J Zoo Wildl Med. 2016 Dec;47(4):1114-1117

UTERINE ADENOMYOSIS AND AN ENDOMETRIAL POLYP IN A ROCK HYRAX (PROCAVIA CAPENSIS).

Holman HJ, Gailbreath K.

 

Abstract

An 8-yr-old nulliparous, female rock hyrax ( Procavia capensis ) had intermittent mucoid to bloody discharge late winter-early spring for two consecutive years. Fragments of necrotic tissue, suspected to be vaginal or rectal in origin, were passed on two occasions. Physical examination, radiographs, and ultrasound did not identify the source of the tissue. Exploratory laparotomy and ovariohysterectomy were performed. On histopathology, a diagnosis of adenomyosis with a uterine polyp was made. Postsurgical complications included incisional infection and renal compromise that were medically managed and resolved. No further vaginal discharge was observed. This is the first report of uterine adenomyosis and endometrial polyp in a rock hyrax.

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):745-750.

Conservative approach to rectosigmoid endometriosis: a cohort study.

Egekvist AG^1,2, Marinovskij E³, Forman A^1,2, Kesmodel US^4,5, Riiskjaer M^1,2, Seyer-Hansen M^1,2.

Abstract

INTRODUCTION:

The aim of the study was to assess the risk of surgery after initial conservative treatment of rectosigmoid endometriosis in relation to demographic data.

MATERIAL AND METHODS:

The study was conducted on the tertiary endometriosis referral unit, Aarhus University Hospital. Medical records, from patients seen from January 2009 onwards with a diagnosis of rectosigmoid endometriosis and more than 6 months’ follow up were audited. Demographic data, results of magnetic resonance imaging and time to secondary surgery for rectosigmoid endometriosis were registered.

RESULTS:

Data on 238 patients diagnosed with rectosigmoid endometriosis were included. In all, 78 (32.8%) patients had primary surgery, 27 (11.3%) had secondary surgery and 133 (55.9%) continued conservative treatment throughout the observation period. Patients who underwent primary or secondary surgery were younger than patients continuing conservative treatment.

CONCLUSIONS:

In a tertiary referral center where about half of patients with rectosigmoid endometriosis were scheduled for conservative treatment, more than 80% of these avoided surgery.

 

 

Fertil Steril. 2017 Mar;107(3):707-713.

Does preoperative antimüllerian hormone level influence postoperative pregnancy rate in women undergoing surgery for severe endometriosis?

Stochino-Loi E¹, Darwish B², Mircea O³, Touleimat S², Millochau JC², Abo C², Angioni S⁴, Roman H⁵.

Abstract

OBJECTIVE:

To compare postoperative pregnancy rates as they relate to presurgery antimüllerian hormone (AMH) level in patients with stage 3 and 4 endometriosis.

DESIGN:

Retrospective comparative study using data prospectively recorded in the North-West Inter-Regional Female Cohort for Patients with Endometriosis (CIRENDO) database.

SETTING:

University tertiary referral center.

PATIENT(S):

One hundred eighty patients with stage 3 and 4 endometriosis and pregnancy intention, managed from June 2010 to March 2015, were divided into two groups according to their preoperative AMH levels: group A (AMH ≥2 ng/mL) and group B (AMH <2 ng/mL).

INTERVENTION(S):

Surgical procedure involved ovarian endometrioma ablation by plasma energy along with resection of various localizations of the disease. Postoperative conception was either spontaneous or used assisted reproductive technology, depending on patient characteristics.

MAIN OUTCOME MEASURE(S):

Patient characteristics, preoperative symptoms, infertility history, intraoperative findings, and probability of pregnancy were recorded and compared between the two groups.

RESULT(S):

Among 180 women enrolled in the study, 134 (74.4%) were assigned to group A and 46 (25.6%) to group B. The women’s ages were, respectively, 30 ± 3.8 and 32 ± 4.6 years. Pregnancy was achieved by 134 (74.4%) patients, and conception was spontaneous in 74 of them (55.2%). Pregnancy rates in groups A and B were, respectively, 74.6% (100 women) and 73.9% (34 women), while spontaneous conception represented 54% (54 women) and 58.8% (20 women). The probability of pregnancy at 12, 24, and 36 months after surgery in groups A and B was comparable, respectively, 65% (95% confidence interval [CI], 55%-75%), 77% (95% CI, 86%-68%), and 83% (95% CI, 90%-75%) versus 50% (95% CI, 69%-34%), 77% (95% CI, 90%-61%), and 83% (95% CI, 94%-68%). Supplementary analysis in women with normal (≥2 ng/mL), low (1-1.99 ng/mL), and very low (<1 ng/mL) AMH level showed an inverse relationship between AMH level, age, and antecedents of miscarriage; however, postoperative pregnancy rates were comparable among the three groups at 12 and 24 months, respectively, 59.5% (95% CI, 49.3%-70%) and 77.4% (95% CI, 68%-85.4%); 57.1% (95% CI, 34%-83%) and 78.6% (95% CI, 55.2%-94.8%); and 46.7% (95% CI, 25.6%-73.7%) and 73.3% (95% CI, 50.4%-91.7%).

CONCLUSION(S):

The probability of postoperative pregnancy was comparable between women with low and normal AMH level who were managed for stage 3 and 4 endometriosis and who were a mean age of 30 years. However, the small sample size might have been unable to detect differences in pregnancy and live-birth rates between the two groups. As the majority of pregnancies were spontaneous, our results suggest that surgical management may be offered to young patients with severe endometriosis and reduced ovarian reserve with good fertility outcomes.

 

 

J Minim Invasive Gynecol. 2017 Mar – Apr;24(3):466-472

Laparoscopic Management of Ureteral Endometriosis and Hydronephrosis Associated With Endometriosis.

Alves J¹, Puga M², Fernandes R³, Pinton A⁴, Miranda I⁵, Kovoor E⁴, Wattiez A⁶.

Abstract

STUDY OBJECTIVE: To evaluate if laparoscopic treatment of ureteral endometriosis is feasible, safe, and effective and to determine if ureteral dilatation and/or the number of incisions increases complications.

DESIGN:

An institutional review board-approved retrospective cohort study of consecutive patients who underwent surgery for deep infiltrating endometriosis involving the ureter with hydronephrosis (Canadian Task Force classification III).

SETTING:

A university hospital.

PATIENTS:

Of 658 patients who had surgery for deep infiltrating endometriosis between November 2004 and December 2013, 198 of the 658 patients had ureteral endometriosis and required ureterolysis, and 28 of the 198 patients were identified with ureteral dilatation and hydronephrosis associated with endometriosis.

INTERVENTIONS:

Of these 28 cases, 15 ureterolyses, 12 reanastomoses, and 1 reimplantation were performed.

MEASUREMENTS AND MAIN RESULTS:

Medical, operative, and pathological data on the evolution of pain, urinary complaints, fertility, complications, and recurrences were collected from clinical records. Additionally, telephone interviews were performed for the follow-up of long-term outcomes. All 28 patients had concomitant surgical procedures because of endometriosis elsewhere in the pelvis or abdomen; 12 (42.9%) underwent surgery of the bowel, whereas 5 (17.9%) had bladder surgery. The evolution of pain after surgery showed a positive response (mean dysmenorrhea evaluation measured by the Numeric Pain Rating Scale from 0-10 preoperatively at the short-term follow-up and the long-term follow-up: 7.25-1.73 and 0.25, respectively). Three complications were noted in the group of 28 patients with ureterohydronephrosis; 1 required surgical reintervention. Logistic regression analyses found vaginal incision (odds ratio = 2.08; 95% CI 0.92-4.73), bladder incision (odds ratio = 8.77; 95% CI 3.25-23.63), number of incisions (odds ratio = 2.12; 95% CI 1.29-3.47), and number of previous surgeries (odds ratio = 1.26; 95% CI 0.93-1.71) as independent risk factors for complications in the group of 198 patients. Three patients underwent reoperation in the group of 28 patients: 1 for ureterovaginal fistula, 1 for persistent ureter dilatation and hydronephrosis, and 1 for persistent pain.

CONCLUSION:

Laparoscopically assisted ureterolyses, ureteral reanastomoses, and ureteral reimplantation are feasible, safe, and effective treatments for ureteral endometriosis. Complete laparoscopic excision is possible with minimal complications, which seem to be associated with the number of incisions. Ureteral endometriosisshould be suspected in all cases of deep infiltrating endometriosis.

 

 

Clin Exp Reprod Med. 2016 Dec;43(4):215-220.

Efficacy and safety of dienogest in patients with endometriosis: A single-center observational study over 12 months.

