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Cancer risk among infertile women with androgen excess and menstrual disorders (including polycystic ovarian syndrome)
MATERIALS AND METHODS: Sperm selected via the evaluation of motility and morphology were used in the ICSI of the control group and HBsperm meeting the same criteria were used in the study group. The PICSIÒ plate used in the study provides microdots of H for sperm selection. Chisquare analyses for nominal data and independent t tests for normal continuous data were used to evaluate the data with SPSS 15.0. RESULTS: Overall, the clinical pregnancy rate (cpr) in the PICSI study group was greater than that observed in the ICSI control group (44.8%, 37.9%, n ¼ 67, 58). Stratifying by HBAÒ indices, patients with a low HBAÒ index (<65%) demonstrated a greater cpr in the PICSI study group (44.8%, n ¼ 29) than those patients in the ICSI control group (33.3%, n¼33). CONCLUSIONS: A clinically significant increase in cpr is associated with the use of HB-sperm, the increase being greater in those patients carrying an abnormal HBA score. The use of HB-sperm in ICSI may allow the isolation of more functionally competent sperm, thereby exerting a positive paternal influence on preimplantation embryogenesis and cpr. The ongoing study will continue to explore the enhanced embryonic potential associated with PICSI-derived embryos. Supported by: Support: PICSIÒ dishes by Biocoat, Inc.
O-124 Tuesday, October 20, 2009 5:45 PM HUMAN EMBRYOS SURVIVING VITRIFICATION-WARMING CYCLE HAVE SAME PREGNANCY RATES THAN FRESH EMBRYOS. B. C. Barros, R. Cossiello, T. S. Paula, J. R. Alegretti, A. L. S. Rossi, E. L. A. Motta. Huntington Medicina Reprodutiva, S~ao Paulo, Brazil; Departamento de Ginecologia, Universidade Federal de S~ao Paulo, S~ao Paulo, Brazil. OBJECTIVE: Vitrification/warming (V/W) has been considered the best option for oocyte and embryo cryopreservation. While fundamental studies have shown excellent survival, implantation and pregnancy rates (IR and PR, respectively) with V/W technique no research has focused on embryos with high developmental potential (eHDP) separately. The aim of this study was to compare pregnancy rates produced by fresh (F) and V/W eHDP. DESIGN: retrospective laboratory study MATERIALS AND METHODS: All consecutive women transferred with eHDP (R6 cells; grade 1-2 according to Steer) on day 3 from 10/07 to 01/09 were included in this study. Standard IVF laboratory techniques were used. Embryo V/W was performed according to the manufacturer’s instructions (Irvine Scientific). Statistical analysis was performed by Chi-square test, binary logistic regression, Z test for 2 proportions, Mann-Whitney U test (median, range) and student’s t test. Significance level was attained at p<0.05. RESULTS: Nine hundred seventy-six eHDP were transferred in 332 fresh cycles while 514 eHDP were transferred after 156 V/W cycles. Similar PR were noted (F¼44.8% vs. V/W¼50%; p¼0.3). There no significant odds for pregnancy (odds ratio¼1.23; 95% confidence interval-CI). The number of embryos needed for the achievement of pregnancy was comparable (F¼6.5 embryos vs. V/W¼ 6.5 embryos/pregnancy; 95%CI¼-0.03; 0.03; p¼0.9). Number of blastomeres (F¼7 [6-12] vs. V/W¼7 [6-12]; p¼0.9), fragmentation grade (F¼1 [1-2] V/W¼1 [1-2]; p¼0.6) and number of embryos transferred (F¼31 vs. V/W¼31; p¼0.38) were also similar between groups. CONCLUSIONS: Transference of vitrified embryos with high developmental potential produces pregnancy rates comparable to those following fresh ET. These findings add strength to counseling of infertile couples bringing vitrification of embryos with high developmental potential as a viable alternative for ET whenever circumstances might be needed.
