Macrophages and Natural Killer Cells Characteristics in Variously Colored Endometriotic Lesions: A Cross-Sectional Analytic Study.

Background: Dysregulation of the immune response contribute to a significant role in endometriosis. This research examined macrophages and natural killer (NK) cells numbers in endometriotic lesions and their association with the different lesion colors: red, black, and white. To investigate the amount of the CD68 and CD56 in eutopic endometrium and different type of the endometriotic lesions. Materials and Methods: A cross-sectional analytic study was conducted. Women suspected endometriosis requiring laparoscopic surgery between July 2016 and January 2017 were recruited. Their lesions were classified as red, black, or white and these lesions were excised by standard laparoscopic surgery. Twenty-four endometriotic lesions from each color group were obtained from 45 women who met the inclusion criteria. One type of lesion was collected from 25 women. Two different lesion types and three-color lesion types were collected from the same women in 13 and 7 subjects, respectively. Immunohistochemistry staining with anti-human mouse cluster of differentiation (CD) 68 monoclonal antibody for macrophages and mouse anti-human CD56 monoclonal antibody for NK cells were performed. Results: The number of CD68 macrophages in red lesions was higher than in black and white lesions [median (25th-75th percentile); 10 (5-19.4), 0 (0-6.9), 0 (0-2.5) cells per mm2, respectively, adjusted P=0.001 for red vs. black lesions and red vs. white lesions, and adjusted P=1.000 for black and white lesions]. The number of CD56 NK cells was not significantly different among red, black, and white lesions [median (25th-75th percentile; 5 (2-16.5), 3.8 (0-14.4), 1.3 (0-6.9) respectively, adjusted P=1.000 for red vs. black lesions and black vs. white lesions, and adjusted P=0.617 for red vs. white lesions]. Conclusion: The dynamic changes in the immune cells in ectopic endometrium were specific to the macrophages but not to the NK cells, as demonstrated by the highest number of CD68 macrophages in the red lesion, the earliest established ectopic endometrium. NK cells in endometriosis may have a role in the uterus.

Outcomes of Laparoscopic Partial Cystectomy of Bladder Endometriosis: A Report of 18 Thai Women.

Aim: To determine the outcomes of laparoscopic partial cystectomy (LPC) for bladder endometriosis (BE). Methods: This was a retrospective study using medical records of women who underwent LPC for BE between January 2009 and December 2017. Demographic characteristics, surgical findings, including surgical site and size of the bladder lesion, endometriosis at other locations, and pre- and postoperative hormonal treatment data were collected. Results: We analyzed data of 18 women with full-thickness BE. The patients had a mean age of 34 (range, 26-45) years and body mass index of 21.6 (range, 16.1-25) kg/m2. All women had dysmenorrhea. Other symptoms noted include dysuria, gross hematuria, and infertility. BE with a mean diameter of 2.7 cm (range, 1-5) was most commonly found at the posterior wall of the bladder (94.4%). Peritoneal endometriosis (94.4%), endometrioma (33.3%), and deep endometriotic nodules (22.2%) in the posterior compartment were also found. No surgical complications were observed. Postoperative hormonal treatment was administered to 14 (77.8%) patients. All symptoms improved after the surgery. No recurrence was found after 30 (range, 12-74) months of follow-up. Conclusion: LPC is an effective treatment option for BE.

Effects of Ethinyl Estradiol in Combined Oral Contraceptives on Cell Proliferation and Apoptosis in Ectopic Endometrial Tissue: A Randomized Controlled Study.

