- Email: [email protected]
Pregnant patients with ovarian hyperstimulation syndrome have lower human chorionic gonadotropin levels and doubling time
DESIGN: Retrospective cohort study. MATERIALS AND METHODS: AMH was assayed in 204 sera from 166 cycles. Residual sera had been stored below -70 C until analyzed by ELISA (DSL, Webster, TX) in duplicate. The values were merged with ART database to allow comparison with outcomes. RESULTS: Assays with dynamic range of 0.01 to 15.0 ng/mL had intraand inter-assay coefficients of variation of 3.5% and 7.3%, respectively. In 35 cases, paired samples, on the average of 6 days apart (range 3 to 14 days), were assayed with one sample obtained in patients suppressed with GnRH agonist and a second obtained on day 3 to 6 of gonadotropin treatment. The values, 1.3 versus 1.0 ng/mL, respectively, did not differ (p¼0.10, paired Student’s t test), and the regression coefficient of 0.81 was significant (p<0.001). In further analyses performed using single samples or the average of repeat samples for 166 cases, AMH levels were related to age (p<0.001) with a regression coefficient of -0.26. In ART cycles where ova were retrieved, AMH levels were significantly (p < 0.001) related to number of ova collected, number of mature ova, and number of ova fertilized by either IVF or ICSI with regression coefficients of 0.37, 0.44, and 0.44, respectively. Considering pregnancy outcomes for initiated ART cycles, ROC analyses were performed for biochemical pregnancies and clinical pregnancies. AMH greater than 1.0 ng/mL was a significant (p<0.001) criterion for biochemical pregnancy with sensitivity of 68% and specificity of 64%, and a significant (p<0.001) criterion for clinical pregnancy with sensitivity of 70% and specificity of 63%. CONCLUSIONS: AMH levels at the time of initiation of ART cycles were found to be related to number of oocytes retrieved and fertilized, and to pregnancy outcomes suggesting a potential use in patient prospective management. Supported by: Funding provided by Noble Endowment.
P-40 Tuesday, October 20, 2009 LEPTIN IN SERUM AND FOLLICULAR FLUID AFTER STIMULATION WITH HIGHLY PURIFIED MENOTROPIN AND RECOMBINANT FSH IN CONTROLLED OVARIAN STIMULATION. J. Smitz, J. Schiettecatte, B. M. Klein, J.-C. Arce. Hormone Laboratory, UZ Brussel, Brussel, Belgium; Clinical Research & Development (Biometrics), Ferring Pharmaceuticals A/S, Copenhagen, Denmark; Clinical Research & Development (OB&GYN), Ferring Pharmaceuticals A/S, Copenhagen, Denmark. OBJECTIVE: To explore the effects of controlled ovarian stimulation with highly purified menotropin (HP-hMG) and recombinant FSH (rFSH) on leptin in serum and follicular fluid and its association with ovarian response and treatment outcome. DESIGN: Exploratory retrospective analysis of a randomized, active-controlled, assessor-blind, multicenter, multinational trial. MATERIALS AND METHODS: 731 women undergoing IVF in a long GnRH agonist cycle were randomized to HP-hMG (MENOPUR; Ferring Pharmaceuticals) (N¼363) or rFSH (GONAL-F; Merck Serono) (N¼368) [Nyboe Andersen et al, Hum Reprod 2006, 21, 3217]. The starting dose was 225 IU SC for five days followed by potential adjustments of 75 IU. rhCG 250 mg SC was given when R3 follicles of R17 mm. Leptin in serum on day 1, day 6 and last day of stimulation and in fluid from a follicle of R17 mm was analyzed centrally using Millipore Human Leptin assay. Ongoing pregnancy was assessed 10-11 weeks after embryo transfer. RESULTS: Serum concentrations of leptin increased significantly during stimulation (p<0.001). Significantly higher levels of serum leptin were noted in the HP-hMG group at all time points compared to the rFSH group (p<0.001), but the elevations during stimulation were not significantly different between groups. Leptin in follicular fluid and serum at the end of stimulation were significantly correlated (correlation coefficient 0.89, p<0.001). Number of oocytes retrieved and ongoing pregnancy were not associated with leptin levels in serum at any time or with leptin levels in follicular fluid, even when corrected for BMI. CONCLUSIONS: Serum leptin levels increase during controlled ovarian stimulation irrespective of type of gonadotropin. Concentrations of leptin in follicular fluid are strongly correlated with the circulating leptin concentrations at the end of stimulation. Neither serum nor intra-follicular leptin concentrations are associated with ovarian response or treatment outcome. Supported by: Ferring Pharmaceuticals A/S.
