current knowledge of equine endometrosis: pathogenesis, diagnosis, and optional treatment. Also describes the histomorphological and immunohistochemical characterization of endometrosis as well as potential etiological factors which may influence disease progression. Unfortunately, the etiology and pathogenesis of endometrosis still remains unclear, and consequently no effective treatment has been proposed so far. Therefore future studies are needed for explanation of this disease.

 

Taiwan J Obstet Gynecol. 2014 Sep;53(3):303-8.

Laparoscopic surgery for subfertility related to endometriosis: a meta-analysis.

Jin X¹, Ruiz Beguerie J².

 

Abstract

OBJECTIVE:

Endometriosis is the presence of an endometrial gland or stroma in sites other than the uterine cavity and it is frequently diagnosed in infertile women. It has not been well established whether laparoscopic surgery improves fertility. The objective of this study was to assess the effectiveness of laparoscopic surgery for subfertility related to endometriosis.

MATERIALS AND METHODS:

Main electronic databases were searched for randomized and nonrandomized controlled trials. Trials were included if they were randomized or nonrandomized controlled trials that compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment methods or diagnostic laparoscopy only. Six studies were included in this meta-analysis. Outcomes analyzed included live birth rate, pregnancy rate, fetal losses, and surgical complications.

RESULTS:

An overall advantage of laparoscopic surgery was demonstrated when analyzing live birth rate [relative risk (RR) 1.52, 95% confidence interval (CI) 1.26-1.84, p < 0.01]. An increase in pregnancy rate after laparoscopic surgery was seen (RR of 1.44, 95% CI 1.24-1.68, p < 0.01). No significant difference in foetal losses.

CONCLUSION:

The use of laparoscopic surgery in the treatment of subfertility related to minimal endometriosismay increase the chances of future pregnancy and live birth.

 

 

Acta Obstet Gynecol Scand. 2015 Feb;94(2):183-90.

Anti-Müllerian hormone reduction after ovarian cyst surgery is dependent on the histological cyst type and preoperative anti-Müllerian hormone levels.

Lind T¹, Hammarström M, Lampic C, Rodriguez-Wallberg K.

 

Abstract

OBJECTIVE:

To investigate changes in serum anti-Müllerian hormone (AMH) concentrations following ovarian cyst surgery, and predictors of these changes.

DESIGN:

Prospective cohort study with follow up at 3 and 6 months.

SETTING:

University hospital.

POPULATION:

Women of reproductive age scheduled for ovarian cyst surgery.

METHODS:

Women were recruited between March 2011 and March 2012 (n = 75). Serum AMH concentrations were measured preoperatively and at 3 and 6 months postoperatively.

MAIN OUTCOME MEASURES:

Changes in AMH after surgery and predictors for these changes.

RESULTS:

After surgery, median AMH levels decreased significantly from 2.7 μg/L (0.2-16.9) to 1.6 μg/L (0.2-9.9) at 3 months and were still low, 1.6 μg/L (0.2-8.3) at 6 months (both p < 0.001). In patients with unilateral cysts, a significant and more rapid AMH decrease was seen after enucleation of endometriomas (n = 19) vs. dermoid cysts (n = 22) (p = 0.010). The reduction was long-lasting at 6 months. In a multivariate regression analysis, a higher baseline AMH concentration was predictive of AMH reduction at 3 [odds ratio (OR) 1.9, 95% CI 1.1-3.1] and 6 months postoperatively (OR 2.5, 95% CI 1.2-5.2). Women with normal or elevated baseline AMH presented with a significant reduction of -23% and -43% at 3 and 6 months, respectively, whereas women with low or very low AMH had minimal or no changes over time. Patient’s age, cyst size, duration of surgery or intraoperative bleeding were not predictive of a postoperative AMH decrease.

CONCLUSIONS:

Reduction of AMH was of greater magnitude and longer duration after enucleation of endometriomas and in women with normal and high preoperative AMH levels.

 

 

Aust N Z J Obstet Gynaecol. 2014 Oct;54(5):462-8

Can anyone screen for deep infiltrating endometriosis with transvaginal ultrasound?

Piessens S¹, Healey M, Maher P, Tsaltas J, Rombauts L.

 

Abstract

BACKGROUND:

Surgical treatment of deep infiltrating endometriosis (DIE) is complex, and preoperative diagnosis benefits both surgeon and patient. Studies in expert centres have reported high accuracy for transvaginal ultrasound (TVUS) diagnosis of DIE. External validation of these findings has been limited, and no information is available on how quickly these skills can be acquired. The aim of this study was to measure the learning curve of DIE-TVUS and to identify the causes for inaccuracies in the diagnosis of bowel lesions and Pouch of Douglas (POD) obliteration.

METHODS:

Following one week of training at the University of São Paulo (Brazil), 205 consecutive women with a history of endometriosis symptoms were prospectively assessed by TVUS after minimal bowel preparation. TVUS findings were correlated with laparoscopic findings in eighty-five cases to assess the accuracy. The LC-CUSUM and CUSUM were used to assess the learning curve and maintenance of competency, respectively.

RESULTS:

The sensitivity and specificity for DIE of the bladder, vagina and bowel were 33% and 100%, 80% and 100%, and 88% and 93%, respectively. The sensitivity and specificity for the presence of POD obliteration were 88% and 90%, respectively. LC-CUSUM analysis confirmed that competency for DIE-TVUS was achieved within 38 scans for the detection of POD obliteration and within 36 scans for the detection of bowel nodules. Competency was maintained for the remainder of the scans as assessed by the CUSUM.

CONCLUSIONS:

After one week of DIE-TVUS training, competency can be achieved within forty procedures, allowing diagnosis of DIE with similar diagnostic accuracy as reported by centres of excellence.

 

 

Aust N Z J Obstet Gynaecol. 2014 Oct;54(5):480-6

Relating historical variables at first presentation with operative findings at laparoscopy for endometriosis.

Menakaya U¹, Lu C, Infante F, Lam A, Condous G.

 

Abstract

OBJECTIVES:

To determine the correlation between historical variables at presentation with the phenotype and location of biopsy proven endometriosis at laparoscopy.

METHODS:

Prospective observational study. Consecutive women had laparoscopic surgery following clinical suspicion of endometriosis. Standardised history and clinical examination were taken, and the presenting complaints were evaluated within four subsets of women: (i) primary laparoscopy for endometriosis (ii) previous laparoscopically confirmed endometriosis (iii) biopsy positive for endometriosis and (iv) all biopsies negative for endometriosis. Historical pain variables within the four subsets were compared with disease location and phenotype (superficial, deep infiltrating, endometriomata) at laparoscopy. A stringent P-value of 0.01 was used as the cut-off for significance.

RESULTS:

Overall 104 consecutive women were included: mean age 34.3 years, 66/104 (63.5%) had reoperation and 38/104 (36.5%) had primary laparoscopy. 89/104 (85.6%) were biopsy positive for endometriosis, and 11/104 (10.6%) were biopsy negative. Superficial endometriosis was most common phenotype. Site of pain did not correlate with ipsilateral location of disease. Significant correlations included as follows: dyspareunia and endometrioma (P = 0.0009) in women undergoing reoperation; dyspareunia and posterior compartment (P = 0.0086) and lateral compartment (P = 0.0004) disease in women with histology proven endometriosis; left iliac fossa pain and biopsy proven posterior compartment endometriosis(P = 0.0041).

