• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4971-4975
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• 2015

Background: Several methods have been presented for the evaluation of the endometrium in patients with abnormal uterine bleeding, which include minimal invasive and invasive approaches such as diagnostic curettage or endometrial biopsy by Pipelle. Many studies have been performed in order to compare two methods; diagnostic curettage and outpatient endometrial biopsy. This investigation compared sampling adequacy, endometrial histopathology, failure rates, duration and costs between diagnostic curettage in a hospital and endometrial biopsy. Materials and Methods: This single blind clinical trial was performed on 130 patients older than 35 years who was referred to Amir training hospital in 2013 for elective diagnostic curettage because of abnormal uterine bleeding. For all patients eligible for the study, an endometrial sample by Pipelle was taken without anesthesia or dilatation. Then under general anesthesia diagnostic curettage was performed by sharp curette. Sampling duration was calculated and both samples were sent to the same pathologist. The diagnostic values of two methods in the diagnosis of normal endometrium, endometrial hyperplasia and carcinoma were compared. The costs of these two methods were also compared. Data analysis was performed by SPSS (version 16.0) software. Chi-Square, Fisher, and Pearson tests were used and were considered statistically significant at P values less than 0.05. Results: Two methods were agreed upon 88% of sampling adequacy and 94% of pathological results. Specificity of 100% and sensitivity of 90% for detection of proliferative endometrium, secretory endometrium, simple hyperplasia without atypia and 100% for cancer were recorded. Pipelle diagnostic accuracy in comparison with curettage, have been reported over 97%, so the failure rate in this study was below 5%. Sensitivity of Pipelle for detection of atrophic endometrium was reported below 50%. Duration and cost was lower in Pipelle versus curettage. Conclusions: It is concluded that due to high agreement and cohesion coefficient between curettage and Pipelle on the issue of sampling adequacy, histopathology finding (except atrophic endometrium), low failure rate, duration of sampling and cost, Pipelle can be introduced as a suitable alternative of diagnostic curettage.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.1
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• pp.15-21
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• 2003

Objective : Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citratetreated infertile women with luteal phase defect. Methods : The endometrial samples from infertile women with luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. Results: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). Conclusion: In this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5935-5939
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• 2013

Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. ${\beta}$-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of ${\beta}$-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P<0.001), but a lower rate than endometrial adenocarcinoma (72% vs. 96.2%, respectively, P<0.001). In benign endometrial hyperplasia, high ${\beta}$-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.

• Development and Reproduction
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• v.4 no.1
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• pp.101-108
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• 2000

Objectives: The pleiotrophin (PTN) and midkine (MK) are secreted heparin-binding neurokines that share 50％ sequence homology. PTN and MK are expressed in the range of primary human tumors. The association of PTN and MK with carcinogenesis, enhancement of plasminogen activator activity and angiogenic factor are reported. Patients with endometriosis are characterized by the ability of the endometrium to implant; angiogenic and growth factors may play a significant role in the pathogenesis of endometriosis. To test the hypothesis that higher expression of PTN and MK in endometrium from women with endometriosis might be increase angiogenesis and growth ectopic endometriosis implants, we investigated PTN and MK expression by quantitative and competitive polymerase chain reaction (QC-PCR) in endometrium from women with and without endometriosis throughout the menstrual cycle. Design: MK and PTN mRNA expression in endomeoium from women with endometriosis and control patients without endometriosis were determined by QC-PCR throughout the menstrual cycle. Methods: Endometrial tissue was obtained from 25 patients with severe endometriosis and 30 patients without endometriosis undergoing hysterectomy or endometrial biopsy. Stage of endometrial cycle and a diagnosis of endometriosis were confirmed histologically. Total RNA was extracted and reverse transcribed into c-DNA. QC-PCR was performed to evaluate PTN and MK mRNA expression. Results were analysed by Post Hoc test. Results: MK and PTN were expressed throughout the menstrual cycle in both groups. MK expression was higher in follicular phase than luteal phase in endometrium from normal women. endometrium from endometriosis patients showed increased expression of PTN and MK compared to endometrium from normal women in the luteal phase (p<0.05). Conclusion: Our results suggest that uterine endometrium from women with endometriosis expresses higher levels of MK and PTN than endometrium from normal women during luteal phase. Increased MK and PTN expression may be related to the initiation of ectopic endometrial implants and their subsequent peritoneal invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10067-10070
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• 2015

Background: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. Materials and Methods: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. Results: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. Conclusions: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.126-134
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• 2011

Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence $in-situ$ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.

• Annals of Geriatric Medicine and Research
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• v.22 no.4
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• pp.189-193
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• 2018

Background: This study aimed to reveal the clinicopathologic features and causes of bleeding in older patients with postmenopausal bleeding (PMB) and to investigate the correlation between the ultrasonographic findings and etiology of PMB. Methods: We retrospectively analyzed the causes and clinical characteristics of PMB in 498 patients who were diagnosed between January 2007 and December 2017. The population with PMB was divided into 2 groups according to age: Group A (n=204) included individuals more than 65 years of age and group B (n=294) included those less than 65 years of age. Clinical characteristics such as age, parity, underlying conditions, previous surgical history, and previous menopausal hormone therapy were compared between the groups. Cervical cytology testing and transvaginal ultrasonography were performed in all patients with PMB. Endometrial biopsy was performed in all cases of endometrial thickness ${\geq}5mm$. Results: We examined 498 patients with PMB. In group A, atrophic endometrium (n=125, 61.27%) was the most common cause of PMB. Twenty-three patients had gynecological malignancy (cervical cancer: n=12, 5.88%; endometrial cancer: n=8, 3.42%; ovarian cancer: n=3, 1.46%), and 30 patients had benign gynecological disease (endometrial polyp: n=10, 4.90%; submucosal myoma: n=6, 2.94%; uterine prolapse: n=7, 3.42%; cervical dysplasia; n=5, 2.45%; cervical polyp: n=2, 0.98%). Forty patients had endometrial thickness ${\geq}5mm$. Eight patients were diagnosed with endometrial cancer. All cases of endometrial cancer were diagnosed with endometrial thickness >10 mm. Conclusion: Atrophic endometrium was the most common cause of PMB in both groups, and approximately 12% of cases were associated with gynecological malignancy in older patients.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7635-7638
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• 2013

Background: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. Materials and Methods: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. Results: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was $58.7{\pm}1.1$. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). Conclusions: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.1
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• pp.42-46
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• 2011

Objective: This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). Methods: We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, menstrual status from 117 women with PCOS. Statistical analysis was performed with chi square and t-test, p-value<0.05 was considered as statistically significant. And receiver operating characteristic curve was used to find predictable clinical factors for endometrial disease and to decide the cuff off values. Results: In 117 women with PCOS, endometrial histologic profiles are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%), 6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were significantly related with endometrial disease, p=0.013 and p=0.001, respectively. At the cut off level of 25.5 years in age, sensitivity and specificity predicting for endometrial disease were 70.4% and 55.6%, respectively (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity and specificity were 77.8% and 56.7%, respectively (p=0.000). Conclusion: In women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4% and 1.7%. The age and endometrial thickness may be used as clinical determining factors for endometrial biopsy.