Protein inhibitor of activated STAT-3 (PIAS-3) is down-regulated in eutopic endometrium of infertile women with endometriosis by stromal-derived cxcl10 (IP-10)

P-484 Wednesday, October 22, 2014 PROTEIN INHIBITOR OF ACTIVATED STAT-3 (PIAS-3) IS DOWNREGULATED IN EUTOPIC ENDOMETRIUM OF INFERTILE WOMEN WITH ENDOMETRIOSIS BY STROMAL-DERIVED J.-W. Jeong,b J.-Y. Yoo,b CXCL10 (IP-10). B. A. Lessey,a J. F. Langenheim,a A. T. Fazleabas,b S. L. Young,c C. Tayade.d aDepartment of Obstetrics and Gynecology, Greenville Health System, Greenville, SC; b Department of Obstetrics and Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, MI; cDepartment of Obstetrics and Gynecology, University of North Carolina Chapel Hill, Chapel Hill, NC; dDepartment of Biomedical and Molecular Sciences, Queens University, Kingston, ON, Canada. OBJECTIVE: Activation of STAT-3 appears central to the inflammatory phenotype of eutopic endometrium in women with endometriosis. Our objective was to determine how changes in the eutopic endometrium contribute to infertility. DESIGN: Case-control study of protein levels of Protein Inhibitor of Activated STAT-3 (PIAS-3) and p-STAT3 in eutopic endometrium from women with endometriosis. Cytokine analysis was performed on media from cultured endometrial stromal cells (ESCs) from normal and endometriosis subjects. Ishikawa cells were used to study cytokine/chemokine effect on PIAS-3. MATERIALS AND METHODS: The activation of STAT3 and levels of PIAS-3 were compared in endometrium from women with and without endometriosis using Western blot and immunohistochemical analysis (IHC). ESCs were cultured from similar patients and cytokines measured using Bioplex asay. Ishikawa cells were treated with the interferon-g induced CXCL10 (IP-10) and PIAS-3 mRNA assessed by qRT-PCR. RESULTS: PIAS-3 is a negative regulator of pSTAT3 activity. In our samples pSTAT-3 was elevated in eutopic endometrium of infertile women with endometriosis. CXCL10 was significantly increased (p < 0.05) in ESC cells derived from endometriosis patients compared to normal controls. Activation of pSTAT3 was significantly increased and expression of PIAS-3 was significantly decreased in epithelial compartment in eutopic endometrium from women with endometriosis compared to controls by western blot and IHC. Ishikawa cells treated with CXCL10 had an 8-fold decrease in PIAS-3 mRNA expression within 1 hr. CONCLUSION: These results demonstrate for the first time that PIAS-3 is reduced in women with endometriosis and that CXCL10 down-regulates endometrial PIAS-3 expression. The activation of pSTAT3 associated with inflammation and infertility appears to be due, in part, to aberrant regulatory pathways involving over-expression of stromal CXCL10. Activation of pSTAT3 and down-stream events affecting endometrial receptivity appears to be a central feature of endometriosis-related infertility. STAT3 and PIAS-3 represent new therapeutic targets for the treatment of this disease. Supported by: We would like to thank the Human Female Reproductive Tract Biorepository and the Spectrum Health Medical Group, Department of Obstetrics, Gynecology and Reproductive Biology and Angela Houwing at GHS. This work was Supported by NIH R01 HD067721 to S.L.Y and B.A.L and NIH R01 HD057873 to J.W.J. FEMALE REPRODUCTIVE SURGERY P-485 Wednesday, October 22, 2014 HYSTEROSCOPIC ADHESIOLYSIS FOR ASHERMAN’S SYNDROME: LIVE-BIRTH RATE AND FACTORS AFFECTING REPRODUCTIVE OUTCOME AFTER SURGERY. W.-S. Han. Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. OBJECTIVE: The objective of this study is to investigate the impact of various factors of hysteroscopic adhesiolysis of Asherman’s syndrome on live-birth rate after surgery. DESIGN: It is a retrospective study. MATERIALS AND METHODS: Fifty four women who were suffered from infertility or recurrent spontaneous abortion were selected. Medical records were retrospectively analyzed. The independent variables were degree of intrauterine adhesion, surgical technique, use of intrauterine Foley catheter after adhesiolysis, insertion of intrauterine device after adhesiolysis, and dose of postoperative estradiol after adhesiolysis. Multivariate analysis as well as univariate analysis was performed.