CONCLUSIONS:

Although a history of dyspareunia in women with previous endometriosis was significantly correlated with endometrioma, site-specific locations of pain symptoms did not correlate with ipsilateral locations of endometriosis at laparoscopy. The phenotype – combined deep and superficial endometriosis – was associated with dyspareunia among women with previous history of endometriosis.

 

 

Arch Gynecol Obstet. 2015 Mar;291(3):611-21.

Accuracy of magnetic resonance in deeply infiltrating endometriosis: a systematic review and meta-analysis.

Medeiros LR¹, Rosa MI, Silva BR, Reis ME, Simon CS, Dondossola ER, da Cunha Filho JS.

 

Abstract

OBJECTIVE:

To estimate the accuracy of pelvic magnetic resonance imaging (MRI) in the diagnosis of deeply infiltrating endometriosis (DIE).

METHODS:

A comprehensive search of the Medline, Pubmed, Lilacs, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, and ISI Web of Science databases was conducted from January 1990 to December 2013. The medical subject headings (MeSHs) and text words “deep endometriosis”, “deeply infiltrating endometriosis”, “DIE”, “magnetic resonance”, and “MRI” were searched. Studies that compared the parameters of pelvic MRIs with those of paraffin-embedded sections for the diagnosis of DIE were included.

RESULTS:

Twenty studies were analyzed, which included 1,819 women. Pooled sensitivity and specificity were calculated across eight subgroups: for all sites, these were 0.83 and 0.90, respectively; for the bladder, 0.64 and 0.98, respectively; for the intestine, 0.84 and 0.97, respectively; for the pouch of Douglas, 0.89 and 0.94, respectively; for the rectosigmoid, 0.83 and 0.88, respectively; for the rectovaginal, 0.77 and 0.95, respectively; for the uterosacral ligaments, 0.85 and 0.80, respectively; and for the vagina and the posterior vaginal fornix, 0.82 and 0.82, respectively.

CONCLUSION:

In summary, pelvic MRI is a useful preoperative test for predicting the diagnosis of multiple sites of deep infiltrating endometriosis.

 

 

Surg Endosc. 2015 Jul;29(7):1879-87.

Long-term symptoms, quality of life, and fertility after colorectal resection for endometriosis: extended analysis of a randomized controlled trial comparing laparoscopically assisted to open surgery.

Touboul C¹, Ballester M, Dubernard G, Zilberman S, Thomin A, Daraï E.

 

Abstract

BACKGROUND:

To evaluate the long-term symptoms, quality of life (QOL), and fertility after colorectal resection for endometriosis.

METHODS:

Extended analysis of a randomized controlled trial including 52 patients with colorectal endometriosis, comparing laparoscopically assisted to open colorectal resection. All included patients were invited to complete questionnaires evaluating the presence and intensity of symptoms and QOL using the SF-36 and fertility at a mean (SD) follow-up of 50.7 (13.8) months. We compared symptoms intensity and QOL before and after surgery at short- (mean follow-up of 19 months) and long-term (mean follow-up of 51 months).

RESULTS:

Persistent improvement in QOL was noted after surgery without differences between short and long term. Self-catheterization >6 months was the sole factor decreasing the long-term QOL (P = 0.02). No difference in symptoms and QOL was noted according to the route. Among the 28 patients (53.8%) wishing to conceive, 12 (42.9%) conceived within a mean (SD) time of 17 (13) months. No difference in fertility including pregnancy after IVF was noted between the routes, but spontaneous pregnancy occurred only after laparoscopy (P = 0.016).

CONCLUSIONS:

Symptoms and QOL improvements after colorectal resection last for over 4 years without difference between the routes. Thank to a lower intra- and postoperative complications and higher spontaneous pregnancy rate, laparoscopic colorectal resection should be the first surgical approach.

 

 

Clin Cancer Res. 2014 Dec 1;20(23):6163-74.

Complement pathway is frequently altered in endometriosis and endometriosis-associated ovarian cancer.

Suryawanshi S¹, Huang X¹, Elishaev E², Budiu RA¹, Zhang L¹, Kim S³, Donnellan N⁴, Mantia-Smaldone G⁵, Ma T³, Tseng G³, Lee T⁴, Mansuria S⁴, Edwards RP⁶, Vlad AM⁷.

 

Abstract

PURPOSE:

Mechanisms of immune dysregulation associated with advanced tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear-cell ovarian tumors partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here a comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC).

EXPERIMENTAL DESIGN:

RNA was extracted from 120 paraffin tissue blocks comprising of normal endometrium (n = 32), benign endometriosis (n = 30), atypical endometriosis (n = 15), and EAOC (n = 43). Serous tumors (n = 15) were included as nonendometriosis-associated controls. The immune microenvironment was profiled using Nanostring and the nCounter GX Human Immunology Kit, comprising probes for a total of 511 immune genes.

RESULTS:

One third of the patients with endometriosis revealed a tumor-like inflammation profile, suggesting that cancer-like immune signatures may develop earlier, in patients classified as clinically benign. Gene expression analyses revealed the complement pathway as most prominently involved in both endometriosis and EAOC. Complement proteins are abundantly present in epithelial cells in both benign and malignant lesions. Mechanistic studies in ovarian surface epithelial cells from mice with conditional (Cre-loxP) mutations show intrinsic production of complement in epithelia and demonstrate an early link between Kras- and Pten-driven pathways and complement upregulation. Downregulation of complement in these cells interferes with cell proliferation.

CONCLUSIONS:

These findings reveal new characteristics of inflammation in precursor lesions and point to previously unknown roles of complement in endometriosis and EAOC.

 

 

 

Reprod Sci. 2015 May;22(5):551-5.

Diagnostic accuracy of urinary cytokeratin 19 fragment for endometriosis.

Lessey BA¹, Savaris RF², Ali S³, Brophy S³, Tomazic-Allen S⁴, Chwalisz K⁵.

 

Abstract

Endometriosis affects up to 10% of women of reproductive age and 176 million women worldwide. The prevalence in women with infertility is between 30% and 50% but may be higher in women with pelvic pain, interstitial cystitis, or irritable bowel syndrome. Cytokeratin 19 has been suggested as a potential biomarker in urine for the diagnosis of this condition. The objective of this study was to prospectively determine the accuracy and the performance of a urinary cytokeratin 19 (uCYFRA 21-1) test for diagnosing endometriosis. Ninety-eight consecutive women who underwent laparoscopy had a urinary sample obtained before surgery and were included in the study. Endometriosis was diagnosed by laparoscopy and pathology in 64.3% (63 of 98 women). The estimates and 95% confidence intervals for sensitivity, specificity, positive and negative predictive values, and likelihood ratios were 11.1% (4.5%-21.5%), 94.3% (80.8%-99.3%), 77.7% (39.9-97.1), 37% (27-47.9), 1.94 (0.43-8.86), and 0.94 (0.84-1.06), respectively. Despite the high specificity, the uCYFRA 21-1 test has limited value for clinical practice to discriminate between women with and without endometriosis.

