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The eutopic endometrial response to chorionic gonadotrophin is abnormal in a baboon model of endometriosis: a possible explanation for endometriosis associated implantation failure
ANOVA/unpaired t-test or c-square. Differences were considered significant at P<0.05. RESULTS: Day 15 implantation rates of embryos generated from DYNAMIC culture (81%) were similar to IN VIVO-derived controls (90%) and significantly greater than embryos derived from STATIC culture (65%). Placental weights were similar between all groups, yet fetal weight was significantly lower in DYNAMIC (2668.1 mg; meanSE) and STATIC (2608.2 mg) compared to IN VIVO (2946.1 mg). Fetal morphological ages were similar between groups. Placental H19 gene expression was significantly reduced in embryo culture groups compared to IN VIVO; placental IGF2 expression was similar between IN VIVO and DYNAMIC, whereas STATIC placental IGF2 expression was significantly reduced compared to IN VIVO. CONCLUSIONS: Embryos derived from dynamic culture have implantation rates similar to in utero-derived embryos, and better than static culturederived embryos. Reduced fetal weight results from embryo culture and placental gene expression is different between in utero-derived and cultured embryos. Lastly, placental imprinted gene expression can be influenced differentially by static versus dynamic culture conditions of early embryos. Supported by: NIH and USDA.
Monday, November 10, 2008 11:00 am O-4 IN THE TRANSITION TO MENOPAUSE: WHICH COMES FIRST, HOT FLASHES OR DEPRESSIVE SYMPTOMS? M. D. Sammel, H. Lin, E. W. Freeman. Biostatistics and Epidemiology, Univ. of Pennsylvania, Philadelphia, PA; Center for Res. in Reprod. and Women’ Health, Univ. of Pennsylvania, Philadelphia; Obstetrics and Gynecology, Univ. of Pennsylvania, Philadelphia. OBJECTIVE: To evaluate the incidence and timing of hot flashes and depressive symptoms during the menopausal transition. We examine whether these 2 symptom processes are operating independently or whether symptoms co-occur. In those women who experience both symptoms we identified which symptom was reported first. DESIGN: Prospective Cohort. MATERIALS AND METHODS: The experience of 170 symptom free women at baseline from the ongoing PENN ovarian aging cohort were evaluated. Reports of hot flashes and depressive symptoms were assessed annually beginning in 1997 using validated questionnaires. The incidence of hot flashes and depression are estimated, and statistical tests of independence between these symptoms was computed using chi-squared methods. Additional comparisons looked at which symptom was reported first and the observed frequencies were compared to expected quantities under the assumption of independence. RESULTS: Women were aged 35-47, average 41.9 (þ/-3.4) years, with regular menstrual periods for 3 months enrollment. Reproductive hormones reflected pre-menopausal levels, estradiol average 43.6 (þ/-31.9), FSH average 8.0 (þ/-4.5). Forty-one percent were African American and 59% Caucasian. Over 10 years these women contributed 1220.6 person-years of followup. The incidence of hot flashes was statistically significantly increased in these women compared to the incidence of depression, 62.5% versus 50% respectively, chi-squared test of homogeneity¼14.3, p-value¼0.0002. Women were more likely to experience both symptoms, whether sequentially or concurrently, than expected if these processes were independent, Chisquare¼18.5; df¼3; p¼0.0007. Seventy women (41.2%) reported experiencing both hot flashes and depressed mood. Depressive symptoms occurred first, prior to reports of hot flashes for 23.5% of women, this was 2.1 times higher than would be expected if these 2 symptoms operated independently. Only 7.7% of women reported hot flashes that proceeded depressive symptoms, this was 31% fewer women than expected under independence, RR¼0.69. CONCLUSIONS: Large numbers of women in their late reproductive years report symptoms of hot flashes and depressed mood. Symptoms of depression were more likely to occur first, prior to reports of hot flashes. This pattern is contrary to the theory that hot flashes are a likely cause of depression. Both processes have been associated with changes in reproductive hormones, but these patterns of reporting indicate the potential for different underlying mechanisms. Supported by: R01-AG012745.