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Abstracts
P-41 Tuesday, October 20, 2009 TGFß1 AND IGFBP-1 IN FOLLICULAR FLUID AFTER STIMULATION WITH HIGHLY PURIFIED MENOTROPIN AND RECOMBINANT FSH IN CONTROLLED OVARIAN STIMULATION. J. Smitz, J. Schiettecatte, B. M. Klein, J.-C. Arce. Hormone Laboratory, UZ Brussel, Brussels, Belgium; Clinical Research & Development (Biometrics), Ferring Pharmaceuticals A/S, Copenhagen, Denmark; Clinical Research & Development (OB&GYN), Ferring Pharmaceuticals A/S, Copenhagen, Denmark. OBJECTIVE: To explore the effects of controlled ovarian stimulation with highly purified menotropin (HP-hMG) and recombinant FSH (rFSH) on transforming growth factor b 1(TGFb1) and insulin-like growth factor binding protein-1 (IGFBP-1) in follicular fluid and its association with ovarian response and treatment outcome. DESIGN: Exploratory retrospective analysis of a randomized, active-controlled, assessor-blind, multicenter, multinational trial. MATERIALS AND METHODS: 731 women undergoing IVF in a long GnRH agonist cycle were randomized to HP-hMG (MENOPUR; Ferring Pharmaceuticals) (N¼363) or rFSH (GONAL-F; Merck Serono) (N¼368) [Nyboe Andersen et al, Hum Reprod 2006]. The starting dose was 225 IU SC for five days followed by potential adjustments of 75 IU. rhCG 250 mg SC was given when R3 follicles of R17 mm. Fluid was collected from a follicle of R17 mm and analyzed centrally for TGFb1 and IGFBP-1. Ongoing pregnancy was assessed 10-11 weeks after embryo transfer. RESULTS: Intra-follicular TGFb1 concentrations were comparable between the two treatment groups, with a mean of 1,319 mg/L and 1,286 mg/ L with HP-hMG and rFSH, respectively (p¼0.278). Number of oocytes retrieved and ongoing pregnancy were not associated with TGFb1 levels in follicular fluid. There was no significant difference between gonadotropin preparations with respect to the intra-follicular concentration of IGFBP-1, with an average of 164 mg/L in the HP-hMG group and 156 mg/L in the rFSH group (p¼0.187). No association with IGFBP-1 levels in follicular fluid was found for number of oocytes retrieved or ongoing pregnancy. CONCLUSIONS: Intra-follicular levels of TGFb1 and IGFBP-1 are not affected by type of gonadotropin used during controlled ovarian stimulation. Concentrations of TGFb1 and IGFBP-1 in follicular fluid are not associated with ovarian response or treatment outcome. Supported by: Ferring Pharmaceuticals A/S.