 

 

Hum Mol Genet. 2015 Feb 15;24(4):1185-99.

Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.

Rahmioglu N¹, Macgregor S², Drong AW¹, Hedman ÅK³, Harris HR⁴, Randall JC⁵, Prokopenko I⁶; International Endogene Consortium (IEC), The GIANT Consortium, Nyholt DR⁷, Morris AP⁸, Montgomery GW⁹, Missmer SA¹⁰, Lindgren CM¹¹, Zondervan KT¹².

 

Abstract

Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other.

 

 

Biol Reprod. 2014 Nov;91(5):122.

The p160/steroid receptor coactivator family: potent arbiters of uterine physiology and dysfunction.

Szwarc MM¹, Kommagani R¹, Lessey BA², Lydon JP³.

 

Abstract

The p160/steroid receptor coactivator (SRC) family comprises three pleiotropic coregulators (SRC-1, SRC-2, and SRC-3; otherwise known as NCOA1, NCOA2, and NCOA3, respectively), which modulate a wide spectrum of physiological responses and clinicopathologies. Such pleiotropy is achieved through their inherent structural complexity, which allows this coregulator class to control both nuclear receptor and non-nuclear receptor signaling. As observed in other physiologic systems, members of the SRC family have recently been shown to play pivotal roles in uterine biology and pathobiology. In the murine uterus, SRC-1 is required to launch a full steroid hormone response, without which endometrial decidualization is markedly attenuated. From “dovetailing” clinical and mouse studies, an isoform of SRC-1 was recently identified which promotes endometriosis by reprogramming endometrial cells to evade apoptosis and to colonize as endometriotic lesions within the peritoneal cavity. The endometrium fails to decidualize without SRC-2, which accounts for the infertility phenotype exhibited by mice devoid of this coregulator. In related studies on human endometrial stromal cells, SRC-2 was shown to act as a molecular “pacemaker” of the glycolytic flux. This finding is significant because acceleration of the glycolytic flux provides the necessary bioenergy and biomolecules for endometrial stromal cells to switch from quiescence to a proliferative phenotype, a critical underpinning in the decidual progression program. Although studies on uterine SRC-3 function are in their early stages, clinical studies provide tantalizing support for the proposal that SRC-3 is causally linked to endometrial hyperplasia as well as with endometrial pathologies in patients diagnosed with polycystic ovary syndrome. This proposal is now driving the development and application of innovative technologies, particularly in the mouse, to further understand the functional role of this elusive uterine coregulator in normal and abnormal physiologic contexts. Because dysregulation of this coregulator triad potentially presents a triple threat for increased risk of subfecundity, infertility, or endometrial disease, a clearer understanding of the individual and combinatorial roles of these coregulators in uterine function is urgently required. This minireview summarizes our current understanding of uterine SRC function, with a particular emphasis on the next critical questions that need to be addressed to ensure significant expansion of our knowledge of this underexplored field of uterine biology.

 

 

J Ovarian Res. 2014 Jul 10;7:73.

Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis.

Ren F, Wang DB, Li T, Chen YH, Li Y.

 

Abstract

BACKGROUND:

Key roles for epigenetic mechanisms in tumorigenesis are well accepted, while the relationship between gene methylation and malignant transformation of ovarian endometriosis (EMS) was seldom reported. In this study, we aimed to screen for aberrantly methylated genes associated with the malignant transformation of ovarian EMS and to preliminarily verify the reliability of screened results by detecting the methylation status and protein expression of the candidate gene in a larger scale of formaldehyde-fixed and paraffin-embedded (FFPE) samples.

METHODS:

Methylated CpG island amplification coupled with representational difference analysis (MCA-RDA) was performed on 3 couples of endometriosis-associated ovarian carcinoma (EAOC) fresh samples to identify differentially methylated candidate genes related to malignant transformation of ovarian EMS; Methylation-specific PCR (MSP) and immunohistochemistry were performed in 30 EAOC samples to detected the methylation status and protein expression of RASSF2 gene to verify the reliability of MCA-RDA results.

RESULTS:

Nine differentially methylated genes were obtained by MCA-RDA as candidate genes for malignant transformation of EMS; Methylation frequency of RASSF2 in the neoplastic tissues of EAOC group was higher than that in the ectopic endometria (p < 0.05). While protein expression of RASSF2 in the neoplastic tissues was lower than that in the ectopic endometria of the EAOC group (p < 0.05) Absence of protein expression of RASSF2 was significantly correlated with the promoter methylation of the gene (p < 0.05).

CONCLUSIONS:

RASSF2, RUNX3, GSTZ1, CYP2A, GBGT1, NDUFS1, SPOCK2, ADAM22, and TRIM36 were candidate genes for malignant transformation of ovarian EMS and epigenetic inactivation of RASSF2 by promoter hypermethylation is an early event in malignant transformation of ovarian EMS. The screen results were reliable and worthy of further study.

 

 

Avicenna J Med. 2014 Oct;4(4):99-101.

An unusual cause of abdominal pain in a male patient: Endometriosis.

Jabr FI¹, Mani V².

 

Abstract

A rare case of abdominal pain secondary to endometriosis in a 52-year-old man with cirrhosis is presented. The patient had a repair of recurrent inguinal hernia 7 months prior to presentation. An exploratory laparotomy revealed a 4.5 cm × 2.5 cm cystic mass attached to the urinary bladder and the inguinal area. The mass pathology showed a cystic lumen of diameter of 1.5 cm filled with old blood and surrounded by thick muscular mass. Microscopically, the lesion consisted of thick smooth muscle fibers that concentrically surround a central lumen that is bordered by endometrium such as glands and stroma. Immunostains were positive for estrogen receptors and progesterone receptors in the glandular component and for CD10 in the stroma, which is consistent with endometriosis.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:167-71.

Effects of repeated propranolol administration in a rat model of surgically induced endometriosis.

Uzunlar O¹, Ozyer S², Engin-Ustun Y², Moraloglu O², Gulerman HC², Caydere M³, Keskin SM², Mollamahmutoglu L².

 

Abstract

OBJECTIVES:

To determine whether propranolol has an inhibitory effect on the angiogenesis of endometriosisin an experimental rat model or not.

STUDY DESIGN:

This was an experimental animal model study. Twenty-four female Wistar albino rats (200-250 g) were used to create a model for surgical induction of endometriosis. Two rats died during the surgeries. The rats were randomly divided into treatment (n=11) and control groups (n=10), which were treated with daily intraperitoneal propranolol (10 mg/kg) and saline (2 mL), respectively. Study duration was 8 weeks. The volumes and histopathological findings of the implants, and immunochemistry for vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-2, and MMP-9 were evaluated.

