Arch Gynecol Obstet. 2014 Nov;290(5):1015-22.

Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis.

Pabalan N1Salvador AJarjanazi HChristofolini DMBarbosa CPBianco B.

 

Abstract

BACKGROUND:

Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis have been inconsistent.

AIM OF THE STUDY:

To evaluate the association between the PROGINS polymorphism and the risk of endometriosis.

METHODOLOGY:

A meta-analysis of 12 published case-control studies with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis association with the PROGINS polymorphism.

RESULTS:

An association between the presence of the variant allele and risk of endometriosis was found, more in the homozygous and recessive models (OR 1.41-1.43, p = 0.15-0.17), and less in the dominant and co-dominant models (OR 1.22, p = 0.11-0.15). Reanalysis without the studies whose controls deviated from the Hardy-Weinberg Equilibrium did not materially alter the dominant and co-dominant effects (OR 1.19-1.22, p = 0.19-0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09). The subgroups based on geography showed increased risk associations, consistently significant in the European (OR 1.52-2.72, p = 0.0008-0.03) but not in the Brazilian studies, where ORs ranged from reduced (OR 0.70-0.74, p = 0.54-0.61) to increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all comparisons to the dominant and co-dominant models (I (2) = 38-70 %), except in the European subgroup, which had zero heterogeneity (I (2) = 0 %) in all genetic models, as did all homozygous and recessive effects.

CONCLUSION:

This meta-analysis provides a comprehensive profile of the role of the PROGINS polymorphism in endometriosis by exploring the magnitude of the summary effects with modifier analysis. This magnitude is expressed with modulation or exacerbation of the summary effects, as defined by the parameters of the analysis. Thus, the results showed trend towards an increased risk of the variant PROGINS allele and susceptibility for the endometriosis.

 

 

Hum Fertil (Camb). 2015 Mar;18(1):30-7.

Levels of oestrogen receptor, progesterone receptor and αB-crystallin in eutopic endometrium in relation to pregnancy in women with endometriosis.

Moberg C1Bourlev VIlyasova NOlovsson M.

 

Abstract

Endometriosis affects fertility in many women and may partly be due to decreased endometrial receptivity. Several mechanisms have been suggested, notably, progesterone resistance for which a number of candidate biomarkers have been suggested. Here we demonstrate aberrant levels of steroid hormone receptors and the small heat shock protein αB-crystallin in eutopic endometrial epithelium from 38 women with peritoneal endometriosis diagnosed during investigation for secondary infertility. Spontaneous pregnancies within 1 year after medical and surgical treatment for endometriosis were recorded and semi-quantitative immunohistochemistry data compared between women with endometriosis who did or did not become pregnant and healthy controls. Stronger immunostaining for ER-α was detected in luminal and glandular endometrial epithelium from women with endometriosis who did not become pregnant during the post-treatment observation period versus endometriosis patients who became pregnant and controls. Staining levels of PR and PR-B were lower in patients without subsequent pregnancies than in the two other groups. Endometrial levels of αB-crystallin in endometriosis patients similar to those in controls were strongly correlated with the chance of becoming pregnant, whereas higher or lower levels were not.

 

 

PLoS Genet. 2014 Jun 19;10(6):e1004451.

The epidermal growth factor receptor critically regulates endometrial function during early pregnancy.

Large MJ1Wetendorf M1Lanz RB1Hartig SM1Creighton CJ2Mancini MA1Kovanci E3Lee KF4Threadgill DW5Lydon JP1Jeong JW6DeMayo FJ1.

 

Abstract

Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.

 

 

Niger J Med. 2014 Jan-Mar;23(1):77-82.

Pattern of cardiothoracic surgical diseases in a new cardiothoracic surgery unit in Nigeria.

Ekpe EEEtte VFAkpan A.

 

Abstract

BACKGROUND:

Cardiothoracic surgical pathologies are available in all geographical regions of the world. Human and material resources are necessary for prompt diagnosis and proper treatment of these cases.

METHODOLOGY:

Retrospective analysis of cardiothoracic surgical cases in the first five years of our new cardiothoracic surgery unit was done.

RESULTS:

A total of 714 cases were seen during the study period with age range one month to 76 years with mean age of 37.12 +/- 11.24 and male female ratio of 2:1. The yearly admissions from 2007 to 2011 were 14%, 17%, 21%, 21% and 26% respectively. Cardiovascular diseases occurred in 22.30%, with 6% of children suffering from congenital heart defect and 6% of men suffering from acquired vascular disease. Surgical complications of pleuropulmonary tuberculosis occurred in 21.4% while thoracic trauma occurred in upto 21% of the patients. Aerodigestive tract foreign bodies were encountered in 10.1% of cases and Pyogenic diseases occurred in 8.68%. Oesophageal lesions were diagnosed in 6.4% of the patients, pulmonary tumours including primary and secondary tumours were found in 4.3% while nontraumatic chest wall pathologies which included chest wall tumours, congenital deformities and chronic osteomyelities accounted for 3.2%. Mediastinal pathologies occurred in 0.98% and in the remaining 1.5% rare diseases were diagnosed such as third degree heart block, pulmonary embolism and thoracic endometriosis syndrome.

CONCLUSION:

This study shows that cardiothoracic surgical pathologies are common in our centre with predominance of thoracic pathologies, and therefore need to prioritize and ensure manpower development for treatment of all kinds of thoracic pathologies.

 

 

Reprod Biomed Online. 2014 Aug;29(2):259-66.

Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?

Coccia ME1Rizzello F2Barone S3Pinelli S3Rapalini E3Parri C3Caracciolo D3Papageorgiou S3Cima G3Gandini L4.

 

Abstract

This study investigated the relationships between ovarian endometrioma size, ovarian responsiveness and the number of retrieved oocytes following ovarian stimulation. A prospective study was conducted in a public clinical assisted reproduction centre. A total of 64 infertile women with monolateral endometriomas undergoing IVF or intracytoplasmic sperm injection were included in the study. The total number of follicles, number of follicles ≥ 16 mm and number of oocytes retrieved of ovaries containing endometrioma and normal ovaries were compared. Multivariate linear regression was used to assess whether number of follicles and collected oocytes varied by endometrioma size, age, basal FSH concentration. Significantly lower numbers of follicles ≥ 16 mm (P = 0.024) and oocytes retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In patients with endometriomas ≥ 30 mm, endometrioma size was the most influential contributor to the total number of follicles and oocytes retrieved. Ovarian endometriomas result in reduced response to ovarian stimulation, compared with the response of the contralateral normal ovary in the same individual. In case of endometriomas <30 mm, basal FSH concentration remains the most important prognostic factor for oocyte retrieval.

 

 

Curr Opin Obstet Gynecol. 2014 Aug;26(4):237-42.

Selective progesterone receptor modulators.

Whitaker LH1Williams ARCritchley HO.

 

Abstract

PURPOSE OF REVIEW:

Review of recent data from clinical trials and descriptions of endometrial morphology with administration of selective progesterone receptor modulators (SPRMs).

RECENT FINDINGS:

Recent reports concerning administration of SPRMs, specifically the efficacy of ulipristal acetate in reducing fibroid size and rapid control of menstrual blood loss, have renewed clinical interest in this class of compound. Histological data from studies with SPRMs report that this class of drugs is associated with progesterone receptor modulator-associated endometrial changes. Data on mechanisms of action are lacking. The antagonistic progesterone effect of SPRMs has shown promising results in animal studies with endometriosis. Sex steroid receptor effects of PRMs outside the reproductive tract raise the potential for use in neurology and oncology, and although there are several randomized trials in these areas, there are limited small studies published to date.

SUMMARY:

The SPRM ulipristal acetate is an effective treatment for preoperative treatment of fibroids and a reliable emergency contraceptive. This class of compounds holds the potential for long-term effective medical management of fibroids and may have utility in the management of other sex steroid-dependent conditions.

 

 

Hum Reprod. 2014 Sep;29(9):1925-30.

Reproductive choices and outcomes after freezing oocytes for medical reasons: a follow-up study.

Dahhan T1Dancet EA2Miedema DV2van der Veen F2Goddijn M2.

 

Abstract

STUDY QUESTION:

What reproductive choices do women make after they have cryopreserved oocytes for medical reasons?

SUMMARY ANSWER:

Women who had cryopreserved oocytes for medical reasons and tried to become pregnant, either attempted natural conception or resorted to assisted reproduction with fresh oocytes.