Park SY¹, Kim SH¹, Chae HD¹, Kim CH¹, Kang BM¹.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of dienogest treatment in patients who had received dienogest for 12 months or more to treat endometriosis.

METHODS:

We analyzed the clinical data of 188 women with endometriosis who had been treated with 2 mg of dienogest once a day for 12 months or more at a single institute. We evaluated changes in endometriosis-associated pain and endometrioma size, recurrence rate, and adverse events following dienogest administration. Bone mineral density (BMD) was measured in patients who were prescribed dienogest for more than 18 months.

RESULTS:

Pain was significantly reduced at 12 months after dienogest medication. In those treated with dienogest due to recurrent endometrioma, the size of the endometrioma was significantly decreased at the 12-month and 18-month follow-ups. We found only one case of sonographic recurrence during dienogest administration among those who were treated postoperatively to prevent recurrence (1 of 114, 0.9%). The most common adverse drug reaction was uterine bleeding (3.2%), and other adverse events were generally tolerable and associated with low discontinuation rates (5.2%). Among the 50 patients in whom BMD was measured, 10 patients (20%) had a Z-score below the expected range for age.

CONCLUSION:

The administration of dienogest for a year or more seems to be highly effective in preventing recurrence after surgery, reducing endometriosis-associated pain, and decreasing the size of recurrent endometrioma, with a favorable safety and tolerability profile. However, BMD should be checked in patients on long-term medication due to possible bone loss in some women.

 

 

Reprod Sci. 2017 Oct;24(10):1410-1418.

Myofibroblasts Are Evidence of Chronic Tissue Microtrauma at the Endometrial-Myometrial Junctional Zone in Uteri With Adenomyosis.

Ibrahim MG¹, Sillem M², Plendl J³, Chiantera V¹, Sehouli J¹, Mechsner S¹.

Abstract

BACKGROUND:

Adenomyosis (AM) uteri exhibit hyperperistalsis. The latter causes a chronic tissue trauma at the endometrial-myometrial junctional zone (EMJZ). Upon tissue trauma, microdehiscences in the myometrium facilitate the translocation of basal endometrial fragments into the myometrium. There, a metaplasia (mediated by transforming growth factor β1 [TGFβ1] and connective tissue growth factor [CTGF]) occurs and AM lesions develop. The abundance of myofibroblasts in a tissue hallmarks metaplasia and points to a tissue microtrauma.

MATERIALS AND METHODS:

To study if myofibroblasts-as an evidence of tissue microtrauma-are more abundant at EMJZ in AM-uteri, a case-control experimental study was carried out at Charité University Hospital-Endometriosis Research Centre. In all, 18 uteri with AM and 14 uteri without AM were obtained during laparoscopy-assisted vaginal hysterectomy. The immunolabeling of myofibroblastic metaplasia (alpha smooth muscle actin [ASMA] and collagen I), differentiated smooth muscle marker (desmin) and metaplasia mediators (TGF-β receptors 1, 2, 3 and CTGF) was investigated. The ultrastructure of myofibroblasts at EMJZ of AM uterus was characterized by transmission electron microscopy, in addition to an in vitro study to characterize myofibroblasts in the endometrium of non-AM uterus.

RESULTS:

Immunolabeling of ASMA and collagen I was significantly higher at EMJZ of AM uteri versus non-AM uteri. Furthermore, myofibroblasts were ultrastructurally characterized at EMJZ of AM. Endometrium of non-AM uterus exhibited 5% to 8% of its cells, expressing ASMA and collagen I. No difference was noted regarding metaplasia mediators immunolabeling between both the groups.

CONCLUSION:

The abundant and persistent myofibroblasts (expressing ASMA/collagen I) at EMJZ in AM uteri are ultra-/microscopic evidence of chronic tissue trauma. They are of nonmyometrial origin, as they lack desmin immunolabeling.

 

Reprod Sci. 2017 Oct;24(10):1371-1381.

 

Impact of Psychological Stress on Pain Perception in an Animal Model of Endometriosis.

Hernandez S¹, Cruz ML¹, Seguinot II², Torres-Reveron A^1,3, Appleyard CB¹.

Abstract

PURPOSE:

Pain in patients with endometriosis is considered a significant source of stress but does not always correlate with severity of the condition. We have demonstrated that stress can worsen endometriosis in an animal model. Here, we tested the impact of a psychological stress protocol on pain thresholds and pain receptors.

METHODS:

Endometriosis was induced in female rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats had sutures only. Rats were exposed to water avoidance stress for 7 consecutive days or handled for 5 minutes (no stress). Fecal pellets and serum corticosterone (CORT) levels were measured as an index of anxiety. Pain perception was assessed using hot plate and Von Frey tests. Substance P, enkephalin, endomorphin-2, Mu opioid receptor (MOR), and neurokinin-1 receptor expression in the spinal cord were measured by immunohistochemistry.

RESULTS:

Fecal pellets and CORT were significantly higher in the endo-stress (ES) group than endo-no stress (ENS; P < .01) and sham-no stress groups (SNS; P < .01). The ES rats had more colonic damage ( P < .001 vs SNS; P < .05 vs ENS), vesicle mast cell infiltration ( P < .01 vs ENS), and more severe vesicles than ENS. The ES developed significant hyperalgesia ( P < .05) but stress reversed the allodynic effect caused by endo ( P < .001). The MOR expression was significantly reduced in ENS versus SNS ( P < .05) and more enkephalin expression was found in endo groups.

CONCLUSION:

Animals subjected to stress develop more severe symptoms but interestingly stress seems to have beneficial effects on abdominal allodynia, which could be a consequence of the stress-induced analgesia phenomenon.

 

 

Biol Chem. 2017 Aug 28;398(9):995-1007.

Iron overload and altered iron metabolism in ovarian cancer.

Rockfield S¹, Raffel J¹, Mehta R¹, Rehman N¹, Nanjundan M¹.

 

Abstract

Iron is an essential element required for many processes within the cell. Dysregulation in iron homeostasis due to iron overload is detrimental. This nutrient is postulated to contribute to the initiation of cancer; however, the mechanisms by which this occurs remain unclear. Defining how iron promotes the development of ovarian cancers from precursor lesions is essential for developing novel therapeutic strategies. In this review, we discuss (1) how iron overload conditions may initiate ovarian cancer development, (2) dysregulated iron metabolism in cancers, (3) the interplay between bacteria, iron, and cancer, and (4) chemotherapeutic strategies targeting iron metabolism in cancer patients.

 

 

J Midlife Health. 2016 Oct-Dec;7(4):185-188.

Intestinal obstruction associated with ovarian remnant in postmenopausal female.

Gupta R¹, Gupta P².

 

Abstract

Ovarian remnant syndrome (ORS) is a rare condition, in which the ovarian tissue is inadvertently left behind after difficult oophorectomy. The most common preexisting conditions associated for this complication include endometriosis, pelvic inflammatory disease, and prior abdominal surgery as in these conditions, removal of ovarian tissue becomes difficult. This is likely due to the presence of the dense fibrotic adhesions between an ovary and the surrounding structures. This residual ovarian tissue can become functional and cystic. A 56-year-old multigravida postmenopausal female was diagnosed with intestinal obstruction. She had multiple abdominal surgeries in the past, including cholecystectomy, appendectomy, hysterectomy, and bilateral salpingo-oophorectomy. Patient underwent exploratory laparotomy. Intraoperatively, extensive adhesions and scarring of bowel wall were present and approximately 15 cm proximal to the terminal ileum, a small bowel mesenteric nodule was present. Histopathology of the mesenteric nodule was consistent with the diagnosis of overian remnant. ORS can be prevented with careful resection of the entire ovarian tissue during the difficulty oophorectomy so that no ovarian tissue is left behind.

 

 

Cureus. 2016 Dec 12;8(12):e926.

A Case of Umbilical Endometriosis: Villar’s Nodule.

Krantz AM¹, Dave AA², Margolin DJ³.

 

Abstract

Umbilical endometriosis is a fairly rare clinical entity with unclear pathogenesis. We report the case of a 27-year-old woman who presented with a painful umbilical mass and discharge. Imaging performed was inconclusive, and surgical excision of the site with margins revealed endometriosis on microscopic examination. The incidence of umbilical endometriosis, its pathogenesis, clinical manifestations, workup, and management are discussed.

 

 

Int J Gynaecol Obstet. 2017 Feb;136(2):200-204.

The impact of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral endometrioma.

Mehdizadeh Kashi A¹, Chaichian S², Ariana S¹, Fazaeli M¹, Moradi Y³, Rashidi M⁴, Najmi Z⁵.

