Front Biosci (Schol Ed). 2015 Jun 1;7:83-93.

Colorectal endometriosis and pregnancy wish: why doing primary surgery.

Roman H¹.

 

Abstract

One of the most interesting debates surrounding deep endometriosis concerns the management of patients with colorectal lesions and pregnancy intention, for which no strong first level of evidence data exists to recommend performing surgical excision of colorectal endometriosis or ART. Studies assessing the policy of primary IVF have recorded pregnancy rates inferior to 45% and estimated cumulative pregnancy rates after up to 3 cycles or IVF as high as 68%. Other authors have reported pregnancy rates over 60% in patients undergoing primary surgery for colorectal endometriosis, with spontaneous conception representing up to 60% of pregnancies. Although overall pregnancy rates appear roughly comparable in patients undergoing either IVF followed by surgery or surgery followed if required by IVF, questions remain as to whether delaying surgery for months or years impairs health. Delaying surgery may lead to bowel occlusion, higher rates of radical colorectal procedures, increased postoperative morbidity and prolonged painful complaints. To provide definitive answers requires a randomized trial on an international scale with a sample size exceeding 400 patients and follow up averaging 4 years.

 

 

Reprod Sci. 2015 Dec;22(12):1496-508

Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis.

Ruiz LA¹, Báez-Vega PM², Ruiz A³, Peterse DP⁴, Monteiro JB⁵, Bracero N⁶, Beauchamp P⁷, Fazleabas AT⁸, Flores I⁹.

Abstract

Lysyl oxidases (LOXs) are enzymes involved in collagen deposition, extracellular membrane remodeling, and invasive/metastatic potential. Previous studies reveal an association of LOXs and endometriosis. We aimed to identify the mechanisms activated by upregulation of lysyl oxidases (LOX) in endometriotic cells and tissues. We hypothesized that LOX plays a role in endometriosis by promoting invasiveness and epithelial to mesenchymal transition (EMT).

METHODS:

The LOX protein expression levels were measured by immunohistochemistry in lesions and endometrium on a tissue microarray (TMA) and in endometrial biopsies from patients and controls during the window of implantation (WOI). Estradiol regulation of LOX expression was determined by quantitative polymerase chain reaction (qPCR). Proliferation, invasion, and migration assays were performed in epithelial (endometrial epithelial cell), endometrial (human endometrial stromal cell), and endometriotic cell lines (ECL and 12Z). Pathway-focused multiplex qPCR was used to determine transcriptome changes due to LOX overexpression.

RESULTS:

LOX protein was differentially expressed in ovarian versus peritoneal lesions. During WOI, LOX levels were higher in luminal epithelium of patients with endometriosis-associated infertility compared to controls. Invasive epithelial cell lines expressed higher levels of LOX than noninvasive ones. Transfection of LOX into noninvasive epithelial cells increased their migration in an LOX inhibitor-sensitive manner. Overexpression of LOX did not fully induce EMT but the expression of genes related to fibrosis and extracellular matrix remodeling were dysregulated.

CONCLUSIONS:

This study documents that expression of LOX is differentially regulated in endometriotic lesions and endometrium. A role for LOX in mediating proliferation, migration, and invasion of endometrial and endometriotic cells was observed, which may be implicated in the establishment and progression of endometriotic lesions.

 

 

Reprod Sci. 2015 Nov;22(11):1445-51.

Effects of Pazopanib, Sunitinib, and Sorafenib, Anti-VEGF Agents, on the Growth of Experimental Endometriosis in Rats.

Yildiz C¹, Kacan T², Akkar OB³, Karakus S³, Kacan SB⁴, Ozer H⁵, Cetin A³.

 

Abstract

We aimed to compare the effects of pazopanib, sunitinib, and sorafenib on endometriotic tissue morphology and histological characteristics as well as ovarian reserve in a rat model. Experimental endometriosis was established in 32 rats. They were randomly divided into 4 groups (8 rats for each group) to administer study drugs: pazopanib, sunitinib, sorafenib, and normal saline. Histological examination with hematoxylin and eosin staining to determine endometriosis score and immunostaining with primary vascular endothelial growth factor (VEGF), CD117, and Bax antibodies were performed. Bilateral ovaries excised to determine the ovarian follicle number. The endometriosis score was significantly reduced by pazopanib compared to other study drugs and by sunitinib compared to sorafenib and normal saline (P < .05). Sorafenib did not affect endometriosis score (P > .05). The VEGF score was significantly decreased similarly by pazopanib, sunitinib, and sorafenib compared to normal saline (P < .05). The CD117 score was reduced by pazopanib and sunitinib similarly compared to both sorafenib and normal saline that provided similar effect on the score (P < .05). The Bax scores of all the groups were found similar (P > .05). No study drugs caused meaningful change in the ovarian follicle number (P > .05). Pazopanib reduces the growth of endometriotic implants. This effect may be related to the suppressive effect of pazopanib on the endometriotic tissue expressions of VEGF and CD117 but not Bax. The study drugs do not affect ovarian reserve. The inconsistent effects of study drugs regarding study parameters require further studies to elucidate the molecular bases of their effects on the growth of endometriotic implants.

 

 

Eur J Obstet Gynecol Reprod Biol. 2015 Jul;190:31-5.

Contribution of sacral neuromodulation to manage persistent voiding dysfunction after surgery for deep infiltrating endometriosis with colorectal involvement: preliminary results.

Nyangoh Timoh K¹, Canlorbe G², Verollet D³, Peyrat L⁴, Ballester M⁵, Amarenco G³, Darai E⁵.

Abstract

OBJECTIVE:

Around 5% of women experience persistent voiding dysfunction after surgery for deep infiltrating endometriosis (DIE) with colorectal involvement. The gold standard to manage persistent voiding dysfunction is intermittent self-catherization, but this treatment may reduce quality of life of the patients due to care constraints. The objective of our study was to assess the contribution of sacral neuromodulation (SNM) in the management of persistent voiding dysfunction secondary to surgery for DIE with colorectal resection.

STUDY DESIGN:

Five patients referred for persistent voiding dysfunction after surgery for DIE with colorectal resection were included and fitted with a temporary SNM system to test for feasibility. This consisted of placing an electrode unilaterally next to the S3 sacral nerve root and connecting it to an external pacemaker. The patients wore the electrode and the external neurostimulator for 21 days and kept a voiding diary. The SNM test was considered positive when a 50% decrease in self-catheterization was achieved after removal of the electrode. The system was implanted permanently in patients with a positive SNM test. Urodynamic tests were performed before and after the SNM test.

RESULTS:

Two of the five patients had a positive SNM test and were implanted permanently. At 40 months the first patient had completely stopped self-catheterization and the second patient was performing self-catheterization twice a day with a post voiding residue volume of less than 100ml at 52 months.

CONCLUSION:

SNM could be a curative technique in some patients with persistent voiding dysfunction after surgery for DIE. Further studies are required to better select patients who might benefit from SNM testing and subsequent device implantation.

 

 

Eur Rev Med Pharmacol Sci. 2015 Apr;19(8):1334-7.

Analysis of laparoscopy on endometriosis patients with high expression of CA125.

Ruan YQ¹, Liang WG, Huang SH.

Abstract

OBJECTIVE:

To analyze the clinical effect of laparoscopy on patients with endometriosis and a high expression of CA125.

PATIENTS AND METHODS:

One hundred cases of endometriosis treated in our hospital from May 2012 to August 2014 were selected as research subjects, after approval from the hospital and the informed consent of patients. The subjects were randomly divided into a control group and a study group with 50 cases in each group. The control group underwent the traditional surgery, while the research group underwent laparoscopy. The clinical curative effect were compared between the two groups of patients.

RESULTS:

The research group’s postoperative 6h, 12h, 24h CA125 levels were compared to those of the control group. There was statistically significant difference between groups (p < 0.05). Surgery and hospitalization time, intraoperative bleeding volume, and and incision length index of the two groups of patients were compared. There were statistically significant differences between the two groups (p < 0.05).

CONCLUSIONS:

Laparoscopic surgery in endometriosis patients with high expression of CA125 is curative, and the patients’recovery after surgery is promising.