O-125 Tuesday, October 20, 2009 6:00 PM PRODUCTION OF PARTHENOGENETIC BLASTOCYSTS FROM IN VITRO MATURED CUMULUS-FREE HUMAN OOCYTES. S. McElroy, J. Byrne, B. Behr, A. Hsueh, R. Reijo Pera. Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Palo Alto, CA; Department of Obstetrics & Gynecology, Stanford University, Palo Alto, CA. OBJECTIVE: Identification of hormonal receptors in human oocytes and the use of their cognate ligands to improve in vitro maturation (IVM) of cumulus-free oocytes. DESIGN: Consented cumulus-free immature oocytes prior to intracytoplasmic sperm injection were obtained from the IVF center, and matured
FERTILITY & STERILITYÒ
in vitro supplemented with hormonal factors based on the expressions of their receptors in oocytes. Developmental potential of parthenogenetic activated embryos were monitored to determine the effect of exogenous factors. MATERIALS AND METHODS: A total of 27 of candidate oocyte receptors and 16 of their cognate ligands were selected based on published literature deposited in online databases. Single cell gene expression profiling was performed for GV (germinal vesicle), MI (metaphase I), MII (spontaneously matured MII), and IVM-MII oocytes together with cumulus cells. Cumulusfree immature oocytes were collected at 6-8h after retrieval, and matured in vitro in IVM-medium without or with selected factors based on the expressions of their receptors in oocytes. Cytoplasmic maturation was monitored based on early embryo development after parthenogenetic activation. At day 3 of development, embryos were used for deriving parthenogenetic embryonic stem cells. RESULTS: With hormonal supplementation, more embryos were cleaved (86.3%) after parthenogenetic activation as compared to those without supplementation (55.6%) (P<0.05). Furthermore, two blastocysts were produced only from the supplemented group. Blastomeres isolated from 8-cell stage parthenogenetic embryos on day 3 were cleaved further, and outgrowths were observed in vitro. CONCLUSIONS: Exogenous supplementation based on the gene expression profiling of oocytes improves the competence of in vitro matured cumulus-free oocytes after parthenogenetic activation. This cohort of oocytes can be used to understand mechanisms underlying oocyte maturation and to derive embryonic stem cells. Supported by: The California Institute for Regenerative Medicine.
ANDROGEN EXCESS SPECIAL INTEREST GROUP O-126 Tuesday, October 20, 2009 4:15 PM CANCER RISK AMONG INFERTILE WOMEN WITH ANDROGEN EXCESS AND MENSTRUAL DISORDERS (INCLUDING POLYCYSTIC OVARIAN SYNDROME). L. A. Brinton, K. S. Moghissi, C. L. Westhoff, E. J. Lamb, B. Scoccia. Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI; Department of Obstetrics and Gynecology, Columbia University, New York, NY; Department of Obstetrics and Gynecology, Stanford University, Stanford, CA; Department of Obstetrics and Gynecology, University of Illinois, Chicago, IL. OBJECTIVE: To clarify cancer risks associated with androgen excess conditions., including polycystic ovarian syndrome (PCOS) DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Among 12,193 women evaluated for infertility between 1965-1988 at five clinical sites, extensive clinical workups identified 401 who met established criteria for PCOS, an additional 454 with hirsuitism, hyperandrogenism, or polycystic ovaries, and an additional 1,705 with oligomenorrhea or amenorrhea. Follow-up through 1999 allowed derivation of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for cancer risk comparisons with the general population and rate ratios (RRs) for internal comparisons with other infertility patients. RESULTS: Among the 2,560 patients with androgen excess or menstrual disorders, significant SIRs were observed for breast cancer (1.31, 95% CIs 1.05-1.62), uterine cancer (2.02, 1.13-3.34) and melanoma (1.96, 1.123.18). Significant associations for breast and uterine cancers were restricted to primary infertility patients (respective SIRs of 1.53 and 3.48). After adjustment for other cancer predictors through internal analyses, the only persistent excess risk was for uterine cancer among primary infertility patients. Compared to women with secondary infertility and no androgen excess or menstrual disorder, those with primary infertility and such a disorder had a RR of 1.88 (0.82-4.32). Cancer risks among the smaller groups of women with diagnoses of PCOS or androgen excess disorders were similar to the broader group of women studied. CONCLUSIONS: Previous findings linking androgen excess disorders to elevated uterine cancer risks may reflect underlying risk profiles (e.g., obesity, nulliparity). Our finding of the highest uterine cancer risk among primary infertility patients may indicate that only the more severe forms of androgen excess or menstrual disorders predispose to cancer. Supported by: This research was supported in part by funds from the intramural research program of the National Cancer Institute.
