Altern Ther Health Med. 2015 May-Jun;21(3):36-44.

Ten-year Retrospective Study on the Efficacy of a Manual Physical Therapy to Treat Female Infertility.

Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ.

 

Abstract

BACKGROUND:

Female infertility is a complex issue encompassing a wide variety of diagnoses, many of which are caused or affected by adhesions.

OBJECTIVES:

The study intended to examine the rates of successful treatment of infertile women using a protocol of manual physical therapy to address underlying adhesive disease leading to infertility. Methods • The research team designed a retrospective chart review.

SETTING:

The study took place in a private physical therapy clinic.

PARTICIPANTS:

Participants were 1392 female patients who were treated at the clinic between the years of 2002 and 2011. They had varying diagnoses of infertility, including occluded fallopian tubes, hormonal dysfunction, and endometriosis, and some women were undergoing in vitro fertilization (IVF). Intervention • All patients underwent whole-body, patient-centered treatments that used a protocol of manual physical therapy, which focused on restoring mobility and motility to structures affecting reproductive function.

OUTCOME MEASURES:

Improvements demonstrated in the condition(s) causing infertility were measured by improvements in tubal patency and/or improved hormone levels or by pregnancy. Results • The results included a 60.85% rate of clearing occluded fallopian tubes, with a 56.64% rate of pregnancy in those patients. Patients with endometriosis experienced a 42.81% pregnancy rate. The success rate was 49.18% for lowering elevated levels of follicle stimulating hormone (FSH), with a 39.34% pregnancy rate in that group, and 53.57% of the women with polycystic ovarian syndrome (PCOS) achieved pregnancy. The reported pregnancy rate for patients who underwent IVF after the therapy was 56.16%. The results also suggested that the treatment was effective for patients with premature ovarian failure (POF).

CONCLUSION:

The manual physical therapy represented an effective, conservative treatment for women diagnosed as infertile due to mechanical causes, independent of the specific etiology.

 

 

Ugeskr Laeger. 2015 May 18;177(21):V12140687.

Ureteral endometriosis as the cause of septic shock and single-sided renal failure.

 

Hult M¹, Pilt AP, Norus TP.

 

Abstract

Ureteral endometriosis is a rare variant of an otherwise common condition, which is primarily seen among premenopausal women. The symptoms and the clinical findings include silent loss of kidney function, gross haematuria, abdominal pain, hypertension and tumour suspicion. We present a rare case of intrinsic ureteral endometriosis resulting in a life-threatening infection and loss of a kidney. Involvement of gynaecologists for early diagnosis and medical treatment in combination with surgical intervention could be of importance in order to prevent the serious consequences as described in this case.

 

 

Quant Imaging Med Surg. 2015 Jun;5(3):485-7.

A rare cyclic recurrent hematuria case; bladder endometriosis.

Akpınar S¹, Yılmaz G¹, Çelebioğlu E¹.

 

Abstract

Endometriosis is a benign gynecological disease that is characterized by the presence of functional endometrial tissue outside the uterus. Although the ovaries and uterine ligaments are the most common locations, urinary tract involvement especially the bladder endometriosis is a rare entity in women of reproductive age with clinical symptoms of cyclical urgency, hematuria and suprapubic pain. We herein present magnetic resonance imaging (MRI) findings of spontaneous bladder endometriosis case with cyclical hematuria symptoms.

 

 

Lab Invest. 2015 Aug;95(8):962-72.

Transcriptional upregulation of HNF-1β by NF-κB in ovarian clear cell carcinoma modulates susceptibility to apoptosis through alteration in bcl-2 expression.

Suzuki E¹, Kajita S¹, Takahashi H¹, Matsumoto T¹, Tsuruta T¹, Saegusa M¹.

 

Abstract

Hepatocyte nuclear factor-1β (HNF-1β) is a transcriptional factor that has an important role in endometriosis-ovarian clear cell carcinoma (OCCC) sequence by modulating cell kinetics and glucose metabolism. However, little is known about the detailed molecular mechanisms that govern its regulation and function. Herein, we focus on upstream and downstream regulatory factors of HNF-1β in OCCCs. In clinical samples, HNF-1β expression was positively correlated with the active form of NF-κB/p65 in OCCCs, and closely linked with a low nuclear grade and non-solid architecture. In cell lines, transfection of p65 resulted in increased HNF-1β mRNA and protein expression in TOV-21G cells (OCCC cell line with endogenous HNF-1β expression), in line with activation of the promoter, probably through interacting with the basic transcriptional machinery. Suppression of endogenous HNF-1β expression by siRNA increased apoptosis in TOV-21G cells, while treatment of Hec251 cells (endometrial carcinoma cell line with extremely low endogenous HNF-1β expression) stably overexpressing exogenous HNF-1β with doxorubicin abrogated apoptosis of the cells, along with increased ratio of bcl-2 relative to bax. Moreover, overexpression of HNF-1β led to upregulation of bcl-2 expression at the transcriptional level in TOV-21G cells, which provided evidence for a positive correlation between HNF-1β and bcl-2 expression in OCCCs. These data, therefore, suggest that association between HNF-1β and NF-κB signaling may participate in cell survival by alteration of apoptotic events, particularly in mitochondria-mediated pathways, through upregulation of bcl-2 expression in OCCCs.

 

 

Am J Obstet Gynecol. 2015 Nov;213(5):716.e1-6.

Removal of normal ovaries in women under age 51 at the time of hysterectomy.

Karp NE¹, Fenner DE², Burgunder-Zdravkovski L³, Morgan DM².

 

Abstract

OBJECTIVE:

Despite recommendation for ovarian conservation in low-risk, premenopausal women, bilateral oophorectomy is often performed. The purpose of this study was to investigate factors associated with removal of normal ovaries at the time of hysterectomy for benign indication in women age <51 years.

STUDY DESIGN:

Demographics, indication for surgery, adnexal pathology, and surgical approach were analyzed for hysterectomies from a voluntary, statewide surgical quality collaborative. Cases were excluded if the surgical indication was cancer, pelvic mass, or obstetric, or if age was >50 years. Cases were categorized according to pathology of the adnexal specimen as cancer, benign findings, normal ovary, or no ovarian specimen. Variables including demographics, medical comorbidities, and surgical characteristics were analyzed to identify characteristics associated with oophorectomy at the time of hysterectomy. A logistic regression model was then developed to identify factors independently associated with removal of normal ovaries.

RESULTS:

A total of 6789 subjects were included. Oophorectomy was performed in 44.2% of women (n = 3002). In all, 23.1% (n = 1565) had normal ovaries on pathology. Incidental ovarian cancer was found in 0.2% (n = 12), and benign pathology was found in 21% (n = 1425). Removal of normal ovaries was less likely when the surgical approach was vaginal (18%) as opposed to laparoscopic (23.1%) or abdominal (26.0%). With adjustment, abdominal (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.43-2.09]) and laparoscopic (OR, 1.27; 95% CI, 1.08-1.50) approach showed significantly higher odds of normal ovary removal compared to vaginal hysterectomy. Age 46-50 years was also significantly associated (OR, 1.78; 95% CI, 1.53-2.07). Surgical indications associated with increased oophorectomy with normal resultant pathology were family history of cancer (OR, 3.09; 95% CI, 1.94-4.94), endometrial hyperplasia (OR, 2.36; 95% CI, 1.38-4.01), endometriosis (OR, 2.01; 95% CI, 1.30-3.09), and cervical dysplasia (OR, 1.91; 95% CI, 1.12-3.28).

CONCLUSION:

Removal of histologically normal ovaries is performed in nearly 1 of every 4 women age <51 years undergoing hysterectomy for benign indications. Factors associated include age closer to menopause, surgical approach, and certain indications for hysterectomy. Reducing the rate of elective oophorectomy in low-risk, premenopausal women may be a target for quality improvement efforts. Future work should continue to evaluate this practice, associated factors, physician counseling, and patient decision-making.

 

 

Nutrients. 2015 May 29;7(6):4139-53.

The role of vitamin D in reproductive health–a Trojan Horse or the Golden Fleece?

Dabrowski FA¹, Grzechocinska B², Wielgos M³.