 

 

 

 

 

Indian J Radiol Imaging. 2015 Apr-Jun;25(2):193-5.

Tumefactive intramural gossypiboma of the urinary bladder mimicking an invasive adnexal malignancy.

Jain S¹, Verma A¹, Jain M², Trivedi S³, Shukla RC¹, Srivastava A¹.

 

Abstract

A surgical swab retained in the body after surgery is known as ‘Gossypiboma’. The purpose of this report is to highlight an intramural vesical gossypiboma mimicking an invasive adnexal malignancy. A 28-year-old multiparous, with open-tubal ligation three years ago, presented with painless hematuria and a nontender mass on vaginal examination. USG suggested ‘pelvic endometriosis’ infiltrating into the bladder and cystoscopy showed no intraluminal extension of the mass. Contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) misdiagnosed it as invasive malignancy of the fallopian tube. Exploratory laparotomy found it to be an intramural vesical gossypiboma. A pelvic gossypiboma infiltrating into the wall of the urinary bladder may easily be misinterpreted as an invasive pelvic malignancy on imaging and may make one consider unwarranted radical surgery.

 

 

Rev Med Chir Soc Med Nat Iasi. 2015 Jan-Mar;119(1):127-34.

Pregnancy and recurrence rates in infertile patients operated for ovarian endometriosis.

Luţuc MH, Nemescu D, Onofriescu A, Târnovanu M, Moscalu M, Onofriescu M.

Abstract

AIM:

The study deals with the preoperative ultrasound diagnosis of ovarian endometriosis, postoperative ultrasound reassessment, laparoscopic surgical resolution of ovarian endometriosis, estimation of recurrence risk 12 months after surgery by ultrasound, reappearance of clinical symptoms (such as pain) or second-look laparoscopy, and pregnancy rate 2 years after surgery.

MATERIAL AND METHODS:

140 patients with en- dometriosis and infertility admitted to the Iasi “Cuza-Vodă” Clinical Hospital of Obstetrics and Gynecology between the years 2009-2011 were included in the study. The patients were divided into 2 groups: group 1-59 cases that refused in vitro fertilization procedures, did not afford in vitro fertilization (IVF) or had minimal endometriosis and young ages and thus a possibility of delaying treatment, and group 2–62 cases which underwent IVF procedures immediately after surgery.

RESULTS:

No significant differences in the chance of becoming pregnant were found between the two groups (χ2 = 2.06, p = 0.0891, 95% CI); in group 1, 11.86% pregnancies were obtained while in group 2 the pregnancy rate was 11.29%. Based on the nonparametric method of analysis of contingency tables we could estimate the odds of becoming pregnant in the study groups, obtaining an odds ratio (OR = 1.16, CI: 1.04-2.23, 95% CI). This result indicated that in group 1 the odds of becoming pregnant was not significantly higher, and the estimation was made for a confidence interval of 95%. The study had in view the assessment of pregnancies obtained in the study groups and the time interval (number of weeks) from the time of intervention until the occurrence of pregnancy. The Kaplan-Meier analysis enabled the assessment of the mean value and the median value of the number of weeks until becoming pregnant, and these values did not show significant differences (χ2 = 1.55, p = 0.212, 95% CI).

CONCLUSIONS:

For endometriosis associated with infertility, hormonal suppression does not improve fertility, and therefore surgery followed by controlled ovarian hyperstimulation and intrauterine insemi- nation (IUI), provided the anatomy of the pelvis is preserved in early cases or in vitro fertilization in severe cases is preferred.

 

 

Rev Med Chir Soc Med Nat Iasi. 2015 Jan-Mar;119(1):170-4.

Pelvic endometriosis and uretero-hydronephrosis: clinical, imagistic and surgical implications–case report.

Ilea C, Lupaşcu I, Socolov D, Cărăuleanu A.

Abstract

Endometriosis represent the presence and proliferation of functional endometrial-like tissue outside the uterine cavity, and is a chronic, recurrent, debilitating desease, in which kidney implications are rare, but complex.

OBJECTIVE:

Evaluation of clinical, imagistic and surgical implications of uretero-hydronephrosis secondary to recurrent pelvic endometriosis.

MATERIAL AND METHODS:

30 year old patient diagnosed with primary infertility and left ovarian endometriosis(treated with classically conservative surgical procedure), presented acute onset of obstructive urinary symptoms, requiring internal drainage of the upper urinary straight path (Cook probe) for uretero-hydronephrosis grade III. CT and MRI examination reveals the presence of a imprecise pelvic mass incorporating right distal ureter and uretero-bladder ostium.

RESULTS:

In this clinical and laboratory context, classic surgery is practicing with right anexectomy and direct right uretero-vesical reimplantation, also with psoas bladder-hitch. Histopathological examination confirmed the presence of recurrent ovarian endometriosis with right distal ureteral invasion.

CONCLUSION:

Recurent endometriosis, although considered a benign condition, often present invasive characters, determining considerable anatomical destructions and severe symptoms.

 

 

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1165-74.

Vascular endothelial growth factor receptor-2 inhibitor cediranib causes regression of endometriotic lesions in a rat model.

Liu F¹, Wang L¹, Zhang XX¹, Min SY¹, Liu YX¹, Zuo Z¹, Jin ZX¹, Zhu ZL¹.

 

Abstract

Vascular endothelial growth factor (VEGF) receptor-2 plays an essential role in angiogenesis, and it also expressed in the glandular epithelium and stromal cells of ectopic endometrium. Cediranib is a protein tyrosine kinase inhibitor that potently inhibits VEGF receptor-2, but there is no study about its effects on the endometriosis. We induced endometriosis on both sides of the abdominal wall in 20 female Sprague-Dawley rats and randomly divided them into 2 groups. They were administered: cediranib 4 mg/kg/day (group 1), equal saline (group 2) for 12 days. Then, the lesion volumes were calculated, and Masson trichrome was used to detect fibrosis. Angiogenesis was evaluated by CD-31 immunohistochemistry and serum VEGF levels. Proliferation was indicated by proliferating cell nuclear antigen immunohistochemistry. Apoptosis was measured by a TUNEL assay and cleaved caspase-3 immunohistochemistry. In the treatment group, the lesion volumes were smaller (P < 0.05), and the degree of fibrosis was greater. The microvessel density was lower (P < 0.05) than control, however, serum VEGF was up-regulated by a negative feedback mechanism (P < 0.01). In addition, proliferation was significantly suppressed (P < 0.01), and apoptosis in the lesions was more obvious in the treatment group. These data indicated that cediranib can inhibit development of endometriotic lesions in rats.

 

 

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1810-5.

Expression of focal adhesion kinase in endometrial stromal cells of women with endometriosis was adjusted by ovarian steroid hormones.

Mu L¹, Ma YY¹.

 

Abstract

The aim of our study is to investigate the effects of ovarian steroid hormones on focal adhesion kinase (FAK) expression in ESCs and whether there is alteration in women with endometriosis. FAK expression was assessed by western blotting analysis. Elevated expression of FAK was seen in the cultured ESCs treated with estrogen (P < 0.05). Expression of FAK protein was not changed in ESCs after treated by progesterone or treated by estrogen and progesterone. The level of up-regulation by estrogen in endometriosis is significantly higher than that from women without endometriosis (P < 0.05). FAK expression in endometrial stromal cells from endometriosis was more sensitive to estrogen, which might contribute to the pathogenesis and progress of endometriosis.

 

 

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1867-77.

Mismatch repair system in endometriotic tissue and eutopic endometrium of unaffected women.

Grassi T¹, Calcagno A¹, Marzinotto S², Londero AP³, Orsaria M², Canciani GN⁴, Beltrami CA², Marchesoni D¹, Mariuzzi L².

Abstract

OBJECTIVE:

To test the immunohistochemical staining pattern of some mismatch repair (MMR) system proteins in endometriotic tissue (ET) and eutopic endometrium.