Abstract

OBJECTIVE:

To evaluate the effects of laparoscopic cystectomy on serum anti-Müllerian hormone (AMH) level as a marker of ovarian reserve in patients with endometrioma.

METHODS:

A prospective observational study enrolled patients aged younger than 40 years who were referred to a tertiary center in Tehran, Iran, between January 1, 2013 and December 31, 2014 to undergo laparoscopic cystectomy for ovarian endometriomas at least 30 mm in diameter, or regardless of size for patients with infertility, dysmenorrhea, dyspareunia, or dyschezia. Baseline and 6-month post-operative AMH levels were compared.

RESULTS:

Data from 70 patients were included in the analyses. Among patients with unilateral endometriomas, lower pre-operative AMH levels were observed in patients with endometriomas at least 50 mm in diameter (P=0.027), whereas cyst size was not associated with differences in pre-operative AMH level in patients with bilateral endometriomas (P=0.227). Across the entire study population, post-operative AMH levels were lower than the baseline (P=0.008). Greater post-operative decreases in AMH were associated with bilateral cysts compared with unilateral cysts (P=0.046), cysts being at least 50 mm in diameter among patients with unilateral cysts (P=0.028), and both cysts being at least 50 mm in diameter among patients with bilateral cysts (P=0.025).

CONCLUSION:

Laparoscopic cystectomy was associated with post-operative decreases in serum AMH, particularly with bilateral involvement and endometriomas at least 50 mm in diameter.

 

 

Rev Endocr Metab Disord. 2017 Sep;18(3):273-283

Shedding new light on female fertility: The role of vitamin D.

Muscogiuri G¹, Altieri B², de Angelis C³, Palomba S⁴, Pivonello R⁵, Colao A⁵, Orio F⁶.

 

Abstract

In the last decades several studies suggested that vitamin D is involved in the modulation of the reproductive process in women due to the expression of VDR and 1α-hydroxylase in reproductive tissues such as ovary, uterus, placenta, pituitary and hypothalamus. Vitamin D has also a role in the regulation of sex hormone steroidogenesis. Increasing evidence suggests that vitamin D might have a regulatory role in polycystic ovary syndrome (PCOS)-associated symptoms, including ovulatory dysfunction, insulin resistance and hyperandrogenism. Vitamin D deficiency also has been reported to contribute to the pathogenesis of endometriosis due to its immunomodulatory and anti-inflammatory properties. Although most of the studies supported a role of vitamin D in the onset of these diseases, randomized controlled trials to assess the efficacy of vitamin D supplementation have never been performed. In this review we critically discuss the role of vitamin D in female fertility, starting from in vitro and in vivo studies, focusing our attention on the two most frequent causes of female infertility: PCOS and endometriosis.

 

 

Cancer Causes Control. 2017 May;28(5):393-403.

Hormonal and reproductive factors and the risk of ovarian cancer.

Koushik A^1,2, Grundy A^3,4, Abrahamowicz M^5,6, Arseneau J^7,8, Gilbert L⁸, Gotlieb WH⁹, Lacaille J³, Mes-Masson AM^3,10, Parent MÉ^3,4,11, Provencher DM^3,12, Richardson L³, Siemiatycki J^3,4.

Abstract

PURPOSE:

Hormone-related factors have been associated with ovarian cancer, the strongest being parity and oral contraceptive use. Given reductions in birth rates and increases in oral contraceptive use over time, associations in more recent birth cohorts may differ. Furthermore, consideration of ovarian cancer heterogeneity (i.e., Type I/II invasive cancers) may contribute to a better understanding of etiology. We examined hormone-related factors in relation to ovarian cancer risk overall, for Type I and Type II cancers, as well as borderline tumors.

METHODS:

A population-based case-control study was carried out in Montreal, Canada from 2011 to 2016, including 496 cases and 908 controls. For each hormone-related variable, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for ovarian cancer overall, and using polytomous logistic regression for associations by tumor behavior and ovarian cancer type.

RESULTS:

Parity was inversely associated with risk overall and by tumor behavior and type, with a stronger OR (95% CI) for Type I [0.09 (0.04-0.24) for ≥3 full-term births vs. nulliparity] vs. Type II [0.66 (0.43-1.02)] invasive cancers; the OR (95% CI) for borderline tumors was 0.41 (0.22-0.77). Oral contraceptive ever use was not associated with risk overall, but ≥10 years of use vs. never use reduced risk, particularly for invasive cancers. A history of endometriosis was most strongly associated with Type I cancers. Associations with other factors were less clear.

CONCLUSIONS:

These results suggest that associations with some hormone-related factors may differ between borderline and invasive Type I and II ovarian cancers.

J Minim Invasive Gynecol. 2017 Mar – Apr;24(3):478-484.

Risk Factors, Clinical Presentation, and Outcomes for Abdominal Wall Endometriosis.

Khan Z¹, Zanfagnin V², El-Nashar SA³, Famuyide AO⁴, Daftary GS⁵, Hopkins MR⁴.

Abstract

STUDY OBJECTIVE:

To evaluate the risk factors, presentation, and outcomes in cases of abdominal wall endometriosis.

DESIGN:

A case-control study (Canadian Task Force classification II-2).

SETTING:

An academic medical center.

PATIENTS:

A total of 102 (34 cases and 68 controls) were included.

INTERVENTIONS:

Surgical resection of abdominal wall endometriosis.

MEASUREMENTS AND MAIN RESULTS:

Cases underwent surgical excision for abdominal wall endometriosis at Mayo Clinic from January 1, 2000, through December 31, 2013. For each case, 2 controls were randomly selected from a list of women who had surgery in the same year with minimal (American Society for Reproductive Medicine stage I-II) endometriosis. A chart review was completed for variables of interest. Regression models were used to identify independent risk factors associated with abdominal wall endometriosis.

RESULTS:

In 14 years, 2539 women had surgery for endometriosis at Mayo Clinic. Of these, only 34 (1.34%) had abdominal wall endometriosis. The mean age was 35.2 ± 5.9 years, and the median parity was 2 (range, 0-5). Clinical examination diagnosed abdominal wall endometriosis in 41% of cases, with the cesarean delivery scar being the most common site (59%). There was a strong correlation between the size of the lesion on clinical examination compared with the size of the pathology specimen (r² = 0.74, p < .001). When compared with controls, cases had significantly higher parity and body mass index, more cyclic localized abdominal pain, less dysmenorrhea, longer duration from the start of symptoms to surgery, and more gynecologic surgeries for symptoms without cure. In the final multivariable model, cyclic localized abdominal pain, absence of dysmenorrhea, and previous laparotomy were independently associated with abdominal wall endometriosis with adjusted odds ratios of 10.6 (95% CI 1.85-104.4, p < .001), 12.4 (95% CI 1.64-147.1, p < .001), and 70.1 (95% CI 14.8-597.7, p < .001), respectively, with an area under the curve for the receiver operating characteristic of 0.94 (95% CI, 0.87-0.98). After excision of the disease, repeat surgery was needed in 2 (5.9%) patients with a median time to recurrence of 50.5 (range, 36-65) months.

CONCLUSIONS:

Abdominal wall endometriosis is a rare but unique form of endometriosis. Careful history and clinical examination can provide accurate diagnosis and avoid unnecessary delay before surgical intervention. Localized cyclic abdominal pain with the absence of dysmenorrhea and a history of prior laparotomy are independent risk factors with very high accuracy for diagnosis.

 

 

Clin Obstet Gynecol. 2017 Mar;60(1):27-37.

Imaging in Endometriosis and Adenomyosis.

Hoyos LR¹, Benacerraf B, Puscheck EE.

 

Abstract

Endometriosis and adenomyosis may be accurately diagnosed using ultrasound (US). Several findings are characteristic and various US modalities have been described. Recent development of 3-dimensional transvaginal US has resulted in a major advance in the evaluation of adenomyosis. Endometriotic manifestations can also be accurately evaluated with US, which is and should remain the first-line approach for the evaluation of these conditions. Obvious advantages over magnetic resonance imaging include its wide-availability, tolerability, less time-consumption, more accessible price and familiarity of gynecologists with its use. This technology’s full potential can be achieved using 3-dimensional imaging and/or modified techniques according to the particular clinical scenario.

 

 

Acta Obstet Gynecol Scand. 2017 Apr;96(4):421-425.

Risk factors for trachelectomy following supracervical hysterectomy.

Tsafrir Z¹, Aoun J¹, Papalekas E², Taylor A³, Schiff L⁴, Theoharis E¹, Eisenstein D¹.