RESULTS:

Viable endometriotic implants were created in all animals. In the propranolol-treated group, the mean implant volume significantly decreased after treatment (142.5 vs. 32.1 mm(3), respectively; p=0.008), while the mean implant volume significantly increased in the control group (141.0 vs. 174.2 mm(3), respectively; p=0.009). There were also significant reductions in VEGF immunoreactivity scores and both stroma and epithelium MMP-2 and MMP-9 immunoreactivity scores in the propranolol-treated group compared with the control group (p<0.005 for all scores).

CONCLUSIONS:

Propranolol may suppress endometrial tissue by its antiangiogenic activity through inhibitory actions on VEGF, MMP-2, and MMP-9. Therefore, propranolol is a promising candidate drug for effective treatment of patients with endometriosis, which needs to be confirmed with further studies.

 

 

Pain Manag. 2014 Jul;4(4):293-301.

Diagnosing the bladder as the source of pelvic pain: successful treatment for adults and children.

Parsons CL.

 

Abstract

The key to successful therapy of interstitial cystitis (IC) is to correctly diagnose it. The significant majority of patients with IC have a dysfunctional bladder epithelium that allows urinary solutes (primarily potassium) to leak into the bladder wall, causing symptoms and tissue damage. Drugs that correct this dysfunction and suppress symptoms are important to achieve successful outcomes in patients. Today over 95% of females with IC are misdiagnosed as having gynecologic chronic pelvic pain, vulvodynia, vaginitis, endometriosis, overactive bladder or urinary tract infection. Men are misdiagnosed as having prostatitis. Often children are not diagnosed at all. Multimodal drug therapy may be required and can achieve successful resolution of IC in over 90% of patients. IC in children can be treated successfully with pentosan polysulfate.

 

 

Minerva Ginecol. 2014 Oct 10.

Fertility before and after surgery for deep infiltrating endometriosis with and without bowel involvement: a literature review.

Cohen J¹, Thomin A, Mathieu d’Argent E, Laas E, Canlorbe G, Zilberman S, Belghiti J, Thomassin-Naggara I, Bazot M, Ballester M, Daraï E.

 

Abstract

OJECTIVE:

Endometriosis affects from 10 to 15% of women of childbearing age and 20% of these women have deep infiltrating endometriosis (DIE). The goal of this review was to assess the impact of various locations of DIE on spontaneous fertility and the benefit of surgery and Medically Assisted Reproduction (MAR) (in vitro fertilization and intrauterine insemination) on fertility outcomes.

METHODS:

MEDLINE search for articles on fertility in women with DIE published between 1990 and April 2013 using the following terms: “deep infiltrative endometriosis”, “colorectal”, “bowel”, “rectovaginal”, “uterosacral”, “vaginal”, “bladder” and “fertility” or “infertility”. Twenty–nine articles reporting fertility outcomes in 2730 women with DIE were analysed.

RESULTS:

Among the women with DIE and no bowel involvement (n=1295), no preoperative data on spontaneous pregnancy rate (PR) were available. The postoperative spontaneous PR rate in these women was 50.5% (95% Confidence Interval (CI) = 46.8–54.1) and overall PR (spontaneous pregnancies and after MAR) was 68.3% (95% CI = 64.9–71.7). No evaluation of fertility outcome according to locations of DIE was feasible. For women with DIE with bowel involvement without surgical management (n=115), PR after MAR was 29%;; 95% CI = 20.7–37.4). For those with bowel involvement who were surgically managed (n=1320), postoperative spontaneous PR was 28.6% (95% CI = 25–32,3) and overall postoperative PR was 46.9 % (95% CI = 42,9–50,9).

CONCLUSION:

For women with DIE without bowel involvement, surgery alone offers a high spontaneous PR. For those with bowel involvement, the low spontaneous and relatively high overall PR suggests the potential benefit of combining surgery and MAR.

 

 

 

 

J Obstet Gynaecol Res. 2015 Apr;41(4):601-7.

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan.

Cakmak B¹, Cavusoglu T, Ates U, Meral A, Nacar MC, Erbaş O.

 

Abstract

AIM:

Endometriosis is a common disease in women of reproductive age, and many different treatments have been developed, although none has provided a cure. In this study, the efficacy of losartan, an angiotensin II type 1 receptor blocker and an antiangiogenic and anti-inflammatory agent, on regression of experimental endometriotic implants in a rat model was investigated.

METHODS:

Peritoneal endometriosis was surgically induced in 16 mature female Sprague-Dawley rats. The peritoneal endometriotic implant was confirmed after 28 days, and the animals were divided randomly into two groups. The control group (n = 8) was given 4 mL/day tap water by oral gavage, and the losartan group (n = 8) was given 20 mg/kg per day losartan p.o. We compared endometriotic implant size, extent and severity of adhesion, as well as plasma and peritoneal lavage fluid cytokine levels including vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, plasma inflammatory factor pentraxin-3 (PTX-3) and C-reactive protein (CRP) between the treatment groups.

RESULTS:

Mean surface endometriotic area, histological score of implants, adhesion formation, plasma VEGF, TNF, PTX-3 and CRP levels were significantly lower in the losartan group compared with control (P < 0.05). Furthermore, the peritoneal VEGF level was lower in the losartan group than in the control group (P < 0.001), but peritoneal TNF-α was similar in both groups (P > 0.05).

CONCLUSION:

Losartan suppressed the implant surface area of experimental endometriosis in rats and reduced the levels of plasma VEGF, TNF-α, PTX-3 and CRP.

 

 

J Obstet Gynaecol Res. 2015 Feb;41(2):309-13.

Dienogest for the treatment of deep endometriosis: case report and literature review.

Agarwal S¹, Fraser MA, Chen I, Singh SS.

 

Abstract

A 38-year-old woman was found to have a deep 3.3-cm endometriotic nodule of the bladder, confirmed by cystoscopic resection and imaging. Ultrasound also confirmed a 2.6-cm vaginal fornix implant with similar appearance to the bladder mass. The patient’s primary symptoms were mild dysmenorrhea, catamenial dysuria and hematuria. The patient conceived shortly after referral and 3 months post-delivery was offered surgical management but declined in favor of medical management. Dienogest 2 mg once a day was started and after 16 months of treatment, more than 50% reduction in the size of the bladder nodule was seen (pretreatment: 3.3 × 3.0 × 2.7 cm, volume: 13.9 cm(3) ; post-treatment: 2.8 × 2.3 × 1.0 cm, volume: 6.4 cm(3) ). The vaginal mass also decreased in size from a pretreatment value of 2.0 × 2.6 × 1.4 cm (3.8 cm(3) ) to 1.1 × 1.4 × 0.5 mm (0.40 cm(3) ) after the treatment. The patient remained asymptomatic with no significant adverse drug reaction during management. Dienogest may be one of the options for medical management of deep endometriosis in young women especially when surgical intervention is declined.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:208-10.

Clinical analysis of transvaginal hydrolaparoscopy in infertile patients.

Zhang YX¹, Liu XQ², Du LR¹, Li GZ¹, Lu LH¹, Tian HY¹, Gao Y¹, Zhang Y¹.

 

Abstract

OBJECTIVE:

To evaluate the application of transvaginal hydrolaparoscopy for exploration of the pelvic cavity exploration in infertile women.