P-42 Tuesday, October 20, 2009 PREGNANT PATIENTS WITH OVARIAN HYPERSTIMULATION SYNDROME HAVE LOWER HUMAN CHORIONIC GONADOTROPIN LEVELS AND DOUBLING TIME. C. E. Alford, K. S. Richter, J. H. Segars, M. J. Levy. Combined Federal Fellowship Program, National Institutes of Health, NICHD, Program in Reproductive and Adult Endocrinology, Bethesda, MD; Shady Grove Fertility and Reproductive Science Center, Rockville, MD. OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is accompanied by hemoconcentration. In late-onset OHSS, human chorionic gonadotropin (hCG) levels used to assess normal intrauterine pregnancy (IUP) may be altered by hemoconcentration and misinterpreted by both patients and clinicians. Only one prior study of 9 patients with OHSS reported a 33% slower rise for hCG in patients with OHSS. Therefore, our aim was to quantify hCG levels and rise in patients with OHSS and a singleton IUP compared to control patients without OHSS. DESIGN: Case-control. MATERIALS AND METHODS: Singleton IVF IUPs with a live birth but, complicated by moderate or severe OHSS, were matched in a 1:1 ratio to singleton IUPs without OHSS. Cases were matched based on age, diagnosis, peak estradiol, and number of embryos transferred. Patient and cycle characteristics were compared by t-test or chi-square as appropriate. Serum hCG levels were measured from days 15-24 after oocyte retrieval. Intraassay and interassay coefficients of variation were 3 and 6.5%, respectively. Differences in hCG levels (log transformed) and rate of hCG rise between the OHSS cases and controls were compared using Analysis of Covariance (ANCOVA). RESULTS: 82 eligible OHSS cases were identified. The mean hCG level was 13% lower for the OHSS cases versus the 82 control cases (p¼0.012). There was an 18% slower rise of hCG in the OHSS cases versus, the controls (p¼0.014). The ANCOVA model (R¼0.69, p<0.0001) indicated that both the mean hCG level (adjusted for day after retrieval) and the rate of rise differed significantly between the two patient groups.
Vol. 92., No. 3, Supplement, September 2009
CONCLUSIONS: Patients with a normal IUP and OHSS had lower serum hCG levels and slower doubling times compared to matched patients without OHSS. These data are of use when interpreting hCG values in the clinical setting of OHSS. Supported by: This research was supported, in part, by the intramural research Program in Reproductive and Adult Endocrinology, NICHD, NIH and by Shady Grove Fertility and Reproductive Science Center.
P-43 Tuesday, October 20, 2009 ¨ LLERIAN HORMONE (AMH) LEVELS AGE SPECIFIC ANTI-MU DISCRIMINATE AT EACH AGE BETWEEN POORER AND BETTER OOCYTE YIELDS. D. H. Barad, A. Weghofer, A. Goyal, N. Gleicher. Center for Human Reproduction (CHR) – New York and Foundation for Reproductive Medicine, New York, NY; Departments of Epidemiology and Social Medicine as well as Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY; Department of Obstetrics and Gynecology, Vienna University School of Medicine, Innere Stadt, Wien, Austria; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT. OBJECTIVE: Anti-Mu¨llerian hormone (AMH) is more specific in predicting ovarian reserve (OR) than FSH. This study attempted to determine whether age-specific (AS) -AMH, like AS- FSH, offers advantages. DESIGN: Age-binned cohort study. MATERIALS AND METHODS: 702 consecutive patients were organized by age into % 30, 31-35, 36-40, R 41 years. AS-AMH was calculated based on 95% confidence interval (CI) for age. 262 women reaching IVF were investigated for oocytes yields, based on normal or low AS-AMH. RESULTS: AMH decreased with advancing female age (p<0.000). Mean AMH differed in each age category (p < 0.001, Table). AMH also declined in IVF cases with advancing age in all age categories but was less pronounced with normal AS-AMH than with abnormally low levels (p < 0.001). Adjusted for age, oocyte yields were significantly higher in each age category [5.4 times (4.1 to 6.8) more oocytes with normal AS-AMH]. TABLE 1
Age (years) % 30 31 – 35 36 - 40 R 41
Mean AMH (ng/mL)
Minimum AMH
Max AMH
2.6 2.1 1.2 0.6
2.1 1.7 1.1 >0.5
3.1 2.5 1.4 0.7
CONCLUSIONS: This is the first report of AS-AMH. As previously reported for AS-FSH (Barad et al. Obstet Gynecol 2007;109:1404-10), ASAMH discriminates between oocytes yields at all ages. It, therefore, appears superior to universal AMH cut offs as indicators of OR. As AS levels, based on 95% CI, are center-specific, and since our center serves highly unfavorable patients, reported values, likely, are conservative. More favorable patients should be evaluated with slightly higher AMH cut offs, and/or centers should establish own cut offs until availability of universal AS OR tests based on general population data. Supported by: The Foundation for Reproductive Medicine and intramural CHR funds.