 

Abstract

In the last decade, vitamin D was in the spotlight in many fields of research. Despite numerous publications, its influence on reproductive health remains ambiguous. This paper presents an up-to-date review of current knowledge concerning the role of cholecalciferol in human reproduction. It covers various infertility issues, such as polycystic ovary syndrome, endometriosis, myoma-induced infertility, male infertility, premature ovary failure and in vitro fertilization techniques. Vitamin D deficiency, defined as serum concentration of 25-hydroxycalciferol of less than 50 nmol/L, is commonly noted more frequently than only in fertility clinic patients. It is a global trend that is observed in all age groups. The results of original publications dated up to 2015 have been summarized and discussed in a critical manner. Most experts agree that vitamin D supplementation is a necessity, particularly in women suffering from obesity, insulin resistance or small ovarian reserve, as well as in men with oligo- and asthenozoospermia if serum concentration should fall below 50 nmol/L (normal range up to 125 nmol/L). High concentration of vitamin D and its metabolites in decidua during the 1st trimester suggests its important role in the implantation process and a local immunological embryo-protection. On the other hand, evidence-based research did not prove a significant difference so far in ovulation stimulation or embryo development depending on vitamin D level. In one of the publications, it was also found that vitamin D binding protein (VDBP) has a molecular similarity to anti-sperm antibodies, and another one concluded that both low (<50 nmol/L) and high (>125 nmol/L) concentration of vitamin D are associated with decreased number and quality of spermatozoa in semen. Vitamin D is definitely not a Trojan Horse in reproductive health, since there were no adverse effects reported for vitamin D intake of up to 10,000 IU/day, but to proclaim it the Golden Fleece, more evidence is needed.

 

 

Semin Reprod Med. 2015 May;33(3):220-4.

Molecular biology of endometriosis: from aromatase to genomic abnormalities.

Bulun SE¹, Monsivais D¹, Kakinuma T¹, Furukawa Y¹, Bernardi L¹, Pavone ME¹, Dyson M¹.

 

Abstract

Endometriosis has been initially described as the presence of ectopic endometrial tissue on pelvic organs or in extrapelvic sites; and this has been used as its key pathologic feature ever since. Endometriosis responds to fluctuations in estrogen and progesterone by growth and inflammation, leading to pain aggravated by menses. It was proposed that pelvic endometriosis primarily originate from retrograde menstruation of a critical number of eutopic endometrial cells with stem characteristics. This postulate is supported by the molecular defects found in ectopic endometriotic tissue. Genome-wide differences in CpG methylation between eutopic endometrial and endometriotic stromal cells are present. Defective CpG methylation affecting several genes that encode key transcription factors such as GATA6, steroidogenic factor-1, and estrogen receptor-β in endometriosis gives rise to overproduction of local estrogen and prostaglandins and suppression of progesterone receptor. Progesterone receptor deficiency leads to progesterone resistance, resulting in decreased retinol uptake and retinoic acid production and altered retinoic acid action. These molecular defects collectively give rise to poor cellular differentiation, enhanced survival, and increased inflammation, which are the biological hallmarks of endometriotic tissue.

 

 

 

Hum Reprod Update. 2015 Sep-Oct;21(5):640-51.

Non-contraceptive benefits of hormonal and intrauterine reversible contraceptive methods.

Bahamondes L¹, Valeria Bahamondes M², Shulman LP³.

 

Abstract

BACKGROUND:

Most contraceptive methods present benefits beyond contraception; however, despite a large body of evidence, many healthcare professionals (HCPs), users and potential users are unaware of those benefits. This review evaluates the evidence for non-contraceptive benefits of hormonal and non-hormonal contraceptive methods.

METHODS:

We searched the medical publications in PubMed, POPLINE, CENTRAL, EMBASE and LILACS for relevant articles, on non-contraceptive benefits of the use of hormonal and intrauterine reversible contraceptive methods, which were published in English between 1980 and July 2014. Articles were identified using the following search terms: ‘contraceptive methods’, ‘benefits’, ‘cancer’, ‘anaemia’, ‘heavy menstrual bleeding (HMB)’, ‘endometrial hyperplasia’, ‘endometriosis’ and ‘leiomyoma’.

RESULTS:

We identified, through the literature search, evidence that some combined oral contraceptives have benefits in controlling HMB and anaemia, reducing the rate of endometrial, ovarian and colorectal cancer and ectopic pregnancy as well as alleviating symptoms of premenstrual dysphoric disorder. Furthermore, the use of the levonorgestrel-releasing intrauterine system also controls HMB and anaemia and endometrial hyperplasia and cancer, reduces rates of endometrial polyps in users of tamoxifen and alleviates pain associated with endometriosis and adenomyosis. Depot medroxyprogesterone acetate controls crises of pain associated with sickle cell disease and endometriosis. Users of the etonogestrel-releasing contraceptive implant have the benefits of a reduction of pain associated with endometriosis, and users of the copper intrauterine device have reduced rates of endometrial and cervical cancer.

CONCLUSIONS:

Despite the high contraceptive effectiveness of many hormonal and intrauterine reversible contraceptive methods, many HCPs, users and potential users are concerned mainly about side effects and safety of both hormonal and non-hormonal contraceptive methods, and there is scarce information about the many benefits that these methods offer beyond contraception.

 

 

 

 

Reprod Sci. 2015 Sep;22(9):1153-61

Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants.

Bedaiwy MA¹, Dahoud W², Skomorovska-Prokvolit Y², Yi L², Liu JH², Falcone T³, Hurd WW², Mesiano S².

 

Abstract

BACKGROUND:

Several studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis.

METHODS:

This in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively.

RESULTS:

The PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis.

CONCLUSIONS:

Endometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis.

 

 

Arch Gynecol Obstet. 2015 Dec;292(6):1295-9.

Diagnosis and treatment of perineal endometriosis: review of 17 cases.

Li J¹, Shi Y¹, Zhou C¹, Lin J².

 

Abstract

PURPOSE:

To demonstrate the appropriate diagnosis and treatment of perineal endometriosis.

METHODS:

Seventeen patients who presented with a tender perineal mass coinciding with the menstrual cycle on the scar of a previous vaginally procedure were examined retrospectively. Their clinical features and treatment were analyzed.

RESULTS:

All patients presented with a palpable painful lesion. All of them had had vaginal delivery with episiotomy. The mean age of the patients was 34.35 years. The mean latent period was 46.82 months. The mean size was 2.38 cm. Thirteen patients presented with one subcutaneous nodule and four had multiple nodules. Color Doppler ultrasound revealed a subcutaneous nodule with an irregular outline and echo-complex density underlying the episiotomy scar. Only one patient suffered from perineal endometriosis combined with pelvic endometriosis. All endometriotic masses in perineum were completely excised and cured, and confirmed by the microscopic examination.

CONCLUSIONS:

A detailed history and thorough pelvic examination are essential in diagnosing perineal endometriosis. Surgical intervention is the first choice of treatment.

 

 

Digestion. 2015;92(1):14-21.

Intestinal Endometriosis: Mimicker of Inflammatory Bowel Disease?

Guadagno A¹, Grillo F, Vellone VG, Ferrero S, Fasoli A, Fiocca R, Mastracci L.

 

Abstract

BACKGROUND/AIMS:

Endometriosis of the intestinal tract (IE) is thought to mimic inflammatory bowel disease (IBD) both clinically and pathologically but robust data on a large unselected series are missing. Diagnostic problems arise both at colonoscopy as well as on resection specimens for IE when IBD-like features are encountered. The aim was to establish the frequency of IBD-like histology in IE and which type of histological lesions are shared by these two entities.

METHODS:

One hundred consecutive, unselected cases of surgically resected IE were collected and clinical features and histopathology reviewed and reevaluated.

RESULTS:

Seventy-five surgical specimens showed no histological alterations except for endometriosis foci. Twenty-two cases showed focal architectural alterations in the absence of significant inflammation. Three cases showed marked inflammatory and architectural mucosal changes making a differential diagnosis with IBD particularly challenging. On follow-up, however, these patients remained symptom-free and with no need for anti-inflammatory therapy after surgical resection of IE.

CONCLUSIONS:

Diagnostic problems may arise in women who have IBD-like symptoms and histology at colonoscopy but who lack a known diagnosis of endometriosis. Clinicians must be aware that the diagnosis of IBD in patients with IE should be reevaluated over time.

 

 

J Minim Invasive Gynecol. 2015 Sep-Oct;22(6):1036-44

Reproducibility of Endometrial Pathologic Findings Obtained on Hysteroscopy, Transvaginal Sonography, and Gel Infusion Sonography in Women With Postmenopausal Bleeding.

Dueholm M¹, Hjorth IM², Secher P³, Jørgensen A³, Ørtoft G².

 

Abstract

STUDY OBJECTIVE:

To evaluate and compare interobserver variation in endometrial pattern recognition with hysteroscopy (HY) and transvaginal sonography (TVS) and gel infusion sonography (GIS) with regard to the diagnosis of endometrial pathology.

DESIGN:

Prospective study (Canadian Task Force II-1).

SETTING:

University clinic.

PATIENTS:

One hundred twenty-two consecutive women with postmenopausal bleeding and an endometrium thickness ≥ 5 mm.