WHAT IS KNOWN ALREADY:

Women confronted with a risk of premature ovarian insufficiency, due to gonadotoxic therapy, ovarian surgery or genetic predisposition, have an indication to cryopreserve oocytes. Many of these women will retain ovarian function, thus will retain the possibility of natural conception. The added value of cryopreserved oocytes to reproductive outcomes is unknown as there is a lack of follow-up of women who have cryopreserved oocytes for medical reasons.

STUDY DESIGN, SIZE AND DURATION:

This follow-up study included a cohort of 85 women who cryopreserved their oocytes for medical reasons between 2009 and 2012.

PARTICIPANTS/MATERIALS, SETTING AND METHODS:

Medical data from women who cryopreserved their oocytes at the Centre for Reproductive Medicine in the Academic Medical Centre in Amsterdam were extracted and self-report questionnaires were disseminated. The collected data considered demographics, outcomes of ovarian stimulation, fertility-threatening treatments, menstrual cycle changes, pregnancy attempts and outcomes and intended plans for the cryopreserved oocytes.

MAIN RESULTS AND THE ROLE OF CHANCE:

A total of 68 women, followed up for an average 25.3 months, returned the questionnaire (response rate: 80%). None of the women had used her cryopreserved oocytes although 16 women had tried to conceive. Of these women, eight were trying to conceive naturally, five had conceived naturally within 2 months and three had conceived with assisted reproduction not requiring cryopreserved oocytes (two women with conventional IVF because of tubal pathology and endometriosis and one woman with IUI because of polycystic ovary syndrome). Three out of the eight pregnancies had resulted in live births, two resulted in miscarriages and three were ongoing. Most women (71%) intended to conceive with their cryopreserved oocytes as a last resource option.

LIMITATIONS, REASONS FOR CAUTION:

Transferability of our findings is challenged by the small sample but positively affected by our high response rate. As the time span between cryopreservation of oocytes and follow-up was short, follow-up of the cohort should be repeated in 2 years.

WIDER IMPLICATIONS OF THE FINDINGS:

After a mean follow-up of 2 years, none of the women with a medical reason to cryopreserve oocytes had used her oocytes. Women who were trying to conceive during follow-up were doing so without using their stored oocytes. It is unclear whether starting assisted reproduction while having cryopreserved oocytes is the most appropriate clinical decision. Our findings emphasize the relevance of taking the chances of natural conception into account in counselling women about cryopreservation of oocytes.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:170-4.

Progesterone and synthetic progestin, dienogest, induce apoptosis of human primary cultures of adenomyotic stromal cells.

Yamanaka A1Kimura F2Kishi Y3Takahashi K4Suginami H3Shimizu Y5Murakami T2.

 

Abstract

OBJECTIVES:

To investigate the direct effects of progesterone receptor (PR) agonists on proliferation and apoptosis of human adenomyotic cells.

STUDY DESIGN:

Human primary cultures of adenomyotic stromal cells (ASCs) from 24 patients with adenomyosis were co-treated with estradiol (E2) plus the PR agonists, endogenous progesterone (P) or the synthetic progestin dienogest (DNG), which is used to treat endometriosis. In ASCs, anti-proliferative effects and induction of apoptosis were evaluated in the presence or absence of P (10(-8)-10(-6)M) or DNG (10(-8)-10(-6)M) in culture medium containing E2. Cellular proliferation was analyzed with bromodeoxyuridine incorporation and flow cytometry. Apoptosis was detected with annexin V/7-amino-actinomycin D (7-AAD) staining with flow cytometry and cellular caspase 3/7 activity.

RESULTS:

P and DNG significantly decreased the proportion of cells in the S phase. In addition, both P and DNG increased apoptosis as measured by annexin V-positive/7-AAD -negative cells and caspase 3/7 activity.

CONCLUSIONS:

Both endogenous P and synthetic progestin directly inhibited cellular proliferation and induced apoptosis in human ASCs. These pharmacological features of progestational compounds provide insight into the therapeutic strategy for the treatment of adenomyosis.

 

 

J Coll Physicians Surg Pak. 2014 Jun;24(6):438-40.

Giant intraabdominal endometrial cyst.

Shah AA1Soomro NA2Talib RK3Sadhayo AN4Soomro SA4.

 

Abstract

Endometriosis is the condition where endometrium gets implanted and flourishes outside the uterine cavity, most commonly in ovary and on the peritoneum which lines the abdominal cavity and viscera. Endometrial cells in areas outside the uterus are influenced by hormonal changes and respond in a way similar to the endometrium inside the uterus. Symptoms often worsen with the menstrual cycle. We present a case of 50 years old female who presented with gross abdominal distension and abdominal pain over years. CT scan showed a huge intraabdominal cyst of unknown origin which was compressing adjacent structures. Patient underwent a high risk operation and whole cyst weighing 214 kg (471 lbs) was removed along with both ovaries and uterus. Histopathologically, it was reported as endometrial cyst.

 

 

PLoS One. 2014 Jun 23;9(6):e100481

CRISPLD2 is a target of progesterone receptor and its expression is decreased in women with endometriosis.

Yoo JY1Shin H2Kim TH1Choi WS3Ferguson SD1Fazleabas AT1Young SL4Lessey BA5Ha UH6Jeong JW1.

 

Abstract

Endometriosis, defined as the presence of endometrial cells outside of the uterine cavity, is a major cause of infertility and pelvic pain, afflicting more than 10% of reproductive age women. Endometriosis is a chronic inflammatory disease and lipopolysaccharide promotes the proliferation and invasion of endometriotic stromal cells. Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) has high affinity for lipopolysaccharide and plays a critical role in defense against endotoxin shock. However, the function of CRISPLD2 has not been studied in endometriosis and uterine biology. Herein, we examined the expression of CRISPLD2 in endometrium from patients with and without endometriosis using immunohistochemistry. The expression of CRISPLD2 was higher in the secretory phase in human menstrual cycle compared to proliferative phase. The expression of CRISPLD2 was significantly decreased in the endometrium of women with endometriosis in the early secretory phase compared to women without endometriosis. The increase of CRISPLD2 expression at the early secretory and dysregulation of its expression in endometriosis suggest progesterone (P4) regulation of CRISPLD2. To investigate whether CRISPLD2 is regulated by P4, we examined the expression of the CRISPLD2 in the uteri of wild-type and progesterone receptor knock out (PRKO) mice. The expression of CRISPLD2 was significantly increased after P4 treatment in the wild-type mice. However, CRISPLD2 expression was significantly decreased in the (PRKO) mice treated with P4. During early pregnancy, the expression of CRISPLD2 was increased in decidua of implantation and post-implantation stages. CRISPLD2 levels were also increased in cultured human endometrial stromal cells during in vitro decidualization. These results suggest that the CRISPLD2 is a target of the progesterone receptor and may play an important role in pathogenesis of endometriosis.

 

 

J Clin Ultrasound. 2015 Sep;43(7):443-6.

A case of intussusception of the appendix secondary to endometriosis: US and CT findings.

Lee DJ1Kim HC1Yang DM1Kim SW1Ryu JK1Won KY2Lee SH3.

 

Abstract

Intussusception of the appendix is an uncommon condition that is difficult to diagnose with radiology. Endometriosis causing appendiceal intussusception is a rare condition that has only been reported a few times in the literature. Here, we report a case of appendiceal intussusception caused by endometriosis in a 33-year-old woman who presented with intermittent right lower abdominal pain. Sonography revealed a hypoechoic mass invaginating into the cecum, which was covered by echogenic cecal wall with central dimpling indicating the appendiceal orifice. On CT, the mass was identified as an enhancing mass invaginating into the cecum at the level the appendiceal orifice.

 

 

Oncol Lett. 2014 Jul;8(1):3-6.

Malignant neoplasia arising from ovarian remnants following bilateral salpingo-oophorectomy (Review).

Imai A1Matsunami K1Takagi H1Ichigo S1.

 

Abstract

Ovarian remnant syndrome (ORS) is a rare, but well-known gynecological complication, most often induced by difficult bilateral salpingo-oophorectomy (BSO) procedures that leave residual ovarian tissue on the pelvic wall. The most common preexisting conditions for this complication include endometriosis, pelvic inflammatory disease and prior abdominal surgery. The residual ovarian tissue may eventually cause malignant development. A total of 12 cases of malignant and benign tumors (clear cell adenocarcinoma in 1 case, mucinous-type tumors in 2, endometrioid-type tumors in 5, adenocarcinoma in 3 and border serous neoplasia in 1) and 21 benign cysts developing from an ovarian remnant have been described in the literature to date. Endometriosis, known to increase the risk of ovarian cancer, predisposes patients to ORS, with an incidence rate of 30 to 50% in ORS patients with ovarian carcinoma. Although the true incidence of ORS remains unknown, when endometriotic adhesions are diagnosed during BSO, the possibility of ORS and subsequent ovarian malignant transformation may mandate complete surgical resection.