Objective: Since endometriosis is an estrogen-dependent disease; therefore, combined oral contraceptives (COCs) may not be the best choice for the treatment of endometriosis. The objective of the present study was to investigate the effects of ethinyl estradiol (EE) and desogestrel (DSG) in COCs on cell proliferation and apoptosis in ectopic endometrial tissue as compared to DSG alone. Materials and methods: Forty-five women of reproductive age with at least one endometriotic cyst were recruited into this single-blind randomized controlled trial study and randomly divided equally into three groups. EE-DSG and DSG groups received EE (0.03 mg) and DSG (0.15 mg) or DSG alone daily for 28-35 days before surgery. The control group was prescribed nothing. Endometriotic cyst tissues were collected during ovarian cystectomy for immunohistochemistry. Results: Levels of Ki-67 positive cells in the ectopic endometrial tissue of the EE-DSG group were significantly higher than the DSG group (median [IQR]; 1.4[1.2] vs 0.6 [0.7], P <0.016). There were significantly more TUNEL-positive cells in the EE-DSG group compared to the DSG group (median [IQR]; 2.8[0.7] vs 1.8[1.4], P < 0.016, respectively). Moreover, the number of TUNEL-positive cells in the EE-DSG and DSG groups were significantly higher than the control (median [IQR]; 2.8[0.7] vs 0.2[0.2] and 1.8[1.4] vs 0.2[0.2], P <0.016). The levels of cells that positively stained for Bcl2 were not different among all groups. Conclusion: Progestin alone increased cell apoptosis in ectopic endometria. However, concurrent EE in COCs enhanced proliferation and promoted a greater apoptotic effect in ectopic endometria compared to progestin alone.

Effect of combined contraceptive pill on immune cell of ovarian endometriotic tissue.

BACKGROUND: Dysregulation of immune response is associated with development of endometriosis. The study aim was to evaluate effect of combined oral contraceptive pills (COCs) consisting of ethinyl estradiol (EE) and desogestrel on the expression of macrophage, natural killer cells, and regulatory T cells of ovarian endometriotic cysts. METHODS: Endometriotic cyst wall tissues were collected from women with endometriosis who were treated (n = 22) with COCs (one table per day of EE 0.03 mg and desogestrel 0.15 mg administered for 28 to 35 days before surgery) or untreated (n = 22). The tissues were collected from endometriotic cyst wall during laparoscopic or laparotomy ovarian cystectomy. Immunohistochemistry for anti-CD68, anti-CD56, and anti-forkhead-winged helix transcription factor (FoxP3), a marker for macrophages, natural killer cells, and regulatory T cells, respectively, were investigated. RESULTS: The median (interquartile range [IQR]) number of anti-CD68 positive cells in the COC group was significantly lower than in the untreated group (12.7; 4.9-19.3) versus 45.7 (26.0-70.7), p < 0.001). Tissue infiltration of anti-CD56 positive cells in endometriotic cyst was significantly higher after the treatment when compared with tissue from untreated group (42.9, 27.4-68.9 versus 25.3 (14.1-37.3; p = 0.009). The number of regulatory T cells was also significantly increased in the COC group (6.3, 2.8-15.5) versus 0 (0-1.8; p < 0.001). CONCLUSIONS: The effects of COC, containing EE 0.30 mg with desogestrel 0.15 mg, on the immune system was demonstrated by a significant decrease in the number of macrophages and an increase in natural killer and regulatory T cells.

Successful pregnancy outcome in Herlyn-Werner-Wunderlich syndrome with pyocolpos: A case report and literature review.

The presence of pelvic pain, a pelvic/paravaginal mass, and purulent vaginal discharge in primigravida should raise the possibility of obstructed hemivagina and uterine didelphys. Though conservative management could result in successful pregnancy outcomes, early excision of vaginal septum and adequate drainage offer a shorter course of management and complication avoidance.

Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review.

Most cases of Klinefelter syndrome (KS) have 47,XXY karyotype. We reported the first case of 46,XX/47,XXY KS whose genital ambiguity was detected prenatally with postnatal confirmation of the mosaicism and ovotesticular disorder of sex development (OT-DSD). The paternal origin of the extra X chromosome was identified using trio cytogenomic single-nucleotide polymorphism array. Additional 18 cases were also reviewed. The clinical presentation of 46,XX/47,XXY is age-dependent with two age peaks, including ambiguous genitalia during infancy and gynecomastia with or without cyclical hematuria and left scrotal pain and mass in adolescence. The 46,XX is the predominant karyotype both in peripheral blood and gonadal tissue. The risk of germ cell tumor is very high throughout life in these individuals. Individuals with 46,XX/47,XXY mosaicism should be treated more as OT-DSD other than a simple mosaic KS. A multidisciplinary approach and long-term monitoring are necessary.