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O-124 Tuesday, October 20, 2009 5:45 PM HUMAN EMBRYOS SURVIVING VITRIFICATION-WARMING CYCLE HAVE SAME PREGNANCY RATES THAN FRESH EMBRYOS. B. C. Barros, R. Cossiello, T. S. Paula, J. R. Alegretti, A. L. S. Rossi, E. L. A. Motta. Huntington Medicina Reprodutiva, S~ao Paulo, Brazil; Departamento de Ginecologia, Universidade Federal de S~ao Paulo, S~ao Paulo, Brazil. OBJECTIVE: Vitrification/warming (V/W) has been considered the best option for oocyte and embryo cryopreservation. While fundamental studies have shown excellent survival, implantation and pregnancy rates (IR and PR, respectively) with V/W technique no research has focused on embryos with high developmental potential (eHDP) separately. The aim of this study was to compare pregnancy rates produced by fresh (F) and V/W eHDP. DESIGN: retrospective laboratory study MATERIALS AND METHODS: All consecutive women transferred with eHDP (R6 cells; grade 1-2 according to Steer) on day 3 from 10/07 to 01/09 were included in this study. Standard IVF laboratory techniques were used. Embryo V/W was performed according to the manufacturer’s instructions (Irvine Scientific). Statistical analysis was performed by Chi-square test, binary logistic regression, Z test for 2 proportions, Mann-Whitney U test (median, range) and student’s t test. Significance level was attained at p<0.05. RESULTS: Nine hundred seventy-six eHDP were transferred in 332 fresh cycles while 514 eHDP were transferred after 156 V/W cycles. Similar PR were noted (F¼44.8% vs. V/W¼50%; p¼0.3). There no significant odds for pregnancy (odds ratio¼1.23; 95% confidence interval-CI). The number of embryos needed for the achievement of pregnancy was comparable (F¼6.5 embryos vs. V/W¼ 6.5 embryos/pregnancy; 95%CI¼-0.03; 0.03; p¼0.9). Number of blastomeres (F¼7 [6-12] vs. V/W¼7 [6-12]; p¼0.9), fragmentation grade (F¼1 [1-2] V/W¼1 [1-2]; p¼0.6) and number of embryos transferred (F¼31 vs. V/W¼31; p¼0.38) were also similar between groups. CONCLUSIONS: Transference of vitrified embryos with high developmental potential produces pregnancy rates comparable to those following fresh ET. These findings add strength to counseling of infertile couples bringing vitrification of embryos with high developmental potential as a viable alternative for ET whenever circumstances might be needed.