 

 

J Clin Diagn Res. 2014 Apr;8(4)

Scar endometriosis-a sequel of caesarean section.

Patil NJ1Kumar V2Gupta A1.

 

Abstract

Endometriosis is presence of functioning endometrial tissue outside the uterine cavity, usually in the pelvis. However, its occurrence is very rare (0.03%-0.4%) in the scars which follow obstetrical and gynaecological surgeries. We are reporting two cases of scar endometriosis which occurred after caesarean sections. Both cases presented with abdominal pain at caesarean scar sites, one of which gave a cyclical history. Clinical examination revealed painful swellings in both cases, which were misdiagnosed as stitch granulomas. Wide surgical excisions were done and histopathology examination revealed a diagnosis of scar endometriosis. We are presenting these cases because of their rarity, their uncommon sites and difficulty in diagnosing the conditions clinically.

 

 

Semin Reprod Med. 2014 Sep;32(5):365-75.

Homeostasis imbalance in the endometrium of women with implantation defects: the role of estrogen and progesterone.

Lessey BA1Young SL2.

 

Abstract

Embryo implantation is regulated by an inflammatory process in response to sequential exposure to estrogen and progesterone, followed by resolution and repair. The actions of estrogen and progesterone on these inflammatory processes are tightly and reciprocally controlled through regulated expression of steroid receptors, cofactors, chaperone proteins, and downstream signaling components. In endometriosis, the inflammatory cascades, normally seen at menstruation, are prematurely activated and endogenous endometrial mechanisms of inflammation resolution appear defective. The temporally abnormally inflammation is also associated with an imbalance between estrogen and progesterone actions; the normal luteal-phase dominance of progesterone action appears to be lost and is replaced by progesterone resistance and estrogen dominance. In this review, we examine these relationships in greater detail and argue that estrogen action is a prime target for future therapeutic solutions to endometriosis and implantation failure that result from this chronic, inflammatory disease.

 

 

J Obstet Gynaecol. 2015 Jan;35(1):49-52.

Evaluation of quality of life in fertile Turkish women with severe endometriosis.

Kiykac Altinbas S1Bayoglu Tekin YDilbaz BDilbaz S.

 

Abstract

We assessed the impact of pain, dysmenorrhoea and dyspareunia on the quality of life among Turkish fertile women with severe endometriosis. A total of 33 patients with histopathologically diagnosed severe endometriosis (Stage IV, revised criteria of the American Fertility Society (rAFS score) were enrolled into the study. Patients reported chronic pelvic pain using a visual analogue scale (VAS) and severity of dysmenorrhoea, dyspareunia and pelvic tenderness using the verbal rating scale (VRS). Quality of life (physical, psychological, social, environmental domains) was evaluated using the World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF). There were no correlations between quality of life and VRS and VAS scores of chronic pelvic pain in patients with dyspareunia (p > 0.05). VRS in patients with dysmenorrhoea negatively correlated with physical, social and environmental dimensions of quality of life (r = -0.382, r = -0.221, r = -0.373 and p = 0.028, p = 0.013, p = 0.033, respectively). Although the severity of dysmenorrhoea seems to be related with lower quality of life, chronic pelvic pain and dyspareunia due to endometriosis may not have any deleterious effects on the quality of life.

 

 

JSLS. 2014 Apr-Jun;18(2):191-6.

Laparoendoscopic single-site surgery for management of ovarian endometriomas.

Bedaiwy MA1Farghaly T2Hurd W2Liu J2Mansour G2Fader AN3Escobar P4.

 

Abstract

BACKGROUND AND OBJECTIVES:

To compare our initial experience in laparoscopic surgery for ovarian endometriomas performed through an umbilical incision using a single 3-channel port and flexible laparoscopic instrumentation versus traditional laparoscopy.

METHODS:

This study was conducted in 3 tertiary care referral centers. Since September 2009, we have performed laparoendoscopic single-site surgery in 24 patients diagnosed with ovarian endometriomas. A control group of patients with similar diagnoses who underwent traditional operative laparoscopy during the same period was included (n = 28). In the laparoendoscopic single-site surgery group, a multichannel port was inserted into the peritoneum through a 1.5- to 2.0-cm umbilical incision.

RESULTS:

Patients in the laparoendoscopic single-site surgery group were significantly older (P = .04) and had a higher body mass index (P = .005). Both groups were comparable regarding history of abdominal surgery, lateral pelvic side wall involvement, and cul-de-sac involvement. After we controlled for age and body mass index, the size of the resected endometriomas, duration of surgery, and amount of operative blood loss were comparable in both groups. When required, an additional 5-mm port was inserted in the right or left lower quadrant in the laparoendoscopic single-site surgery group to allow the use of a third instrument for additional tissue retraction or manipulation (10 of 24 patients, 41.6%). However, adhesiolysis was performed more frequently in the conventional laparoscopy group. The duration of hospital stay was <24 hours in both groups. No intraoperative complications were encountered. All incisions healed and were cosmetically satisfactory.

CONCLUSION:

The laparoendoscopic single-site surgery technique is a reasonable initial approach for the treatment of endometriomas. In our experience, an additional side port is usually needed to treat pelvic side wall and cul-de-sac endometriosis that often accompanies endometriomas.

 

 

JSLS. 2014 Apr-Jun;18(2):357-60.

Endometriosis of the bladder as a cause of obstructive uropathy.

Gyang AN1Gomez NA2Lamvu GM2.

 

Abstract

A 47-year-old woman (gravida 1, para 1) with menorrhagia and pelvic pain was found to have an enlarged fibroid uterus and bladder mass on ultrasonographic imaging. The patient underwent an abdominal supracervical hysterectomy and transurethral bladder mass resection. Histopathologic findings revealed leiomyoma uteri, intramural adenomyosis, and bladder endometriosis. Most case series of bladder endometriosis include women that present with urinary symptoms. This is a rare case of obstructive uropathy secondary to bladder endometriosis in a patient without any urinary signs or symptoms.

 

 

J Clin Endocrinol Metab. 2014 Oct;99(10):E1913-21.

Dysregulated sphingolipid metabolism in endometriosis.

Lee YH1Tan CWVenkatratnam ATan CSCui LLoh SFGriffith LTannenbaum SRChan JK.

 

Abstract

BACKGROUND:

In endometriosis, the establishment and subsistence of ectopic lesions outside the endometrium suggest an altered cellular state for pathological hyperplasia. Sphingolipids are bioactive compounds, and their biosynthesis and metabolism modulate a range of cellular processes including proliferation, migration and apoptosis. We demonstrate that aberrations in sphingolipid metabolism occur in women with endometriosis.

METHODS:

Targeted mass spectrometry on >120 sphingolipids were measured in the sera (n = 62), peritoneal fluid (n = 63), and endometrial tissue (n = 14) of women with and without endometriosis. Quantitative RT-PCR and immunohistochemistry were performed on endometrial tissues determine the expression levels of sphingolipid enzymes.

RESULTS:

Sphingolipidomics identified the in vivo accumulation of numerous sphingolipids, including the functionally antagonistic glucosylceramides and ceramides in the serum and PF of women with endometriosis. We found upregulation of specific sphingolipid enzymes, namely sphingomyelin synthase 1 (SMS1), sphingomyelinase 3 (SMPD3), and glucosylceramide synthase (GCS) in the endometrium of endometriotic women with corresponding increased GlcCer, decreased sphingomyelin levels, and decreased apoptosis in the endometrium.

CONCLUSIONS:

Our sphingolipidomics approach provided evidence of altered sphingolipid metabolism flux in serum, peritoneal fluid, and endometrial tissue in women with endometriosis. The results provide new information on how sphingolipids and eutopic endometrium may contribute to the pathophysiology of endometriosis. The results also have implications for the use of sphingolipids as potential biomarkers.

 

 

Pathologe. 2014 Jul;35(4):327-35.

Mucinous ovarian neoplasms. Prognostically mostly excellent, infrequently a wolf in sheep’s clothing.