RESULTS: Immunoreactivity for CYP17 was easily detected in the cytoplasm of syncytiotrophoblasts, it was weakly positive in intermediate trophoblasts, and was not detected in cytotrophoblasts. Similar findings were noted in all placentas (8). CYP17 mRNA was easily detected by 30 to 33 cycles of standard RT-PCR in all cells. Evidence of CYP17 expression and activity was further demonstrated by the secretion of 17a-hydroxyprogesterone, androstenedione and their aromatized products. The rate of estradiol synthesis was similar for all three cell types at approximately 4 pg per gram of protein per day. The steroidgenesis rate of CYP17 products greatly varied though, ranging from 22 – 47 pg/mg/d for 17a-hydroxyprogesterone and 37 – 0.4 pg/g/d for androstenedione, to a minimal amount of dehydroepiandrosterone. All cell lines studied here produced CYP17 products within the aforementioned ranges, with Jeg-3 and BeWo cell lines having comparable rates, and primary placental cells usually higher. CONCLUSIONS: We demonstrated that human placental and choriocarcinoma cells are capable of producing androgens and thus estradiol de novo, without the need of fetal or maternal androgen precursors. We suggest that when considering the mass discrepancy between the human placenta and the fetal adrenal gland, that the contribution of placental androgens as precursors for estrogen production in human gestation is measurable and significant.
P-45 Tuesday, October 20, 2009 SUCCESS IN DETECTION OF LH SURGE BY HOME OVULATION TESTS. S. R. Johnson, R. Shaw, J. Ellis. SPD Diagnostic Company Limited, Bedford, Bedfordshire, United Kingdom. OBJECTIVE: Home ovulation tests can maximise chance of a natural conception by identifying the surge in lutenising hormone (LH) to enable appropriate timing of intercourse. A number of products are available with differing numbers of test sticks and strategies for their use. This analysis examines how successful these are in detecting the LH surge. DESIGN: The percentage of successful detection of LH surge per cycle was calculated for differing numbers of LH tests (5-20), and for different test strategies. MATERIALS AND METHODS: Daily urines samples from fertile women with cycle lengths 21-42 days were collected, and urinary LH was measured by AutoDelfia. Data from 1170 cycles of 101 women were considered as 195 6-consecutive cycle segments, with the first 3 cycles used as historical data, and the second 3 as test data. The analysis was based on modelling using LH surge day, rather than actual use of home ovulation tests. RESULTS: Not unexpectedly, use of only 5 test sticks produced the worst performance with detection of only 62.6% of LH surges using the typical cycle-17 days strategy. An increase to 7 tests provided a large increment in successful detection identifying 80.9% of surges, and 10 tests produced 89.9% detection. Addition of further tests only added small benefits (92.1% for 14 tests, 92.3% for 20 tests). Using shortest cycle-17 tended to increase successful detection, whereas a start date of day 10, increased detection using 20 tests (95.4%), but decreased it for 7 (77.6%). CONCLUSIONS: Both number of test sticks used, and the testing strategy can lead to very different success rates for detection of LH surge. Use of 5 sticks (with any strategy) provided very poor performance, whereas 7 tests provided a high level of detection. Additional tests only had a small benefit on performance. Supported by: Study investigators all employees of, and study funded by SPD development company limited.
P-46 Tuesday, October 20, 2009 P-44 Tuesday, October 20, 2009 DE NOVO SYNTHESIS OF ANDROGENS BY THE HUMAN PLACENTA. J. C. Escobar, V. E. Beshay, S. S. Patel, B. R. Carr. OBGYN, UT Southwestern Medical Center, Dallas, TX. OBJECTIVE: To analyze if the human placenta and human choriocarcinoma cell lines are capable of expressing CYP17 and producing androgens de novo. DESIGN: Experimental MATERIALS AND METHODS: Tissue from human placentas raging from 4 to 40 weeks of gestation (n¼8) were stained by immunohistochemistry for CYP17. Cells originating from 18 week human placentas and choriocarcinoma cell lines, Jeg-3 and BeWo, were used for analysis of CYP17 mRNA as well as its steroid products. Steroid analysis was performed via radioimmunoassays using cells exposed to regular media without precursor supplementation.