Differential expressions of estrogen and progesterone receptors in endometria and cyst walls of ovarian endometrioma from women with endometriosis and their responses to depo-medroxyprogesterone acetate treatment.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) is an injectable progestin contraceptive that provides a highly effective reduction of pelvic pain in women with endometriosis. Despite its wide use to treat pain associated with endometriosis, its precise mechanisms of action remain unclear. The aims of this study were to investigate the differential expressions of estrogen receptors (ERs), and progesterone receptors (PRs) in endometria and ovarian endometrioma cyst walls of women with endometriosis with and without DMPA treatment. METHODS: Endometria and cyst walls of endometrioma were obtained from 25 to 45 year-old women who suffered from endometriosis and had ovarian endometrioma with the size ≥3 cm. The expression levels of ERs and PRs and the numbers of ER- and PR-positive cells before and after treatment with DMPA were evaluated by Western blot, real-time PCR, and immunohistochemistry. RESULTS: The levels of ERα and ERß expression, their corresponding mRNAs, and numbers of ERα- and ERß-immunoreactive cells in stroma and glands of endometria of the DMPA group were significantly decreased when compared with those of the untreated groups (p < 0.05). In contrast, the levels of PRA/B expression and numbers of PRA/B positive cells in stroma and number of PRB positive cells in stroma and endometrial glands were significantly increased in endometria of the DMPA group when compared with those of the untreated groups. However, in cyst wall the expression levels of these proteins, their corresponding mRNAs, and immonoractive cells were low compared to those in endometria, and DMPA-treatment did not cause any significant changes in these parameters. CONCLUSION: These data indicated that DMPA could upregulate the expressions of PRA/B and down-regulate ERα and ERß in endometria but not in cyst walls from women with endometriosis.

The Effects of Dienogest on Macrophage and Natural Killer Cells in Adenomyosis: A Randomized Controlled Study.

BACKGROUND: Progestin has been used for symptomatic treatment of adenomyosis, although its effect on the immune system has not been studied. The aim of this study was to investigate the changes of macrophage and natural killer (NK) cell infiltration in tissues obtained from women with adenomyosis who did or did not receive oral progestin dienogest. MATERIALS AND METHODS: In this randomized controlled clinical trial study, 24 patients with adenomyosis who required hysterectomy were enrolled. Twelve patients received dienogest 28-35 days before surgery, and the other 12 patients were not treated with any hormones. The endometrial and myometrial tissue samples were immediately collected after hysterectomy, and immunohistochemistry for a macrophage marker (CD68) and a NK cells marker (CD57) was performed. RESULTS: The number of CD57 cells was significantly increased in endometrial glands of the treated group compared to the untreated group (P=0.005) but not in stroma in the endometrium of the treated patients (P=0.416). The difference in the number of CD68 cells was not statistically significant between treated and untreated groups in the endometrial glands (P=0.055) or stromal tissues (P=0.506). CONCLUSION: Administration of oral progestin dienogest to patients with adenomyosis increased the number of uterine infiltrating NK cells in glandular structure of eutopic endometrium. The differential effects of progestin on NK cells depended on the site of immune cell infiltration. The effects of oral progestin on uterine NK cells in adenomyosis have the potentials to be beneficial to pregnancies occurring following discontinuation of treatment in terms of embryo implantation and fetal protection (Registration number: TCTR20150921001).

DMPA Suppresses Cell Proliferation and Enhances Cell Apoptosis of Eutopic Endometrium in Women with Endometriosis: A Randomized Controlled Study.