Lax S1Staebler A.

 

Abstract

Mucinous ovarian neoplasms represent the second largest group of epithelial ovarian tumors after serous neoplasms, of which benign cystadenomas constitute more than 80 %. Mucinous cystadenomas and carcinomas cannot be distinguished by the clinical features or the mean age of onset of the disease. They typically occur unilaterally, are confined to the adnexae (FIGO stage I) and clinically present with non-specific abdominal symptoms or are diagnosed by chance. The mean age of disease onset is around 50 years old. The prognosis is excellent. Implants, peritoneal metastases and bilateral occurrence of ovarian mucinous neoplasms should lead to the suspicion of metastasis particularly from a gastrointestinal tumor. Neither microinvasion defined as a maximum extent of invasion of 5 mm, nor intraepithelial carcinoma characterized by high grade atypia without invasion, affect the prognosis of mucinous borderline tumors. Mucinous carcinomas typically show confluent glandular, expansile growth that leads to a labyrinth-like pattern. A destructive infiltrative or nodular growth pattern, however, should lead to the consideration of metastasis. Mural nodules that may reveal a spindle cell sarcomatous or anaplastic carcinomatous pattern occur infrequently in mucinous and do not affect the prognosis. Pax8 positivity is indicative of a primary ovarian neoplasm. In this case, however, mucinous tumors associated with teratomas may show the colonic immunoreaction pattern (CK7-/CK20+/CDX2+). The rare mucinous tumors with endocervical differentiation are now designated as seromucinous tumors and consist of two or more distinct cell types, are frequently associated with endometriosis and seem to show a molecular genetic relationship to endometrioid neoplasms.

 

 

Hum Reprod. 2014 Sep;29(9):1906-11.

DNA methylation of HOXA10 in eutopic and ectopic endometrium.

Andersson KL1Bussani C2Fambrini M2Polverino V2Taddei GL3Gemzell-Danielsson K4Scarselli G2.

 

Abstract

STUDY QUESTION:

Does the methylation status of the promoter region of the HOXA10 gene differ in eutopic and ectopic endometrium?

SUMMARY ANSWER:

The eutopic endometrium in women with endometriosis is significantly more methylated when compared with controls.

WHAT IS KNOWN ALREADY:

Expression of the HOXA10 gene, which is important for successful implantation, is reduced in women affected by endometriosis.

STUDY DESIGN, SIZE AND DURATION:

A pilot study was carried out including 18 women admitted for surgery for endometriosis-related pain (cases) and 12 women admitted for surgery because of non-endometriotic disease (control). Sample collection and analysis were performed between November 2010 and July 2013.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Endometrial tissue (eutopic and ectopic) underwent sodium bisulfite DNA modification, PCR amplification of two regions of the HOXA10 promoter and pyrosequencing analysis.

MAIN RESULTS AND THE ROLE OF CHANCE:

The eutopic endometrium of women with endometriosis was significantly more methylated compared with endometrium from the control group (sequence 1: 8.68% in cases and 6.25% in the control group: P = 0.037, sequence 2: 11.89% in cases and 9.25% in the control group: P = 0.032). The eutopic endometrium was significantly more methylated than the ectopic tissue in patients with endometriosis (mean difference -3.6 sequence 1: P = 0.001 and -6.0 sequence 2: P = 0.0001).

LIMITATIONS, REASONS FOR CAUTION:

The study had a limited sample size and the fertility status of the majority of patients in our study was unknown.

WIDER IMPLICATIONS OF THE FINDINGS:

Our data regarding methylation state of the ectopic tissues contribute to a better etiopathologic understanding of endometriosis.

STUDY FUNDING/COMPETING INTERESTS:

No external funding was either sought or obtained for this study. The authors have no conflicts of interests to declare.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:17-21.

COMT 158G/A and CYP1B1 432C/G polymorphisms increase the risk of endometriosis and adenomyosis: a meta-analysis.

Tong X1Li Z1Wu Y1Fu X1Zhang Y2Fan H3.

 

Abstract

OBJECTIVE:

Catechol-O-methyltransferase (COMT) 158G/A and cytochrome P450-1B1 (CYP1B1) 432C/G gene polymorphisms have been associated with the risk of endometriosis and adenomyosis, but results remain inconclusive. The aim of this study was to investigate the relationships between these polymorphisms and the risk of endometriosis and adenomyosis by meta-analysis.

STUDY DESIGN:

A search was performed using PubMed, Embase, the Chinese Journals Full-text Database and Wanfang databases up to September 2013. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the relationships. Statistical analyses were undertaken using STATA Version 11.0.

RESULTS:

The literature search identified 10 articles, involving 1770 cases and 2057 controls. The two polymorphisms were found to be significantly associated with the risk of endometriosis and adenomyosis (COMT 158 G/A: AA+AG vs GG: OR 1.20, 95% CI 1.01-1.43; CYP1B1 432 C/G: GG+GC vs CC: OR 1.28, 95% CI 1.01-1.68). In the subgroup analysis by ethnicity, the two polymorphisms were significantly associated with the risk of endometriosis and adenomyosis among Asian populations but not among Caucasian populations.

CONCLUSIONS:

COMT 158G/A and CYP1B1 432C/G polymorphisms may contribute to the risk of endometriosis and adenomyosis, particularly in Asian populations. Larger studies are required to evaluate this association further.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:51-7.

Prevalence and severity of cyclic leg pain in women with endometriosis and in controls – effect of laparoscopic surgery.

Walch K1Kernstock T2Poschalko-Hammerle G2Gleiß A3Staudigl C2Wenzl R2.

 

Abstract

OBJECTIVE:

In addition to dysmenorrhea, dyspareunia, and subfertility, pain in the lower extremities has been described to be a further complaint in women affected by endometriosis, and lysis of nerve entrapment was thought to be associated with amelioration of leg pain. Therefore, we aimed to compare the prevalence of cyclic leg pain and pain intensity between women with endometriosis and without endometriosis, and to evaluate the effect of laparoscopic surgery.

STUDY DESIGN:

Forty-four women with endometriosis and 58 controls were included in a prospective, controlled clinical trial at a University hospital/tertiary referral center. Participants were asked to complete questionnaires the day before and six to nine weeks after laparoscopy. The prevalence and intensity of leg pain and improvement after laparoscopic surgery, quantified according to a visual analog scale (VAS) score, were evaluated. We also recorded involvement of dermatomes, the presence and intensity of dysmenorrhea, and correlations between age, stage of endometriosis (rAFS-score), and preoperative VAS scores.

RESULTS:

Before surgery, more women were affected by leg pain in the endometriosis group, compared to the control group (45.5% and 25.9%, respectively). Preoperative VAS scores for leg pain, however, were not significantly different between the two groups. A moderate correlation in the preoperative VAS scores between leg pain and dysmenorrhea was observed. After laparoscopy, we found a significant improvement in leg pain intensity in both groups. The mean difference in the VAS score for pain reduction between the study group and the control group was 0.74 (95% CI: -0.61-2.08), which was not statistically significant.

CONCLUSIONS:

The prevalence of leg pain is increased in endometriosis, while leg pain intensity is not, compared to women without endometriosis. Laparoscopic surgery-even without preparation and decompression of nerve tissue-is associated with an improvement in pain intensity in women with endometriosis, as well as in the group without endometriosis.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:63-8.

Progestogen-only contraceptive pill compared with combined oral contraceptive in the treatment of pain symptoms caused by endometriosis in patients with migraine without aura.

Morotti M1Remorgida V2Venturini PL2Ferrero S2.

 

Abstract

OBJECTIVE:

Evaluate patient satisfaction at 6-month treatment in women with symptomatic rectovaginal endometriosis and migraine without aura with (progestogen-only contraceptive pill, POP versus sequential combined oral contraceptives, COC) STUDY DESIGN: A patient preference trial including 144 women (82 in the group COC and 62 in the group POP). Main outcome measure was the degree of patient satisfaction by using a Likert scale. Secondary objectives were to evaluate differences in endometriosis-related pain and changes in migraine features during the treatment.

RESULTS:

In group POP, 38/62 women (61.2%) were satisfied or very satisfied after treatment, compared to 31/82 women (37.8%) in group COC (p=0.005). The intensity of chronic pelvic pain and dyspareunia significantly decreased at 6-month treatment in both the groups. At 6-month treatment, the number of migraine attacks was lower than at baseline in group POP (p=0.002), while it was not reduced in group COC (p=0.521). The intensity of migraine attacks was significantly different between baseline and 6-month treatment in group POP (p<0.001) but not in group COC (p=0.078).