INTERVENTION:

Two observers using HY and 2 others using TVS and GIS evaluated the endometrial pattern in recorded video clips. Interobserver agreement regarding findings obtained with TVS, GIS, and HY for a diagnosis of cancer, hyperplasia, polyps, and no endometrial pathology was expressed by κ coefficients and compared.

MEASUREMENT AND MAIN RESULTS:

Interobserver agreement (κ) was as follows: identification of normal endometrium: HY (.74), TVS (.68), and GIS (.48); diagnosis of cancer: HY (.56), TVS (.59), and GIS (.34); classification in all categories of endometrial pathology: HY (.70), TVS (.47), and GIS (.41) (p < .05 HY vs GIS). The presence of additional endometrial polyps decreased agreement on HY in patients with hyperplasia or cancer. Observer agreement was poor regarding the diagnosis of hyperplasia by all techniques.

CONCLUSION:

Observer agreement regarding both HY and TVS was reliable for the diagnosis of a normal endometrium but poor with HY, TVS, and especially GIS for a diagnosis of cancer. In patients with hyperplasia or cancer, agreement between observers was especially low in the presence of additional polyps when HY was used. These findings call attention to the need for systematic methods to improve reliability in endometrial pattern recognition.

 

 

J Obstet Gynaecol Res. 2015 Sep;41(9):1457-62

Effect of S100A6 over-expression on β-catenin in endometriosis.

Liu Z¹, Zhang X², Chen M², Cao Q³, Huang D².

 

Abstract

AIM:

S100A6 is over-expressed in several human tumors, including pancreatic carcinoma, malignant fibrous histiocytoma, breast, colon, and gastric carcinoma, but little is known about the role of S100A6 in endometriosis. The aim of the present study was to investigate the effect of S100A6 over-expression on β-catenin in endometrial stromal cells.

METHODS:

Endometrial stromal cells were transfected with an hS100A6-expressing recombinant lentivirus construct. The expression of β-catenin was assessed using western blot and reverse transcription-polymerase chain reaction.

RESULTS:

S100A6 over-expression promoted β-catenin expression at the RNA and protein levels, in endometrial stromal cells.

CONCLUSIONS:

S100A6 induces expression of β-catenin in endometrial stromal cells.

 

 

Int J Clin Exp Pathol. 2015 Mar 1;8(3):3370-3.

Nodular smooth muscle metaplasia in multiple peritoneal endometriosis.

Kim HS¹, Yoon G², Ha SY³, Song SY³.

 

Abstract

We report here an unusual presentation of peritoneal endometriosis with smooth muscle metaplasia as multiple protruding masses on the lateral pelvic wall. Smooth muscle metaplasia is a common finding in rectovaginal endometriosis, whereas in peritoneal endometriosis, smooth muscle metaplasia is uncommon and its nodular presentation on the pelvic wall is even rarer. To the best of our knowledge, this is the first case of nodular smooth muscle metaplasia occurring in peritoneal endometriosis. As observed in this case, when performing laparoscopic surgery in order to excise malignant tumors of intra-abdominal or pelvic organs, it can be difficult for surgeons to distinguish the metastatic tumors from benign nodular pelvic wall lesions, including endometriosis, based on the gross findings only. Therefore, an intraoperative frozen section biopsy of the pelvic wall nodules should be performed to evaluate the peritoneal involvement by malignant tumors. Moreover, this report implies that peritoneal endometriosis, as well as rectovaginal endometriosis, can clinically present as nodular lesions if obvious smooth muscle metaplasia is present. The pathological investigation of smooth muscle cells in peritoneal lesions can contribute not only to the precise diagnosis but also to the structure and function of smooth muscle cells and related cells involved in the histogenesis of peritoneal endometriosis.

 

 

 

Am J Cancer Res. 2015 Feb 15;5(3):869-79

Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma.

Wang Y¹, Mang M², Wang Y¹, Wang L³, Klein R⁴, Kong B³, Zheng W⁵.

 

Abstract

Current research has strongly proposed that contrary to prior beliefs, many ovarian epithelial cancers (OECs) do not, as their name suggests, originate in the ovaries. Recent findings regarding both high-grade and low-grade serous carcinomas has implicated the fallopian tube as a cell source for these OECs, but until now, there has been little insight into the cellular source for clear cell and endometrioid carcinomas. In this commentary review article, we aimed to discuss the new findings that support the possible contribution from the fallopian tube in clear cell and endometrioid carcinomas. Specifically, we have provided results that showcased ovarian surface epithelia (OSE) and ovarian epithelial inclusions (OEIs) as having mesothelial and tubal origins and have strongly recognized the secondary müllerian system and the ability for tubal epithelia to implant upon the ovarian surface as contributing to fallopian tube-derived OEIs (F-OEIs). We have provided initial indications of these F-OEIs and their relationship to endometriosis and then clear cell and endometrioid carcinomas and subsequently offer our new proposal of a probable tubal origin. This new proposal is a paradigm that drastically changes the understanding behind the origin of these OECs and has significant clinical implications in the near future.

 

 

Abdom Imaging. 2015 Oct;40(7):2573-88

Suburothelial and extrinsic lesions of the urinary bladder: radiologic and pathologic features with emphasis on MR imaging.

Chung AD¹, Schieda N², Flood TA³, Cagiannos I⁴, Kielar AZ¹, McInnes MD¹, Siegelman ES⁵.

 

Abstract

OBJECTIVE:

The purpose of this article is to present a contemporary review of the imaging appearance of diseases which affect the deeper layers of the urinary bladder, including both suburothelial and extrinsic pathologies, using radiologic-pathologic correlation.

CONCLUSION:

Compared to the more common urothelial lesions, at cystoscopy, suburothelial and extrinsic diseases of the urinary bladder wall often have a non-specific appearance or may be occult. Cross-sectional imaging, in particular MRI, plays an integral role in diagnosis. Mesenchymal tumors have distinct imaging features on MRI. Leiomyomas are characteristically low signal intensity on T2-weighted (T2W) imaging and progressively enhance. Lipomas and lipomatous hypertrophy are diagnosed by the presence of macroscopic fat. Neurofibromas, hemangiomas, and paragangliomas are hyperintense on T2W sequences and hypervascular. Reactive lesions occur in the setting of chronic inflammation and include: nephrogenic adenoma, cystitis cystica, and cystitis glandularis. Imaging findings are commonly non-specific; however, a mass with internal cystic spaces in association with pelvic lipomatosis is suggestive of cystitis glandularis. Urachal anomalies may be complicated by infection or malignancy. Urachal mucinous adenocarcinoma has a poor prognosis and may present as a T2-hyperintense suburothelial/extrinsic mass centered in the bladder dome. Other diseases may extrinsically involve the urinary bladder by hematogenous and peritoneal spread, including infection, endometriosis, and malignancy. A familiarity with suburothelial and extrinsic pathologies of the urinary bladder is critical for the radiologist, who may be the first to suggest these diagnoses.

 

 

Fertil Steril. 2015 Aug;104(2):491-7.e2.

Invasion process of induced deep nodular endometriosis in an experimental baboon model: similarities with collective cell migration?

Donnez O¹, Orellana R¹, Van Kerk O¹, Dehoux JP², Donnez J³, Dolmans MM⁴.

 

Abstract

OBJECTIVE:

To determine the implications of collective cell migration in the invasion phenomenon observed in deep endometriotic lesions induced in a baboon model.

DESIGN:

Study of morphology and collective cell migration markers in invasive and noninvasive deep endometriotic lesions induced in a baboon model. Invasive lesions were defined as the presence of endometrial glands and stroma in surrounding organs, and a distinction was made between the center of the lesion (glands present in the main lesion) and the invasion front (glands present in surrounding organs).

SETTING:

Academic research unit.

ANIMAL(S):

Ten female baboons (Papio anubis).

INTERVENTION(S):

Recovery of induced deep nodular endometriotic nodules.

MAIN OUTCOME MEASURE(S):

Evaluation of the morphology of glands by analysis of noninvasive and invasive lesions (center of the lesion and invasion front); staining with specific antibodies (Ki67, E-cadherin, β-catenin) for immunohistochemical study of mitotic activity and cell-cell junctions.

RESULT(S):

Glands from invasive lesions, particularly from the invasion front, showed a significantly lower thickness coefficient, higher mitotic activity, and lower expression of E-cadherin and β-catenin than glands from noninvasive lesions and the center of invasive lesions.

CONCLUSION(S):

We report altered morphology, increased mitotic activity, and fewer adhesion molecules in invasive glands present in induced nodular endometriosis, particularly along the invasion front, suggesting that collective cell migration is involved in the invasion process of deep endometriotic lesions induced in a baboon model.

 

 

J Pediatr Adolesc Gynecol. 2015 Dec;28(6):420-6

Uterine Cystic Adenomyosis: A Disease of Younger Women.