Background: Although Depo-medroxyprogesterone acetate (DMPA), an injectable contraceptive progestin, is very effective for pain relief and prevention of recurrence in women with endometriosis, there is no report on the mechanism of this medication about cell proliferation and apoptosis. Objective: To investigate the effects of DMPA on cell proliferation and apoptosis in the eutopic endometrium of women with endometriosis. Material and Method: A randomized controlled study was conducted in 28 women with endometriosis. The DMPA-treated group included 14 women who were scheduled to undergo laparoscopic surgery after 150 mg of DMPA injections. The control group included 14 women who were scheduled to undergo the surgery without DMPA injection. The endometrial tissue was obtained from each woman by endometrial aspiration before surgery. The ELISA formats of PCNA and the quantitative colorimetric analysis of TUNEL were used for estimating cell proliferation and apoptosis of the eutopic endometrium. Results: There were no differences in the women characteristics between the two groups. The relative level of cell proliferation was significantly less in the DMPA than the control groups (1.08±0.57 vs. 1.73±0.50, p = 0.014). Whereas the relative level of cell apoptosis was greater in the DMPA group than that in the control group (1.12±0.36 vs. 0.82±0.39, p = 0.034). Conclusion: Three months of 150 mg DMPA treatment could suppress cell proliferation and enhance cell apoptosis of the eutopic endometrium of women with endometriosis.

Labial aggressive angiomyxoma associated with endometrial hyperplasia and uterine leiomyoma: a case report and review of the literature.

A case of aggressive angiomyxoma of the left labia majora in a 48-year-old woman with clinically presenting progressive enlarged labial mass is reported. The histopathological examination of the lesion characterized was by fibroblasts, myofibroblasts in the myxoid stroma with prominent thick-walled blood vessels. The uterus showed intramural leiomyomata with simple hyperplastic endometrium. The labial mass, uterine leiomyoma and endometrial hyperplasia were immunoreactive for estrogen and progesterone receptors. Clinical and pathologic features with briefly reviewed relevant literatures were discussed. This is the first reported description in the literature of synchronous labial angiomyxoma, endometrial hyperplasia, and uterine leiomyoma.

Can adiponectin predict abnormal glucose tolerance in Thai women with polycystic ovary syndrome?

AIM: To evaluate whether adiponectin levels could predict abnormal glucose tolerance (AGT) in Thai women with polycystic ovary syndrome (PCOS). METHODS: A 75-g oral glucose tolerance test (OGTT) with fasting adiponectin and insulin (FI) blood sampling in 170 women with PCOS were performed consecutively. RESULTS: The prevalence of AGT was 45.9%. The body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose and 2-h postload glucose were greater in the PCOS women with AGT than those without AGT (P<0.001). In addition, the PCOS women with AGT had more severe insulin resistance (IR) and lower adiponectin levels than those without AGT. However, the area under the ROC curve of adiponectin and insulin in predicting AGT was smaller than that of homeostatic model of IR (HOMA-IR) (P<0.01). The arbitrary cut-off values at 12 ug/mL of adiponectin, 10 microiu/mL of FI and 2 of HOMA-IR showed the sensitivity and specificity of 80.8% and 33.7%; 87.2% and 34.8%; and 89.7% and 31.5%, respectively. With these cut-off points, 46 (27.1%), 42 (24.7%) and 37 (21.8%) women, respectively, could be eliminated from performing OGTT. However, 15 (19.2%), 10 (12.8%) and 8 (10.3%), respectively, missed the diagnosis. In addition, with WHR and acanthosis nigricans adjustment, HOMA-IR, but not adiponectin, was a significant predictor of AGT. CONCLUSION: Our study demonstrated that almost half of the women with PCOS had AGT. Adiponectin levels were significantly lower in the PCOS women with AGT than those without AGT. However, adiponectin was not shown to be as strong a predictive factor and might not be such an excellent screening test as FI and HOMA-IR.

Laparoscopic nephrectomy, hysterectomy and rectovaginal endometriotic mass removal in a single session.

The authors reported the first case of endometriosis with ureteral involvement causing nonfunctioning kidney, which was managed by laparoscopic nephrectomy, hysterectomy, and endometriotic mass removal in a single session.

Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling.