METHODS:

This was a retrospective study conducted at the Pathology and Obstetrics and Gynecology Departments of the Udine University Hospital. We analyzed 528 samples obtained from 246 patients affected by endometriosis and 71 samples from 71 patients with normal endometrium. A tissue microarray model was used to analyze the immunohistochemical expression of MMR system proteins.

RESULTS:

Significant loss of MMR proteins was found in the stromal component of ETs. We found MSH2 to be expressed at a higher level than any other MMR system proteins in eutopic endometrium and ETs, to be significantly correlated to Ki-67 expression in both stromal and glandular components of ETs, and to be expressed at a significantly higher level in ETs than in eutopic endometrium. When considering the subgroup of endometriosis with high recurrence rate and glandular cytoplasmic staining for aurora A kinase, we found MMR proteins expressed at a significantly higher level in these ETs than in other ETs and eutopic endometrium of unaffected women.

CONCLUSIONS:

We found significant loss of MMR proteins (known to be associated with microsatellite instability) in the stromal component of ETs. The group of ETs with glandular cytoplasmic staining for aurora A kinase had higher MMR protein expression, suggesting an increased activity of this system. Our result suggests a novel role of increased MSH2 expression in cellular proliferation of endometriosis.

 

 

Pain. 2016 Jan;157(1):80-91.

Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells.

Iuvone T¹, Affaitati G, De Filippis D, Lopopolo M, Grassia G, Lapenna D, Negro L, Costantini R, Vaia M, Cipollone F, Ialenti A, Giamberardino MA.

 

Abstract

The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg(-1)·d(-1), orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats showed significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004); a significantly higher percentage of expelled stones (P < 0.0001); significantly lower MC number (P < 0.01), vessel number (P < 0.01), chymase (P < 0.05), NGF (P < 0.05), VEGF (P < 0.01), and Flk-1 (P < 0.01) expression in cysts and NGF expression in DRG (P < 0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics.

 

 

J Tradit Chin Med. 2015 Apr;35(2):184-91.

Effect of Bushenwenyanghuayu decoction on nerve growth factor and bradykinin/bradykinin B1 receptor in a endometriosis dysmenorrhea mouse model.

Jingwei C, Huilan D, Ruixiao T, Hua Y, Huirong M.

Abstract

OBJECTIVE:

To observe the effects of Bushenwenyanghuayu decoction (BD), a Traditional Chinese Medicine (TCM), on the serum concentration of nerve growth factor (NGF) and bradykinin (BK), and protein and mRNA levels of NGF and bradykinin B1 receptor (BKB1R) in a mouse model of endometriosis dysmenorrhea.

METHODS:

Seventy-five experimental female BALB/c mice were randomly divided into five groups, 15 mice each: sham, model, BD high dose (61.67 g/kg), BD low dose (15.42 g/kg), and gestrinone (0.4 mg/kg) groups. All the mice except for those in the sham group underwent auto-transplantation surgery and were gavaged estradiol valerate (0.5 mg/kg, daily for 12 days) after surgery. On the 12th day, 1 h after administration, writhing response was induced by intraperitoneal injection of oxytocin at 2 U/mouse. The writhing frequency and latency were recorded and the volume of the ectopic foci was measured. The concentration of serum NGF and BK was detected by enzyme-linked immunosorbent assay, the protein expression of NGF and BKB1R was tested by immunohistochemistry and western blotting, and NGF and BKB1R mRNAs were detected by real-time PCR.

RESULTS:

Compared with the model group, the volume of the ectopic foci in the treatment groups was significantly lower (P < 0.01), the writhing frequency was decreased (P < 0.05), and the writhing latency was prolonged (P < 0.01). Compared with the sham group, serum NGF and BK levels in the model group were significantly increased (P < 0.01). There were positive correlations for writhing frequency among the NGF and BK groups (P < 0.01). The serum NGF and BK levels were significantly lower in the treatment groups than the model group (P < 0.05). The protein expression of NGF, BKB1R was significantly decreased in the treatment groups compared with the model group (P < 0.01). NGF and BKB1R mRNA expression was significantly decreased in the treatment groups compared with the model group (P < 0.01).

CONCLUSION:

NGF and BK/BKB1R may play an important role in the development of endometriosis-associated dysmenorrhea, and BD was found to inhibit the development of endometriosis and relieve dysmenorrhea by influencing NGF and BK/ BKB1R mRNA and protein levels.

 

 

Zhonghua Yi Xue Za Zhi. 2015 Mar 10;95(9):685-8.

Relationship between endometriosis stage, characteristics of enodmetriotic lesions and severity of dysmenorrhoea.

Ye M¹, Guo H², Han J, He H, Zhang K, Xiong G, Yang Y.

Abstract

OBJECTIVE:

To explore the association between endometriosis stage, characteristics of endometriotic lesions and severity of dysmenorrhoea.

METHODS:

The clinical data were collected from 140 patients with laparoscopically diagnosed endometriosisbetween May 2013 and December 2013. They were scored by visual analogue scale (VAS) according to their preoperative dysmenorrhoea. Endometriotic lesions were recorded by their anatomical distributions. And endometriosis was staged and scored according to the score of Revised American Fertility Society (r-AFS). The relationship between dysmenorrhoea and endometriosis stage as well as endometriotic foci was analyzed. Chi-square test and Logistic regression were used for statistical analyses.

RESULTS:

Among them, there were 95 (67.86%) patients with dysmenorrhoea and 45(32.14%) without dysmenorrhoea. No significant inter-group difference existed in age (P > 0.05). The interval from menarche to the onset of dysmenorrhoea was (8 ± 9) years and duration of dysmenorrhoea (2.3 ± 1.5) days each month. A correlation existed between endometriosis stage and severity of dysmenorrhoea (χ² = 20.677, P < 0.05). A strong association was found between posterior cul-de-sac obliteration and severity of dysmenorrhoea (χ² = 8.471, P < 0.05). No significant difference was found for ovarian endometriomas, ovarian adhesion, superficial peritoneal lesions and deep infiltrating endometriosis in non- and minimal dysmenorrhoea groups with moderate and severe dysmenorrhoea (P > 0.05). Posterior cul-de-sac obliteration was an independent influencing factor for dysmenorrhoea. The odds ratio (OR) was 3.291 and 95% confidence interval (CI) 1.453-7.454. However, no relevance existed between ovarian endometriomas and dysmenorrhoea by Logistic analysis.

CONCLUSION:

The severity of dysmenorrhoea has close correlation with posterior cul-de-sac obliteration. However, there is a weak relevance with ovarian endometreaiomas.

 

 

J Obstet Gynaecol Res. 2015 Aug;41(8):1255-9.

High rate of nickel allergy in women with endometriosis: a 3-year population-based study.

Yuk JS^1,2, Kim YJ³, Yi KW³, Tak K³, Hur JY³, Shin JH³.

Abstract

AIM:

The aim of this study was to evaluate the prevalence rates of nickel allergy, contact dermatitis, drug allergy, allergic rhinitis and atopic dermatitis among women with and without endometriosis.

MATERIAL AND METHODS:

Data were obtained from the National Patient Sample of the Republic of Korea, which was provided by the Korean Health Insurance Review and Assessment Service. We evaluated women aged 20-40 years who visited a health care institution from 2009-2011. We estimated the prevalence of allergic diseases among women with and without endometriosis.

RESULTS:

We extracted a sample of 1 843 447 women from the total patient sample of approximately 3 million. We identified 7259 women with endometriosis and 535 818 women without endometriosis. After adjusting for age and data year, the women with endometriosis had higher rates of nickel allergy (odds ratio = 1.175; 95% confidence interval, 1.011-1.366; P = 0.04). Additionally, after adjusting for age, data year and other allergic diseases, the women with endometriosis had higher rates of nickel allergy (odds ratio = 1.167; 95% confidence interval, 1.004-1.357; P = 0.04). After adjusting for other covariates, we found that other allergic disorders, such as allergic rhinitis, atopic dermatitis and contact dermatitis, were not associated with endometriosis.

CONCLUSION:

Women with endometriosis had higher rates of nickel allergy. Further research is required to clarify the relation between nickel allergy and endometriosis.

 

 

J Obstet Gynaecol Res. 2015 Aug;41(8):1287-90.