Brosens I¹, Gordts S², Habiba M³, Benagiano G⁴.

 

Abstract

PURPOSE OF REVIEW:

We adopted a life-cycle approach to further our understanding of the natural history of the cystic forms of uterine adenomyosis first described by Cullen in 1908.

SEARCH STRATEGY:

Scopus and PubMed were searched for all terms referring to cystic variant of adenomyosis or adenomyoma. References found in major publications were also included in the review.

MAIN FINDINGS:

With the introduction of non-invasive imaging techniques, a number of cases of cystic variants of adenomyosis have been reported. Progressive, severe, medication-resistant dysmenorrhea is the main clinical feature but delay in diagnosis remains problematic. The life-cycle approach demonstrates that cystic adenomyosis is more relevant to adolescent and young adulthood. Congenital müllerian and wolffian cysts and the uterus-like masses are more frequent in women >30 years of age. The latter is frequently located outside the uterus and may represent a form of endometriosis rather than adenomyosis. Differential diagnosis includes ovarian cysts and congenital uterine anomalies. Menstruation suppression with continuous oral contraceptive pill with ultrasonographic monitoring of cyst regression may prove successful in the young woman, but surgical excision using minimally invasive endoscopy is highly effective. The various terms used in literature to describe these lesions cause considerable confusion. Here we propose a classification into 3 subtypes and standardized reporting criteria to enable comparison.

CONCLUSIONS:

Endometrial lined myometrial cysts are almost specific to adolescent and young women. We propose a new classification system.

 

 

Int Urogynecol J. 2015 Nov;26(11):1661-5.

The indication for hysterectomy as a risk factor for subsequent pelvic organ prolapse repair.

Lykke R¹, Blaakær J², Ottesen B³, Gimbel H⁴.

 

Abstract

INTRODUCTION AND HYPOTHESIS:

The aim of this study was to investigate whether the indication for hysterectomy was itself a risk factor for subsequent pelvic organ prolapse (POP) in Danish women who underwent hysterectomy from 1977 to 2009.

METHODS:

Data from 154,882 women who underwent hysterectomy for benign conditions during the period 1977 – 2009 were extracted from the Danish National Patient Register. Patients were followed up from hysterectomy to POP surgery, death/emigration, or end of study period. Hazard ratios (HR) for the first POP surgery in each woman were calculated using the Cox proportional hazards model. Survival analysis for each indication for hysterectomy was performed using the Kaplan-Meier product limit method.

RESULTS:

Fibroids/polyps as the indication was used as the reference when calculating HRs. After adjustment for calendar period, patient age, and hysterectomy route, the HR for POP was 6.57 (95% confidence interval 5.91 – 7.30). The HR for abnormal uterine bleeding (AUB), pain, endometriosis, and “other indications” was significantly higher than the reference. POP surgery was performed predominantly in the posterior compartment for all indications except benign ovarian tumors.

CONCLUSIONS:

POP as the indication for hysterectomy was associated with the highest cumulative incidence of subsequent POP surgery 32 years after hysterectomy. But the indications AUB, pain, endometriosis, and “other indications” were associated with a higher risk of subsequent POP surgery after hysterectomy than the indication fibroids/polyps. The predominant compartment for POP surgery was the posterior compartment for almost all indications. The indication for hysterectomy and the compartment in which POP surgery was performed subsequent to hysterectomy were associated.

 

 

Expert Opin Emerg Drugs. 2015 Sep;20(3):449-61

Emerging therapy for endometriosis.

Lindsay SF¹, Luciano DE, Luciano AA.

 

Abstract

INTRODUCTION:

Endometriosis is a chronic disease manifested by pain and infertility due to ectopic implantation of endometrial glands and stroma causing inflammation. Treatment of endometriosis utilizes a significant amount of health-care resources and requires chronic therapy. Management involves a combination of surgical and medical interventions and requires long-term treatment to avoid repeated surgeries.

AREAS COVERED:

Whereas medical therapies exist for management of endometriosis-related pain, each class has its limitations including side effects, cost, and known duration of relief of symptoms. Development of effective, well-tolerated medical therapies that are appropriate for long-term use is crucial to provide adequate treatment for this chronic disease. This review discusses the various medical therapies available, their limitations, and emerging therapies being developed to address many of these concerns.

EXPERT OPINION:

The authors recommend chronic suppressive therapy for management of endometriosissymptoms, particularly in the postoperative setting. Empiric treatment is appropriate for those patients without evidence of severe disease. Currently available option may not be effective for nor tolerated by all patients. Newer compounds, including gonadotropin-releasing antagonists and aromatase inhibitors combined with hormonal contraceptives, offer possible alternatives to currently available therapies.

 

 

Fertil Steril. 2015 Aug;104(2):333-8.

Mild ovarian stimulation with clomiphene citrate launch is a realistic option for in vitro fertilization.

Ferraretti AP¹, Gianaroli L², Magli MC², Devroey P².

 

Abstract

OBJECTIVE:

To validate the use of clomiphene citrate in IVF when mild stimulation approaches are chosen to reduce patient discomfort, risk, and cost.

DESIGN:

Prospective cohort study.

SETTING:

Private IVF clinic.

PATIENT(S):

A total of 163 patients undergoing IVF and with a good prognosis (defined as ≤38 years old with normal ovarian reserve and normovulatory cycles, body mass index <29 kg/m(2), no previous assisted reproductive technology cycles, no severe endometriosis, no history of recurrent miscarriage, no endocrine/autoimmune diseases, and no surgical semen extraction).

INTERVENTION(S):

Mild stimulation using a fixed protocol of clomiphene citrate (100 mg/d from cycle days 3 to 7) in combination with low doses of gonadotropins (150 IU of recombinant FSH on cycle days 5, 7, and 9) and GnRH antagonist.

MAIN OUTCOME MEASURE(S):

The cumulative delivery rate per patient after three fresh and/or frozen embryo transfers and time to pregnancy.

RESULT(S):

No dropouts were observed. The cumulative delivery rate was 70%, and the mean time to pregnancy was 2.4 months.

CONCLUSION(S):

Mild stimulation using clomiphene citrate in combination with low doses of gonadotropins can be considered a realistic option for good-prognosis patients undergoing IVF.

 

 

Fertil Steril. 2015 Aug;104(2):366-83.e2.

Ultrasound techniques in the diagnosis of deep pelvic endometriosis: algorithm based on a systematic review and meta-analysis.

Noventa M¹, Saccardi C¹, Litta P¹, Vitagliano A¹, D’Antona D¹, Abdulrahim B², Duncan A², Alexander-Sefre F², Aldrich CJ², Quaranta M³, Gizzo S⁴.

 

Abstract

OBJECTIVE:

To collate all available evidence with respect to ultrasound techniques in the management of deep pelvic endometriosis (DPE) and compare the sensitivity and specificity of each to determine the most suitable site-specific method. We aim to provide clinicians with information to improve the diagnosis and management of patients with DPE.

DESIGN:

Systematic review of the literature and meta-analysis.

SETTING:

Not applicable.

PATIENT(S):

None.

INTERVENTIONS(S):

Review of MEDLINE, EMBASE, ScienceDirect, Cochrane Library.

MAIN OUTCOME MEASURE(S):

For each study we calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and positive/negative likelihood ratio regarding DPE sites. We then compared the specificity and sensitivity of each technique. Forest plots with the corresponding 95% confidence interval using fixed/random effects for each approach (both separately and summarized according to the weight of any single study) were used.

RESULT(S):

A key word search strategy identified 441 manuscripts, 35 of which were eligible for the review (32 for meta-analysis). Standard transvaginal sonography (TVS) showed specificity greater than 85% for all DPE sites, despite sensitivity ranging between 50% (bladder, vaginal wall, and rectovaginal septum) and 84% (rectosigmoid). Modified techniques such as bladder site tenderness-guided TVS showed a value of 97.4% for both sensitivity and specificity. Rectal endoscopy-sonography and rectal water contrast TVS were both superior to TVS in detecting rectosigmoid endometriosis with sensitivities and specificities over 92%. Promising data were reported by using rectal water contrast TVS for rectovaginal septum disease (sensitivity, 97.1%; specificity, 99.3%).

CONCLUSION(S):

The summary of data regarding diagnostic specificity and sensitivity of TVS in women undergoing surgery for deep endometriosis may allow us to conclude that TVS should remain the first-line method in the evaluation of patients with suspicion of DPE. When TVS is insufficient, second-line “modified-techniques” should be considered. Choosing the most effective technique is a challenge and should be based on patient history and clinical signs/symptoms.

 

 

Fertil Steril. 2015 Sep;104(3):655-64.e1.

Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1/2, and mTOR.