CONCLUSIONS:

POP is better tolerated than COC and it seems to ameliorate migraine attacks compared to COC in symptomatic patients with rectovaginal endometriosis and migraine without aura. Both drugs efficaciously relieve endometriosis-related pain symptoms. This study supports the use of the POP in women with rectovaginal endometriosis and coexisting migraine without aura.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:69-74.

Do women with endometriosis have to worry about sex?

Di Donato N1Montanari G2Benfenati A2Monti G2Bertoldo V2Mauloni M3Seracchioli R2.

 

Abstract

OBJECTIVE(S):

Sexual function is negatively influenced by endometriosis and women with endometriosis show less sexual and partnership satisfaction compared to patients with other gynaecological disorders. This study aims to compare sexual function between patients with deep infiltrating endometriosis (DIE) and healthy women using Sexual Health Outcomes in Women Questionnaire (SHOW-Q).

STUDY DESIGN:

Case-control study including 182 patients with histological diagnosis of DIE and 182 healthy women, who referred to our tertiary care university hospital from 2010 to 2012. SHOW-Q was used to collect data concerning satisfaction, orgasm, desire and pelvic problem interference with sex. The un-paired t-test was performed to compare the means of a continuous variable between groups when the data were normally distributed; otherwise the Mann-Whitney test was used to check t-test results. Pearson’s χ(2) test and Z-test for proportions – independent groups were performed to investigate the difference among grouping variables.

RESULTS:

As described in a previous study, the prevalence of sexual dysfunction in women with endometriosisis around 61% and in women with other gynaecological disorders is 35%. Assuming 5% significance and 95% power, 106 women would be required for the study. Every area of sexual function investigated through the SHOW-Q questionnaire (satisfaction, desire, orgasm and pelvic problem interference) was significantly impaired compared to healthy women. Among patients with DIE, 58% (105/182) reported that pelvic pain severely affected sexual function, while only 1% (2/182) of healthy women (p<0.0001). Moreover, sexual desire was absent or less than one or two times per month in 45% (82/182) of women with DIE compared to 14% (26/182) of healthy women (p<0.0001).

CONCLUSION(S):

DIE severely affects sexual function. Endometriosis is a global disease, which affects patients physically, psychologically and sexually. The potential sexual consequences of this disease need to be considered.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:135-40.

Evaluation of urinary dysfunction by urodynamic tests, electromyography and quality of life questionnaire before and after surgery for deep infiltrating endometriosis.

Ballester M1Dubernard G1Wafo E1Bellon L1Amarenco G2Belghiti J1Daraï E3.

 

Abstract

OBJECTIVE:

To evaluate urinary dysfunction and quality of life before and after surgery for deep infiltrating endometriosis (DIE).

METHODS:

This prospective study included 50 patients with DIE who required surgery. Urinary dysfunction was evaluated before and after surgery by both urodynamic tests and electromyography, and the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) quality-of-life questionnaire.

RESULTS:

Preoperative electromyography showed that 14 patients (28%) had neurogenic alteration involving sacral reflex and pelvic floor muscles correlated with the presence of colorectal endometriosis (p=0.003). Postoperative quality of life and BFLUTS total scores were improved compared to preoperative scores (p=0.001 and p=0.005, respectively). After an initial improvement in BFLUTS, an alteration is observed at long-term (median follow-up of 66 months). In the 34 patients with pre- and postoperative urodynamic measurements, no difference was found before and after surgery. De novo peripheral neuropathy was only observed in patients who underwent DIE resection with colorectal resection (p=0.02).

CONCLUSIONS:

Our results support that patients with DIE have a high incidence of preoperative urinary symptoms and neurogenic dysfunction. Colorectal resection appears to be a determinant factor of de novo peripheral neuropathy.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:153-8.

Could statins constitute a novel treatment for endometriosis? Systematic review of the literature.

Gibran L1Maranhão RC2Abrão MS3Baracat EC3Podgaec S3.

 

Abstract

Endometriosis, defined as the presence of endometrial glands and/or stroma outside the uterine cavity, is an estrogen-dependent disease that affects about 10% of reproductive age women. Theories to explain the etiology of endometriosis abound. These include the alteration of epithelial cells on peritoneal surface, metaplasia of embryonic remnants of the mullerian ducts, immune system abnormalities, and the dissemination of endometrial cells through the circulation or lymphatic system, as well as retrograde menstruation, the hypothesis currently favored for the development of endometriosis. Angiogenesis, the development of new capillaries from pre-existing blood vessels, has been proposed as a key mechanism in the pathogenesis of endometriosis. Again from an etiological perspective, the formation of endometriotic implants requires ectopic fixation and proliferation of endometrial stroma and glands. The process of invasive insertion of endometriotic tissues involves the degradation of the extracellular matrix, and altered expression of matrix metalloproteinases (MMPs) in the eutopic and ectopic endometrium. Considering the antiproliferative, antiangiogenic, antioxidant, anti-inflammatory properties and matrix metalloproteinase activity inhibition of statins and the original studies addressing the possible mechanisms of action in endometriosis, the aim of this systematic review was to synthesize the research conducted to date in order to propose statins as possible and effective tools for controlling this disease.

 

 

 

Int J Clin Exp Pathol. 2014 Apr 15;7(5):1889-99.

TSLP induced by estrogen stimulates secretion of MCP-1 and IL-8 and growth of human endometrial stromal cells through JNK and NF-κB signal pathways.

Chang KK1Liu LB1Li H1Mei J1Shao J1Xie F1Li MQ1Li DJ1.

 

Abstract

It has reported that human endometrial stromal cells (ESCs) express thymic stromal lymphopoietin (TSLP), and TSLP concentrations in the serum and peritoneal fluid were higher in women with endometriosis. Endometriosisis an estrogen-dependent disease. The present study aimed to elucidate whether and how estrogen regulates the growth of ESCs through TSLP. The ESCs behaviors in vitro were verified by SRB assay and Ki67 level detection, respectively. In addition, the effects of estrogen on TSLP and TSLP on the correspondent functional molecules were investigated by ELISA and flow cytometry. Here we found that estrogen stimulated the secretion of TSLP in a dosage-dependent manner. Recombinant human TSLP stimulates the secretion of MCP-1 and IL-8, and markedly promotes the viability and proliferation relative gene Ki-67 expression of ESCs. These effects could be abolished by the inhibitor for JNK or NF-κB signal, respectively. Moreover, not only anti-TSLP neutralizing antibody, but also blocking JNK or NF-κB signal by inhibitor abrogated the stimulatory role in the production of MCP-1 and IL-8, and the growth of ESCs induced by estrogen. Our current study has demonstrated that TSLP is involved in the regulation of estrogen on the secretion of MCP-1 and IL-8, and the growth of ESCs through JNK and NF-κB signal pathways, which suggests that the abnormal high expression of TSLP induced by estrogen may play an important role in ESCs growth and finally contribute to the origin and development of endometriosis.

 

 

Int J Clin Exp Pathol. 2014 Apr 15;7(5):2273-82.

Antioxidant capacity of follicular fluid from patients undergoing in vitro fertilization.

Huang B1Li Z1Ai J1Zhu L1Li Y1Jin L1Zhang H1.

 

Abstract

This study measured the antioxidant activity of follicular fluid (FF) in infertile patients and assessed its possible correlation between ovarian stimulation and pregnancy outcomes. Samples from 191 infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET) were determined by α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging, reducing power, superoxide radical scavenging, β-Carotene bleaching assay, ferrothiocyanate and thiobarbituric acid assays. The comparison between a positive IVF outcome and FF’s antioxidant activity was also studied. The results showed FF had strong antioxidant activity, which equated to common antioxidants Vc and BHT (100 μg/mL). Patients with endometriosis had less efficient antioxidant activity in FF than that of patients with tubal occlusion or polycystic ovary syndrome. In conclusion, this study detected, for the first time, the antioxidant activity of FF from patients undergoing an IVF and the FF exhibited strong antioxidant activity.

 

 

 

Exp Mol Med. 2014 Jun 27;46:e103.

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women.

Wang L1Lu X1Wang D1Qu W1Li W1Xu X1Huang Q1Han X1Lv J1.

 

Abstract

An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case-control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06-6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.

 

Hum Mol Genet. 2014 Nov 15;23(22):6008-21.

Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes.