FERTILITY & STERILITYÒ
ROUX-EN-Y GASTRIC BYPASS (RYGB) – INDUCED WEIGHT LOSS IMPROVES 2HYDROXYESTROGEN: THE GOOD ESTROGEN. S. Nair, R. Tamboli, N. Abumrad, A. Al-Hendy. Dept of Obstetrics and Gynecology, Center for Women’s Health and Research, Meharry Medical College, Nashville, TN; Dept of Surgery, Vanderbilt University, Nashville, TN. OBJECTIVE: Reproductive problems like menstrual dysfunctions, risk of miscarriages and low fertility found in polycystic ovary syndrome (PCOS) are strongly associated with obesity.Weight loss improves ovulation and pregnancy rates in obese women with PCOS. 2 hydroxyestrogen (2OHE), an estrogen metabolite is methylated by catechol-O-methyltransferase (COMT). In ovary, 2OHE improves the action of FSH by enhancing hormone stimulated cAMP production. We demonstrated low urinary 2OHE and high COMT levels in PCOS women. The aim of this study is to monitor changes in urinary 2OHE levels in obese women who have undergone RYGB surgery.
S101
P-40 Tuesday, October 20, 2009 LEPTIN IN SERUM AND FOLLICULAR FLUID AFTER STIMULATION WITH HIGHLY PURIFIED MENOTROPIN AND RECOMBINANT FSH IN CONTROLLED OVARIAN STIMULATION. J. Smitz, J. Schiettecatte, B. M. Klein, J.-C. Arce. Hormone Laboratory, UZ Brussel, Brussel, Belgium; Clinical Research & Development (Biometrics), Ferring Pharmaceuticals A/S, Copenhagen, Denmark; Clinical Research & Development (OB&GYN), Ferring Pharmaceuticals A/S, Copenhagen, Denmark. OBJECTIVE: To explore the effects of controlled ovarian stimulation with highly purified menotropin (HP-hMG) and recombinant FSH (rFSH) on leptin in serum and follicular fluid and its association with ovarian response and treatment outcome. DESIGN: Exploratory retrospective analysis of a randomized, active-controlled, assessor-blind, multicenter, multinational trial. MATERIALS AND METHODS: 731 women undergoing IVF in a long GnRH agonist cycle were randomized to HP-hMG (MENOPUR; Ferring Pharmaceuticals) (N¼363) or rFSH (GONAL-F; Merck Serono) (N¼368) [Nyboe Andersen et al, Hum Reprod 2006, 21, 3217]. The starting dose was 225 IU SC for five days followed by potential adjustments of 75 IU. rhCG 250 mg SC was given when R3 follicles of R17 mm. Leptin in serum on day 1, day 6 and last day of stimulation and in fluid from a follicle of R17 mm was analyzed centrally using Millipore Human Leptin assay. Ongoing pregnancy was assessed 10-11 weeks after embryo transfer. RESULTS: Serum concentrations of leptin increased significantly during stimulation (p<0.001). Significantly higher levels of serum leptin were noted in the HP-hMG group at all time points compared to the rFSH group (p<0.001), but the elevations during stimulation were not significantly different between groups. Leptin in follicular fluid and serum at the end of stimulation were significantly correlated (correlation coefficient 0.89, p<0.001). Number of oocytes retrieved and ongoing pregnancy were not associated with leptin levels in serum at any time or with leptin levels in follicular fluid, even when corrected for BMI. CONCLUSIONS: Serum leptin levels increase during controlled ovarian stimulation irrespective of type of gonadotropin. Concentrations of leptin in follicular fluid are strongly correlated with the circulating leptin concentrations at the end of stimulation. Neither serum nor intra-follicular leptin concentrations are associated with ovarian response or treatment outcome. Supported by: Ferring Pharmaceuticals A/S.