Choi J¹, Jo M², Lee E¹, Lee DY¹, Choi D³.

 

Abstract

OBJECTIVE:

To elucidate the therapeutic mechanisms of progestin and the effects of progesterone and progestin (dienogest) on autophagy induction and regulation in endometriotic cells, specifically the effects of progesterone and dienogest on the phosphoinositide-3/protein kinase B (PI3K-AKT) and mitogen-activated protein kinase kinases 1 and 2 (MEK1/2)/extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways, which activate mammalian target of rapamycin (mTOR), a major negative regulator of autophagy.

DESIGN:

In vitro study using human endometriotic cyst stromal cells (ECSCs).

SETTING:

University medical center.

PATIENT(S):

Fifteen patients with ovarian endometrioma.

INTERVENTION(S):

ECSCs treated with progesterone or dienogest.

MAIN OUTCOME MEASURE(S):

Autophagy as measured by the expression of the microtubule-associated protein light chain 3-II (LC3-II) and autophagosome formation, and levels of AKT, ERK1/2, and mTOR activity to quantify the phosphorylation of AKT, ERK1/2, and S6K (the downstream target of mTOR).

RESULT(S):

Progesterone treatment had not statistically significant effect on LC3-II expression, autophagosome formation, or phosphorylation of AKT, ERK1/2, or S6K in estrogen-treated ECSCs. However, dienogest treatment up-regulated LC3-II expression and stimulated autophagosome formation. These effects were accompanied by decreased activation of AKT, ERK1/2, and S6K. Furthermore, incubation of ECSCs with AKT and ERK1/2 inhibitors, which mimicked dienogest-mediated inhibition of AKT and ERK1/2 activity, suppressed S6K activity, followed by an increase in LC3-II expression. In addition, cotreatment with dienogest and 3-methyladenine (autophagy inhibitor) decreased the levels of apoptosis of ECSCs compared with the single treatment with dienogest.

CONCLUSION(S):

Our results suggest that dienogest treatment of endometriotic cells suppresses AKT and ERK1/2 activity, thereby in turn inhibiting mTOR, inducing autophagy, and promoting apoptosis.

 

 

 

J Pediatr Adolesc Gynecol. 2015 Oct;28(5):e123-6.

An Atypical Presentation of Vaginal Agenesis.

Huguelet PS¹, May LT², Scott SM³.

 

Abstract

BACKGROUND:

Vaginal agenesis is rare and generally presents with primary amenorrhea and cyclic abdominal pain. We describe a case in which the diagnosis was delayed due to lack of initial pelvic examination and atypical findings on imaging.

CASE:

A 13-year-old girl with a known renal anomaly presented to the emergency department with primary amenorrhea and cyclic abdominal pain. She declined a pelvic examination and had normal laboratory testing and pelvic magnetic resonance imaging results. At 16 months later, she presented again and was diagnosed with vaginal agenesis and a large endometrioma.

SUMMARY AND CONCLUSION:

This case illustrates the importance of the physical examination in the evaluation of primary amenorrhea. Further, it demonstrates that hematometra may not be present on imaging. Here, an endometrioma was the only abnormality noted on magnetic resonance imaging after 18 months of retrograde menstruation.

 

 

Clin Exp Obstet Gynecol. 2015;42(2):156-60.

Decreased Bcl-6 and increased Blimp-1 in the peritoneal cavity of patients with endometriosis.

Yeol SG, Won YS, Kim YI, Lee JW, Choi YJ, Park DC.

 

Abstract

PURPOSE OF INVESTIGATION:

The authors investigated the expression patterns of interleukin (IL)-lβ and tumor necrosis factor (TNF)-α, cytokines associated with peritoneal inflammatory reactions, and of B cell leukemia lymphoma (Bcl)-6 and B lymphocyte inducer of maturation program (Blimp)-1, transcriptional factors associated with immunoglobulin (Ig) production; the concentrations of Igs, and their correlation, in patients with and without endometriosis.

MATERIALS AND METHODS:

The authors analyzed the peritoneal fluid of 98 patients, 46 with endometriosis, and 52 with benign tumors.

RESULTS:

IL-1 and TNF-α mRNAs and IgG and IgA concentrations were higher in the endometriosis group, but the differences were not statistically significant. However, Bcl-6 mRNA level was significantly lower and Blimp-1 mRNA level was significantly higher in the endometriosis group with significant correlations among transcriptional factors, Igs, and cytokines (p < 0.05).

CONCLUSION:

Peritoneal immune responses in patients with endometriosis may be due to increased IgG and IgA concentrations, as well as to changes in expression of proinflammatory cytokines and transcriptional factors.

 

 

Clin Exp Obstet Gynecol. 2015;42(2):168-72.

Genetic variation in COX-2 -1195 and the risk of endometriosis and adenomyosis.

Wang Y, Qu Y, Song W.

 

Abstract

AIM:

Ths study aims to explore the relationship between COX-2 gene polymorphism and the hereditary susceptibility or endoomeyriosis and adenomyosis.

MATERIALS AND METHODS:

Gene polymorphism in COX-2 gene was genotyped in 170 cases of endometriosis, 150 cases of adenomyosis, and 240 matched non-endometriosis and non-adenomyosis controls.

RESULTS:

Genotypic frequencies of GG, AG, and AA in COX-2 locus in endometriosis and adenomyosis were 16.5%, 51.2%, 32.4% and 16.0%, 49.3%, 34.7%, respectively. They were both significantly different from those in the control group (24.6%, 53.3%, and 22.1%) (p < 0.05). An allele frequency in endometriosis and adenomyosis were significantly higher than that in the control group. The risk of endometriosis or adenomyosis for those carrying two A alleles were 2.19 and 2.41 times to non-A genotype.

CONCLUSION:

Genetic variation of G to A at -1195 locus in the promoter region of COX-2 gene increases the risk of endometriosis and adenomyosis, and the genetic susceptibility of these two diseases are similar.

 

 

 

Zhongguo Zhen Jiu. 2015 Apr;35(4):323-6.

Efficacy on endometriosis treated with electroacupuncture.

Zhang X, Li W.

Abstract

OBJECTIVE:

To compare the difference in the clinical efficacy on endometriosis (EM) between electroacupuncture (EA) and western medication.

METHODS:

Seventy-two EM patients were divided into an EA group and a western medication group according to visiting departments, 36 cases in each one. In the EA group, acupuncture was applied to Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), Zigong (EX-CA 1), Diji (SP 8), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). After qi arrival, G6805-I pulse electronic apparatus was attached to bilateral Zigong (EX-CA 1), Guanyuan (CV 4) and Zhongji (CV 3), with continuous wave, 70 Hz in frequency, 3 mA in intensity. The EA was given once every two days. In the western medication group, mifepristone tablets were prescribed for oral administration, 12. 5 mg per treatment, once a day, for 6 months. The pain degree was observed before and after treatment and the clinical efficacy and recurrence rate were evaluated in the two groups. The enzyme-linked immunoassay (ELISA) was adopted to determine the tumor marker serum CA125 before and after treatment in the two groups.

RESULTS:

The total effective rate was 94. 4% (34/36) in the EA group and was 91. 7% (33/36) in the western medication group, without significant difference (P>0. 05). The pain score after treatment was lower than that before treatment in the two groups (both P< 0. 01), but the score after treatment in the EA group was lower than that in the western medication group (P<0. 05). Serum CA125 was reduced after treatment in the patients of the two groups (both P<0. 01), and serum CA125 after treatment in the EA group was lower than that in the western medication group (P<0. 05). In the follow-up visit of one year, the reoccurrence rate was 17. 6% (6/34) in the EA group and was 33. 3% (11/33) in the western medication group, indicating the significant difference (P<0. 05).

CONCLUSION:

EA achieves the significant clinical efficacy and the reoccurrence rate in 1 year in the EA group is obviously lower than that in the western medication group. This therapy could be promoted in clinical practice of acupuncture and moxibustion.

 

 

 

 

 

Arch Gynecol Obstet. 2015 Dec;292(6):1301-9.

Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation.

Wan L^1,2, Zou Y², Wan LH³, Wang LQ², Huang MZ^1,2, Wu J^1,2, Zhu YB², Huang OP^4,5.

 

Abstract

BACKGROUND:

Adenomyosis is a specific subtype of endometriosis and recent evidences have indicated that Tanshinone IIA (TSIIA) might be a potential therapeutic option for endometriosis. Meanwhile, endometrial stromal cells (ESCs) of adenomyosis might play crucial roles in the progression of this disease, emphasizing the importance of targeting ESCs in the treatment of adenomyosis. Furthermore, previous evidences also implicated that deregulated 14-3-3ζ expression might be associated with therapeutic effects of certain drugs.