Li X1Zhang Y2Zhao L3Wang L4Wu Z1Mei Q1Nie J1Li X1Li Y3Fu X5Wang X1Meng Y6Han W7.

 

Abstract

Endometriosis is a complex and enigmatic disease that arises from the interplay among multiple genetic and environmental factors. The defining feature of endometriosis is the deposition and growth of endometrial tissues at sites outside of the uterine cavity. Studies to date have established that endometriosis is heritable but have not addressed the causal genetic variants for this disease. Here, we conducted whole-exome sequencing to comprehensively search for somatic mutations in both eutopic and ectopic endometrium from 16 endometriosispatients and five normal control patients using laser capture microdissection. We compared the mutational landscape of ectopic endometrium with the corresponding eutopic sample from endometriosis patients compared with endometrium from normal women and identified previously unreported mutated genes and pathway alternations. Statistical analysis of exome data identified that most genes were specifically mutated in both eutopic and ectopic endometrium cells. In particular, genes that are involved in biological adhesion, cell-cell junctions, and chromatin-remodeling complex(es) were identified, which partially supports the retrograde menstruation theory that proposes that endometrial cells are refluxed through the fallopian tubes during menstruation and implanted onto the peritoneum or pelvic organs. Conspicuously, when we compared exomic mutation data for paired eutopic and ectopic endometrium, we identified a mutational signature in both endometrial types for which no overlap in somatic single nucleotide variants were observed. These mutations occurred in a mutually exclusive manner, likely because of the discrepancy in endometriosis pathology and physiology, as eutopic endometrium rapidly regrows, and ectopic endometrial growth is inert. Our findings provide, to our knowledge, an unbiased view of the landscape of genetic alterations in endometriosis and vital information for indicating that genetic alterations in cytoskeletal and chromatin-remodeling proteins could be involved in the pathogenesis of endometriosis, thus implicating a novel therapeutic possibility for endometriosis.

 

 

Gynecol Oncol. 2014 Oct;135(1):100-7.

Src as a novel therapeutic target for endometriosis.

Lawrenson K1Lee N2Torres HA3Lee JM4Brueggmann D5Rao PN6Noushmehr H7Gayther SA8.

 

Abstract

BACKGROUND:

Endometriosis is a common condition that is associated with an increased risk of developing ovarian carcinoma. Improved in vitro models of this disease are needed to better understand how endometriosis, a benign disease, can undergo neoplastic transformation, and for the development of novel treatment strategies to prevent this progression.

METHODS:

We describe the generation and in vitro characterization of novel TERT immortalized ovarian endometriosis epithelial cell lines (EEC16-TERT).

RESULTS:

Expression of TERT alone was sufficient to immortalize endometriosis epithelial cells. TERT immortalization induces an epithelial-to-mesenchymal transition and perturbation in the expression of genes involved in the development of ovarian cancer. EEC16-TERT was non-tumorigenic when xenografted into immunocompromised mice but grew in anchorage-independent growth assays in an epidermal growth factor and hydrocortisone dependent manner. Colony formation in agar was abolished by inhibition of Src, and the Src pathway was found to be activated in human endometriosis lesions.

CONCLUSIONS:

This new in vitro model system mimics endometriosis and the early stages of neoplastic transformation in the development of endometriosis associated ovarian cancer. We demonstrate the potential clinical relevance of this model by identifying Src activation as a novel pathway in endometriosis that could be targeted therapeutically, perhaps as a novel strategy to manage endometriosis clinically, or to prevent the development of endometriosis-associated ovarian cancer.

 

 

Mol Biol Rep. 2014 Sep;41(9):5793-7.

miR-20a contributes to endometriosis by regulating NTN4 expression.

Zhao M1Tang QWu WXia YChen DWang X.

 

Abstract

Endometriosis is a chronic disease that affects roughly 5-15 % of women of reproductive age. The pathophysiology of the disease occurrence and progression is unclear. MicroRNAs (miRNAs) are short, non-coding RNAs that have important regulatory function. It has been postulated that abnormal expression of miRNA is associated with ovarian endometriosis. Forty patients with ovarian endometriosis and 20 controls with benign ovarian tumor were included to examine the expression level of miR-20a. Quantitative real-time PCR (qPCR) was performed to detect the expression level of miR-20a. The target genes and pathways involved in aberrantly expressed miR-20a were identified by computational algorithms. Furthermore, selected target genes expression level were analyzed by qPCR. Significantly increased miR-20a expression level was observed in patients with ovarian endometriosis as compared with controls. Further stratified analysis showed that the increased expression level of miR-20a was only associated with advanced endometriosis (stage III-IV), but not mild endometriosis (stage I-II). The cell cycle was identified to be one of the most relevant pathways in the pathogenesis of endometriosis conducted by miR-20a. The expression level of target gene NTN4 (netrin-4) was significantly decreased in patients with ovarian endometriosis. The results of this study suggest that increased expression of miR-20a may play an important role in the pathogenesis of ovarian endometriosis by suppressing NTN4.

 

 

J Surg Case Rep. 2014 Jun 27;2014(6).

Mesothelial cyst with endometriosis mimicking a Nuck cyst.

Uno Y1Nakajima S1Yano F1Eto K1Omura N1Yanaga K2.

 

Abstract

We report a case of mesothelial cyst protruding from the right femoral ring with suspected endometriosis in a 35-year-old woman, who complained of a lump with a diameter of 6 cm in the right inguinal region. Although she had the hormone therapy during the next 8 months for the diagnosis of extragenital endometriosis, her symptoms did not improve. The clinical suspicion of a Nuck cyst with endometriosis, supported by ultrasonography and magnetic resonance imaging, was confirmed by histopathological examination of the surgical specimen. Authors herein report this unusual case and review the literature.

 

 

J Med Ultrason (2001). 2014 Jul;41(3):325-32.

Reproducibility of two different methods for performing mean gray value evaluation of cyst content in endometriomas using VOCAL.

Guerriero S1Alcazar JL2Pilloni M3Ajossa S3Olartecoechea B2Sedda F3Piras A3Melis GB3Saba L4.

 

Abstract

OBJECTIVE:

To compare two different methods (manual sampling of the entire cyst and semi-automated spherical sampling from the central part of the cyst) for calculating the mean gray value (MGV) from the cystic content in endometriomas using virtual organ computer-aided analysis (VOCAL).

METHODS:

Forty-one volumes from histologically confirmed endometriomas were retrieved from our database and the volumes were analyzed to compare the MGVs obtained via the two modalities. In addition, to evaluate the reproducibility in a sample of 20 volumes, two different observers calculated the MGV from cyst content using VOCAL software. For each method, each examiner analyzed the volumes twice, 3 weeks apart, for assessment of intra-observer agreement. First, manual sampling of the internal contour of all the cysts was performed, and 1 week later semi-automated 2-cm sphere sampling from the central part of the cyst was carried out. In addition, the observers recorded the time spent performing each analysis. Inter- and intra-observer reproducibility was evaluated for each method using intra-class correlation coefficients (ICC).

RESULTS:

There was no difference in the mean MGV between manual sampling (22.211 ± 7.541) and the semi-automated modality of sampling (23.840 ± 8.621, p = 0.439). The correlation between manual and semi-automated sampling measurement was high (r = 0.92). According to the ICCs, there was no significant difference in interobserver reliability between manual sampling (0.931; 95 % CI, 0.824-0.973) and the semi-automated modality of sampling (0.924; 95 % CI, 0.809-0.970). Intra-observer reproducibility for both examiners was good (ICC > 0.94). Semi-automated measurements were obtained faster than those obtained by manual evaluation (p = 0.0001 for observer 1 and p = 0.083 for observer 2).

CONCLUSIONS:

Both methods seem to be reliable, but the semi-automated method using the sphere should be preferred because it is a less time-consuming procedure.

 

 

Am J Reprod Immunol. 2014 Nov;72(5):496-503.

IL-1β increases expression of tryptophan 2,3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells.

Urata Y1Koga KHirota YAkiyama IIzumi GTakamura MNagai MHarada MHirata TYoshino OKawana KFujii TOsuga Y.

 

Abstract

PROBLEM:

Immune tolerance to endometriotic cells is important to promote endometriosis. Tryptophan 2,3-dioxygenase (TDO) enhances immune tolerance by catabolizing tryptophan to kynurenine. We studied whether interleukin-1β (IL-1β), a typical endometriosis-associated cytokine, affects the expression of TDO and the catabolism of tryptophan in endometrioma stromal cells (ESCs). We also studied whether the expression of TDO is involved in IL-1β-induced secretion of IL-6 and IL-8 in ESCs.