Diagnosis and laparoscopic management of a rare endometriosis-related peritoneal mass with rapid growth in early pregnancy.

Di Donato N¹, Facchini C¹, Leggieri C¹, Caprara G², Seracchioli R¹.

 

Abstract

Herein is described the diagnosis, clinical management and laparoscopic removal of a rapid growing retro-uterine mass in a pregnant woman. After laparoscopic removal of the pelvic mass, diagnosis of peritoneal endometriotic cyst was made on histology. The patient was asymptomatic and no history of endometriosis was reported. The laparoscopic management of the peritoneal mass was safe and effective and to our knowledge this is the first case report describing a decidualized endometriotic lesion in the absence of a pre-pregnancy endometriosisdiagnosis.

 

 

Hum Reprod. 2015 Jul;30(7):1677-89.

Estrogen promotes the survival of human secretory phase endometrial stromal cells via CXCL12/CXCR4 up-regulation-mediated autophagy inhibition.

Mei J¹, Zhu XY², Jin LP², Duan ZL³, Li DJ⁴, Li MQ⁵.

Abstract

STUDY QUESTION:

What mechanism is involved in regulating the autophagy of endometrial stromal cells (ESCs), and does it participate in the pathogenesis of endometriosis?

SUMMARY ANSWER:

CXCL12 down-regulates secretory phase ESC autophagy.

WHAT IS KNOWN ALREADY:

mTOR (mammalian target of rapamycin), the major negative regulator of autophagy, is abnormally increased in endometriotic lesions and is involved in the direct regulation of endometrial stromal cell (ESC) apoptosis.

STUDY DESIGN, SIZE, DURATION:

Autophagy was measured by transmission electron microscopy and immunofluorescence, and in vitro analysis was used to measure estrogen/CXCL12/CXCR4 signaling-mediated ESC autophagy.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 31 controls and 31 women with histologically confirmed endometriosis were included. We measured the autophagy level of normal and endometriosis-derived endometrium, and its relationship to the stage of endometriosis, as well as the potential molecular and signaling pathways that mediate the aberrant autophagy in endometriosis.

MAIN RESULTS AND THE ROLE OF CHANCE:

Compared with control secretory phase ESCs, a significant reduction of the autophagy grade (as observed in TEM), punctuate LC3B staining (as observed in immunofluorescence assays), and autophagy-associated protein levels were exhibited in secretory phase eutopic ESCs (P < 0.05) and ectopic ESCs (P < 0.05) from women with endometriosis. In addition, the autophagy level was strongly negatively correlated with the CXCL12 concentration in ESCs (R(2) = -0.9694). However, there was no significant difference in autophagy grade or CXCL12 concentration between stage I-II and stage III-IV endometriosis-derived ectopic ESCs (P > 0.05). Based on a human autophagy PCR array, CXCL12 and CXCR4, which is the CXCL12 receptor, in ESCs were predicted to be molecules that mediate the abnormally lower autophagy in endometriosis. Accordingly, after estradiol (E2) treatment a marked increase in CXCL12 secretion (1.71-fold, P < 0.01) and CXCR4 expression (5.07-fold, P < 0.01) in secretory phase ESCs was observed together with decreases in autophagy grade (TEM), punctuate LC3B immunofluorescent staining and autophagy-associated protein levels (P < 0.05). These changes could be reversed by progesterone (P4) (P < 0.05). The suppression of autophagy induced by E2 and recombinant human CXCL12 protein could be abrogated by an anti-CXCR4 neutralizing antibody and by a NF-κB inhibitor (P < 0.05), respectively. In addition, estrogen-stimulated CXCL12 secretion led to a low population of S phase cells (P < 0.05), as well as a low level of apoptosis (P < 0.05) in secretory phase ESCs.

LIMITATIONS, REASONS FOR CAUTION:

Further studies are needed to examine the mechanism of autophagy on ESC apoptosis.

WIDER IMPLICATIONS OF THE FINDINGS:

Measures to increase in endometrial autophagy might be a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.

STUDY FUNDING/COMPETING INTERESTS:

This study was supported by the National Natural Science Foundation of China (NSFC) (81471513, 81471548 and 81270677), the Training Program for Young Talents of Shanghai Health System XYQ2013104, the Program for Zhuoxue of Fudan University, and the Program for Creative Talents Education of Key Disciplines of Fudan University. None of the authors has any conflict of interest to declare.

 

 

Hum Reprod. 2015 Jul;30(7):1606-16.

Co-operation between the AKT and ERK signaling pathways may support growth of deep endometriosis in a fibrotic microenvironment in vitro.

Matsuzaki S¹, Darcha C².

Abstract

STUDY QUESTION:

How can deep endometriotic stromal cells proliferate and persist in a fibrotic environment?

SUMMARY ANSWER:

The serine/threonine kinase AKT and extracellular regulated kinase (ERK) signaling pathways may co-operate to support growth of deep endometriotic lesions by enhancing endometriotic stromal cell proliferation and survival in a fibrotic microenvironment in vitro.

WHAT IS KNOWN ALREADY:

Endometriosis, particularly deep infiltrating endometriosis, is characterized histologically by dense fibrous tissue that is primarily composed of type I collagen. This tissue may cause pelvic pain and infertility, which are major clinical issues associated with endometriosis. Proliferation of normal fibroblasts is tightly regulated, and fibrillar, polymerized type I collagen inhibits normal fibroblast proliferation. However, no studies to date have investigated how deep endometriotic stromal cells can proliferate and persist in a fibrotic environment.

STUDY DESIGN, SIZE, DURATION:

Endometrial and/or endometriotic tissues from 104 patients (61 with and 43 without endometriosis) of reproductive age with normal menstrual cycles were analyzed. A total of 25 nude mice received a single injection of endometrial fragments from a total of five samples.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

We evaluated cell proliferation, caspase 3/7 activity, and the AKT and ERK signaling pathways in endometrial and endometriotic stromal cells on three-dimensional (3D) polymerized collagen matrices in vitro. In addition, to determine whether aberrant activation of the AKT and ERK pathways is involved during progression of fibrosis in endometriosis in vivo, we evaluated the expression of phosphorylated AKT and ERK1/2 in endometriotic implants in a nude mouse model of endometriosis. Finally, we evaluated the effects of MK2206 (an AKT inhibitor) and U0126 (a MEK inhibitor) on cell proliferation, caspase 3/7 activity, and phosphorylation of AKT and ERK1/2 of endometriotic stromal cells on 3D polymerized collagen matrices.

MAIN RESULTS AND THE ROLE OF CHANCE:

Proliferation of endometriotic stromal cells was significantly less inhibited than that of endometrial stromal cells (P < 0.05) on 3D polymerized collagen. Levels of phosphorylated AKT, phosphorylated p70S6K and phosphorylated ERK1/2 were significantly higher in endometriotic stromal cells than in endometrial stromal cells at 24 h (P < 0.05) and at 72 h (P < 0.05) on 3D polymerized collagen. Phosphorylated AKT expression was significantly increased on Days 21 and 28 compared with those on Days 3 and 7 (all P < 0.05) in endometriotic implants during progression of fibrosis in a nude mouse model of endometriosis. Inhibition of AKT or ERK1/2 with MK2206 or U0126, respectively, did not significantly increase caspase 3/7 activity in endometriotic stromal cells on either two-dimensional or 3D collagen matrices. Western blot analysis showed that MK2206 alone decreased levels of phosphorylated AKT; however, it increased levels of phosphorylated ERK in endometriotic cells compared with vehicle-treated cells (both P < 0.05). In addition, U0126 treatment decreased levels of phosphorylated ERK; however, it resulted in increased levels of phosphorylated AKT in endometriotic stromal cells compared with vehicle-treated cells (both P < 0.05).

LIMITATIONS, REASONS FOR CAUTION:

Endometriosis involves a number of processes, such as invasion, metastasis, angiogenesis, and apoptosis resistance, and a variety of signaling pathways may be involved in promoting development and progression of the disease. In addition, further animal experiments are required to determine whether the AKT and ERK signaling pathways co-operate to support growth of endometriotic lesions in a fibrotic microenvironment in vivo.