Abstract

INTRODUCTION:

We identified risk factors for trachelectomy after supracervical hysterectomy (SCH) due to persistence of symptoms.

MATERIAL AND METHODS:

A retrospective case-control study in a university-affiliated hospital. Seventeen women who underwent a trachelectomy following SCH for nonmalignant indications between June 2002 and October 2014 were compared with 68 randomly selected women (controls) who underwent a SCH within the same time period. Demographics and clinical characteristics were compared between the study and control groups. Univariate analysis identified potential risk factors for trachelectomy following SCH. Univariate logistic regression models predicted which patients would have a trachelectomy following SCH.

RESULTS:

The occurrence of trachelectomy following SCH during the study period was 0.9% (17/1892). The study group was younger than the control group (mean age 38 ± 6 years vs. 44 ± 5 years; p < 0.001). Patients who had a history of endometriosis [odds ratio (OR) 6.23, 95% CI 1.11-40.5, p = 0.038] had increased risk for trachelectomy. Pathology diagnosed endometriosis only among women in the study group. Preoperative diagnosis of abnormal uterine bleeding (OR 0.22, 95% CI 0.06-0.075, p = 0.016), anemia (OR 0.12, 95% CI 0.01-0.53; p = 0.003), and fibroid uterus (OR 0.24, 95% CI 0.07-0.82, p = 0.024) reduced the risk for future trachelectomy.

CONCLUSION:

Young age and endometriosis are significant risk factors for trachelectomy following SCH.

 

 

 

Reprod Biomed Online. 2017 Apr;34(4):375-382.

Investigation of anogenital distance as a diagnostic tool in endometriosis.

Sánchez-Ferrer ML¹, Mendiola J², Jiménez-Velázquez R³, Cánovas-López L³, Corbalán-Biyang S³, Hernández-Peñalver AI³, Carmona-Barnosi A³, Maldonado-Cárceles AB⁴, Prieto-Sánchez MT¹, Machado-Linde F³, Nieto A¹, Torres-Cantero AM⁵.

 

Abstract

An association between anogenital distance (AGD) and endometriosis has been reported, suggesting that AGD may be a useful clinical tool in endometriosis. The predictive ability of AGD of women in discriminating presence and type of endometriosis was examined. A case-control study was conducted at the University Hospital ‘Virgen de la Arrixaca’, Murcia, Spain, between 2014 and 2015. A total of 114 participants diagnosed with endometriosisusing ultrasound findings and 105 controls were recruited. Two AGD measurements were obtained: one from the anterior clitoral surface to the upper verge of the anus (AGD_AC), and another one from the posterior fourchette to the upper verge of the anus (AGD_AF). Parametric and non-parametric tests andreceiver operator characterstic analyses were used to determine relationships between AGD and presence of endometriosis and subgroups (ovarian endometriomas or deep infiltrating endometriosis [DIE]). The AGD_AF, but not AGD_AC, was associated with presence of endometriomas, DIE (P-values, <0.001-0.02), or both. The highest area under curve (0.91; 95% CI 0.84 to 0.97) was obtained for the DIE subgroup with the AGD_AF measurement, with a sensitivity and specificity of 84.4% and 91.4%, respectively. AGD_AF can therefore efficiently discriminate the presence of DIE and may be a useful clinical tool.

 

 

 

J Steroid Biochem Mol Biol. 2017 Apr;168:19-25.

Disruption of aromatase homeostasis as the cause of a multiplicity of ailments: A comprehensive review.

Patel S¹.

 

Abstract

Human health is beset with a legion of ailments, which is exacerbated by lifestyle errors. Out of the numerous enzymes in human body, aromatase, a cytochrome P450 enzyme is particularly very critical. Occurring at the crossroads of multiple signalling pathways, its homeostasis is vital for optimal health. Unfortunately, medications, hormone therapy, chemical additives in food, and endocrine-disrupting personal care products are oscillating the aromatase concentration beyond the permissible level. As this enzyme converts androgens (C19) into estrogens (C18), its agitation has different outcomes in different genders and age groups. Some common pathologies associated with aromatase disruption include breast cancer, prostate cancer, polycystic ovary syndrome (PCOS), endometriosis, osteoporosis, ovarian cancer, gastric cancer, pituitary cancer, Alzheimer’s disease, schizophrenia, male hypogonadism, and transgender issues. Several drugs, cosmetics and pesticides act as the activators and suppressors of this enzyme. This carefully-compiled critical review is expected to increase public awareness regarding the threats resultant of the perturbations of this enzyme and to motivate researchers for further investigation of this field.

 

 

Reprod Sci. 2017 Sep;24(9):1304-1311.

Peritoneal Fluid From Infertile Women With Minimal/Mild EndometriosisCompromises the Meiotic Spindle of Metaphase II Bovine Oocytes: A Pilot Study.

Jianini BTGM¹, Giorgi VSI¹, Da Broi MG¹, de Paz CCP², Rosa E Silva JC¹, Ferriani RA^1,3, Navarro PA^1,3.

 

Abstract

Some studies have demonstrated alterations in the composition of peritoneal fluid (PF) from women with endometriosis. Controversial studies have suggested that impaired oocyte quality may be involved in the pathogenesis of endometriosis-related infertility. The aim of this study was to evaluate the spindle and chromosome distribution of in vitro-matured oocytes in the presence of 2 concentrations of PF from infertile women with minimal/mild endometriosis (EI/II) compared to fertile controls. We performed an experimental study using a bovine model. Samples of PF were obtained from 12 women who underwent videolaparoscopy-6 infertile women with EI/II and 6 fertile women without endometriosis (control group). Immature bovine oocytes underwent in vitro maturation (IVM) in the absence of PF and in the presence of 2 concentrations (1% and 10%) of PF from fertile women and from infertile women with EI/II. After 22 to 24 hours of IVM, oocytes were fixed for subsequent immunofluorescence staining for the visualization of microtubules and chromosomes by confocal microscopy. The percentage of meiotically normal oocytes was significantly lower for oocytes that underwent IVM in the presence of 1% (62.50%) and 10% (56.25%) of PF from infertile women with EI/II than in the absence of PF (88.46%) and in the presence of 1% (78.57%) and 10% (84.61%) of PF from fertile women ( P < .01). We demonstrated that PF from infertile women with EI/II promotes meiotic abnormalities in in vitro-matured bovine oocytes. Therefore, our results contribute to the understanding of the etiopathogenic mechanisms of infertility related to EI/II.

 

 

Cochrane Database Syst Rev. 2017 Jan 23;1

Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis.

Brown J¹, Crawford TJ¹, Allen C², Hopewell S³, Prentice A⁴.

Abstract

BACKGROUND:

Endometriosis is a common gynaecological condition that affects women and can lead to painful symptoms and infertility. It greatly affects women’s quality of life, impacting their careers, everyday activities, sexual and nonsexual relationships and fertility. Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used as first-line treatment for women with pain associated with endometriosis.

OBJECTIVES:

To assess effects of NSAIDs used for management of pain in women with endometriosiscompared with placebo, other NSAIDs, other pain management drugs or no treatment.

SEARCH METHODS:

We searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials (October 2016), published in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, as well as MEDLINE (January 2008 to October 2016), Embase (date limited from 1 January 2016 to 19 October 2016, as all earlier references are included in CENTRAL output as a result of the Embase project), registers of ongoing trials and the reference lists of relevant publications. We identified no new randomised controlled trials. Unless we identify new evidence in the future, we will not update this review.

SELECTION CRITERIA:

We included all randomised controlled trials (RCTs) describing use of NSAIDs for management of pain associated with endometriosis in women of all ages.

DATA COLLECTION AND ANALYSIS:

In the 2009 update of this review, two review authors (CA and SH) independently read and extracted data from each of the included studies. We analysed cross-over trials using the inverse variance method of RevMan to calculate odds ratios for binary outcomes.

MAIN RESULTS:

We identified no new trials for the 2016 update. This review includes two trials, but we included only one trial, with 24 women, in the analysis.The overall risk of bias was unclear owing to lack of methodological detail. Using the GRADE method, we judged the quality of the evidence to be very low. We downgraded evidence for risk of bias and for imprecision (wide confidence intervals and evidence based on a single small trial).Comparison of NSAIDs (naproxen) versus placebo revealed no evidence of a positive effect on pain relief (odds ratio (OR) 3.27, 95% confidence interval (CI) 0.61 to 17.69; one trial, 24 women; very low-quality evidence) in women with endometriosis. Evidence indicating whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12, 95% CI 0.01 to 1.29; one trial, 24 women; very low-quality evidence) or to experience side effects (OR 0.46, 95% CI 0.09 to 2.47; one trial, 24 women; very low-quality evidence) when compared with placebo was inconclusive.Studies provided no data on quality of life, effects on daily activities, absence from work or school, need for more invasive treatment or participant satisfaction with treatment.