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Abstracts
P-41 Tuesday, October 20, 2009 TGFß1 AND IGFBP-1 IN FOLLICULAR FLUID AFTER STIMULATION WITH HIGHLY PURIFIED MENOTROPIN AND RECOMBINANT FSH IN CONTROLLED OVARIAN STIMULATION. J. Smitz, J. Schiettecatte, B. M. Klein, J.-C. Arce. Hormone Laboratory, UZ Brussel, Brussels, Belgium; Clinical Research & Development (Biometrics), Ferring Pharmaceuticals A/S, Copenhagen, Denmark; Clinical Research & Development (OB&GYN), Ferring Pharmaceuticals A/S, Copenhagen, Denmark. OBJECTIVE: To explore the effects of controlled ovarian stimulation with highly purified menotropin (HP-hMG) and recombinant FSH (rFSH) on transforming growth factor b 1(TGFb1) and insulin-like growth factor binding protein-1 (IGFBP-1) in follicular fluid and its association with ovarian response and treatment outcome. DESIGN: Exploratory retrospective analysis of a randomized, active-controlled, assessor-blind, multicenter, multinational trial. MATERIALS AND METHODS: 731 women undergoing IVF in a long GnRH agonist cycle were randomized to HP-hMG (MENOPUR; Ferring Pharmaceuticals) (N¼363) or rFSH (GONAL-F; Merck Serono) (N¼368) [Nyboe Andersen et al, Hum Reprod 2006]. The starting dose was 225 IU SC for five days followed by potential adjustments of 75 IU. rhCG 250 mg SC was given when R3 follicles of R17 mm. Fluid was collected from a follicle of R17 mm and analyzed centrally for TGFb1 and IGFBP-1. Ongoing pregnancy was assessed 10-11 weeks after embryo transfer. RESULTS: Intra-follicular TGFb1 concentrations were comparable between the two treatment groups, with a mean of 1,319 mg/L and 1,286 mg/ L with HP-hMG and rFSH, respectively (p¼0.278). Number of oocytes retrieved and ongoing pregnancy were not associated with TGFb1 levels in follicular fluid. There was no significant difference between gonadotropin preparations with respect to the intra-follicular concentration of IGFBP-1, with an average of 164 mg/L in the HP-hMG group and 156 mg/L in the rFSH group (p¼0.187). No association with IGFBP-1 levels in follicular fluid was found for number of oocytes retrieved or ongoing pregnancy. CONCLUSIONS: Intra-follicular levels of TGFb1 and IGFBP-1 are not affected by type of gonadotropin used during controlled ovarian stimulation. Concentrations of TGFb1 and IGFBP-1 in follicular fluid are not associated with ovarian response or treatment outcome. Supported by: Ferring Pharmaceuticals A/S.
P-42 Tuesday, October 20, 2009 PREGNANT PATIENTS WITH OVARIAN HYPERSTIMULATION SYNDROME HAVE LOWER HUMAN CHORIONIC GONADOTROPIN LEVELS AND DOUBLING TIME. C. E. Alford, K. S. Richter, J. H. Segars, M. J. Levy. Combined Federal Fellowship Program, National Institutes of Health, NICHD, Program in Reproductive and Adult Endocrinology, Bethesda, MD; Shady Grove Fertility and Reproductive Science Center, Rockville, MD. OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is accompanied by hemoconcentration. In late-onset OHSS, human chorionic gonadotropin (hCG) levels used to assess normal intrauterine pregnancy (IUP) may be altered by hemoconcentration and misinterpreted by both patients and clinicians. Only one prior study of 9 patients with OHSS reported a 33% slower rise for hCG in patients with OHSS. Therefore, our aim was to quantify hCG levels and rise in patients with OHSS and a singleton IUP compared to control patients without OHSS. DESIGN: Case-control. MATERIALS AND METHODS: Singleton IVF IUPs with a live birth but, complicated by moderate or severe OHSS, were matched in a 1:1 ratio to singleton IUPs without OHSS. Cases were matched based on age, diagnosis, peak estradiol, and number of embryos transferred. Patient and cycle characteristics were compared by t-test or chi-square as appropriate. Serum hCG levels were measured from days 15-24 after oocyte retrieval. Intraassay and interassay coefficients of variation were 3 and 6.5%, respectively. Differences in hCG levels (log transformed) and rate of hCG rise between the OHSS cases and controls were compared using Analysis of Covariance (ANCOVA). RESULTS: 82 eligible OHSS cases were identified. The mean hCG level was 13% lower for the OHSS cases versus the 82 control cases (p¼0.012). There was an 18% slower rise of hCG in the OHSS cases versus, the controls (p¼0.014). The ANCOVA model (R¼0.69, p<0.0001) indicated that both the mean hCG level (adjusted for day after retrieval) and the rate of rise differed significantly between the two patient groups.