O-125 Tuesday, October 20, 2009 6:00 PM PRODUCTION OF PARTHENOGENETIC BLASTOCYSTS FROM IN VITRO MATURED CUMULUS-FREE HUMAN OOCYTES. S. McElroy, J. Byrne, B. Behr, A. Hsueh, R. Reijo Pera. Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Palo Alto, CA; Department of Obstetrics & Gynecology, Stanford University, Palo Alto, CA. OBJECTIVE: Identification of hormonal receptors in human oocytes and the use of their cognate ligands to improve in vitro maturation (IVM) of cumulus-free oocytes. DESIGN: Consented cumulus-free immature oocytes prior to intracytoplasmic sperm injection were obtained from the IVF center, and matured
FERTILITY & STERILITYÒ
in vitro supplemented with hormonal factors based on the expressions of their receptors in oocytes. Developmental potential of parthenogenetic activated embryos were monitored to determine the effect of exogenous factors. MATERIALS AND METHODS: A total of 27 of candidate oocyte receptors and 16 of their cognate ligands were selected based on published literature deposited in online databases. Single cell gene expression profiling was performed for GV (germinal vesicle), MI (metaphase I), MII (spontaneously matured MII), and IVM-MII oocytes together with cumulus cells. Cumulusfree immature oocytes were collected at 6-8h after retrieval, and matured in vitro in IVM-medium without or with selected factors based on the expressions of their receptors in oocytes. Cytoplasmic maturation was monitored based on early embryo development after parthenogenetic activation. At day 3 of development, embryos were used for deriving parthenogenetic embryonic stem cells. RESULTS: With hormonal supplementation, more embryos were cleaved (86.3%) after parthenogenetic activation as compared to those without supplementation (55.6%) (P<0.05). Furthermore, two blastocysts were produced only from the supplemented group. Blastomeres isolated from 8-cell stage parthenogenetic embryos on day 3 were cleaved further, and outgrowths were observed in vitro. CONCLUSIONS: Exogenous supplementation based on the gene expression profiling of oocytes improves the competence of in vitro matured cumulus-free oocytes after parthenogenetic activation. This cohort of oocytes can be used to understand mechanisms underlying oocyte maturation and to derive embryonic stem cells. Supported by: The California Institute for Regenerative Medicine.
ANDROGEN EXCESS SPECIAL INTEREST GROUP O-126 Tuesday, October 20, 2009 4:15 PM CANCER RISK AMONG INFERTILE WOMEN WITH ANDROGEN EXCESS AND MENSTRUAL DISORDERS (INCLUDING POLYCYSTIC OVARIAN SYNDROME). L. A. Brinton, K. S. Moghissi, C. L. Westhoff, E. J. Lamb, B. Scoccia. Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI; Department of Obstetrics and Gynecology, Columbia University, New York, NY; Department of Obstetrics and Gynecology, Stanford University, Stanford, CA; Department of Obstetrics and Gynecology, University of Illinois, Chicago, IL. OBJECTIVE: To clarify cancer risks associated with androgen excess conditions., including polycystic ovarian syndrome (PCOS) DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Among 12,193 women evaluated for infertility between 1965-1988 at five clinical sites, extensive clinical workups identified 401 who met established criteria for PCOS, an additional 454 with hirsuitism, hyperandrogenism, or polycystic ovaries, and an additional 1,705 with oligomenorrhea or amenorrhea. Follow-up through 1999 allowed derivation of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for cancer risk comparisons with the general population and rate ratios (RRs) for internal comparisons with other infertility patients. RESULTS: Among the 2,560 patients with androgen excess or menstrual disorders, significant SIRs were observed for breast cancer (1.31, 95% CIs 1.05-1.62), uterine cancer (2.02, 1.13-3.34) and melanoma (1.96, 1.123.18). Significant associations for breast and uterine cancers were restricted to primary infertility patients (respective SIRs of 1.53 and 3.48). After adjustment for other cancer predictors through internal analyses, the only persistent excess risk was for uterine cancer among primary infertility patients. Compared to women with secondary infertility and no androgen excess or menstrual disorder, those with primary infertility and such a disorder had a RR of 1.88 (0.82-4.32). Cancer risks among the smaller groups of women with diagnoses of PCOS or androgen excess disorders were similar to the broader group of women studied. CONCLUSIONS: Previous findings linking androgen excess disorders to elevated uterine cancer risks may reflect underlying risk profiles (e.g., obesity, nulliparity). Our finding of the highest uterine cancer risk among primary infertility patients may indicate that only the more severe forms of androgen excess or menstrual disorders predispose to cancer. Supported by: This research was supported in part by funds from the intramural research program of the National Cancer Institute.
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