AUTHORS’ CONCLUSIONS:

Owing to lack of high-quality evidence and lack of reporting of outcomes of interest for this review, we can make no judgement as to whether NSAIDs (naproxen) are effective in managing pain caused by endometriosis. No evidence shows whether any individual NSAID is more effective than another. As shown in other Cochrane reviews, women taking NSAIDs must be aware that these drugs may cause unintended effects.

 

 

Reprod Biol Endocrinol. 2017 Jan 24;15(1):8.

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

González-Comadran M^1,2, Schwarze JE^3,4, Zegers-Hochschild F^3,5, Souza MD^3,6, Carreras R^1,7, Checa MÁ.

Abstract

BACKGROUND:

Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF.

METHODS:

A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred.

RESULTS:

A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40.

CONCLUSIONS:

Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

 

 

 

 

 

J Menopausal Med. 2016 Dec;22(3):174-179.

Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis: Effects on Bone Mineral Density.

Cho YH¹, Um MJ², Kim SJ², Kim SA³, Jung H³.

Abstract

OBJECTIVES:

To evaluate the efficacy of raloxifene in preventing bone loss associated with long term gonadotropin-releasing hormone agonist (GnRH-a) administration.

METHODS:

Twenty-two premenopausal women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3.75 mg/4 weeks, for 48 weeks. Bone mineral density (BMD) was evaluated at admission, and after 12 treatment cycles.

RESULTS:

At cycle 12 of GnRH-a plus raloxifene treatment, lumbar spine, trochanter femoral neck, and Ward’s BMD differed from before the treatment. A year after treatment, the lumbar spine and trochanter decreased slightly, but were not significantly different.

CONCLUSIONS:

Our study shows that the administration of GnRH-a plus raloxifene in pre-menopausal women with severe endometriosis, is an effective long-term treatment to prevent bone loss.

 

 

Chin J Integr Med. 2017 Jan 24. doi: 10.1007/s11655-017-2401-4.

Differential proteomics analysis of endometriosis in blood stasis syndrome.

Wen Y¹, Wang Y¹, Feng TT¹, Wei SB².

Abstract

OBJECTIVE:

To investigate the innate characters of 3 endometriosis (EMT) syndromes, blood stasis (BS), qi stagnation and blood stasis (QSBS) as well as Shen (Kidney) deficiency and blood stasis (KDBS) in terms of proteomics, lay a molecular biological basis for the differentiation of various blood stasis syndromes of EMT, establish a EMT microscopic syndrome differentiation and diagnosis system in terms of proteomics, discover the evolution principles and therapeutic targets of these EMT syndromes, and search their significant molecular markers and genetic intervention targets.

METHODS:

Six specimens from the ectopic and entopic endometrium tissues of patients with EMT in each syndrome, BS, QSBS as well as KDBS, in the early proliferative phase of the menstrual cycle, and 6 specimens from normal endometrium tissues in the early proliferative phase of the menstrual cycle were obtained. Three groups were formed in each syndrome by mixing two random specimens in equal amount, and then their respective two-dimensional electrophoresis graphs were obtained after total protein extraction. Finally, the detected differences in protein expression were identified through matrix-assisted laser desorption Ionization-time of flight mass spectrometry (MALDI-TOF/MS) and protein database.

RESULTS:

The results of differential proteins expressed in each syndrome were shown as follows: BS syndrome had 2 differential proteins in entopic endometrium and 1 differential protein in ectopic endometrium; KDBS syndrome had 3 in entopic endometrium and 3 in ectopic endometrium; and QSBS syndrome had 3 in entopic endometrium and 4 in ectopic endometrium. It was found out that annexin was highly expressed in both entopic and ectopic endometrium of KDBS syndrome; and myosin light chain 3 was highly expressed in both entopic and ectopic endometrium of QSBS syndrome.

CONCLUSION:

There are differential protein expressions among the 3 EMT syndromes, which might be the inner origin of syndrome characters, and these differential proteins might be the candidate biomarkers for the pathogenesis of various EMT syndromes.

 

 

Am J Reprod Immunol. 2017 Apr;77(4).

Hepatitis B virus infection status and infertility causes in couples seeking fertility treatment-Indicator of impaired immune response?

Lao TT^1,2, Mak JSM^1,2, Li TC^1,2.

Abstract

PROBLEM:

The relationship between hepatitis B (HBV) infection in infertile couples seeking in vitro fertilization (IVF) treatment and infertility causes is unknown.

METHODS OF STUDY:

A total of 831 infertile couples attending our unit seeking IVF during January to December 2015 were recruited.

RESULTS:

HBV infection was found in 6.3% and 7.3% of female and male partners, respectively, and infection in one or both partners was associated with less primary infertility (44.2% vs 55.1%, P=.038). Infected female partners had increased tubal (69.2% vs 43.2%, P<.001) and uterine (13.7% vs 3.1%, P<.001) causes and reduced idiopathic infertility, while infected male partners were associated with increased tubal (62.3% vs 43.4%, P=.004) causes and reduced endometriosis (62.3% vs 73.9%, P=.050).

CONCLUSION:

Our results suggest HBV infection in either partner was associated with tubal infertility. HBV infection in either partner probably increases the risk of pelvic infection in female partner through impaired immune response to sexually transmitted infections, with consequent tubal damage and infertility.

Am J Reprod Immunol. 2017 Apr;77(4).

Abnormal peritoneal regulation of chemokine activation-The role of IL-8 in pathogenesis of endometriosis.

Sikora J¹, Smycz-Kubańska M¹, Mielczarek-Palacz A¹, Kondera-Anasz Z¹.

Abstract

PROBLEM:

Endometriosis is a chronic inflammatory disease associated with an impairment in immune response. Disorders in the peritoneal fluid and ectopic endometrium macrophage populations and their secretory products create a specific microenvironment inducing the development of the disease. The important factors involved in inflammation associated with endometriosis are chemokines, especially interleukin (IL)-8. For this reason, the current study briefly reviews the role of IL-8 in the pathogenesis of endometriosis.

METHOD OF STUDY:

A systematic review was done on all published studies that compared IL-8 expression and concentration in patients with and without endometriosis to evaluate their potential as biomarkers for the disease.

RESULTS:

IL-8 induces chemotaxis of neutrophils and other immune cells; also, it is a potent angiogenic agent. Most researchers pointed to the increased peritoneal and serum IL-8 levels and showed correlation with the severity of the disease, size and number of the active lesions. IL-8 takes part in all processes during the development of the disease: adhesion, invasion, and implantation of ectopic tissue. Additionally, the chemokine plays a role in growth and maintenance of ectopic endometrial tissue directly affecting endometrial cell proliferation. IL-8 might also protect ectopic cells against death by apoptosis.

CONCLUSION:

It may act as an autocrine growth factor in the endometrium and promotes the vicious circle of endometrial cell attachment and, in consequence, may lead to a transformation from acute to chronic inflammation stage.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:342-347.

Intrauterine insemination-No more Mr. N.I.C.E. guy?

Geisler ME¹, Ledwidge M², Bermingham M², McAuliffe M³, McMenamin MB³, Waterstone JJ³.

Abstract

OBJECTIVE:

To determine the per cycle chance of a live birth and to identify factors that may support a more individualised application of IUI in view of National Institute for Health and Care Excellence (NICE) updated guideline on fertility 2013.

STUDY DESIGN:

A retrospective, cohort study of 851 couples (1688 cycles) with unexplained, mild endometriosis, one patent Fallopian tube (with ovulation occurring in the corresponding ovary), mild male factor or ovulatory dysfunction, who initiated their first cycle of IUI/COH during the study period 2009-2013 and completed up to 3 cycles. Exclusion criteria included donor sperm and diminished ovarian reserve. Success factors and probabilities were determined based on live birth rates.

RESULTS:

Mean age was 33.8±3.3years and mean duration of subfertility was 2.28±1.47years. Independent associates of successful outcome factors were lower age (AOR 0.93; 95%CI 0.89-0.98, p=0.007) and multiparity (AOR 1.72; 95%CI 1.17-2.52). Live-birth rates declined independently of other factors from 15.3% (n=130/851) in cycle 1-7.0% (n=19/273) in cycle 3 (AOR 0.76; 95%CI, 0.62-0.93, p=0.008). Per cycle probabilities of live birth ranged from 21.4% to 5.1% dependent on age, cycle number and previous parity. The unadjusted cumulative pregnancy rate for live birth per cycle started, over three cycles, was 34.9% with a multiple live birth rate per cycle started of 5.4%. The associates of live birth amongst those with unexplained sub-fertility only (n=632, first cycle attempt) were also analysed, yielding similar results.