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ASRM Abstracts

RESULTS: Among the fifty four women, seventeen women gave livebirth. The degree of intrauterine adhesion was found to be a sole factor affecting the live-birth rate by univariate and multivariate analysis. The mechanical dissection with scissors had been resulted a higher live-birth rate against resectoscopic electrosurgery, but the difference was not statistically significant. Also use of intrauterine Foley catheter, insertion of intrauterine device, and dose of postoperative estradiol were not significantly affecting to reproductive outcome after hysteroscopic adhesiolysis.

Multivariate analysis of factors affecting live-birth rate

Factors Grade Surgical technique Foley Intrauterine device Estrogen

Coefficient 95% confidence estimate Odd ratio interval p-value -0.566 -0.295 0.522 -9.115 -0.284

0.271 0.507 3.332 0.000 0.519

-0.709-1.251 -1.350-2.364 1.664-4.999 -35214.1-35214.1 -1.086-2.214

0.009 0.473 0.157 0.999 0.423

CONCLUSION: The degree of intrauterine adhesion is the most important factor affecting the live-birth rate after hysteroscopic adhesiolysis. The uses of intrauterine Foley catheter after hysteroscopic adhesiolysis, insertion of intrauterine device after hysteroscopic adhesiolysis and dose of postoperative estradiol have no significant impact to live-birth rate.

P-486 Wednesday, October 22, 2014 THE EFFECT OF PRESENCE AND MANAGEMENT OF HYDROSALPINX ON MISCARRIAGE IN IVF. H. Harb, F. Al-rshoud, A. Coomarasamy. School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, West Midlands, United Kingdom. OBJECTIVE: To investigate the effect of hydrosalpinx on miscarriage. DESIGN: Systematic review and meta-analysis of randomised controlled trials and observational studies. MATERIALS AND METHODS: Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inceptionMarch2014) in all languages, together with reference lists of retrieved papers. Studies comparing miscarriage rate in women with hydrosalpinges with women without hydrosalpinges were included. Moreover, studies in which women underwent trearment for hydrosalpinx were identified. The outcome of interest was miscarriage. Study selection was conducted independently by two reviewers. The Cochrane scale for the randomised trials, and the Newcastle-Ottawa Quality Assessment Scale were used for quality assessment. Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed using RevMan. RESULTS: This review includes 22 studies. Pooling of results from 11 studies that reported miscarriage as an outcome showed a 2-fold increase in the risk of miscarriage in women with hydrosalpinges compared to women without hydrosalpinx (OR¼2.25, 95% CI 1.67, 3.03, p¼0.00001). There was moderate variation across studies as indicated by an I2 value of 33% (p¼0.13). Pooling of results from 6 randomised controlled trials that reported miscarriage as an outcome showed a reduction in miscarriage in women who had treatment for hydrosalpinges in comparison with women with untreated hydrosalpinx ( OR¼0.39, 95% CI 0.17- 0.88, p¼0.02). There was little variation across studies as indicated by an I2 value of 0% (p¼0.58).Pooling of results from 5 observational studies that reported miscarriage as an outcome showed a reduction in miscarriage in women who had treatment for hydrosalpinges in comparison with women with untreated hydrosalpinx ( OR¼0.34, 95% CI 0.17- 0.88, p¼0.0003). There was little variation across studies as indicated by an I2 value of 0% (p¼0.68). CONCLUSION: There is evidence to suggest that the presence of hydrosalpinges increases the risk of miscarriage in IVF/ICSI pregnancies. Treatment for hydrosalpinges may reduce the risk of miscarriage.

Vol. 102, No. 3, Supplement, September 2014