OBJECTIVE: To evaluate ovarian reserve assessed by hormones and sonography in women with polycystic ovary syndrome (PCOS) undergoing laparoscopic ovarian drilling (LOD). METHODS: This was a cross-sectional study. Twenty-one PCOS women undergoing LOD were enrolled in the study (the LOD group). Their day-3 anti-Müllerian hormone (AMH), inhibin B, follicle-stimulating hormone (FSH) levels, antral follicles count (AFC) and summed ovarian volume representing ovarian reserve were compared with those of PCOS women who did not undergo LOD (the PCOS group) and those of normal ovulatory women (the control group). RESULTS: There were no differences in age and body mass index between groups. AMH levels seemed to be lower in the LOD (4.60 +/- 3.16 ng/ml) than in the PCOS (5.99 +/- 3.36 ng/ml) groups, but did not reach statistical significance. Day-3 FSH levels were significantly higher and AFC was significantly lower in the LOD than in the PCOS group. AMH levels, AFC and summed ovarian volume were significantly greater, but FSH was significantly lower, in the PCOS group compared with the control group. There were no differences in inhibin B levels between groups. CONCLUSION: This study showed that ovarian reserve assessed by hormonal levels and sonography seems to be lower in the LOD than in the PCOS group. The PCOS women both with and without LOD had significantly greater ovarian reserve than the age-matched controls having normal ovulatory menstruation.

Prevalence and clinical predictors of endometrial hyperplasiain anovulatory women presenting with amenorrhea.

The aim of the present study was to determine the prevalence and clinical predictors of endometrial hyperplasia (EH) in amenorrheic women with anovulation. Fifty-seven women were enrolled in the study. Of these, 43 were diagnosed to have polycystic ovary syndrome (PCOS) and 14 to have idiopathic anovulation. All women received transvaginal sonography to assess endometrial thickness (ET), patterns and abnormalities. At the same time, an endometrial biopsy was taken using a Pipelle instrument. The women's age, body mass index (BMI) and waist-to-hip ratio (WHR) were 32.0+/-6.0 years, 27.3+/-6.5 kg/m(2) and 0.82+/-0.06 (mean+/-standard deviation), respectively. Twenty (35.1%) and 19 (33.3%) women were classified as obese by BMI and WHR, respectively. Hypertension was found in 17 (29.8%) women. The prevalence of EH was 45.6%. Most cases were simple EH, and only one (1.75%) was simple EH with atypia. EH prevalence was 48.8% and 35.7% in PCOS and idiopathic anovulatory women, respectively. Age, BMI, WHR and ET did not predict EH, whereas the endometrial hyperechogenic pattern was a clinical predictor of EH with borderline significance. In conclusion, this study demonstrated that almost half of the anovulatory women with amenorrhea had EH and no significant predictor was found. In view of these findings, an endometrial biopsy should be performed in all women with this disorder.

Acanthosis nigricans: clinical predictor of abnormal glucose tolerance in Asian women with polycystic ovary syndrome.

The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS). Data from the record forms and electronic form of 121 PCOS women who consecutively attended the Reproductive Endocrinology and Infertility Unit were reviewed. In accordance with the unit's guidelines, all women received a physical examination, had anthropometric measurements taken and underwent as a 75-g oral glucose tolerance test after diagnosis. Their age, body mass index (BMI) and waist/hip ratio (WHR) was 29.1+/-6.1 years, 27.4+/-6.8 kg/m2 and 0.84+/-0.6 (mean+/-standard deviation), respectively. The prevalence of AGT was 42.9%, with 1.6% having impaired fasting glucose, 32.3% having impaired glucose tolerance and 9.1% having type 2 diabetes mellitus. The PCOS women with acanthosis nigricans had significantly higher BMI, WHR, fasting glucose, 2-h post-load glucose, fasting insulin, 2-h post-load insulin and prevalence of AGT compared with those without acanthosis nigricans. By logistic regression analysis, acanthosis nigricans and WHR were independent predictors for AGT, with an odds ratio (95% confidence interval) of 2.7 (1.1-7.1) and 10.1 (1.8-20.7), respectively. In conclusion, acanthosis nigricans was demonstrated as a predictive factor for AGT in Asian women with PCOS.