WIDER IMPLICATIONS OF THE FINDINGS:

Co-targeting the AKT and ERK pathways may be an effective therapeutic strategy for endometriosis treatment.

STUDY FUNDING/COMPETING INTERESTS:

This study was supported in part by Karl Storz Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are declared.

 

 

Immunol Lett. 2015 Jul;166(1):1-5.

Soluble ST2 and IL-33: Potential markers of endometriosis in the Tunisian population.

Mbarik M¹, Kaabachi W², Henidi B³, Sassi FH⁴, Hamzaoui K⁵.

 

Abstract

Interleukin-33 is an IL-1 family cytokine which signals via its T1/ST2 receptor, and acts as a key regulator of inflammation. This study aims to measure the expression of soluble ST2 (sST2) and IL-33 in endometriosis. We investigated thirty women with laparoscopic and histopathological confirmed endometriosis and 20 control women without pelvic pathology. Peripheral blood mononuclear cells and peritoneal fluid (PF) were assessed for sST2 and IL-33 levels that are measured by sandwich enzyme-linked immunosorbent assay. Peritoneal fluid IL-33 mRNA expression was quantified by real-time reverse transcription polymerase chain reaction assays. We found that IL-33 levels in PF and in serum were significantly higher in patients with endometriosis compared to women without endometriosis (P < 0.05). IL-33 increased levels were significantly more important in PF [10.45 ± 14.33 ng/mL] than in serum [2.68 ± 1.54 ng/mL] from endometriosis patients. Higher levels of IL-33 mRNA expression were detected in PF from patients with endometriosis. Soluble ST2 levels in PF were significantly different between patients [2.96 ± 0.98 ng/mL; P < 0.0001] and controls [0.88 ± 0.076 ng/mL]. Serum sST2 levels were similarly expressed in endometriosis patients and in controls (P > 0.05). Significant correlation was observed between IL-33 and sST2 levels in PF. In conclusion, IL-33 and sST2 values observed in PF were found to correlate with endometriosis severity. Elevated and correlated PF IL-33 and sST2 levels from patients with endometriosis suggested a potential role as surrogate markers of disease activity.

 

 

Int J Surg Case Rep. 2015;12:19-22.

Catamenial pneumothorax due to solitary localization of diaphragmatic endometriosis.

Elia S¹, De Felice L², Varvaras D², Sorrenti G³, Mauriello A³, Petrella G².

Abstract

INTRODUCTION:

Catamenial pneumothorax (CP) is a spontaneous recurrent pneumothorax occurring in women in reproductive age. The etiology of CP has been associated with thoracic endometriosis and is its most common presentation.

PRESENTATION OF CASE:

A case of right catamenial pneumothorax in a 38 year old woman is presented in which three episodes of CP occurred within 72h of menses in a 6 month period. The patient underwent videothoracoscopy that revealed a solitary localization of diaphragmatic endometriosis. After surgical pleurodesis and based on final pathology of resected lesion, hormonal treatment was started. The outcome was uneventful and the patients is symptom-free at 6 months.

DISCUSSION:

Catamenial pneumothorax (CP) is a rare clinical entity characterized by lung collapse during menstruation, believed to be secondary to pleural endometriosis. Nearly all catamenial pneumothorax occur on the right side as pleural lesions are almost exclusively right-sided. Diagnostic imaging is based on high resolution computed tomography (HRCT) and, preferably, magnetic resonance imaging (MRI) since it is able to detect the blood products in the endometrial deposits. However the lack of macroscopic findings at surgery makes this condition still under-diagnosed. Based on the solitary diaphragmatic localization of endometriosis in our case we preferred to limit surgery to videothoracoscopic pleurodesis and start hormonal treatment with successful outcome.

CONCLUSION:

Catamenial pneumothorax is the most common presentation of thoracic endometriosis syndrome and should always be suspected in women in childbearing age. Treatment option are still debated but best results are achieved by videothoracoscopic pleurodesis combined with hormonal therapy.

 

 

Reprod Biomed Online. 2015 Jul;31(1):9-19.

Impact of ovarian endometrioma on ovarian responsiveness and IVF: a systematic review and meta-analysis.

Yang C¹, Geng Y¹, Li Y¹, Chen C¹, Gao Y².

 

Abstract

In this systematic review and meta-analysis, the effect of ovarian endometrioma on ovarian responsiveness to stimulation and on assisted reproduction outcomes was evaluated. Nine published studies (1039 cases) were included. The number of oocytes retrieved (mean difference [MD] -1.50; 95% CI, -2.84 to -0.15, P = 0.03), metaphase II (MII) oocytes retrieved (MD -3.61; 95% CI -4.44 to -2.78, P < 0.00001) and total embryos formed (MD -0.66; 95% CI -1.13 to -0.18, P = 0.007) were significantly lower in women with ovarian endometrioma than the control group. Gonadotrophin dose, duration of stimulation, number of good-quality embryos, implantation rate, clinical pregnancy rate and live birth rate were similar. Comparisons between ovaries with endometriomas and healthy ovaries of the same individuals were also made. Number of oocytes retrieved, MII oocytes retrieved and total embryos formed were not statistically significantly different between the affected ovaries and contralateral normal ovaries. Observational studies showed that ovarian endometrioma was associated with fewer oocytes retrieved, fewer MII oocytes retrieved and fewer total formed embryos. Clinical pregnancy rate and live birth rates were not affected. Intra-patient comparisons in women with unilateral endometrioma suggested the number of oocytes retrieved, MII oocytes retrieved and total embryos formed were similar.

 

 

Mol Reprod Dev. 2015 Jun;82(6):410-31.

Non-hormonal targets underlying endometriosis: A focus on molecular mechanisms.

Che XH^1,2,3, Chen YC¹, Chen CL², Ye XL^1,3, Zhu H⁴.

 

Abstract

Endometriosis is regarded as a hormone-dependent disease. Current therapeutic approaches to treating this common gynecological disorder mainly depend on surgical and hormonal interventions, but the high rate of disease recurrence as well as the side effects related to such therapies make it difficult for patients to recover completely. Molecular evidence has recently suggested that the source of endometriosis can be both hormone-dependent and influenced by the dysregulation of some signaling cascades. In this review, we focus on the non-hormonal triggers of endometriosis and the pre-clinical compounds designed to correct these signaling defects in order to achieve a better understanding of the disease as well as novel approaches to treating it.

 

 

Clin Case Rep. 2015 May;3(5):315-8.

Endometriosis coexisting with mature cystic teratoma in the same ovary and ectopic pregnancy of left fallopian tube: a rare coexistence.

Chae H¹, Rheu C¹.

 

Abstract

A coexistence of endometriosis and mature cystic teratoma in the same ovary is a rare occurrence although such tumors of ovaries are said to be common in the reproductive age group. We report a case of fimbrial ectopic pregnancy combined with simultaneous ipsilateral ovarian presentation of endometriosis and mature teratoma.

 

 

Syst Biol Reprod Med. 2015;61(4):238-44

Vascular endothelial growth factor (-460 C/T, +405 G/C, and +936 C/T) polymorphisms and endometriosis risk in Tunisian population.

Henidi B¹, Kaabachi W, Naouali A, Kaabachi S, Zhioua A, Haj Sassi F, Hamzaoui K.

 

Abstract

The vascular endothelial growth factor (VEGF), a major angiogenic factor, is known to play an important role in the development of endometriosis. The aim of this study was to investigate the association of three VEGF (-460 C/T, +405 G/C, and +936 C/T) polymorphisms with the risk of endometriosis in the Tunisian population. This study includes 105 women with endometriosis and 150 women with no laparoscopic evidence of disease. Genotyping of the VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The distribution of genotypes (P = 0.006) and allele (P = 0.0009) frequencies of the +936 C/T polymorphism was significantly different between patients and controls. Patients with stages III-IV endometriosis showed a higher VEGF + 936T allele frequency than controls (P = 0.0001). However, the distribution of genotypes and allele frequencies of the VEGF -460 C/T and +405 G/C polymorphisms did not differ significantly between endometriosis patients and controls. These findings suggest that the VEGF +936 C/T polymorphism may be a risk factor for endometriosis development and the VEGF +936 T allele is associated with an increased risk of stages III-IV endometriosis in the Tunisian population.