S2
Abstracts
Monday, November 10, 2008 11:15 am O-5 THE EUTOPIC ENDOMETRIAL RESPONSE TO CHORIONIC GONADOTROPHIN IS ABNORMAL IN A BABOON MODEL OF ENDOMETRIOSIS: A POSSIBLE EXPLANATION FOR ENDOMETRIOSIS ASSOCIATED IMPLANTATION FAILURE. J. M. Hastings, R. A. Sherwin, P. A. Mavrogianis, K. S. Jackson, A. M. Sharkey, A. T. Fazleabas. Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL; Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United Kingdom; Pathology, University of Cambridge, Cambridge, United Kingdom. OBJECTIVE: To test the hypothesis that the endometrial response to Chorionic Gonadotrophin (CG) the major early, embryo derived signal, is altered by the presence of endometriosis. DESIGN: We assessed endometrial morphology, protein and gene expression changes occurring after in vivo intra-oviductal CG treatment of baboons with endometriosis. MATERIALS AND METHODS: Endometriosis was experimentally induced in female baboons (n¼5) by intraperitoneal inoculation with menstrual endometrium. Three and six months following disease induction, human CG (hCG; 30IU/day) was infused into the oviduct via a subcutaneous osmotic mini-pump and polyurethane cannula. HCG infusion began on day 6 post ovulation (PO). Endometrial tissue was subsequently harvested by endometriectomy between days 9 to 11 PO, corresponding to the approximate time of implantation in the baboon. Control endometria were similarly harvested from disease free animals (n¼6). Total RNA from each animal was hybridized to HumanRef-6 v3.0 Expression BeadChips (Illumina) containing 23,000 unique genes. Microarray data analyses were performed using BRB Array Tools. Verification of microarray data was performed using real time (RT) PCR; protein abundance changes were assayed by immunohistochemistry. All experimental procedures were approved by the Animal Care Committee of the University of Illinois, Chicago. RESULTS: Assessment of an early morphological response of baboon endometrium to hCG, the development of an epithelial plaque, revealed that the endometrium of all control animals was stimulated by hCG. However, an epithelial plaque was only elicited by hCG in two of five animals with endometriosis. Microarray analysis of endometria from baboons three and six months following induction of disease identified 22 and 116 genes, respectively, whose transcript levels differed more than 2-fold from those of control endometria (p<0.05). Several of these genes were previously shown to be regulated by hCG in disease free baboons. RT PCR analysis confirmed aberrant levels of LIF, complement factor C3, sFRP4 and SERPA3 in endometria of baboons with endometriosis. Immunohistochemical analysis revealed that this aberrant gene expression profile was not a result of altered CG receptor distribution in the endometrium of animals with endometriosis. CONCLUSIONS: An altered response to CG may prevent the acquisition of the full endometrial molecular repertoire necessary for implantation and may in part explain the implantation failure associated with endometriosis. Supported by: U54 HD40093 to ATF.
Monday, November 10, 2008 11:30 am O-6 ANTIDEPRESSANT-ASSOCIATED CHANGES IN SEMEN PARAMETERS. C. Tanrikut, A. S. Feldman, M. Altemus, D. A. Paduch, P. N. Schlegel. Urology, Massachusetts General Hospital, Boston, MA; Psychiatry, Weill Medical College of Cornell University, New York, NY; Urology, Weill Medical College of Cornell University, New York, NY. OBJECTIVE: To assess the effects of an SSRI, paroxetine (Paxil), on semen parameters. DESIGN: Prospective clinical trial of normal volunteers. MATERIALS AND METHODS: Thirty-five healthy male volunteers ages 18-65 were enrolled under IRB approval. Intake assessment included physical exam, semen analysis (SA) and the Brief Sexual Function Inventory (BSFI). Repeat SA was obtained prior to SSRI initiation. Paroxetine was given for 5
Vol. 90, Suppl 1, September 2008
Monday, November 10, 2008 11:00 am O-4 IN THE TRANSITION TO MENOPAUSE: WHICH COMES FIRST, HOT FLASHES OR DEPRESSIVE SYMPTOMS? M. D. Sammel, H. Lin, E. W. Freeman. Biostatistics and Epidemiology, Univ. of Pennsylvania, Philadelphia, PA; Center for Res. in Reprod. and Women’ Health, Univ. of Pennsylvania, Philadelphia; Obstetrics and Gynecology, Univ. of Pennsylvania, Philadelphia. OBJECTIVE: To evaluate the incidence and timing of hot flashes and depressive symptoms during the menopausal transition. We examine whether these 2 symptom processes are operating independently or whether symptoms co-occur. In those women who experience both symptoms we identified which symptom was reported first. DESIGN: Prospective Cohort. MATERIALS AND METHODS: The experience of 170 symptom free women at baseline from the ongoing PENN ovarian aging cohort were evaluated. Reports of hot flashes and depressive symptoms were assessed annually beginning in 1997 using validated questionnaires. The incidence of hot flashes and depression are estimated, and statistical tests of independence between these symptoms was computed using chi-squared methods. Additional comparisons looked at which symptom was reported first and the observed frequencies were compared to expected quantities under the assumption of independence. RESULTS: Women were aged 35-47, average 41.9 (þ/-3.4) years, with regular menstrual periods for 3 months enrollment. Reproductive hormones reflected pre-menopausal levels, estradiol average 43.6 (þ/-31.9), FSH average 8.0 (þ/-4.5). Forty-one percent were African American and 59% Caucasian. Over 10 years these women contributed 1220.6 person-years of followup. The incidence of hot flashes was statistically significantly increased in these women compared to the incidence of depression, 62.5% versus 50% respectively, chi-squared test of homogeneity¼14.3, p-value¼0.0002. Women were more likely to experience both symptoms, whether sequentially or concurrently, than expected if these processes were independent, Chisquare¼18.5; df¼3; p¼0.0007. Seventy women (41.2%) reported experiencing both hot flashes and depressed mood. Depressive symptoms occurred first, prior to reports of hot flashes for 23.5% of women, this was 2.1 times higher than would be expected if these 2 symptoms operated independently. Only 7.7% of women reported hot flashes that proceeded depressive symptoms, this was 31% fewer women than expected under independence, RR¼0.69. CONCLUSIONS: Large numbers of women in their late reproductive years report symptoms of hot flashes and depressed mood. Symptoms of depression were more likely to occur first, prior to reports of hot flashes. This pattern is contrary to the theory that hot flashes are a likely cause of depression. Both processes have been associated with changes in reproductive hormones, but these patterns of reporting indicate the potential for different underlying mechanisms. Supported by: R01-AG012745.