CONCLUSIONS:

IUI/COH is a simple treatment that produces good live birth rates, especially in younger patients and/or those with previous parity. More than 90% of total live births with IUI/COH is achieved during the first two cycles. As a retrospective, observational study, there is no comparator group and therefore we cannot comment on the relative efficacy of up to three IUI cycles over expectant management in a similar cohort. Our study suggests that probabilities of success can be used to individualise treatment decisions and that there is merit in continuing to offer IUI before resorting to IVF for certain patients.

 

 

Int Braz J Urol. 2017 Jan-Feb;43(1):87-94.

Cystoscopy-assisted laparoscopy for bladder endometriosis: modified light-to-light technique for bladder preservation.

Stopiglia RM¹, Ferreira U¹, Faundes DG², Petta CA³.

Abstract

INTRODUCTION:

Endometriosis is a disease with causes still unclear, affecting approximately 15% of women of reproductive age, and in 1%-2% of whom it may involve the urinary tract. The bladder is the organ most frequently affected by endometriosis, observed around 85% of the cases. In such cases, the most effective treatment is partial cystectomy, especially via videolaparoscopy. Study Objective, Design, Size and Duration: In order to identify and delimit the extent of the intravesical endometriosis lesion, to determine the resection limits, as well as to perform an optimal reconstruction of the organ aiming for its maximum preservation, we performed a cystoscopy simultaneously with the surgery, employing a modified light-tolight technique in 25 consecutive patients, from September 2006 to May 2012.

SETTING:

Study performed at Campinas Medical Center – Campinas – Sao Paulo – Brazil. Participants/materials, setting and methods: Patients aged 27 to 47 (average age: 33.4 years) with deep endometriosis with total bladder involvement were selected for the study. The technique used was conventional laparoscopy with a transvaginal uterine manipulator and simultaneous cystoscopy (the light-to-light technique). A partial videolaparoscopic cystectomy was performed with cystoscopy-assisted vesical reconstruction throughout the entire surgical time. The lesions had an average size of 2.75cm (ranging from 1.5 to 5.5cm). The average surgical time was 137.7 minutes, ranging from 110 to 180 minutes.

MAIN RESULTS:

Postoperative follow-up time was 32.4 months (12-78 months), with clinical evaluation and a control cystoscopy performed every six months. No relapse was observed during the follow-up period.

CONCLUSIONS:

A cystoscopy-assisted partial laparoscopic cystectomy with a modified light-to-light technique is a method that provides adequate identification of the lesion limits, intra or extravesically. It also allows a safe reconstruction of the organ aiming for its maximum preservation.

 

 

PLoS One. 2017 Jan 26;12(1)

Epigenetic Alterations Affecting Transcription Factors and Signaling Pathways in Stromal Cells of Endometriosis.

Yotova I^1,2, Hsu E¹, Do C¹, Gaba A², Sczabolcs M³, Dekan S⁴, Kenner L^4,5,6, Wenzl R², Tycko B^1,3.

 

Abstract

Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains. Genes found to have DM included examples encoding transporters (SLC22A23), signaling components (BDNF, DAPK1, ROR1, and WNT5A) and transcription factors (GATA family, HAND2, HOXA cluster, NR5A1, OSR2, TBX3). Intriguingly, among the TF genes with DM we also found JAZF1, a proto-oncogene affected by chromosomal translocations in endometrial stromal tumors. Using RNA-Seq we identified a subset of the DM genes showing differential expression (DE), with the likelihood of DE increasing with the extent of the DM and its location in enhancer elements. Supporting functional relevance, treatment of stromal cells with the hypomethylating drug 5aza-dC led to activation of DAPK1 and SLC22A23 and repression of HAND2, JAZF1, OSR2, and ROR1 mRNA expression. We found that global 5hmC is decreased in endometriotic versus normal epithelial but not stroma cells, and for JAZF1 and BDNF examined by oxidative bis-seq, found that when 5hmC is detected, patterns of 5hmC paralleled those of 5mC. Together with prior studies, these results define a consistent epigenetic signature in endometriosisstromal cells and nominate specific transcriptional and signaling pathways as therapeutic targets.

 

 

Asian Pac J Cancer Prev. 2016 Dec 1;17(12):5247-5250.

Evaluation of the Pathogenesis of Tumor Development from Endometriosis by Estrogen Receptor, P53 and Bcl-2 Immunohistochemical Staining

Haidarali E¹, Vahedi A, Mohajeri Sh, Mostafidi E, Azimpouran M, Naghavi Behzad M.

 

Abstract

Objective: Endometriosis, one of the most common estrogen dependent gynecological disorders, can present as both benign and malignant disease. The prevalence of tumoral transformation is 0.7-1.6% and the most common tumors are clear cell and endometrioid carcinomas. Unfortunately, the pathogenesis of transformation is unknown. For this purpose, we examined molecular alterations in ovarian endometriosis and endometriosis-associated tumors. Methods: Using the data bank of Alzahra hospital pathology department and paraffin blocks from appropriate cases were identified. Sections were cut and stained for 3 markers: estrogen receptor, P53 and bcl2. Correlations between findings were investigated. Results: Nineteen cases of endometriosis-associated tumor and 19 cases of endometriosis were identified. Staining for bcl2 was documented in 14 of 19 (73.7%) of endometriosis-associated tumor cases and also 7 of 19 (36.8%) endometriosis cases (P=0.02). Only 3 of the 19 (15.8%) endometriosis-associated tumors exhibited positive staining for estrogen receptors, compared with 14 of 19 (73.7%) endometriosis cases (P<0.001). Positive staining for P53 was noted in 5 of 19 (31.6%) endometriosis-associated ovarian tumor samples but was absent in endometriosis samples (0%), (P =0.008). Conclusions: Endometriosis-associated tumors appear to be associated with overexpression of bcl2 and P53 and reduced expression of Estrogen receptor. These finding may help to diagnose tumoral transformation with a background of endometriosis.

 

 

J Dent (Tehran). 2016 Aug;13(4):271-278.

Comparison of Periodontal Ligament Stem Cells Isolated from the Periodontium of Healthy Teeth and Periodontitis-Affected Teeth.

Soheilifar S¹, Amiri I², Bidgoli M¹, Hedayatipanah M¹.

Abstract

OBJECTIVES:

Stem cell (SC) therapy is a promising technique for tissue regeneration. This study aimed to compare the viability and proliferation ability of periodontal ligament stem cells (PDLSCs) isolated from the periodontium of healthy and periodontitis-affected teeth to obtain an autologous, easily accessible source of SCs for tissue regeneration in periodontitis patients.

MATERIALS AND METHODS:

The PDLSCs were isolated from the roots of clinically healthy premolars extracted for orthodontic purposes and periodontally involved teeth with hopeless prognosis (with and without phase I periodontal treatment). Cells were cultured and viability and proliferation ability of third passage cells in each group were evaluated using the methyl thiazol tetrazolium assay. The results were statistically analyzed using t-test.

RESULTS:

No SCs could be obtained from periodontitis-affected teeth without phase I periodontal treatment. The viability of cells was 0.86±0.13 OD/540 in healthy group and 0.4±0.25 OD/540 in periodontitis-affected group (P=0.035). The proliferation ability (population doubling time) of cells obtained from healthy teeth was 4.22±1.23 hours. This value was 2.3±0.35 hours for those obtained from periodontitis-affected teeth (P=0.02).

CONCLUSIONS:

Viability and proliferation ability of cells isolated from the periodontium of healthy teeth were significantly greater than those of cells isolated from the periodontitis-affected teeth.

 

 

J Obstet Gynaecol. 2017 Apr;37(3):342-346.

Serum anti-Müllerian hormone levels decrease after endometriosis surgery.

Kim YJ¹, Cha SW¹, Kim HO¹.

 

Abstract

The purpose of this study was to evaluate and compare the post-operative decline in serum AMH levels in patients with endometriosis and other benign cysts. This study also attempts to clarify the factors of endometriosis that may influence the AMH level. A total of 75 were recruited prospectively between 2011 and 2012. Fifty-nine patients had endometriosis, while the other 16 had another kind of benign ovarian cyst. In the endometriosis group, the AMH level decreased significantly from pre- to postoperatively (4.3 ± 0.4 vs. 2.8 ± 0.2, p<.001). This significant decrement in AMH levels was present in the endometriosis group regardless of multiplicity (p=.028 vs. p<.001) and bilaterality (p=.003 vs. p<.001). The stage III-IV endometriosis group also demonstrated a significant decrease (p<.001). Laparoscopic ovarian cystectomy in patients with endometriosismay cause a decrease in serum AMH levels. We suggest that preoperative and postoperative AMH levels should be evaluated in reproductive-aged women with endometriosis for their future fertility.