 

 

Clin Imaging. 2015 Sep-Oct;39(5):830-3.

The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts.

Balaban M¹, Idilman IS², Toprak H³, Unal O², Ipek A², Kocakoc E⁴.

 

Abstract

The aim was to determine the utility of diffusion-weighted magnetic resonance imaging (DW MRI) and apparent diffusion coefficient (ADC) measurements in differentiation of endometrioma and hemorrhagic ovarian cyst. A total of 24 female patients who underwent pelvic MRI with an initial diagnosis of ovarian cyst were included in the study. The final diagnosis was endometrioma in 12 patients and hemorrhagic ovarian cyst in 12 patients. We observed significantly lower ADC values in endometriomas compared with hemorrhagic ovarian cysts in all b values. DW MRI with quantitative ADC measurements can be used for differentiation of endometrioma from hemorrhagic ovarian cysts.

 

 

Gynecol Endocrinol. 2015 Jul;31(7):511-5.

The role of TGFβ superfamily members in the pathophysiology of endometriosis.

Dela Cruz C¹, Reis FM.

 

Abstract

The transforming growth factor-beta (TGFβ) superfamily comprises over 30 dimeric proteins with conserved structures, which play important roles in the control of cellular proliferation, differentiation and apoptosis. These proteins are expressed and finely regulated in human endometrium during the menstrual cycle, which is consistent with their effects on endometrial cell proliferation and tissue remodeling. This review is focused on summarizing the role of key members of the TGFβ superfamily in the pathophysiology of endometriosis. Evidence suggests that TGFβ, activins, inhibins, nodal, bone morphogenetic proteins, growth differentiation factors, and anti-Müllerian hormone are produced by endometriotic lesions and could be involved in the establishment and progression of the disease. Their receptors and signaling pathways may also be altered in the presence of endometriosis and may be potential targets to the development of therapeutic agents.

 

 

 

Arch Gynecol Obstet. 2015 Dec;292(6):1267-71.

Comparison of dienogest versus triptorelin acetate in premenopausal women with adenomyosis: a prospective clinical trial.

Fawzy M¹, Mesbah Y².

Abstract

PURPOSE:

To compare the efficacy of the oral dienogest versus triptorelin acetate injection for treatment of premenopausal menorrhagia and pelvic pains in women with uterine adenomyosis.

METHODS:

A total of 41 patients with adenomyosis suffering from pelvic pains and menorrhagia were recruited. First group was managed with oral dienogest (2 mg/day, orally) while the second group received triptorelin acetate (3.75 mg/4 weeks, subcutaneous injection) for 16 weeks. Outpatient follow-up was undertaken after 8 weeks but mean values were calculated at baseline and after 16 weeks (end of treatment).

RESULTS:

A total of 41 women were allocated to treatment with dienogest (n = 22) or triptorelin acetate (n = 19); 19 (86.4 %) and 18 (94.7 %) % of the respective groups completed the trial. Significant reductions in pelvic pains after 16 weeks treatment were obtained in both groups demonstrating the equivalence of dienogest relative to triptorelin acetate. Triptorelin acetate was more effective in controlling of menorrhagia and reduction of uterine volume.

CONCLUSIONS:

Dienogest may be a valuable alternative to depot triptorelin acetate for treatment of premenopausal pelvic pains in women with uterine adenomyosis.

 

J Med Chem. 2015 Oct 8;58(19):7634-58.

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health.

Thomas MP¹, Potter BV².

 

Abstract

In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led to steroidal and nonsteroidal drugs in numerous preclinical and clinical trials, with promising results in oncology and women’s health, including endometriosis. Drugs have been designed to inhibit STS, e.g., Irosustat, as innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as multitargeting agents for hormone-independent tumors, such as the steroidal STX140 and nonsteroidal counterparts, acting inter alia through microtubule disruption. The aryl sulfamate pharmacophore is highly versatile, operating via three distinct mechanisms of action, and imbues attractive pharmaceutical properties. This Perspective gives a personal view of the work leading both to the therapeutic concepts and these drugs, their current status, and how they might develop in the future.

 

 

J Clin Endocrinol Metab. 2015 Jul;100(7):E955-63.

Up-regulation of Bcl-2 by CD147 Through ERK Activation Results in Abnormal Cell Survival in Human Endometriosis.

Wang C¹, Jin A¹, Huang W¹, Tsang LL¹, Cai Z¹, Zhou X¹, Chen H¹, Chan HC¹.

Abstract

CONTEXT:

Human endometriosis (EMS) is characterized by insufficient apoptosis. Our previous studies have shown elevated CD147 expression in human endometriotic tissues and its involvement in endometrial cell apoptosis. However, the exact underlying mechanism remains elusive.

OBJECTIVE:

The objective was to examine the correlation of the highly expressed CD147 with anti-apoptotic factor Bcl-2 in human endometriotic tissues and to determine the CD147-regulated apoptotic pathway in human endometrial epithelial cell line (HES).

DESIGN:

This was a laboratory study using human tissue analysis and HES cell culture.

SETTING:

The setting was an academic research center and hospital.

PATIENTS:

Patients were 30 women with ovarian EMS and 12 women without EMS.

INTERVENTIONS:

mRNA levels of CD147 and Bcl-2 were evaluated in endometriotic tissues by quantitative real-time PCR. HES cells were transfected with pcDNA3.0-CD147 overexpressing plasmid or immune-depleted by CD147 antibody.

MAIN OUTCOME MEASURES:

Main outcome measures were reverse transcription, quantitative real-time PCR, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and Western blotting.

RESULTS:

In human endometriotic tissues, Bcl-2 was up-regulated and positively correlated with CD147 expression, accompanied by activated ERK signaling. In HES cells, overexpression of CD147 increased viable cells and up-regulated Bcl-2 expression by activation of ERK signaling. Interference with CD147 function suppressed ERK signaling and decreased Bcl-2 expression, followed by accumulation of apoptotic factors, including cleaved caspase-9, cleaved caspase-3, and cleaved poly ADP-ribose polymerase.

CONCLUSIONS:

The presently found strong correlations between Bcl-2 and CD147, ERK, and CD147 in human endometriotic lesions and the demonstrated reduced cell apoptosis through CD147-ERK-Bcl-2 intrinsic apoptosis signaling axis suggest that this CD147-regulated signaling may contribute to the enhanced cell survival in the progression of human EMS.

 

 

Pain Res Manag. 2015 May-Jun;20(3):133-6.

Assessment of pain and stress intensity among women with ovarian endometriomas versus teratomas.

Chmaj-Wierzchowska KS, Kampioni M, Wilczak M, Sajdak S, Opala T.

Abstract

BACKGROUND:

In recent years, numerous studies have considered endometriosis to be a subclinical, local inflammatory process in the pelvic peritoneum, the main symptom of which is pain.

OBJECTIVES:

To assess pain intensity and pain-related stress in women with ovarian endometriomas versus teratomas.

METHODS:

In total, 860 women (18 to 38 years of age) treated laparoscopically for lesions in the adnexa between September 2006 and November 2013 were included in the present study. After an intraoperative review of their histopathological lesions, the patients were divided into two study groups: group E (n=480), with histopathologically confirmed ovarian endometriomas; and group T (n=380), after laparoscopic treatment of ovarian teratomas. A questionnaire was generated for the study and completed by each group. Statistical analysis was performed using the Mann-Whitney U test (P≤0.05).

RESULTS:

Median pain scores for group E versus group T were as follows: pain during menstruation, 6 versus 3 (P=0.001); pain outside of menstruation (in professional life), 2 versus 2 (P=0.014); and pain during sexual intercourse, 3 versus 1 (P=0.006). Pain-related stress scores were higher in group T versus group E (5 versus 3; P=0.007).