AIM OF THE STUDY:

The aim of this study is to evaluate the potential involvement of 14-3-3ζ in the process of TSIIA-treated adenomyosis.

MATERIALS AND METHODS:

Ectopic endometrial stromal cells (EESCs) were isolated from a total of 3 patients with adenomyosis. Cells were treated with TSIIA and infected with 14-3-3ζ-overexpressing adenovirus, the expression level of 14-3-3ζ was determined by western blotting (WB), cell viability was detected by Cell Counting Kit-8 (CCK8), cell invasion and migration was evaluated by transwell assay, and cell apoptosis was detected by flow cytometry.

RESULTS:

TSIIA could decrease cell viability, induce cell apoptosis, and inhibit cell migration and invasion in EESCs. Mechanistically, TSIIA markedly reduced the expression of 14-3-3ζ in EESCs, and overexpression of 14-3-3ζ could restore the ability of cell viability, migration and invasion, but has no effect on cell apoptosis.

CONCLUSIONS:

TSIIA could be a promising novel therapeutic agent for adenomyosis, via inducing cell apoptosis, inhibiting cell viability, migration and invasion in EESCs. Furthermore, the effects of cell viability, migration and invasion were mediated in 14-3-3ζ-dependent manner while that of cell apoptosis was mediated in 14-3-3ζ-independent manner.

 

 

 

Surg Technol Int. 2015 May;26:19-24.

Modified Virtual Colonoscopy in the Diagnosis and Quantification of Bowel and Disseminated Endometriosis.

van der Wat J¹, Kaplan MD².

 

Abstract

This article describes the basic technology and technique behind modified virtual colonoscopy (MVC). It is accompanied by images illustrating the possibility of MVC to advance the imaging for endometriosis beyond the current modalities of magnetic resonance imaging (MRI) and ultrasound. A quantification system is described that will ultimately make staging and multicenter prospective scientific studies possible for rectogenital and disseminated endometriosis.

 

 

 

Fertil Steril. 2015 Aug;104(2):356-65.

Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression.

Celik O¹, Unlu C², Otlu B³, Celik N⁴, Caliskan E⁵.

 

Abstract

OBJECTIVE:

To determine whether laparoscopic endometrioma resection alters peri-implantation endometrial HOXA-10, HOXA-11, LIF, ITGB3 and ITGAV mRNA expression.

DESIGN:

Case-control study.

SETTING:

Medical school.

PATIENT(S):

Twenty infertile patients with uni- or bilateral endometrioma, five infertile patients having nonendometriotic benign ovarian cyst, and five fertile control subjects.

INTERVENTION(S):

Mid-luteal-phase endometrial sampling was performed at the time of surgery. Second endometrial biopsies were obtained 3 months after laparoscopic endometrioma resection during the mid-luteal phase of the cycle.

MAIN OUTCOME MEASURE(S):

Endometrial HOXA-10, HOXA-11, LIF, ITGAV, and ITGB3 mRNA expressions were evaluated with the use of reverse-transcription polymerase chain reaction.

RESULT(S):

Significantly decreased endometrial ITGAV mRNA expression was noted in biopsies obtained from endometrioma and nonendometriotic cyst groups before surgery. Trends toward decreased endometrial HOXA-10, HOXA-11, LIF, and ITGB3 mRNA expressions were noted in the endometrioma and nonendometriotic cyst groups before surgery compared with the fertile subjects. However, the differences failed to show statistical significance. Compared with preoperative values, significantly increased HOXA-10 (12.1-fold change) and HOXA-11 (17.2-fold change) mRNA expressions were noted in endometrial biopsies obtained from subjects who were undergoing endometrioma surgery. Fold change in endometrial ITGAV mRNA after endometrioma surgery was found to be 30.1 and indicated a positive regulation. However, this fold increase was statistically insignificant. Expressions of these endometrial receptivity markers did not change significantly after surgical removal of nonendometriotic benign ovarian cysts.

CONCLUSION(S):

Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression, suggesting an improvement in endometrial receptivity.

 

 

BMJ Clin Evid. 2015 Jun 9;2015.

Endometriosis: the effects of dienogest.

Ferrero S¹, Remorgida V, Venturini PL, Bizzarri N.

 

Abstract

INTRODUCTION:

Ectopic endometrial tissue is found in 2% to 6% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings.

METHODS AND OUTCOMES:

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of dienogest for the treatment of endometriosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS:

Five studies were included. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS:

In this systematic review we present information relating to the effectiveness and safety of the following interventions: dienogest versus placebo or no treatment; dienogest versus gonadorelin analogues; dienogest versus combined oral contraceptives; dienogest versus other progestogens.

 

 

Clin Biochem. 2015 Nov;48(16-17):1131-7.

Differentially expressed gene profiles in the serum before and after the ultrasound-guided ethanol sclerotherapy in patients with ovarian endometriomas.

Wang LL¹, Cai HQ¹, Dong XQ², Zhang LW¹, Jiang SS¹, Zhao N¹, Shao XH¹, Wang SM¹, Zhu L³, Zhang T⁴.

 

Abstract

OBJECTIVES:

To detect the differentially expressed genes and subsequently identify disease-related signatures and potential biomarkers for patients with ovarian endometriomas in the serum before and after the ultrasound-guided ethanol sclerotherapy in patients with ovarian endometriomas.

DESIGN AND METHODS:

Venous blood samples were collected from nine patients with ovarian endometriomas before and after ultrasound-guided ethanol sclerotherapy, and the serum were isolated after centrifugation. NimbleGen human gene expression microarrays analysis was conducted to analyse gene ontology categories (GO terms) and signalling pathways of differentially expressed genes. The accuracy of some typical genes from microarray analysis was verified by quantitative PCR (qPCR).

RESULTS:

Approximately 45,033 genes were analysed by NimbleGen human gene expression microarrays, which identified 447 genes that showed differential expressions before and after therapy. Of these, 225 genes were up-regulated and 222 genes were down-regulated. The GO terms of the down-regulated genes were strongly associated with the pathogenesis of ovarian endometriomas; 15 down-regulated genes showed overlaps in both signalling pathways and GO terms. Among these, six genes showed statistical significance including IL6, CD36, JUNB, B4GALT1, HES1, and NR4A1, which were also validated by qPCR analysis.

CONCLUSIONS:

There were differentially expressed genes in the serum before and after ultrasound-guided ethanol sclerotherapy in patients with ovarian endometriomas. Notably, the expressions of IL6, CD36, JUNB, B4GALT1, HES1, and NR4A1, which are strongly associated with the pathogenesis of ovarian endometriomas, were significantly down-regulated after ethanol sclerotherapy. This may not only help us understand EMs pathogenesis, but also provide potential biomarkers for verifying the effects of ethanol sclerotherapy.

 

 

Reprod Sci. 2015 Sep;22(9):1162-70.

Metformin Suppresses Prostaglandin E2-Induced Cytochrome P450 Aromatase Gene Expression and Activity via Stimulation of AMP-Activated Protein Kinase in Human Endometriotic Stromal Cells.

Zhou Y¹, Xu JN¹, Zeng C¹, Li X¹, Zhou YF¹, Qi Y², Xue Q³.

 

Abstract

BACKGROUND:

Cytochrome P450 aromatase (encoded by the CYP19A1/aromatase gene) plays a critical physiologic role in endometriosis. Metformin is known to suppress prostaglandin E2 (PGE2)-induced CYP19A1 messenger RNA (mRNA) expression in human endometriotic stromal cells (ESCs). However, the possible mechanism behind this suppression remains to be determined.

METHODS:

In this study, ESCs were cultured with metformin, PGE2, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitors. Expression of CYP19A1 mRNA and aromatase activity were measured by quantitative polymerase chain reaction and aromatase activity assay, respectively. The binding of the cyclic AMP response element-binding (CREB) protein to CYP19A1 promoter II (PII) was assessed by chromatin immunoprecipitation assay.

RESULTS:

We demonstrated that metformin downregulated the expression of aromatase mRNA (32%) and activity (25%) stimulated by PGE2 (4.18-fold and 2.14-fold) in ESCs via stimulation of AMPK. Following PGE2 treatment, there was a marked increase in CREB binding to aromatase PII, while metformin attenuated the above-mentioned stimulation by 67%.

CONCLUSION:

Metformin could inhibit PGE2-induced CYP19A1 mRNA expression and aromatase activity via AMPK activation and inhibition of CREB to CYP19A1 PII in human ESCs. The results of the present study suggest that metformin may have unique therapeutic potential as an antiendometriotic drug in the future.

 

 

Eur J Cancer. 2015 Sep;51(13):1831-42.

Molecular changes in endometriosis-associated ovarian clear cell carcinoma.