S2
Abstracts
Monday, November 10, 2008 11:15 am O-5 THE EUTOPIC ENDOMETRIAL RESPONSE TO CHORIONIC GONADOTROPHIN IS ABNORMAL IN A BABOON MODEL OF ENDOMETRIOSIS: A POSSIBLE EXPLANATION FOR ENDOMETRIOSIS ASSOCIATED IMPLANTATION FAILURE. J. M. Hastings, R. A. Sherwin, P. A. Mavrogianis, K. S. Jackson, A. M. Sharkey, A. T. Fazleabas. Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL; Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United Kingdom; Pathology, University of Cambridge, Cambridge, United Kingdom. OBJECTIVE: To test the hypothesis that the endometrial response to Chorionic Gonadotrophin (CG) the major early, embryo derived signal, is altered by the presence of endometriosis. DESIGN: We assessed endometrial morphology, protein and gene expression changes occurring after in vivo intra-oviductal CG treatment of baboons with endometriosis. MATERIALS AND METHODS: Endometriosis was experimentally induced in female baboons (n¼5) by intraperitoneal inoculation with menstrual endometrium. Three and six months following disease induction, human CG (hCG; 30IU/day) was infused into the oviduct via a subcutaneous osmotic mini-pump and polyurethane cannula. HCG infusion began on day 6 post ovulation (PO). Endometrial tissue was subsequently harvested by endometriectomy between days 9 to 11 PO, corresponding to the approximate time of implantation in the baboon. Control endometria were similarly harvested from disease free animals (n¼6). Total RNA from each animal was hybridized to HumanRef-6 v3.0 Expression BeadChips (Illumina) containing 23,000 unique genes. Microarray data analyses were performed using BRB Array Tools. Verification of microarray data was performed using real time (RT) PCR; protein abundance changes were assayed by immunohistochemistry. All experimental procedures were approved by the Animal Care Committee of the University of Illinois, Chicago. RESULTS: Assessment of an early morphological response of baboon endometrium to hCG, the development of an epithelial plaque, revealed that the endometrium of all control animals was stimulated by hCG. However, an epithelial plaque was only elicited by hCG in two of five animals with endometriosis. Microarray analysis of endometria from baboons three and six months following induction of disease identified 22 and 116 genes, respectively, whose transcript levels differed more than 2-fold from those of control endometria (p<0.05). Several of these genes were previously shown to be regulated by hCG in disease free baboons. RT PCR analysis confirmed aberrant levels of LIF, complement factor C3, sFRP4 and SERPA3 in endometria of baboons with endometriosis. Immunohistochemical analysis revealed that this aberrant gene expression profile was not a result of altered CG receptor distribution in the endometrium of animals with endometriosis. CONCLUSIONS: An altered response to CG may prevent the acquisition of the full endometrial molecular repertoire necessary for implantation and may in part explain the implantation failure associated with endometriosis. Supported by: U54 HD40093 to ATF.
Monday, November 10, 2008 11:30 am O-6 ANTIDEPRESSANT-ASSOCIATED CHANGES IN SEMEN PARAMETERS. C. Tanrikut, A. S. Feldman, M. Altemus, D. A. Paduch, P. N. Schlegel. Urology, Massachusetts General Hospital, Boston, MA; Psychiatry, Weill Medical College of Cornell University, New York, NY; Urology, Weill Medical College of Cornell University, New York, NY. OBJECTIVE: To assess the effects of an SSRI, paroxetine (Paxil), on semen parameters. DESIGN: Prospective clinical trial of normal volunteers. MATERIALS AND METHODS: Thirty-five healthy male volunteers ages 18-65 were enrolled under IRB approval. Intake assessment included physical exam, semen analysis (SA) and the Brief Sexual Function Inventory (BSFI). Repeat SA was obtained prior to SSRI initiation. Paroxetine was given for 5
Vol. 90, Suppl 1, September 2008