STUDY DESIGN:

A total of 510 infertile women were included in this study from May 1st, 2009 to April 30, 2012 in the clinic of the Hebei Research Institute for Family Planning.

RESULTS:

In 495 of 510 of the patients (97.06%), a successful operation was achieved at the first puncture. Of these 495 patients, 286 (57.78%) showed bilateral patency. Completely normal tubo-ovarian and pelvic structures were observed only in 79 patients (15.96%): 16 patients (3.23%) had bilateral tube obstruction, 18 (3.64%) had hydrosalpinx, and 8 (1.62%) had fimbrial stenosis. Pelvic abnormalities occurred in 240 patients (44.04%), including bilateral and/or unilateral tubo-ovarian adhesions in 80 patients (16.16%) and 160 (32.32%) found with adhesions in other parts of the pelvic cavity. Pelvic endometriosis was found in 82 patients (16.57%) and 19 (3.84%) had two or more lesions in the pelvic cavity. In addition, 9 cases (1.82%) of ovarian cysts, 7 (1.41%) of bilateral vesicular appendices and 43 cases (6.69%) of a unilateral vesicular appendix were observed. In addition, convoluted tubes such as bent or twisted tubes were found in 4 cases of bilateral fallopian tube occlusion patients (0.81%) and 17 cases of unilateral tubal occlusion patients (3.43%).

CONCLUSIONS:

Transvaginal hydrolaparoscopy is a feasible, safe, and cost-effective microinvasive technique. This technique can be considered as an alternative procedure for evaluating female infertility.

 

 

Arch Ital Urol Androl. 2014 Sep 30;86(3):233-4

Endometriosis localized to urinary bladder wall mimicking urinary bladder carcinoma.

Genç M¹, Genç B, Karaarslan S, Solak A, Saraçoglu M.

 

Abstract

Although endometriosis is a common disease in women of reproductive age, urinary system endometriosis is an exceedingly rare disease that may cause important clinical problems. In this paper we discussed a 42-year-old woman who had urinary bladder endometriosis misdiagnosed as urinary bladder tumor in imaging modalities. The diagnosis of endometriosis was made by histopathological examination of the operative material after partial resection of the urinary bladder. Urinary bladder endometriosis causes nonspecific signs and symptoms in many patients. In female patients presenting with unexplained urinary symptoms the differential diagnosis should include urinary bladder endometriosis that may mimic urinary bladder cancer and lead to difficulties in making definitive preoperative diagnosis.

 

 

BMC Womens Health. 2014 Oct 15;14:128

Natural history of ovarian endometrioma in pregnancy.

Pateman K, Moro F, Mavrelos D, Foo X, Hoo WL, Jurkovic D¹.

 

Abstract

BACKGROUND:

Ovarian endometriomas are classified as benign ovarian lesions. During pregnancy endometriomas may undergo major morphological changes which are referred to as ‘decidualisation’. Decidualised ovarian endometrioma may resemble malignant ovarian tumours on ultrasound examination. The aim was to study variations in the morphology and size of ovarian endometriomas diagnosed on ultrasound during pregnancy.

METHODS:

We searched our database to identify pregnant women who were diagnosed with ovarian endometriomas on ultrasound in order to study the effect of pregnancy on their morphological characteristics. In women who underwent serial scans during pregnancy we examined the changes in the size of endometriomas with advancing gestation.

RESULTS:

Twenty four patients with a total of 34 endometriomas were included in the analysis. All women were managed expectantly during pregnancy. On the first ultrasound scan 29/34 (85.3%, 95% CI 73.4 – 97.2) endometriomas appeared unilocular with fine internal echoes (‘ground glass’ contents) and they were poorly vascularised on Doppler examination. 1/34 (2.9% 95% CI 0.0 – 8.5) endometrioma was multilocular, with regular margins, ‘ground glass’ contents and it was also poorly vascularised. 4/34 (11.8%, 95% CI 1.0 – 22.6) had sonographic features suggestive of decidualisation such as thick and irregular inner wall, papillary projections and highly vascular on Doppler examination. The endometriomas showed a tendency to decrease in size during pregnancy.

CONCLUSIONS:

Pregnancy has a major effect on the size and morphological appearances of ovarian endometriomas. Rapid regression of decidualised endometriomas is a helpful feature which could be used to confirm their benign nature.

 

 

Gynecol Oncol. 2014 Dec;135(3):423-7.

Effect of tubal sterilization technique on risk of serous epithelial ovarian and primary peritoneal carcinoma.

Lessard-Anderson CR¹, Handlogten KS², Molitor RJ³, Dowdy SC⁴, Cliby WA⁵, Weaver AL⁶, Sauver JS⁷, Bakkum-Gamez JN⁸.

 

Abstract

OBJECTIVE:

To determine the effect of excisional tubal sterilization on subsequent development of serous epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC).

METHODS:

We performed a population-based, nested case-control study using the Rochester Epidemiology Project. We identified all patients with a diagnosis of serous EOC or PPC from 1966 through 2009. Each case was age-matched to 2 controls without either diagnosis. Odds ratios (ORs) and corresponding 95% CIs were estimated from conditional logistic regression models. Models were adjusted for prior hysterectomy, prior salpingo-oophorectomy, oral contraceptive use, endometriosis, infertility, gravidity, and parity.

RESULTS:

In total, we identified 194 cases of serous EOC and PPC during the study period and matched them with 388 controls (mean [SD] age, 61.4 [15.2] years). Fourteen cases (7.2%) and 46 controls (11.9%) had undergone tubal sterilization. Adjusted risk of serous EOC or PPC was slightly lower after any tubal sterilization (OR, 0.59 [95% CI, 0.29-1.17]; P=.13). The rate of excisional tubal sterilization was lower in cases than controls (2.6% vs 6.4%). Adjusted risk of serous EOC and PPC was decreased by 64% after excisional tubal sterilization (OR, 0.36 [95% CI, 0.13-1.02]; P=.054) compared with those without sterilization or with nonexcisional tubal sterilization.

CONCLUSIONS:

We present a population-based investigation of the effects of excisional tubal sterilization on the risk of serous EOC and PPC. Excisional methods may confer greater risk reduction than other sterilization methods.

 

 

Hum Reprod. 2014 Dec;29(12):2747-55.

Inhibition of dual specificity phosphatase-2 by hypoxia promotes interleukin-8-mediated angiogenesis in endometriosis.

Hsiao KY¹, Chang N¹, Lin SC¹, Li YH², Wu MH³.

 

Abstract

STUDY QUESTION:

How does hypoxia-mediated down-regulation of dual specificity phosphatase-2 (DUSP2) promote endometriotic lesion development?

SUMMARY ANSWER:

Inhibition of DUSP2 by hypoxia enhances endometriotic lesion growth via promoting interleukin-8 (IL-8)-dependent angiogenesis.

WHAT IS KNOWN ALREADY:

Angiogenesis is a prerequisite for the development of endometriosis. DUSP2 is down-regulated in endometriotic stromal cells in a hypoxia inducible factor-1α-dependent manner. Down-regulation of DUSP2 contributes to the pathological process of endometriosis.