 

 

J Steroid Biochem Mol Biol. 2017 Oct;173:223-227.

Differential gene expression by 1,25(OH)2D3 in an endometriosis stromal cell line.

Ingles SA¹, Wu L², Liu BT³, Chen Y⁴, Wang CY⁵, Templeman C⁵, Brueggmann D⁶.

 

Abstract

Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)₂D₃ on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)₂D₃, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH)₂D₃. Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH)₂D₃ treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments.

 

 

 

 

 

Am J Reprod Immunol. 2017 Apr;77(4).

Lipopolysaccharide promotes the development of murine endometriosis-like lesions via the nuclear factor-kappa B pathway.

Azuma Y¹, Taniguchi F¹, Nakamura K², Nagira K¹, Khine YM¹, Kiyama T¹, Uegaki T¹, Izawa M¹, Harada T¹

Abstract

PROBLEM:

Is lipopolysaccharide (LPS) involved in the development of endometriosis?

METHOD OF STUDY:

BALB/c mice (n=69) were used for the murine endometriosis model. Mice with surgically induced endometriosis were injected with LPS intraperitoneally. After 4 weeks of LPS injections with or without the nuclear factor-kappa B (NF-κB) inhibitor, the extent of endometriosis-like lesions was evaluated. Expression of inflammatory factors in the implants was evaluated using real-time RT-PCR. Cell proliferation, angiogenic activity, inflammation, and NF-κB phosphorylation were assessed by immunohistochemical staining.

RESULTS:

Lipopolysaccharide increased total number, size, and mRNA expression of Ptgs-2, Vegf, Ccl-2, and Il-6 in endometriosis-like lesions. LPS also increased the percentage of Ki67-positive cells and enhanced the intensity and rate of positive cells of CD3, F4/80, and PECAM. Intense expression of phospho-NF-κB p65 after LPS administration was observed. Treatment with the NF-kB inhibitor negated these LPS-induced effects.

CONCLUSION:

LPS-induced pelvic inflammation status enhanced the development of murine endometriosis-like lesions via NF-κB pathway.

 

 

Fertil Steril. 2017 Apr;107(4):977-986.e2.

Functional outcomes after disc excision in deep endometriosis of the rectum using transanal staplers: a series of 111 consecutive patients.

Roman H¹, Darwish B², Bridoux V³, Chati R³, Kermiche S³, Coget J³, Huet E³, Tuech JJ⁴.

Abstract

OBJECTIVE:

To assess the postoperative outcomes of patients with rectal endometriosis managed by disc excision using transanal staplers.

DESIGN:

Prospective study using data recorded in the CIRENDO database (NCT02294825).

SETTING:

University tertiary referral center.

PATIENT(S):

A total of 111 consecutive patients managed between June 2009 and June 2016.

INTERVENTION(S):

We performed rectal disc excision using two different transanal staplers: [1] the Contour Transtar stapler (the Rouen technique); and [2] the end to end anastomosis circular transanal stapler.

MAIN OUTCOMES MEASURE(S):

Pre- and postoperative digestive function was assessed using standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index and the Knowles-Eccersley-Scott Symptom Questionnaire.

RESULT(S):

The two staplers were used in 42 (37.8%) and 69 patients (62.2%), respectively. The largest diameter of specimens achieved was significantly higher using the Rouen technique (mean ± SD, 59 ± 11 mm vs. 36 ± 7 mm), which was used to remove nodules located lower in the rectum (5.5 ± 1.3 cm vs. 9.7 ± 2.5 cm) infiltrating more frequently the adjacent posterior vaginal wall (83.3% vs. 49.3%). Associated nodules involving sigmoid colon were managed by distinct procedures, either disc excision (2.7%) or segmental resection of sigmoid colon (9.9%). Postoperative values for the Gastrointestinal Quality of Life Index increased 1 and 3 years after the surgery, but improvement in constipation was not significant. The probability of pregnancy at 1 year after the arrest of medical treatment was 73.3% (95% confidence interval 54.9%-88.9%), with a majority of spontaneous conceptions.

CONCLUSION(S):

Disc excision using transanal staplers is a valuable alternative to colorectal resection in selected patients presenting with rectal endometriosis, allowing for good preservation of rectal function.

 

 

Fertil Steril. 2017 Mar;107(3):555-565.

New developments in the medical treatment of endometriosis.

Bedaiwy MA¹, Alfaraj S², Yong P², Casper R³.

 

Abstract

Endometriosis affects 1 in 10 women of reproductive-age. The current treatments are surgical and hormonal but have limitations, including the risk of recurrence, side effects, contraceptive action for women who desire pregnancy, and cost. New treatments include gonadotropin-releasing hormone analogues, selective progesterone (or estrogen) receptor modulators, aromatase inhibitors, immunomodulators, and antiangiogenic agents. Further research is needed into central sensitization, local neurogenesis, and the genetics of endometriosis to identify additional treatment targets. A wider range of medical options allows for the possibility of precision health and a more personalized treatment approach for women with endometriosis.

 

 

 

Fertil Steril. 2017 Mar;107(3):537-548.

Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy.

Bedaiwy MA¹, Allaire C², Alfaraj S².

 

Abstract

Endometriosis can recur after either surgical or medical therapy. Long-term medical therapy is implemented to treat symptoms or prevent recurrence. Dienogest and gonadotropin-releasing hormone (GnRH) analogues with hormone add-back therapy seem to be equally effective for long-term treatment of pain symptoms associated with endometriosis. There is insufficient evidence to support the superiority of one therapy over the other. However, add-back hormone therapy (HT) is recommended for patients using GnRH agonists. The treatment selection depends on therapeutic effectiveness, tolerability, drug cost, the physician’s experience, and expected patient compliance.

 

 

 

Diagn Cytopathol. 2017 Apr;45(4):359-363.

Fine-needle aspiration cytology of endometriosis.

Song SJ¹, McGrath CM¹, Yu GH¹.

 

Abstract

Endometriosis commonly involves the pelvis, but may also present as a palpable mass in extrapelvic sites, such as the abdominal wall or inguinal region, where it can be evaluated by fine needle aspiration (FNA). In this report, we illustrate the findings seen in seven cases of endometriosis diagnosed by FNA in patients with a chief complaint of pain associated with an abdominal wall or pelvic mass, occurring in a setting of prior pelvic surgery. The most common previous surgery was Cesarean section (n = 6), followed by hysterectomy (n = 2), and hernia repair (n = 1). In all cases, cytologic examination revealed a glandular component composed largely of orderly fragments of cohesive epithelial cells, a spindle cell stromal component presenting either as loosely organized tissue fragments or single cells, and rare hemosiderin-laden macrophages. Four cases showed focal cytologic atypia in the glandular component with extreme nuclear atypia identified in two of these cases. Atypical features included nuclear crowding and disorganization, nuclear enlargement, hyperchromasia with irregular chromatin distribution and anisonucleosis, raising the possibility of a coexistent malignancy and recommendation for excision. Although malignancy was not identified in follow-up surgical excision specimens, the wide range of cytomorphologic changes that can be seen in FNA specimens of endometriosis should be recognized. Diagn. Cytopathol. 2017;45:359-363. © 2016 Wiley Periodicals, Inc.

 

 

Small. 2017 Apr;13(15).

Specific Photothermal Ablation Therapy of Endometriosis by Targeting Delivery of Gold Nanospheres.

Guo X¹, Li W¹, Zhou J², Hou W¹, Wen X³, Zhang H¹, Kong F¹, Luo L¹, Li Q¹, Du Y¹, You J¹.

 

Abstract

Endometriosis is difficult to treat since the side effects of the current therapeutic method and the high recurrence rate; thus, newer and safer therapeutic approaches are urgently needed. This work investigates the enhanced permeability and retention effect of CdTe quantum dots (QDs) and hollow gold nanospheres (HAuNS) in endometriosis to increase the delivery of HAuNS into lesion cells. The surface of HAuNS is successfully conjugated with a TNYL peptide that has specific affinity for the EphB4 receptor, which is a member of the Eph family of receptor tyrosine kinases. It is found that the EphB4 receptor is overexpressed in endometriosis lesions. The data indicate that both QDs and HAuNS can efficiently accumulate in endometriotic lesions through permeable vessels and the TNYL-conjugated HAuNS (TNYL-HAuNS) accumulate more via the interaction with EphB4. The specific photothermal ablation therapy based on TNYL-HAuNS significantly inhibits the growth of the endometriotic volume and induces the atrophy and degeneration of ectopic endometrium with no detectable toxicity to the normal organs. The level of TNF-α and estradiol also significantly decreases in the endometriotic lesions, indicating that the treatment enables a recovery from hormonal imbalance and inflammatory injury. This work can be a valuable reference for future endometriosis therapy.