Worley MJ Jr¹, Liu S¹, Hua Y², Kwok JS³, Samuel A¹, Hou L¹, Shoni M¹, Lu S¹, Sandberg EM¹, Keryan A¹, Wu D⁴, Ng SK⁵, Kuo WP⁶, Parra-Herran CE⁷, Tsui SK³, Welch W⁷, Crum C⁷, Berkowitz RS¹, Ng SW⁸.

 

Abstract

BACKGROUND:

Endometriosis is frequently associated with and thought of having propensity to develop into ovarian clear cell carcinoma (OCCC), although the molecular transformation mechanism is not completely understood.

METHODS:

We employed immunohistochemical (IHC) staining for marker expression along the potential progression continuum. Expression profiling of microdissected endometriotic and OCCC cells from patient-matched formalin-fixed, paraffin-embedded samples was performed to explore the carcinogenic pathways. Function of novel biomarkers was confirmed by knockdown experiments.

RESULTS:

PTEN was significantly lost in both endometriosis and invasive tumour tissues, while oestrogen receptor (ER) expression was lost in OCCC relative to endometriosis. XRCC5, PTCH2, eEF1A2 and PPP1R14B were significantly overexpressed in OCCC and associated endometriosis, but not in benign endometriosis (p ⩽ 0.004). Knockdown experiments with XRCC5 and PTCH2 in a clear cell cancer cell line resulted in significant growth inhibition. There was also significant silencing of a panel of target genes with histone H3 lysine 27 trimethylation, a signature of polycomb chromatin-remodelling complex in OCCC. IHC confirmed the loss of expression of one such polycomb target gene, the serous ovarian cancer lineage marker Wilms’ tumour protein 1 (WT1) in OCCC, while endometriotic tissues showed significant co-expression of WT1 and ER.

CONCLUSIONS:

Loss of PTEN expression is proposed as an early and permissive event in endometriosisdevelopment, while the loss of ER and polycomb-mediated transcriptional reprogramming for pluripotency may play an important role in the ultimate transformation process. Our study provides new evidence to redefine the pathogenic programme for lineage-specific transformation of endometriosis to OCCC.

 

 

Am J Reprod Immunol. 2015 Oct;74(4):379-86.

Chemerin Expression in the Peritoneal Fluid, Serum, and Ovarian Endometrioma of Women with Endometriosis.

Jin CH¹, Yi KW², Ha YR², Shin JH², Park HT², Kim T², Hur JY².

 

Abstract

PROBLEM:

Inflammation is an essential process in the pathogenesis of endometriosis.

METHOD OF STUDY:

Serum and peritoneal fluid (PF) samples were collected from women with endometriosis (n = 31) and women without endometriosis (n = 48). Chemerin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels in serum and PF samples were determined with a specific enzyme-linked immunosorbent assay. Eutopic endometrial tissue from controls and ovarian endometriotic cysts were obtained during surgery. Expression of chemerin and chemerin receptors in ectopic and eutopic endometrial tissues was measured on real-time reverse transcriptase-polymerase chain reaction. Protein expression was examined with Western blot and densitometric analysis.

RESULTS:

Chemerin concentrations were higher in PF from women with endometriosis than that in that from controls. PF chemerin concentrations were significantly correlated with both TNF-α and IL-6 levels in PF. The mRNA and protein of chemerin and its receptor were significantly increased in the ovarian endometrioma tissue compared with eutopic endometrium of controls.

CONCLUSION:

These findings suggest that chemerin plays a role in endometriosis-related pelvic inflammation.

 

 

Practitioner. 2015 Mar;259(1780):13-7, 2.

GPs have key role in early diagnosis of endometriosis.

Coleman L, Overton C.

 

Abstract

Endometriosis is defined as the presence of endometrial-like tissue outside the uterus. Deposits are commonly distributed on the ovaries, uterosacral ligaments, pouch of Douglas, rectum and sigmoid colon, bladder and ureter. Endometriosis is common, affecting 10% of the female adult population and up to 50% of women with infertility. Risk factors include early menarche, late menopause, delayed childbearing, vaginal outflow obstruction and a first-degree relative affected. Women commonly present to their GP with pelvic pain, painful intercourse or subfertility. Classically the pain starts several days before the period which is extremely painful. After the period, symptoms tend to improve until mid-cycle when the pattern repeats again. Patients also complain of fatigue. Abdominal palpation, bimanual and speculum examination are important to identify signs of endometriosis, but also to exclude alternative diagnoses such as fibroid uterus, infection or pregnancy. However, a normal examination does not exclude a diagnosis of endometriosis. Serum CA125 can be raised in endometriosis but is not specific or sensitive for the condition and is therefore not recommended as a screening test. A normal pelvic ultrasound scan does not exclude a diagnosis of endometriosis. The gold standard investigation for endometriosis is laparoscopy and biopsy with histological confirmation. Referral should be considered if pain is not controlled with simple analgesia or the diagnosis is suspected in a woman who is actively trying to conceive. Early referral should be considered in women with abnormal examination findings, or an abnormal ultrasound result.

 

 

J Endocrinol Invest. 2016 Jan;39(1):37-44.

Potential impact of maternal vitamin D status on obstetric well-being.

Triunfo S¹, Lanzone A².

 

Abstract

Despite its discovery 100 years ago, vitamin D (VD) has emerged as one of the most controversial nutrients and prohormones of the 21st century. In the past few years, a growing interest in VD has been observed in the biomedical literature due to evidences demonstrating a relevant relationship not only between regulation of calcium and phosphorus homeostasis, but also multiple disease states and low VD status in the population. Indeed, several studies carried out to decipher its role in the body in almost every cell, tissue, and different organs. Recent findings suggested a significant implication of VD in different physiologic processes , such as vascular health, immune function, metabolism, and placental function. In the attempt to focus the attention on effect of VD on female reproductive health, there has been a paucity of data from randomized controlled trials to establish clear beneficial. Human and animal data suggest that low VD status is associated with impaired fertility, endometriosis, and polycystic ovary syndrome. Findings from observational studies show higher rates of preeclampsia, gestational diabetes, preterm birth, and bacterial vaginosis in women with low VD levels. By recent evidences, this review explored the association between maternal VD status and selected effects on maternal, perinatal, and infant health, and the impact of VD supplementation during pregnancy on obstetric well-being.

 

 

Ultrasonography. 2015 Oct;34(4):258-67.

Ultrasonography of adnexal causes of acute pelvic pain in pre-menopausal non-pregnant women.

Dupuis CS¹, Kim YH¹.

 

Abstract

Acute-onset pelvic pain is an extremely common symptom in premenopausal women presenting to the emergency department. After excluding pregnancy in reproductive-age women, ultrasonography plays a major role in the prompt and accurate diagnosis of adnexal causes of acute pelvic pain, such as hemorrhagic ovarian cysts, endometriosis, ovarian torsion, and tubo-ovarian abscess. Its availability, relatively low cost, and lack of ionizing radiation make ultrasonography an ideal imaging modality in women of reproductive age. The primary goal of imaging in these patients is to distinguish between adnexal causes of acute pelvic pain that may be managed conservatively or medically, and those requiring emergency/urgent surgical or percutaneous intervention.

 

 

Abdom Imaging. 2015 Oct;40(7):2566-72.

The shading sign: is it exclusive of endometriomas?

Dias JL^1,2, Veloso Gomes F^3,4, Lucas R⁵, Cunha TM⁶.

 

Abstract

OBJECTIVES:

To investigate if the shading sign is an exclusive MRI feature of endometriomas or endometrioid tumors, and to analyze its different patterns.

METHODS:

Three hundred and fourty six women with adnexal masses who underwent 1.5/3-T MRI were included in this retrospective, board-approved study. The shading sign was found in 56 patients, but five cases were excluded due to lack of imaging follow-up or histological correlation. The final sample included 51 women. The type of tumor and the pattern of shading were recorded for each case.

RESULTS:

Thirty endometriomas and five endometrioid carcinomas were found. The remaining 16 cases corresponded to other benign and malignant tumors. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 73%, 93%, 59%, and 96%, respectively. Restricting the analysis to cystic lesions without solid or fat component, sensitivity, specificity, positive predictive value, and negative predictive value were 73%, 96%, 94%, and 80%. Five shading patterns were identified: layering (15.7%), liquid-liquid level (11.8%), homogenous (45.1%), heterogeneous (11.8%), and focal/multifocal shading within a complex mass (19.6%). No significant correlation was found between these patterns and the type of tumor.

CONCLUSIONS:

The shading sign is not exclusive of endometriomas or endometrioid tumors. Homogenous shading was the most prevalent pattern in endometriomas and half of the cases with focal/multifocal shading within a complex mass were endometrioid carcinomas.

 

 

 

Minim Invasive Surg. 2015;2015:730513.