METHOD OF STUDY:

Nineteen endometriotic patients of reproductive age with normal menstrual cycles were recruited. Primary cultures of ESCs were treated with IL-1β and TDO siRNA. TDO mRNA was measured using quantitative PCR. TDO protein was measured using Western blotting. Concentrations of kynurenine in condition media were measured using Ehrlich reagent. Concentrations of tryptophan in conditioned media were measured using tryptophan detection kit. Concentrations of IL-6 and IL-8 in conditioned media were measured using ELISA kits.

RESULTS:

IL-1β (1 ng/mL) increased the expression of TDO mRNA and TDO protein in ESCs. IL-1β-treated ESCs increased the production of kynurenine and the effect was inhibited by TDO siRNA. Treatment with the siRNA also decreased IL-1β-induced secretion of IL-6 and IL-8 from ESCs.

CONCLUSION:

IL-1β is suggested to stimulate tryptophan catabolism and production of IL-6 and IL-8 by increasing TDO expression in endometriosis.

 

 

 

 

Curr Opin Obstet Gynecol. 2014 Aug;26(4):266-74.

Review of the management of ovarian endometriosis: paradigm shift towards conservative approaches.

Psaroudakis D1Hirsch MDavis C.

 

Abstract

PURPOSE OF REVIEW:

To describe the current consensus regarding the modern management of ovarian endometriosis and summarize the recent evidence that led to a shift in the management recommendations.

RECENT FINDINGS:

The vast majority of the recent studies demonstrate an adverse effect of surgery on ovarian reserve markers, whereas convincing evidence of a benefit of surgery on fertility outcomes is lacking. Current research is focussing on identifying the optimal surgical technique that affords minimal injury to ovarian function. New medical treatment options in the form of aromatase inhibitors are emerging, whereas the evidence for a role of ultrasound-guided drainage and sclerotherapy is scarce and unconvincing.

SUMMARY:

Consensus from Europe and the USA is for a conservative approach to the treatment of ovarian endometriosis, with early recourse to assisted reproductive technology for subfertility. Surgery is currently only being advised for severe pain or difficult access to growing follicles and only after careful counselling regarding the potential adverse effect on ovarian reserve. Research has still not identified the optimal technique for treating ovarian endometriosis. Laparoscopic ovarian cystectomy not only offers the lowest risk of recurrence and the highest chance of spontaneous pregnancy rate, but also risks significant injury to ovarian function. Medical treatment offers temporary symptom relief but does not improve the fertility outcomes, and the role of ultrasound-guided drainage remains to be established.

 

 

 

Curr Opin Obstet Gynecol. 2014 Aug;26(4):243-52.

Novel agents for the medical treatment of endometriosis.

Platteeuw L1D’Hooghe T.

 

Abstract

PURPOSE OF REVIEW:

Current medical treatments for endometriosis-associated pain, including oral contraceptives, progestins and GnRH agonists, are partially effective and have significant side-effects. The purpose of this review is to present new hormonal and nonhormonal treatment for endometriosis.

RECENT FINDINGS:

At present, the ideal drug that can prevent, inhibit or stop development of endometriosis, reduce associated pain or infertility and allow conception does not exist. New drugs in development for endometriosis modulate GnRH, estrogen and/or progesterone receptors, or target endometriosis-associated inflammation, angiogenesis, adhesion and/or tissue invasion. Most have been tested in rodents, and have been evaluated in more relevant animal models like nonhuman primates (baboons), but only a few, that is GnRH antagonists, have been tested in human randomized controlled trials. Important safety and efficacy issues remain a concern, as steroid receptors, inflammation, adhesion, angiogenesis and tissue invasion are key factors in physiological events like ovulation, menstruation and embryo implantation.

SUMMARY:

New drugs for the medical treatment of endometriosis targeting both hormonal (GnRH, estrogen and progesterone receptors) and nonhormonal pathways (inflammation, angiogenesis, adhesions, tissue invasion) are promising, but their efficacy and safety need to be established in randomized human trials before they can be used in clinical practice.

 

 

J Pathol. 2014 Nov;234(3):329-37.

Targeting galectin-1-induced angiogenesis mitigates the severity of endometriosis.

Bastón JI1Barañao RIRicci AGBilotas MAOlivares CNSingla JJGonzalez AMStupirski JCCroci DORabinovich GAMeresman GF.

 

Abstract

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that causes severe pelvic pain and infertility in women of reproductive age. Although not completely understood, the pathophysiology of the disease involves chronic dysregulation of inflammatory and vascular signalling. In the quest for novel therapeutic targets, we investigated the involvement of galectin-1 (Gal-1), an endogenous glycan-binding protein endowed with both immunosuppressive and pro-angiogenic activities, in the pathophysiology of endometriotic lesions. Here we show that Gal-1 is selectively expressed in stromal and endothelial cells of human endometriotic lesions. Using an experimental endometriosis model induced in wild-type and Gal-1-deficient (Lgals1(-/-) ) mice, we showed that this lectin orchestrates the formation of vascular networks in endometriotic lesions in vivo, facilitating their ectopic growth independently of vascular endothelial growth factor (VEGF) and the keratinocyte-derived CXC-motif (CXC-KC) chemokine. Targeting Gal-1 using a specific neutralizing mAb reduced the size and vascularized area of endometriotic lesions within the peritoneal compartment. These results underline the essential role of Gal-1 during endometriosis and validate this lectin as a possible target for the treatment of disease.

 

 

 

Fertil Steril. 2014 Sep;102(3):856-863.

Regulation of myeloid ecotropic viral integration site 1 and its expression in normal and abnormal endometrium.

Hu L1Li H2Huang CL3Chen H3Zhu G4Qian K5.

 

Abstract

OBJECTIVE:

To identify the expression profile and sex steroid regulation pattern of myeloid ecotropic viral integration site 1 (MEIS1) in endometrium.

DESIGN:

Molecular studies in human and animal tissue.

SETTING:

Reproductive medicine center of a university hospital.

PATIENT(S) AND ANIMAL(S):

Women with normal menstrual cycles for male infertility and female infertility with endometriosis. Sexually mature female mice (Kunming White strain).

INTERVENTION(S):

Primary cultured endometrial stromal cells, Ishikawa cells, and oophorectomized mice were treated with sex steroid.

MAIN OUTCOME MEASURE(S):

MEIS1 expression in the human endometrium during the menstrual cycle, mouse uterus during the peri-implantation period of pregnancy, and eutopic endometrium from patients with endometriosis was analyzed by immunohistochemistry staining and western blot. In addition, MEIS1 expression in response to sex steroid was examined both in vitro and in vivo by immunohistochemistry staining and western blot.

RESULT(S):

MEIS1 expression was markedly increased in endometrium during the implantation period, and in decidualizing stromal cells in human endometrium and murine uterus. Steroid hormones increased MEIS1 expression in primary cultured endometrial stromal cells, Ishikawa cells, and endometrium of oophorectomized mice. The effects of estrogen and progesterone were more marked in oophorectomized mice and were additive. MEIS1 expression was significantly lower in eutopic endometrium compared with normal endometrium in the midsecretory stage.

CONCLUSION(S):

MEIS1 is likely a key mediator between sex steroid and genes for uterine receptivity. Diminished endometrium MEIS1 expression may contribute to implantation failure in endometriosis.

 

 

 

Biomed Res Int. 2014;2014:746705.

Endometriosis patients in the postmenopausal period: pre- and postmenopausal factors influencing postmenopausal health.

Haas D1Wurm P2Schimetta W3Schabetsberger K4Shamiyeh A5Oppelt P1Binder H6.

 

Abstract

OBJECTIVE:

To evaluate patients’ health status and the course of endometriosis from the premenopausal to the postmenopausal period and evaluate influencing factors that may be relevant.

METHODS:

Questionnaire completed by 35 postmenopausal women in whom endometriosis had been histologically confirmed premenopausally. Correlation and regression analyses were carried out to identify factors relevant to their postmenopausal health status.

RESULTS:

Overall, there was clear improvement in typical endometriosis symptoms and sexual life. Clear associations (P < 0.005) were observed between premenopausal factors like physical limitations caused by the disease, impaired social contacts and psychological problems, and postmenopausal pain and impairment of sexual life. Three statistical models for assessing pain and impairment of sexual life in the postmenopausal period were calculated on the basis of clinical symptoms in the premenopausal period, with a very high degree of accuracy (P < 0.001; R(2) = 0.833/0.857/0.931).