STUDY DESIGN, SIZE, DURATION:

A laboratory study recruiting 20 patients of reproductive age with endometriosis and normal menstrual cycles, and an autoimplant-induced mouse model of endometriosis using 13 mice in a 28-day treatment.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

IL-8 mRNA levels were assayed in endometrial stromal cells maintained in normoxic or hypoxic (1% O2) conditions, with or without DUSP2 knockdown. Promoter activity and chromatin immunoprecipitation (ChIP) assays were conducted to characterize the regulation of IL-8 by DUSP2. Conditioned media from cells maintained in normoxic or hypoxic conditions, and cells with/without DUSP2 knockdown were collected to investigate the angiogenic capacity using an in vitro tube formation assay. Reparixin, an IL-8 receptor blocker, was administered to investigate the role of IL-8 in hypoxia-mediated angiogenesis and the development of endometriotic-like lesions in an autotransplanted mouse model.

MAIN RESULTS AND THE ROLE OF CHANCE:

IL-8 mRNA was increased by both hypoxia and DUSP2 knockdown in endometrial stromal cells in an extracellular signal-regulated protein kinase-dependent manner (P < 0.05 versus control). Promoter activity and ChIP assays demonstrated that expression of IL-8 was regulated by CCAAT/enhancer binding protein α (P < 0.05 versus control). Furthermore, conditioned media collected from hypoxia-exposed or DUSP2 knockdown endometrial stromal cells promoted tube formation, which was abolished by co-treatment with reparixin (P < 0.05 versus control). Results from the autotransplanted mouse model demonstrated that number of blood vessels and size of endometriotic-like lesions were markedly reduced in recipient mice treated with reparixin (P < 0.05 versus control).

LIMITATIONS, REASONS FOR CAUTION:

This study was conducted in primary human cell cultures and a mouse model, therefore may not fully reflect the situation in vivo.

WIDER IMPLICATIONS OF THE FINDINGS:

This is the first study to highlight the potential application of an IL-8 receptor blocker as a therapeutic target to treat endometriosis. This study demonstrates IL-8 as a key angiogenic factor regulated by hypoxia/DUSP2, which suggests an alternative mechanism through which hypoxia may promote angiogenesis.

STUDY FUNDING/COMPETING INTERESTS:

This study was funded by the National Science Council of Taiwan (NSC101-2314-B-006-043-MY2). The author declares that there is no conflict of interest.

 

 

 

 

 

 

 

Mol Endocrinol. 2014 Dec;28(12):1934-47.

Estrogen-induced CCN1 is critical for establishment of endometriosis-like lesions in mice.

Zhao Y¹, Li Q, Katzenellenbogen BS, Lau LF, Taylor RN, Bagchi IC, Bagchi MK.

 

Abstract

Endometriosis is a prevalent gynecological disorder in which endometrial tissue proliferates in extrauterine sites, such as the peritoneal cavity, eventually giving rise to painful, invasive lesions. Dysregulated estradiol (E) signaling has been implicated in this condition. However, the molecular mechanisms that operate downstream of E in the ectopic endometrial tissue are unknown. To investigate these mechanisms, we used a mouse model of endometriosis. Endometrial tissue from donor mice was surgically transplanted on the peritoneal surface of immunocompetent syngeneic recipient mice, leading to the establishment of cystic endometriosis-like lesions. Our studies revealed that treatment with E led to an approximately 3-fold increase in the lesion size within a week of transplantation. E also caused a concomitant stimulation in the expression of connective tissue growth factor/Cyr61/Nov (CCN1), a secreted cysteine-rich matricellular protein, in the lesions. Interestingly, CCN1 is highly expressed in human ectopic endometriotic lesions. To address its role in endometriosis, endometrial tissue from Ccn1-null donor mice was transplanted in wild-type recipient mice. The resulting ectopic lesions were reduced up to 75% in size compared with wild-type lesions due to diminished cell proliferation and cyst formation. Notably, loss of CCN1 also disrupted the development of vascular networks in the ectopic lesions and reduced the expression of several angiogenic factors, such as vascular endothelial growth factor-A and vascular endothelial growth factor-C. These results suggest that CCN1, acting downstream of E, critically controls cell proliferation and neovascularization, which support the growth and survival of endometriotic tissue at ectopic sites. Blockade of CCN1 signaling during the early stages of lesion establishment may provide a therapeutic avenue to control endometriosis.

 

 

Med Sci Monit. 2014 Oct 16;20:1950-7.

Efficacy and safety of remifemin on peri-menopausal symptoms induced by post-operative GnRH-a therapy for endometriosis: a randomized study versus tibolone.

Chen J¹, Gao H², Li Q², Cong J¹, Wu J³, Pu D¹, Jiang G².

 

Abstract

BACKGROUND:

The aim of this study was to investigate clinical efficacy and safety of Remifemin on peri-menopausal symptoms in endometriosis patients with a post-operative GnRH-a therapy.

MATERIAL AND METHODS:

We treated 116 women who had endometriosis with either Remifemin (n=56) 20 mg bid po or Tibolone (n=60) 2.5 mg qd po for 12 weeks after GnRH-a injection. The efficacy was evaluated by Kupperman menopausal index (KMI), and hot flash/sweating scores. The safety parameters such as liver and renal functions, lipid profile, endometrial thickness, and serum sex hormone level, as well as the incidence of adverse events were recorded.

RESULTS:

(1) After GnRH-a therapy, KMI and hot flash/sweating scores in both groups increased significantly (P<0.05) but we found no significant difference for KMI (2.87±1.40 for Remifemin and 2.70±1.26 for Tibolone) and hot flash/sweating scores (0.94±1.72 for Remifemin and 1.06±1.78 for Tibolone) between the 2 groups (P>0.05). (2) No statistical change was observed in liver or renal functions and lipid profile in both groups before and after the treatment (P>0.05). The post-therapeutic serum FSH, LH, and E2 level and endometrial thickness decreased remarkably in both groups (P<0.05). E2 level in the Remifemin group was obviously lower than that in the Tibolone group (P<0.05), and FSH and LH levels were strongly higher (P<0.05). No significant difference in thickness were found in either group (P>0.05). The Remifemin group had far fewer adverse events than the Tibolone group (P<0. 05).

CONCLUSIONS:

Compared with Tibolone, Remifemin had a similar clinical efficacy and was safer for the peri-menopausal symptoms induced by GnRH-a in endometriosis patients.

 

 

Ginekol Pol. 2014 Sep;85(9):658-64.

Magnetic resonance imaging as a non-invasive detection tool for extraovarian endometriosis–own experience.

Bekiesińska-Figatowska M.

 

Abstract

INTRODUCTION:

Endometriosis–due to its high incidence, associated pain and infertility–constitutes an important problem in gynecological practice. The Polish Gynecological Society Expert Panel recommends to perform magnetic resonance imaging (MRI) prior to laparoscopy The purpose of this study is to present the usefulness of MRI in the diagnosis of extraovarian endometriosis on the basis of own experience.