CONCLUSION:

Ovarian endometriomas caused more pain than ovarian teratomas, likely due to the endometrial tissue component and not a mass effect. The assessment of pain and pain-related stress associated with the pelvis minor showed a high level of pain intensity and lower level of pain-related stress among patients with ovarian endometriomas.

 

 

Iran J Reprod Med. 2015 Mar;13(3):155-60.

Association between endometriosis and hyperprolactinemia in infertile women.

Esmaeilzadeh S¹, Mirabi P¹, Basirat Z¹, Zeinalzadeh M¹, Khafri S².

Abstract

BACKGROUND:

The association of endometriosis with hyperprolactinemia is controversial.

OBJECTIVE:

The present study aimed to determine the frequency of endometriosis and association of prolactin with endometriosis in infertile women.

MATERIALS AND METHODS:

256 infertile women who underwent diagnostic laparoscopy for the evaluation of infertility, referred to Fatemezahra Infertility and Reproductive Health Research Center were included in a cross-sectional study. The presence of endometriosis was evaluated. To investigate the association of endometriosiswith hyperprolactinemia, the patients whose infertility was not caused by endometriosis were included as control group. Serum prolactin (PRL) level was measured in both groups. The comparison of basal serum PRL levels between the two groups was performed, using independent t-test. One way ANOVA was used to determine PRL association with endometriosis stages.

RESULTS:

The frequency of endometriosis was found to be 29%. PRL levels were significantly higher in endometriosis group compared to control group (23.02±1.25 vs. 17.22±1.22 respectively, p=0.004). Statistically significant associations were found between staging of endometriosis and prolactin levels (p=0.01).

CONCLUSION:

Hyperprolactinemia may be associated with endometriosis and its progression.

 

 

Biomed Res Int. 2015;2015:986281

The pleiotropic effects of vitamin D in gynaecological and obstetric diseases: an overview on a hot topic.

Colonese F¹, Laganà AS², Colonese E³, Sofo V⁴, Salmeri FM⁴, Granese R², Triolo O².

 

Abstract

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.

 

 

Arch Gynecol Obstet. 2015 Aug;292(2):245-53.

Vesicovaginal fistulas: a gynecological experience in 41 cases at a German pelvic floor center.

Reisenauer C¹.

Abstract

PURPOSE:

Etiology, diagnosis and management of vesicovaginal fistulas in women referred to the German pelvic floor center Tuebingen over a 9-year period of time were analyzed.

METHODS:

Records of 41 consecutive women suffering from vesicovaginal fistulas between February 2006 and February 2015 were reviewed retrospectively.

RESULTS:

In the German case series presented, the most common etiology of vesicovaginal fistulas was total abdominal hysterectomy. Other causes, in descending order of frequency, were abdominal radical hysterectomy, endometriosis surgery, total laparoscopical hysterectomy, vaginal hysterectomy, surgical treatment for ovarian cancer, radiotherapy, supracervical laparoscopic hysterectomy, surgery for genital malformation, cesarean section and forceps delivery. The transvaginal approach, for surgical fistula treatment, was primarily adopted whenever the primary or recurrent fistula was accessible vaginally because of its minimally invasive nature and low morbidity. The vesicovaginal fistula cure rate was 97.5 %. 36 out of 41 vesicovaginal fistulas were closed transvaginally. In one case, the postradiation vesicovaginal fistula could not be cured and the patient required urinary diversion.

CONCLUSION:

To avoid repeated surgeries, fistula management in specialized centers is advantageous.

 

 

Handb Clin Neurol. 2015;130:395-412

Genital and sexual pain in women.

Graziottin A¹, Gambini D², Bertolasi L³.

 

Abstract

This chapter discusses the all too common problem of sex-related pain in women. Pain is a complex perceptive experience, involving biologic as well as psychologic and relational meanings. They become increasingly important with the chronicity of pain. Neurologists are quite aware of the painful aspect of many neurologic disorders, but lifelong and acquired genital and sexual pain is still neglected in a consistent percentage of women. One reason is the view – still held by many – that psychologic factors play the most important role in sex-related pain complaints. The consequences of diagnostic delay can be dramatic. Persisting tissue inflammation induces pain to change from acute and “nociceptive,” which indicates a “friendly signal,” alerting one to ongoing tissue damage, to chronic and “neuropathic,” a disease per se. Whilst the primary disease is progressing and neuroinflammation becomes a prominent feature, affected women have to bear years of pain and distress, huge quantifiable and non-quantifiable costs, and a progressive deterioration of personal and relational health and happiness. The scenario is even more dramatic when pain complicates an already disabling disease. The main aspects considered in this chapter include neuroinflammation as a key feature of pain; genital and sexual pain as part of neurologic diseases; and genital and sexual pain syndrome (dyspareunia and vaginismus) as primary problems, and their pelvic comorbidities (bladder pain syndrome, endometriosis, irritable bowel syndrome, provoked vestibulodynia/vulvodynia). Finally, we discuss iatrogenic pain, i.e., genital and sexual pain caused by ill-conceived medical, surgical, pharmacologic or radiologic therapeutic interventions.

 

 

JSLS. 2015 Apr-Jun;19(2).

Endometriosis in adolescents.

Dun EC¹, Kho KA², Morozov VV³, Kearney S⁴, Zurawin JL⁵, Nezhat CH⁴.

Abstract

BACKGROUND AND OBJECTIVES:

Women with endometriosis often report onset of symptoms during adolescence; however, the diagnosis of endometriosis is often delayed. The aim of this study was to describe the experience of adolescents who underwent laparoscopy for pelvic pain and were diagnosed with endometriosis: specifically, the symptoms, time from onset of symptoms to correct diagnosis, number and type of medical professionals seen, diagnosis, treatment, and postoperative outcomes.

METHODS:

We reviewed a series of 25 females ≤21 years of age with endometriosis diagnosed during laparoscopy for pelvic pain over an 8-year period. These patients were followed up for 1 year after surgery.

RESULTS:

The mean age at the time of surgery was 17.2 (2.4) years (range, 10-21). The most common complaints were dysmenorrhea (64%), menorrhagia (44%), abnormal/irregular uterine bleeding (60%), ≥1 gastrointestinal symptoms (56%), and ≥1 genitourinary symptoms (52%). The mean time from the onset of symptoms until diagnosis was 22.8 (31.0) months (range, 1-132). The median number of physicians who evaluated their pain was 3 (2.3) (range, 1-12). The adolescents had stage I (68%), stage II (20%), and stage III (12%) disease. Atypical endometriosis lesions were most commonly observed during laparoscopy. At 1 year, 64% reported resolved pain, 16% improved pain, 12% continued pain, and 8% recurrent pain.

CONCLUSIONS:

Timely referral to a gynecologist experienced with laparoscopic diagnosis and treatment of endometriosis is critical to expedite care for adolescents with pelvic pain. Once the disease is diagnosed and treated, these patients have favorable outcomes with hormonal and nonhormonal therapy.

 

 

Am J Emerg Med. 2015 Dec;33(12):1841.e1-2

A healthy young woman with massive hemorrhagic ascites.

Kishino F¹, Inokuchi R², Komaru Y³, Takaya N⁴, Yamamoto M⁵, Nakajima S⁵, Yahagi N⁵.

 

Abstract

Retrograde menstruation is the backward movement of menstrual fluids. The underlying mechanisms remain unknown. The converse current itself is benign, but the result can be abdominal pain caused by peritoneal irritation and, eventually, endometriosis. The case was of a 25-year-old woman with lower abdominal pain accompanied by significant hemoperitoneum. Physical examination and inspection using abdominal ultrasonography and computed tomography failed to reveal a differential diagnosis. Detailed history taking revealed sexual activities during her menstrual period, which allowed for a diagnosis of retrograde menstruation. These findings emphasize the importance of extensive history taking.

 

 

Gynecol Endocrinol. 2015;31(8):639-42.

Serum salusins levels are increased and correlated positively with cyst size in ovarian endometrioma.

Sahin L¹, Bozkurt M¹, Celik O², Çelik N³, Aydin S⁴, Gencdal S¹.