CONCLUSIONS:

The results of the survey strongly suggest that physical fitness and freedom from physical restrictions, a good social environment, and psychological care in both the premenopausal and postmenopausal periods lead to marked improvements in the postmenopausal period with regard to pain, dyspareunia, and influence on sexual life in endometriosis patients.

 

 

Mol Endocrinol. 2014 Aug;28(8):1304-15.

ERβ– and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis.

Monsivais D1Dyson MTYin PCoon JSNavarro AFeng GMalpani SSOno MErcan CMWei JJPavone MESu EBulun SE.

 

Abstract

In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-β (ERβ) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERβ binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERβ target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ERβ at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ERβ and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention.

 

 

 

Clin Exp Obstet Gynecol. 2014;41(3):272-5.

Effects of laparoscopic ovarian endometriosis cystectomy combined with postoperative GnRH-a therapy on ovarian reserve, pregnancy, and outcome recurrence.

Yang XHJi FAiLi ATuerXun HHe YDing Y.

 

Abstract

OBJECTIVE:

The aim of this study was to investigate the impacts of laparoscopic ovarian endometriosiscystectomy combined with postoperative GnRH-a therapy on ovarian reserve, pregnancy outcome and recurrence.

MATERIALS AND METHODS:

This was a prospective control study. The experimental group: 63 patients with combinations of laparoscopic bilateral ovarian endometrial cystectomies and gonadotropin-releasing hormone agonist (GnRH-a) treatment for three months.

CONTROL GROUP:

62 patients with laparoscopic bilateral ovarian endometrial cystectomies. Benchmarks: the changes of follicle stimulating hormone (FSH) and FSH/luteinizing hormone (LH), etradiol (E2) in preoperative and postoperative three months or menstrual two to three days, menstrual two to three days after surgery, natural pregnancy, and cyst recurrence in 18th month during postoperative follow-up.

RESULTS:

In experimental group after six months, the percentage of returned FSH accounted for 95.3% of normal range, in the control group it was 82.2%, and the difference was significant (p < 0.05). The natural pregnancy rate of preoperative infertility patients (57.1%) was higher than the control (36.8%) (p < 0.05). The recurrence rate of preoperative infertility patients (12.7%) was lower than the control (27.4%) (p < 0.05).

CONCLUSION:

After bilateral laparoscopic ovarian endometrial cystectomy, an implement of GnRH-a therapy can improve the postoperative pregnancy rate, which changes with clinical stage and patient age, reduces ovarian recurrence, and its influence on ovarian reserve is lesser.

 

 

Clin Exp Obstet Gynecol. 2014;41(3):319-22.

Laparoendoscopic single-site surgery (LESS) for large benign adnexal tumors: one surgeon’s experience over one-year period.

Oh NJKim WY.

 

Abstract

OBJECTIVE:

To present the authors’ experience with laparoendoscopic single-site surgery (LESS) surgery for large benign adnexal tumors and to compare the removal time of resected specimen with that of conventional laparoscopy.

STUDY DESIGN:

Ten consecutive patients underwent LESS for huge adnexal tumors at Myongjil Hospital, Korea between March 2011 and July 2012. A modified open Hasson technique was used to gain access to the abdominal cavity. The single-port device was inserted trans-umbilically into the wound opening. After suction of large amount of fluid content, LESS salpingo-oophorectomy was performed. The resected adnexal specimen was placed into a LapBag for removal out of the abdominal cavity. The authors compared the removal time of resected specimen between LESS and previously performed conventional laparoscopy for large benign adnexal tumors.

RESULTS:

The adnexal tumors in this study were all very large cystic tumors reaching near or over the umbilicus. It took less than ten minutes for the removal of the resected adnexal tumors in all LESS cases (three to ten minutes), much less time than that of the conventional laparoscopy (usually ten to 17 minutes).

CONCLUSION:

LESS for large benign adnexal tumors is feasible and removal of resected adnexal tumor is easier than conventional laparoscopic surgery.

 

 

 

Clin Exp Obstet Gynecol. 2014;41(3):328-34.

Study of an antiangiogenesis gene therapy with endostatin on endometriosisin the nude mouse model.

Ma YHe YL.

 

Abstract

AIM:

This work aims to investigate the treatment effect of endostatin (ES) in the nude mouse model with endometriosis (EMs).

MATERIALS AND METHODS:

Recombinant adenovirus Ad-ES carrying ES gene was constructed. Apoptosis of ECV-304 cell induced by Ad-ES was observed. The nude mouse model with EMs was established by subcutaneous implantation. After the local focus was injected with the Ad-ES, the Ad-Track or the physiologic saline, respectively, the morphological features of ectopic focuses were observed under microscopy. The microvessel densities (MVD) and the apoptosis were detected.

RESULTS:

The recombinant Ad-ES was successfully constructed. Apoptosis of ECV 304 cells could be induced by Ad-ES. The nude mouse model with EMs was successfully established by subcutaneous implantation. There were statistical differences in the volumes of endometriotic lesions and MVD after treatment by Ad-ES compared with those in the other two control groups (p < 0.05). Apoptosis of the cells were significantly increased in the group of treatment by Ad-ES compared with those of the two control groups.

CONCLUSION:

ES could induce ECV 304 cells to apoptosis and inhibit the growth ofendometrium in the nude mouse model. The findings suggest that antiangiopoiesis may be used as a promising therapy for the treatment of EMs.

 

 

 

Clin Exp Obstet Gynecol. 2014;41(3):346-8.

Celiac disease and endometriosis: an insidious and worrisome association hard to diagnose: a case report.

Caserta DMatteucci ERalli EBordi GMoscarini M.

Abstract

BACKGROUND:

Primary infertility is an unusual presentation of celiac disease (CD). When non-classical symptoms are present, the diagnosis is not easy and it becomes even more difficult when CD is associated with endometriosis, representing a diagnostic challenge for medical practitioners and gynecologists.

CASE REPORT:

A 34-year-old patient presented to the authors’ observation with primary infertility. Formerly she was treated for endometriosis and the diagnosis of CD was delayed. A favorable clinical and serological response following a gluten-free-diet (GFD) was achieved and a successful pregnancy was obtained.

DISCUSSION:

This case report emphasizes the role of the CD in women’s infertility and the possible association between CD and endometriosis. Even if the relationship between these two diseases is still unclear and further studies to address this issue are required, more attention from gynecologists is needed, considering that the later this association is diagnosed, the greater the probability of adverse outcomes of health developing.

 

 

Clin Exp Obstet Gynecol. 2014;41(3):349-50.

Rare extrapelvic endometriosis on iliac vein wall–diagnosis and treatment.

Zamurovic M.

 

Abstract

Although endometriosis is a relatively common illness in women during the reproductive period, extrapelvic localization of endometriosis is a relatively rare finding which can pose a differential diagnostic problem. Diagnosis and surgical treatment of a patient with endometriotic tumor located on the outer wall of the left common iliac vein are discussed. Patient underwent surgery because of circulatory disorders and left leg edema. Histopathological findings verified endometriosis on the outer wall of the common left iliac vein without other localizations.

 

 

 

Clin Exp Obstet Gynecol. 2014;41(3):360-1

Abdominal wall endometriosis after a caesarian section–an interesting case report.

Chatziparadeisi ADaniilidis ADiavatis SVrachnis NCarcea FGiannoulis C.

 

Abstract

BACKGROUND:

Endometriotic foci can be rarely found on the surgical incision following caesarean delivery and on perineotomy site following vaginal delivery.

CASE:

A 33-year-old woman with a history of caesarian section five years prior was admitted to the present clinic due to right groin pain with increasing intensity during menstruation. Ultrasound revealed an endometrioma-like subcutaneous mass directly under the right edge of the Pfannenstiel scar. The mass (3.5 x 2.4 x 2 cm) was removed en bloc with ultrascissor.

CONCLUSION:

The prevailing argument supports that it is a complication caused by the iatrogenic dispersal of endometrial material. Symptoms onset vary from one to five years postoperatively and mainly include pain and enlargement of the mass during menstruation. Diagnosis may be demanding due to the atypical presentation of the disease. Symptoms exacerbate during menstruation in only 20% of all cases. Abdominal ultrasound is extremely useful for diagnosis. The treatment of choice is surgical excision.

 

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