MATERIAL AND METHODS:

The material consisted of 35 patients, aged 15-52 (mean 36.5 years), who were diagnosed with extraovarian endometriosis on MRI. MR examinations were performed with 1.5 T scanners according to a routine protocol, which incorporates the LAVA sequence of dynamic contrast studies protocol because of thin sections.

RESULTS:

Extraovarian endometriosis was isolated in 24 patients (68.6%), while in 11 (31.4%) it coexisted with ovarian endometriomas. In 23 cases (65.7%) extraovarian endometriosis was found in one place, in 12 (34.3%)–in two or more locations. Endometriosis was found in the following locations: abdominal wall–11 cases (37.4%), uterine body–9 (25.7%), posterior vaginal fornix–7 (20%), wall of the rectum and sigmoid colon–5 (14.3%), pararectal space–5, uterine cervix–4 (11.4%), Douglas pouch–3 (8.6%), Fallopian tube–2 (5.7%), wall of the small intestine–1 (2.8%), and urinary bladder–1. Adhesions were observed in 28.6% of the patients.

CONCLUSIONS:

MRI is an important addition to the non-invasive diagnosis of extraovarian endometriosis and should be performed before treatment, especially surgical one. The inclusion of fat saturated T1 sequence from the dynamic contrast examination in the study protocol increases the likelihood of detecting small endometrial implants.

 

 

Ginekol Pol. 2014 Sep;85(9):699-702.

Endometriosis causing intussusception of the ileum into the colon.

Walczak P, Kruszewski JW, Sobczak E, Szefel J.

 

Abstract

Intussusception of the caecum occurs about twenty times less frequently in adults as compared to children and in 90% of these cases is caused by intestinal tumors. Intussusception of the ileum usually causes intestinal obstruction which requires urgent surgical intervention. So far only a few cases of intussusception due to the presence of endometrial tumor have been described. The clinical course, imaging and laboratory tests are not specific for endometriosis. The macroscopic appearance of the tumor during laparotomy is also not diagnostic. In case of endometriosis, the diagnosis can only be made on the basis of the histopathological examination of the excised tumor In this report, we present the diagnostic process and treatment of a patient with intussusception of the ileum to the ascending and transverse colon due to cecal tumor During the operation, the surgeon suspected a cancerous tumor and performed a right hemicolectomy The final diagnosis of endometriosis was made on the basis of the histopathological analysis.

 

 

 

J Obstet Gynaecol. 2015 May;35(4):386-8.

A prospective study to evaluate the role of laparohysteroscopy in unexplained infertility.

Firmal P¹, Yadav R, Agrawal S.

 

Abstract

Laparoscopy is considered as the preferred modality for the diagnosis of pelvic pathology but its timing and use in the investigation of infertility is an area of debate. A prospective observational study was conducted between 1 November, 2009 and 31 March, 2011, in which 30 women with unexplained infertility with at least three failed cycles of COH and IUI were included and subjected to laparohysteroscopy. On laparoscopy, pelvic abnormalities were found in 11 (36.7%) women. On hysteroscopy, intrauterine lesions were detected in two (6.7%) of the women. The commonest pelvic pathology detected was adhesions followed by minimal to mild endometriosis. Operative procedures were done in nine (30%) cases. Since laparoscopy was not only diagnostic but also therapeutic in a significant number of cases, it was concluded that laparoscopy is beneficial following failure of empirical treatment in women with unexplained infertility while the routine use of hysteroscopy requires further assessment.

 

 

JNMA J Nepal Med Assoc. 2013 Oct-Dec;52(192):608-11.

Laparoscopic management of benign ovarian masses.

Saha R¹, Karki C¹.

 

Abstract

INTRODUCTION:

Laparoscopic surgery is one of the most common procedures performed for benign ovarian masses. The aim of the study was to analyze all benign ovarian masses treated laparoscopically to assess safety, feasibility and outcome.

METHODS:

A prospective study was carried out at Kathmandu Medical College Teaching Hospital, Sinamangal, Nepal. All the patients undergoing laparoscopic surgery for benign ovarian masses from 1st January 2012 to 31st December 2012 were included in the study. The pre-operative findings, intra-operative findings, operative techniques and post-operative complications were analyzed.

RESULTS:

Thirty-six patients were taken for the study. Two cases were excluded since intra-operatively they were tubo-ovarian masses. The most common tumor was dermoid cyst (n=13; 38.23%) and endometriotic cyst (n=14; 41.17%). Out of 34 cases, five cases of endometriotic cyst (14.70%) were converted to laparotomy due to severe adhesions and four cases of endometriotic cyst underwent deroofing surgery. Two cases underwent laparoscopic assisted vaginal hysterectomy with bilateral salphingo-oopherectomy. Successful cystectomies were carried out in 22 cases. None were malignant. Major complications were not noted while minor complications like port-site infection (n=3; 8.82%) and subcutaneous emphysema (n=1; 2.9%) were present.

CONCLUSIONS:

Laproscopic management of benign ovarian masses is safe and feasible.

 

 

Zhonghua Yi Xue Za Zhi. 2014 Jul 15;94(27):2115-8.

Relationship between ultrastructural features of endometrial-myometrial interface and pathogenesis of adenomyosis.

Wang S¹, Duan H², Zhou L¹, Yu P¹, Zhang Y¹.

 

Abstract

OBJECTIVE:

To explore the ultrastructural features of endometrial-myometrial interface (EMI) of adenomyosis and normal myometrium.

METHODS:

From May 2010 to September 2013, 102 uterine myometrial specimens were obtained from 102 patients undergoing hysterectomy. There were 56 adenomyosis patients as ADS group (including proliferative endometrium, n = 26 and secretory endometrium, n = 30) and another 46 with cervical intraepithelial neoplasis (CIN) III as control group. The myometrium underneath endometrium and the outer third of myometrium were immediately harvested after operation. And the samples were processed and observed under transmission electron microscopy.

RESULTS:

(1) In the presence of uterine adenomyosis, the nuclei were significantly larger than controls and significantly enlarged with less prominent collagen fibrils. The cytoplasm was abundant, denoting cellular hypertrophy. The rough endoplasmic reticulum and Golgi apparatus became more prominent. But the dense patches and dense bodies appeared similar to the control; (2) EMI myocytes ultrastructure showed cyclic changes in controls. In proliferative cycle, the average nuclear size was larger than that in secretory cycle [(3.24 ± 0.41), (2.44 ± 0.27) µm, P < 0.05]. But there was not any differences from different cyclic phases in adenomyosis [(2.34 ± 0.17), (2.63 ± 0.39) µm, P > 0.05]; (3) EMI myocytes appeared significantly different than that of outer myometrium. The nuclei of EMI myocytes were much smaller than outer myometrium. And there was less prominent collagen fibrils. The dense patches, dense bodies and myofilament-cytoplasm ratio of EMI were smaller than outer myometrium. The nuclei-to-myocyte ratio was larger than outer myometrium.

CONCLUSION:

Abnormal ultrastructural features of EMI may be correlated with the development of adenomyosis.