Abstract

OBJECTIVES:

The objective of this study is to evaluate plasma concentrations of salusin-α and salusin-β levels in women with endometrioma and non-endometriotic benign ovarian cysts.

METHOD:

Endometrioma patients (n = 14), non-endometriotic ovarian cysts (n = 14), and age-matched normal healthy fertile subjects (n = 14) participated in this study. Plasma salusin-α and salusin-β levels at the time of mid-luteal phase before and 3 months after L/S cystectomy were measured using ELISA and EIA tests, and their relation with demographic parameters was also assessed.

RESULTS:

The mean salusin-α and salusin-β levels were significantly higher in women with endometrioma before the removal of cyst compared with cases with non-endometriotic cyst and fertile cases. Surgical removal of the endometrioma decreased the mean salusin-α and salusin-β levels to the level of those with non-endometriotic cyst before and after the cystectomy and fertile women, in both unilateral and bilateral endometrioma cases. Plasma salusin-β concentrations were found to be positively correlated with age, size of cyst, bilaterality, and salusin-α levels. Salusin-β values showed no correlations to BMI and size of the ovarian cysts.

CONCLUSIONS:

Plasma salusin-α and salusin-β levels are increased in endometrioma patients and positively correlated with endometrioma size. Laparoscopic removal of the endometrioma by stripping technique decreases the salusin levels to a similar level of fertile women.

 

 

J Coll Physicians Surg Pak. 2015 May;25(5):372-3

Primary amenorrhea with bilateral endometriotic cysts.

Jabeen S¹, Raees M¹.

 

Abstract

Primary amenorrhea is a common problem. Diagnosis is usually by going through systematic approach of history, examination and investigations. This case had bilateral large endometriotic cysts in the adnexal region. Uterus was normal sized with well-formed endometrium. She underwent laparotomy followed by drainage of endometriotic cysts, stripping and reconstruction of ovaries was performed. Patient was given a trial of combined oral contraceptive pills for two consecutive cycles to observe withdrawal bleeding, but it failed. Till now we are unable to find out such case in literature. Exact case of primary amenorrhea could not be found.

 

 

J Ultrasound Med. 2015 Jun;34(6):937-47.

Systematic evaluation of women with suspected endometriosis using a 5-domain sonographically based approach.

Menakaya U¹, Reid S², Infante F², Condous G².

 

Abstract

In recent years, knowledge has evolved regarding the role of transvaginal sonography in the assessment of the pouch of Douglas status and the preoperative prediction of extraovarian endometriosis in specific locations. Despite these advances in transvaginal sonography, the challenge of developing a comprehensive, cost-effective, and reproducible preoperative classification system for endometriosis remains. Critical to this classification system should be a sonographically based evaluation protocol that is systematic, evidence based, and reproducible with clearly defined end points. To date, no structured evaluation protocol exists for the assessment of the pelvis in women with suspected endometriosis. In this article, we propose a domain-based evaluation protocol for the assessment of women with suspected endometriosis using transvaginal sonography.

 

 

 

 

Minerva Ginecol. 2016 Aug;68(4):412-7.

Quality of life after total laparoscopic hysterectomy: a one-year follow-up study.

Kayani SI¹, Pundir J, Omanwa K.

Abstract

BACKGROUND:

A small prospective observational cohort study with the aim to evaluate postoperative health-related quality of life (HRQOL) at one-year follow-up after total laparoscopic hysterectomy for benign gynecological conditions and to assess postoperative functions in terms of return to work, sexual activity and driving was conducted.

METHODS:

Sixty out of 65 women with a mean age of 45.7±5.4 responded to the questionnaire. Change in HRQOL was assessed by comparing the preoperative and postoperative QOL on scale of 1-5 grades.

RESULTS:

HRQOL improved significantly at 12 months postoperatively. Multiple logistic regression analysis showed that the presence of irregular periods (P=0.048) and dyspareunia (P=0.017) were significant predictors of overall postoperative improvement in QOL by 3 or more grades. Women with ovarian preservation were more likely to report overall improvement in HRQOL by 3 or more grades compared to those who had bilateral salpingo-oophrectomy (P=0.04). There was statistically significant improvement in QOL postoperatively as compared to preoperatively (P<0.0001).

CONCLUSIONS:

In our study we found that women presenting with dyspareunia were more likely to report higher improvement in postoperative QOL. This highlights that dyspareunia is a symptom which is a marker for chronic pelvic pain conditions like endometriosis, adenomyosis, fibroids and adhesions.

Oocyte quality is decreased in women with minimal or mild endometriosis.

Xu B¹, Guo N¹, Zhang XM¹, Shi W¹, Tong XH¹, Iqbal F², Liu YS¹.

 

Abstract

Endometriosis, a pathological condition in which the endometrium grows outside the uterus, is one of the most common causes of female infertility; it is diagnosed in 25-40% of infertile women. The mechanism by which endometriosis affects the fertility of females remains largely unknown. We examined the ultrastructure of oocytes from patients with minimal or mild endometriosis and control females undergoing in vitro fertilization (IVF) treatment by transmission electron microscopy (TEM) to investigate the physiological significance of oocyte quality for patients with minimal or mild endometriosis. The TEM results revealed that the oocytes from women with minimal or mild endometriosis exhibited abnormal mitochondrial structure and decreased mitochondria mass. Quantitative real time PCR analysis revealed that the mitochondrial DNA copy number was significantly reduced in the oocytes from women with minimal or mild endometriosis compared with those of the control subjects. Our results suggest that decreased oocyte quality because of impaired mitochondrial structure and functions probably an important factor affecting the fertility of endometriosis patients.

 

 

Obstet Gynecol Sci. 2015 May;58(3):223-31.

Clinical features of thoracic endometriosis: A single center analysis.

Hwang SM¹, Lee CW¹, Lee BS¹, Park JH¹.

Abstract

OBJECTIVE:

To analyze the diagnostic profiles and treatment outcomes of patients with thoracic endometriosis at a university hospital.

METHODS:

A retrospective review of medical records was performed for patients diagnosed with thoracic endometriosis at Gangnam Severance Hospital, Yonsei University College of Medicine, between January 2007 and January 2014.

RESULTS:

Fifteen patients (median age, 35 years; range, 23-48 years) were evaluated. Patients presented with catamenial hemoptysis (n=8), or catamenial pneumothorax (n=7). Patients with catamenial pneumothorax were significantly older than those presenting with hemoptysis (P=0.0002). Only 3 patients (20%) had coexisting pelvic endometriosis. All patients underwent chest computed tomography; lesions were shown to predominantly affect the right lung (right lung, n=13, 86.7%; left lung, n=2, 13.3%), and were mainly distributed on the right upper lobe (n=9, 60%). Ten patients underwent video-assisted thoracoscopic surgery, and 1 patient underwent a thoracotomy. Intraoperatively, endometriosis-specific findings were observed in 8/11 patients (72.7%); a further 5/11 patients (45.4%) had histologically detectable endometriosis. Over the follow-up period (mean, 18.4 months; range, 2-65 months) 5/15 patients (33%) had clinical signs of recurrence. Recurrence was not detected in any of the 5 catamenial pneumothorax patients that received adjuvant hormonal therapy after surgery.

CONCLUSION:

The diagnosis and management of thoracic endometriosis requires a multidisciplinary approach, based upon skillful differential diagnosis, and involving careful gynecologic evaluation and assessment of the cyclicity of pulmonary symptoms. Imaging findings are non-specific, though there may be laterality towards the right lung. Since symptom recurrence is more common in those with presenting with pneumothorax, post-operative adjuvant medical therapy is recommended.

 

 

J Minim Invasive Gynecol. 2015 Sep-Oct;22(6):1104-8.

Endometriosis and Ascites: A Strategy to Achieve Pregnancy.

Setubal A¹, Sidiropoulou Z², Soares S³, Barbosa C¹.

 

Abstract

Deep endometriosis presenting with ascites and preserved fertility is an unusual combination. This report describes a unique case of deep endometriosis and primary infertility, with a successful pregnancy after an optimal surgical approach and personalized ovarian stimulation protocol for in vitro fertilization, which shows the importance of a multidisciplinary approach in these patients.