Vol. 92., No. 3, Supplement, September 2009
CONCLUSIONS: Patients with a normal IUP and OHSS had lower serum hCG levels and slower doubling times compared to matched patients without OHSS. These data are of use when interpreting hCG values in the clinical setting of OHSS. Supported by: This research was supported, in part, by the intramural research Program in Reproductive and Adult Endocrinology, NICHD, NIH and by Shady Grove Fertility and Reproductive Science Center.
P-43 Tuesday, October 20, 2009 ¨ LLERIAN HORMONE (AMH) LEVELS AGE SPECIFIC ANTI-MU DISCRIMINATE AT EACH AGE BETWEEN POORER AND BETTER OOCYTE YIELDS. D. H. Barad, A. Weghofer, A. Goyal, N. Gleicher. Center for Human Reproduction (CHR) – New York and Foundation for Reproductive Medicine, New York, NY; Departments of Epidemiology and Social Medicine as well as Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY; Department of Obstetrics and Gynecology, Vienna University School of Medicine, Innere Stadt, Wien, Austria; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT. OBJECTIVE: Anti-Mu¨llerian hormone (AMH) is more specific in predicting ovarian reserve (OR) than FSH. This study attempted to determine whether age-specific (AS) -AMH, like AS- FSH, offers advantages. DESIGN: Age-binned cohort study. MATERIALS AND METHODS: 702 consecutive patients were organized by age into % 30, 31-35, 36-40, R 41 years. AS-AMH was calculated based on 95% confidence interval (CI) for age. 262 women reaching IVF were investigated for oocytes yields, based on normal or low AS-AMH. RESULTS: AMH decreased with advancing female age (p<0.000). Mean AMH differed in each age category (p < 0.001, Table). AMH also declined in IVF cases with advancing age in all age categories but was less pronounced with normal AS-AMH than with abnormally low levels (p < 0.001). Adjusted for age, oocyte yields were significantly higher in each age category [5.4 times (4.1 to 6.8) more oocytes with normal AS-AMH]. TABLE 1
Age (years) % 30 31 – 35 36 - 40 R 41
Mean AMH (ng/mL)
Minimum AMH
Max AMH
2.6 2.1 1.2 0.6
2.1 1.7 1.1 >0.5
3.1 2.5 1.4 0.7
CONCLUSIONS: This is the first report of AS-AMH. As previously reported for AS-FSH (Barad et al. Obstet Gynecol 2007;109:1404-10), ASAMH discriminates between oocytes yields at all ages. It, therefore, appears superior to universal AMH cut offs as indicators of OR. As AS levels, based on 95% CI, are center-specific, and since our center serves highly unfavorable patients, reported values, likely, are conservative. More favorable patients should be evaluated with slightly higher AMH cut offs, and/or centers should establish own cut offs until availability of universal AS OR tests based on general population data. Supported by: The Foundation for Reproductive Medicine and intramural CHR funds.
RESULTS: Immunoreactivity for CYP17 was easily detected in the cytoplasm of syncytiotrophoblasts, it was weakly positive in intermediate trophoblasts, and was not detected in cytotrophoblasts. Similar findings were noted in all placentas (8). CYP17 mRNA was easily detected by 30 to 33 cycles of standard RT-PCR in all cells. Evidence of CYP17 expression and activity was further demonstrated by the secretion of 17a-hydroxyprogesterone, androstenedione and their aromatized products. The rate of estradiol synthesis was similar for all three cell types at approximately 4 pg per gram of protein per day. The steroidgenesis rate of CYP17 products greatly varied though, ranging from 22 – 47 pg/mg/d for 17a-hydroxyprogesterone and 37 – 0.4 pg/g/d for androstenedione, to a minimal amount of dehydroepiandrosterone. All cell lines studied here produced CYP17 products within the aforementioned ranges, with Jeg-3 and BeWo cell lines having comparable rates, and primary placental cells usually higher. CONCLUSIONS: We demonstrated that human placental and choriocarcinoma cells are capable of producing androgens and thus estradiol de novo, without the need of fetal or maternal androgen precursors. We suggest that when considering the mass discrepancy between the human placenta and the fetal adrenal gland, that the contribution of placental androgens as precursors for estrogen production in human gestation is measurable and significant.