 

 

Pharm Dev Technol. 2017 Feb 20:1-8.

Development and characterization of poly(lactic-co-glycolic) acid nanoparticles loaded with copaiba oleoresin.

de Almeida Borges VR¹, Tavares MR¹, da Silva JH², Tajber L³, Boylan F³, Ribeiro AF¹, Nasciutti LE², Cabral LM⁴, Sousa VP¹.

 

Abstract

Copaiba oleoresin (CPO) obtained from Copaifera landgroffii, is described as active to a large number of diseases and more recently in the endometriosis treatment. In this work poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing CPO were obtained using the design of experiments (DOE) as a tool to optimize the production process. The nanoparticles optimized by means of DOE presented an activity in relation to the cellular viability of endometrial cells. The DOE showed that higher amounts of CPO combined with higher surfactant concentrations resulted in better encapsulation efficiency and size distribution along with good stability after freeze drying. The encapsulation efficiency was over 80% for all produced nanoparticles, which also presented sizes below 300 nm and spherical shape. A decrease in viability of endometrial stromal cells from ectopic endometrium of patients with endometriosis and from eutopic endometriotic lesions was demonstrated after 48h of incubation with the CPO nanoparticles. The nanoparticles without CPO were not able to alter the cell viability of the same cells, indicating that this material was not cytotoxic to the tested cells and suggesting that the effect was specific to CPO. The results indicate that the use of CPO nanoparticles may represent a promising alternative for the treatment of endometriosis.

 

 

Mol Hum Reprod. 2017 Mar 1;23(3):187-198.

Angiogenic properties of endometrial mesenchymal stromal cells in endothelial co-culture: an in vitro model of endometriosis.

Canosa S¹, Moggio A², Brossa A², Pittatore G¹, Marchino GL¹, Leoncini S¹, Benedetto C¹, Revelli A¹, Bussolati B².

Abstract

STUDY QUESTION:

Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)?

SUMMARY ANSWER:

E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs.

WHAT IS KNOWN ALREADY:

E-MSCs have been identified in the human endometrium as well as in endometriotic lesions. E-MSCs appear to be involved in formation of the endometrial stromal vascular tissue and the support of tissue growth and vascularization. The use of anti-angiogenic drugs appears as a possible therapeutic strategy against endometriosis.

STUDY DESIGN, SIZE, DURATION:

This is an in vitro study comprising patients receiving surgical treatment of ovarian endometriosis (n = 9).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

E-MSCs were isolated from eutopic and ectopic endometrial tissue and were characterized for the expression of mesenchymal and endothelial markers by FACS analysis and Real-Time PCR. CD31 acquisition was evaluated by FACS analysis and immunofluorescence after a 48 h-direct co-culture with green fluorescent protein +-HUVECs. A tube-forming assay was set up in order to analyze the functional potential of their interaction. Finally, co-cultures were treated with the anti-angiogenic agent Cabergoline.

MAIN RESULTS AND THE ROLE OF CHANCE:

A subpopulation of E-MSCs acquired CD31 expression and integrated into tube-like structures when directly in contact with HUVECs, as observed by both FACS analysis and immunofluorescence. The isolation of CD31+ E-MSCs revealed significant increases in CD31, vascular endothelial growth factor receptor 2, TEK receptor tyrosine kinase and vascular endothelial-Cadherin mRNA expression levels with respect to basal and to CD31neg cells (P < 0.05). On the other hand, the expression of mesenchymal genes such as c-Myc, Vimentin, neuronal-Cadherin and sushi domain containing 2 remained unchanged. Cabergoline treatment induced a significant reduction of the E-MSC angiogenic potential (P < 0.05 versus control).

LARGE SCALE DATA:

Not applicable.

LIMITATIONS, REASONS FOR CAUTION:

Further studies are necessary to investigate the cellular and molecular mechanisms underlying the endothelial cell differentiation.

WIDER IMPLICATIONS OF THE FINDINGS:

E-MSCs may undergo endothelial differentiation, and be potentially involved in the development of endometriotic implants. Cell culture systems that more closely mimic the cellular complexity typical of endometriotic tissues in vivo are required to develop novel strategies for treatment.

STUDY FUNDING/COMPETING INTEREST(S):

This study was supported by the ‘Research Fund ex-60%’, University of Turin, Turin, Italy. All authors declare that their participation in the study did not involve actual or potential conflicts of interests.

 

 

Maturitas. 2017 Mar;97:1-5.

Long-term sequelae of unconfined morcellation during laparoscopic gynecological surgery.

Cohen A¹, Tulandi T².

 

Abstract

Although rare, unconfined morcellation of occult sarcoma has been associated with reduced survival rates. Morcellation of uterus and myoma can also lead to iatrogenic endometriosis, parasitic myoma and, albeit rarely, disseminated peritoneal leiomyomatosis. These benign sequelae of morcellation occur more often than malignant dissemination of sarcomatous tissue. Accordingly, confined morcellation should be performed with a minimally invasive technique while eliminating tissue dissemination inside the abdominal cavity. The ideal technique and device remain to be determined.

 

 

Oncotarget. 2017 Jul 18;8(29):46928-46936.

Association between body mass index and endometriosis risk: a meta-analysis.

Liu Y¹, Zhang W².

Abstract

BACKGROUND:

Epidemiological studies have sought to establish a relationship between a woman’s current body mass index and endometriosis, but with varying results. This meta-analysis was to summarize the current epidemiological evidence.

METHODS:

Pertinent studies were identified by searching PubMed and Web of Science through November 2016. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected.

RESULTS:

A total of 11 studies (two cohort studies and nine case-control studies) was included in the meta-analysis. The pooled relative risk of endometriosis was 0.67 (95% CI: 0.53, 0.84) for each 5 kg/m2 increase in current body mass index, with statistical significant heterogeneity across the studies (P <0.001, I2 =86.9%). Compared with normal weight women, the pooled relative risk for obese women was 0.89 (95% CI: 0.83, 0.96), which was lower than that for overweight women (relative risk =0.97; 95% CI: 0.91, 1.05). The combined estimate was robust across subgroup and sensitivity analyses and no observed publication bias was detected.

CONCLUSION:

This study suggested that higher body mass index may be associated with lower risk of endometriosis. Further work will need to focus on elucidating underlying biologic mechanism that contribute to the initiation of endometriosis.

 

 

J Obstet Gynaecol Res. 2017 Mar;43(3):536-542

Evaluation of the effect of indomethacin and piroxicam administration before embryo transfer on pregnancy rate.

Kumbasar S¹, Gül Ö², Şık A³.

Abstract

AIM:

The aim of this study was to evaluate the effect of non-steroidal anti-inflammatory drug (NSAID) administration before embryo transfer (ET) on pregnancy rates in women undergoing in vitro fertilization/intracytoplasmic sperm injection ET.

METHODS:

Our study included 255 patients diagnosed with primary or secondary infertility caused by a male or tubal-related factor, endometriosis or unexplained factors. The patients were divided randomly into three groups. Two groups were administered oral piroxicam (10 mg capsules) or 100 mg indomethacin (rectal suppository), respectively, 1-2 h before ET. As a control, the third group did not receive any form of treatment before ET. Basal levels of follicle-stimulating hormone, luteinizing hormone, and level 17β-estradiol on the day of human chorionic gonadotropin administration, the collected and transferred number of embryos, and the number of grade A embryos obtained were determined in all patients.

RESULTS:

The implantation, clinical pregnancy, and miscarriage rates of the groups were compared. The clinical pregnancy rate per ET and the implantation rate were 35.2% and 12.15% in the piroxicam group, 31.7% and 10.9% in the indomethacin group, and 32.9% and 12.5% in the control, respectively. The miscarriage rates of groups 1, 2 and 3 were 12%, 11.7% and 11.7%, respectively (P = 0.964). The differences in clinical pregnancy rates among the groups were not statistically significant (P = 0.887). There were also no significant differences in the implantation rates (P = 0.842).

CONCLUSION:

These results suggest that NSAID administration before ET has no additional effect on pregnancy outcome in patients undergoing in vitro fertilization.