Clinical Effectiveness of Modified Laparoscopic Fimbrioplasty for the Treatment of Minimal Endometriosis and Unexplained Infertility.

Franjoine SE¹, Bedaiwy MA², AbdelHafez FF³, Geng C⁴, Liu JH¹.

 

Abstract

Objective. To study the reproductive outcomes of modified laparoscopic fimbrioplasty (MLF), a surgical technique designed to increase the working surface area of the fimbriated end of the fallopian tube. We postulated that an improvement in fimbrial function through MLF will improve reproductive outcomes. Design. Retrospective cohort study. Setting. Academic tertiary-care medical center. Patients. Women with minimal endometriosis or unexplained infertility, who underwent MLF during diagnostic laparoscopy (n = 50) or diagnostic laparoscopy alone (n = 87). Intervention. MLF involved gentle, circumferential dilatation of the fimbria and lysis of fimbrial adhesions bridging the fimbrial folds. Main Outcome Measures. The primary outcome was pregnancy rate and the secondary outcome was time to pregnancy. Results. The pregnancy rate for the MLF group was 40.0%, compared to 28.7% for the control group. The average time to pregnancy for the MLF group was 13 weeks, compared to 18 weeks for the control group. The pregnancy rate in the MLF group was significantly higher for patients ≤35 ys (51.5% versus 28.8%), but not for those >35 ys (17.6% versus 28.6%). Conclusion. MLF was associated with a significant increase in pregnancy rate for patients ≤35 ys.

 

 

Biomed Res Int. 2015;2015:158490.

The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects.

Hughes CL¹, Foster WG², Agarwal SK³.

 

Abstract

In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosisassociated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.

 

 

Yonsei Med J. 2015 Jul;56(4):1079-86.

The Prognostic Value of Individual Adhesion Scores from the Revised American Fertility Society Classification System for Recurrent Endometriosis.

Yun BH¹, Jeon YE², Chon SJ³, Park JH², Seo SK¹, Cho S², Choi YS¹, Lee JS⁴, Lee BS⁵.

 

Abstract

PURPOSE:

This study aimed to evaluate the prognostic value of each component of the revised American Fertility Society (rAFS) classification system for the first recurrence of endometriosis after conservative laparoscopy.

MATERIALS AND METHODS:

As this was a retrospective cohort study, data were collected by reviewing medical records. A total of 379 women ages 18 to 49 years were included. Women who underwent conservative laparoscopy with histologic confirmation of endometriosis at Gangnam Severance Hospital between March 2003 and May 2010 were included. Individual components of the rAFS classification system as well as preoperative serum CA-125 levels were retrospectively analyzed to assess their prognostic values for recurrence of endometriosis.

RESULTS:

Of 379 patients, 80 (21.2%) were found to have recurrence of endometriosis. The median duration of follow-up was 19.0 months, and the mean age at the time of surgery was 31.8±6.7 years. In endometriosis of advanced stage, younger age at the time of surgery, bilateral ovarian cysts at the time of diagnosis, a rAFS ovarian adhesion score >24, and complete cul-de-sac obliteration were independent risk factors of poor outcomes, and a rAFS ovarian adhesion score >24 had the highest risk of recurrence [hazard ratio=2.948 (95% CI: 1.116-7.789), p=0.029].

CONCLUSION:

Our results suggest that of the rAFS adnexal adhesion scores, the ovarian adhesion score rather than the tubal adhesion score was associated with a significantly increased risk of recurrent endometriosis. The preoperative serum CA-125 level may be also a significant prognostic factor for recurrence, as known. However, it seemed to only have borderline significance in affecting recurrence in the current study.

 

 

Int J Gynaecol Obstet. 2015 Sep;130(3):219-22.

A randomized, placebo-controlled, double-blind study of hysteroscopic-guided pertubal diluted bupivacaine infusion for endometriosis-associated chronic pelvic pain.

Shokeir T¹, Mousa S².

 

Abstract

OBJECTIVE:

To assess the effectiveness of hysteroscopic-guided pertubal diluted bupivacaine infusion for endometriosis-associated chronic pelvic pain (CPP).

METHODS:

Between June 2010 and July 2013, a randomized, placebo-controlled, double-blind study was undertaken at Mansoura University Hospital, Mansoura, Egypt. Patients meeting inclusion criteria (laparoscopically confirmed endometriosis, patent fallopian tubes, ≥6 months CPP, pain score on visual analogue scale [VAS] >5) were randomly assigned using a computer-generated randomization sequence to receive either office hysteroscopic-guided pertubal diluted bupivacaine infusion (0.25%) or placebo. Response to treatment was assessed using subjective data for scores on VAS and a monthly verbal rating scale (VRSmonthly) at baseline and at 1, 2, and 3 months of follow-up. Additionally, women completed a questionnaire to evaluate the overall satisfaction at 3 months.

RESULTS:

Thirty patients were assigned to each group. In the bupivacaine group, VAS and VRSmonthly scores were significantly lower at 1, 2, and 3 months than at baseline (P<0.05 for all). Additionally, scores were significantly lower in the bupivacaine group than in the placebo group at 1, 2, and 3 months (P<0.05 for all). At 3 months, 22 (73%) women in the bupivacaine group expressed satisfaction, compared with 2 (7%) in the placebo group (P=0.18).

CONCLUSION:

Office pertubal hysteroscopic-guided diluted bupivacaine infusion could be used to manage endometriosis-associated CPP for at least 3 months. AEARCTR-0000573.

 

 

J Cardiothorac Surg. 2015 Jun 13;10:83.

Juvenile catamenial pneumothorax: institutional report and review.

Inoue T¹, Chida M², Inaba H³, Tamura M⁴, Kobayashi S⁵, Sado T⁶.

 

Abstract

BACKGROUND:

Catamenial pneumothorax (CP) is a type of spontaneous pneumothorax due to thoracic endometriosis occurring in reproductive women, and usually involves the right side of the thorax showing diaphragm lesions. For the present study, we defined juvenile CP (JCP) as patients with CP who were 19 years old and younger. Institutional findings and a systematic literature review are presented.

METHODS:

We retrospectively enrolled all patients with CP treated at our institutions from January 2002 to June 2013. In addition, we conducted a search of medical literature published using the PubMed and Japanese Ichushi databases with “catamenial pneumothorax” as the search term.

RESULTS:

Thirteen female patients with CP, 1 on the left side, were treated at our institutions. The patient with left-side CP was classified as JCP, while that was also identified in 29 of 451 CPs reported in our literature review. Pneumothorax occurred more frequently on the left side in JCP as compared to usual CP (p<0.01). There was a significantly lower ratio of JCP cases with diaphragm lesions as compared to usual CP (p<0.01).

CONCLUSION:

Significant laterality was not seen in JCP patients and fewer had diaphragm lesions as compared to usual CP. JCP may be a new entity of CP.

 

 

J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1287-92.

Robotic Shaving Technique in 25 Patients Affected by Deep Infiltrating Endometriosis of the Rectovaginal Space.

Pellegrino A¹, Damiani GR², Trio C¹, Faccioli P³, Croce P⁴, Tagliabue F⁵, Dainese E⁶.

 

Abstract

Minimally invasive surgery represents the gold standard for the management of deep infiltrating endometriosis(DIE) involving the rectovaginal septum (RVS). This analysis aimed to evaluate the feasibility of robotic-assisted laparoscopy (RAL) and clinical outcomes in terms of long-term complications, pain relief, and recurrence rate for the treatment of DIE of the RVS. A prospective cohort study of robotic procedures was performed between October 2010 and July 2014, including removal of endometriotic nodules from the RVS with rectal shaving alone or in combination with accessory procedures. In all cases, the revised American Society for Reproductive Medicine (rASRM) score for endometriosis was >40 points (stage IV). Twenty-five consecutive patients underwent RAL, with a successful complete nodule debulking by the wall shaving technique. Pathology confirmed the adequacy of the surgical specimen and the median largest endometriotic nodule was of 21 mm (range, 10-60 mm), with free margins in all cases. The median operative time from skin opening to closure was 174 minutes (range, 75-300 minutes), and blood loss was close to 0 mL. The median revised Enzian score for location A (RVS) was 2 (range, 1-3). The most frequent Enzian class was A2B0C0 (48%), followed by A3B0C0 (12%). In 3 cases (12%), partial vaginal resection was required to remove endometriotic nodules of the RVS (1 each in classes A3B0C1FI, A3B0C0FO, and A3B0C0). No intraoperative complications occurred. This series has a median long-term follow up of 22 months (range, 6-50 months) currently available with an optimal operative time, demonstrating good long-term outcomes. Our data support robotics as a safe and attractive alternative for comprehensive surgical treatment of DIE.