P-45 Tuesday, October 20, 2009 SUCCESS IN DETECTION OF LH SURGE BY HOME OVULATION TESTS. S. R. Johnson, R. Shaw, J. Ellis. SPD Diagnostic Company Limited, Bedford, Bedfordshire, United Kingdom. OBJECTIVE: Home ovulation tests can maximise chance of a natural conception by identifying the surge in lutenising hormone (LH) to enable appropriate timing of intercourse. A number of products are available with differing numbers of test sticks and strategies for their use. This analysis examines how successful these are in detecting the LH surge. DESIGN: The percentage of successful detection of LH surge per cycle was calculated for differing numbers of LH tests (5-20), and for different test strategies. MATERIALS AND METHODS: Daily urines samples from fertile women with cycle lengths 21-42 days were collected, and urinary LH was measured by AutoDelfia. Data from 1170 cycles of 101 women were considered as 195 6-consecutive cycle segments, with the first 3 cycles used as historical data, and the second 3 as test data. The analysis was based on modelling using LH surge day, rather than actual use of home ovulation tests. RESULTS: Not unexpectedly, use of only 5 test sticks produced the worst performance with detection of only 62.6% of LH surges using the typical cycle-17 days strategy. An increase to 7 tests provided a large increment in successful detection identifying 80.9% of surges, and 10 tests produced 89.9% detection. Addition of further tests only added small benefits (92.1% for 14 tests, 92.3% for 20 tests). Using shortest cycle-17 tended to increase successful detection, whereas a start date of day 10, increased detection using 20 tests (95.4%), but decreased it for 7 (77.6%). CONCLUSIONS: Both number of test sticks used, and the testing strategy can lead to very different success rates for detection of LH surge. Use of 5 sticks (with any strategy) provided very poor performance, whereas 7 tests provided a high level of detection. Additional tests only had a small benefit on performance. Supported by: Study investigators all employees of, and study funded by SPD development company limited.
P-46 Tuesday, October 20, 2009 P-44 Tuesday, October 20, 2009 DE NOVO SYNTHESIS OF ANDROGENS BY THE HUMAN PLACENTA. J. C. Escobar, V. E. Beshay, S. S. Patel, B. R. Carr. OBGYN, UT Southwestern Medical Center, Dallas, TX. OBJECTIVE: To analyze if the human placenta and human choriocarcinoma cell lines are capable of expressing CYP17 and producing androgens de novo. DESIGN: Experimental MATERIALS AND METHODS: Tissue from human placentas raging from 4 to 40 weeks of gestation (n¼8) were stained by immunohistochemistry for CYP17. Cells originating from 18 week human placentas and choriocarcinoma cell lines, Jeg-3 and BeWo, were used for analysis of CYP17 mRNA as well as its steroid products. Steroid analysis was performed via radioimmunoassays using cells exposed to regular media without precursor supplementation.
FERTILITY & STERILITYÒ
ROUX-EN-Y GASTRIC BYPASS (RYGB) – INDUCED WEIGHT LOSS IMPROVES 2HYDROXYESTROGEN: THE GOOD ESTROGEN. S. Nair, R. Tamboli, N. Abumrad, A. Al-Hendy. Dept of Obstetrics and Gynecology, Center for Women’s Health and Research, Meharry Medical College, Nashville, TN; Dept of Surgery, Vanderbilt University, Nashville, TN. OBJECTIVE: Reproductive problems like menstrual dysfunctions, risk of miscarriages and low fertility found in polycystic ovary syndrome (PCOS) are strongly associated with obesity.Weight loss improves ovulation and pregnancy rates in obese women with PCOS. 2 hydroxyestrogen (2OHE), an estrogen metabolite is methylated by catechol-O-methyltransferase (COMT). In ovary, 2OHE improves the action of FSH by enhancing hormone stimulated cAMP production. We demonstrated low urinary 2OHE and high COMT levels in PCOS women. The aim of this study is to monitor changes in urinary 2OHE levels in obese women who have undergone RYGB surgery.
S101