 

 

J Pregnancy. 2014;2014

Visual acuity changes during pregnancy and postpartum: a cross-sectional study in Iran.

Mehdizadehkashi K¹, Chaichian S², Mehdizadehkashi A³, Jafarzadepour E⁴, Tamannaie Z⁵, Moazzami B¹, Pishgahroudsari M⁶.

 

Abstract

In this research, we represent the changes in visual acuity during pregnancy and after delivery. Changes as myopic shift start during second trimester and will be stopped after delivery; however it is obtained that women will have the same refractive error as what they had in the first trimester, after postpartum. So, any change in their spectacle prescription during this period is forbidden. As a result, not only changing in hormones can cause myopic shift in vision, but also overweight has its retributive role. What we are trying to do is to notify gynecologists and optometrists to be aware of these changes, so as to leave spectacle prescription writing to the session after postpartum period.

 

 

 

PLoS One. 2014 Oct 17;9(10)

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

Rakhila H¹, Girard K², Leboeuf M², Lemyre M², Akoum A³.

 

Abstract

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease’s symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

 

 

J Reprod Med. 2014 Sep-Oct;59(9-10):481-7.

Progesterone reduces neurofilament (NF)–positive nerve fibers in eutopic endometrium of patients with endometriosis and myomata.

Kim YA, Kim JY, Chang SH, Chang DY, Chun KC, Koh JW.

 

Abstract

OBJECTIVE:

To evaluate whether there are neurofilament (NF)-positive nerve fibers in the eutopic endometrium of patients with myoma and endometriosis by using stromal cell culture and to verify whether progesterone has an effect on the NF-positive nerve fiber by using stromal cell culture.

STUDY DESIGN:

Patients with uterine myoma (N = 11), ovarian and pelvic endometriosis (N = 10), and without myoma and endometriosis (N = 10) were included in the study. Human endometrial tissues were obtained from hysterectomy and curettage. The stromal cells were cultured and immunostaining was performed before and after treatment with progesterone by using NF.

RESULTS:

Before progesterone treatment the percentage of NF-positive nerve fibers between the uterine myoma group (4.91 +/- 2.05) and the endometriosis group (2.22 +/- 0.92) was statistically significant, and there was a significantly different percentage of NF-positive nerve fibers between the uterine myoma group (4.91 +/- 2.05) and the levonorgestrel intrauterine device-inserted group (1.50 +/- 0.25). After progesterone treatment the percentage of NF-positive nerve fibers was significantly decreased in the uterine myoma (2.09 +/- 1.73) and the endometriosis (1.48 +/- 0.80) groups.

CONCLUSION:

We showed that the NF-positive nerve fibers were reduced after progesterone treatment by using stromal cell culture and suggest that progesterone could have a role in the decrease of endometriosis/myoma-associated pain.

 

 

J Ovarian Res. 2014 Oct 21;7

A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with endometriosis.

Tamura H, Takasaki A, Nakamura Y, Numa F, Sugino N.

 

Abstract

BACKGROUND:

Additional treatment with a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) before IVF-ET (ultralong GnRHa therapy) has been reported to improve the outcome of IVF-ET in endometriosispatients. However, the mechanism of ultralong GnRHa therapy is unclear. It is suggested that inflammatory cytokines and oxidative stress contribute to infertility in endometriosis patients. Therefore, in order to search a possible mechanism of ultralong GnRHa therapy, we investigated the effect of ultralong GnRHa therapy on intrafollicular concentrations of tumor necrosis factor alpha (TNFα), oxidative stress markers, and antioxidants in patients with endometriosis.

METHODS:

Twenty-three infertile women with Stage III or IV endometriosis were recruited for this study. Eleven patients received three courses of GnRHa (1.8 mg s.c. every 28 days), followed by a standard controlled ovarian hyperstimulation (COH) for IVF-ET (ultralong group). The other 12 patients received a standard COH with mid-luteal phase GnRHa down-regulation (control group). The numbers of matured follicles and retrieved oocytes, fertilization rates, implantation rates, clinical pregnancy rate, and intrafollicular concentrations of TNFα, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL) as oxidative stress markers, and melatonin and Cu,Zu-superoxide dismutase (Cu,Zn-SOD) as antioxidants were compared between the two groups.

RESULTS:

The numbers of mature follicles and retrieved oocytes, and fertilization rates did not differ between the two groups. Implantation rates and pregnancy rates tended to be higher in the ultralong group (21.4% and 27.3%, respectively) compared with the control group (8.3% and 8.3%, respectively). TNFα concentrations in the follicular fluid were significantly lower in the ultralong group (5.8 ± 3.2 pg/ml) than those in the control group (10.6 ± 3.2 pg/ml). Follicular concentrations of 8-OHdG concentrations were significantly lower in the ultralong group (5.7 ± 1.6 ng/ml) than those in the control group (6.6 ± 1.5 ng/ml), while melatonin concentrations were significantly higher in the ultralong group (139 ± 46 pg/ml) compared with the control group (86 ± 27 pg/ml).

CONCLUSIONS:

Ultralong GnRHa therapy reduces the detrimental effects of cytotoxic cytokines and oxidative stress in the ovary in patients with endometriosis.

 

 

Oncol Rep. 2014 Dec;32(6):2580-8.

RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis.

Guo C¹, Ren F¹, Wang D¹, Li Y¹, Liu K¹, Liu S¹, Chen P¹.

 

Abstract

The aim of the present study was to investigate the role of epigenetic inactivation of the runt-related transcription factor 3 gene (RUNX3) in the malignant transformation of ovarian endometriosis. Samples obtained by microdissection and scraping included 30 malignant ovarian endometriotic cyst tissues and 30 corresponding eutopic endometrium tissues from the endometriosis-associated ovarian carcinoma (EAOC) group, 19 benign ovarian endometriotic cyst tissues and 22 corresponding eutopic endometrium tissues from the endometriosis(EM) group and 22 normal eutopic endometrium tissues from the control endometrium (CE) group. RUNX3 methylation status was determined by methylation-specific PCR and bisulfite sequencing, while levels of RUNX3 and ERα protein expression were evaluated using immunohistochemistry. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the malignant ovarian endometriotic cysts from the EAOC group was significantly higher than that in the benign ovarian endometriotic cysts from the EM group. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the eutopic endometrium from the EAOC group was significantly higher than that in the EM and CE groups. An inverse correlation between positive RUNX3 protein expression and methylation was observed and a positive correlation was shown between RUNX3 methylation and ERα protein expression. In the malignant ovarian endometriotic cysts from the EAOC group, there was no significant correlation between methylation frequency of the RUNX3 gene and histological type. However, the percentage of RUNX3 gene methylation was significantly higher in the tissue samples from patients with surgical stage IC EAOC than the percentage in patients with stage IA and IB disease. These results suggest that RUNX3 inactivation by promoter hypermethylation plays a role in the progression of malignant transformation of ovarian EM and is closely related to estrogen metabolism. Negative protein expression and abnormal RUNX3 methylation in the eutopic endometrium could be used as diagnostic markers in patients with ovarian EM who may be at an increased risk of developing EAOC.