- Email: [email protected]
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and 2PN obtained (p⬍0.001). An AFC ⱕ5 together with elevated CD2 FSH⬎12 or E2⬎60 predicted the highest cycle cancellation rates, controlled for age (53.8%; p⬍0.001, Table 1). There was no correlation of antral follicle count with BMI, total ampules used, day of HCG, CD2 LH, or ultrasonographer.
CONCLUSION: In young IVF patients (⬍35 years old), currently used markers of ovarian reserve, such as AFC and FSH levels, do not predict oocyte quality as measured by IR. However, quantity may reflect quality, as demonstrated by the decreased IR in young women who have ⱕ6 oocytes retrieved. However, these younger patients should not be excluded from treatment as even with the lower number of oocytes retrieved, their IR exceeds that of older patients with higher oocyte numbers. This suggests that while there might be some decrease in quality (IR) with decreasing oocyte collection number (quantity), age may still be the primary determinant of IR and pregnancy rates and that quantity does not always predict quality. Younger patients should therefore not be excluded from IVF based on AFC or FSH levels. Supported by: None.
Wednesday, October 25, 2006 3:30 pm O-286 DOES ANTRAL FOLLICLE COUNT PREDICT IVF OUTCOMES IN POOR RESPONDERS? A. E. Reh, G. Schattman, S. Spandorfer, T. Chicketano, Z. Rosenwaks. New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY. OBJECTIVE: To determine the predictive value of initial Antral Follicle Counts (AFC) and early follicular phase Follicle Stimulating Hormone (FSH) to the number of oocytes retrieved and the subsequent pregnancy outcome in patients with poor ovarian response undergoing non-suppressed In Vitro Fertilization (IVF) cycles. DESIGN: Retrospective Chart Analysis of Patients undergoing aggressive stimulation protocols. MATERIALS AND METHODS: Patients who underwent gonadotropin stimulation for IVF using a GnRH antagonist from 4/2003 through 12/2005 were included. Transvaginal ultrasounds and cycle day 2 (CD2) FSH, Estradiol (E2), and Luteinizing Hormone (LH) were performed prior to gonadotropin administration. Subjects were excluded if they had ultrasounds or blood work performed outside our institution (n⫽61), or were undergoing IVF for purposes of cryopreservation or preimplantation genetic diagnosis (n⫽14). The primary outcome was the number of oocytes retrieved. The secondary outcomes evaluated were rates of cycle cancellation, fertilization (2PN), implantation, and clinical (fetal heart) pregnancy. Differences in age, CD2 FSH and E2, body mass index (BMI), ultrasonographer, total ampules, and maximum E2 were analyzed. RESULTS: A total of 398 cycles were reviewed. Mean age of the patients was 39.1 ⫾ 4 years with mean CD2 FSH of 8.0 ⫾ 3 mIU/ml and an average AFC of 7.2 ⫾ 4. Embryos were transferred in 94.5% of cycles with an overall clinical pregnancy rate of 27.3%. There was a negative correlation between AFC and CD2 FSH levels, controlled for age (-0.15; p⫽0.005). An AFCⱕ5 was associated with a higher cycle cancellation rate, lower maximum E2, fewer oocytes retrieved, and fewer 2PN (p⬍0.0001). There was no difference in implantation or clinical pregnancy rates after controlling for age. Having either an AFCⱕ5 or elevated FSH or E2 was associated with a higher rate of cycle cancellation, lower maximum E2, with fewer oocytes
FERTILITY & STERILITY威
CONCLUSION: We present one of the largest retrospective series supporting the role of antral follicle counts together with baseline hormonal levels in predicting ovarian response in patients undergoing non-suppressed IVF cycles. Lower antral follicle counts are associated with a higher rate of cycle cancellation with fewer oocytes obtained, yet outcomes following embryo transfer were not affected. Prior studies with suppressed protocols may have had suboptimal ovarian stimulation and thus underestimated the significance of AFC in poor responders. Moreover, antral follicle counts can be used in conjunction with current endocrine markers in providing crucial prognostic information for the physician evaluating and counseling poor responders before IVF stimulation. Supported by: None.
Wednesday, October 25, 2006 3:45 pm O-287 OVARIAN RESERVE IS IMPAIRED IN CANCER PATIENTS WITH NORMAL BASELINE FSH WHO PREVIOUSLY RECEIVED CHEMOTHERAPY AS DETERMINED BY RESPONSE TO CONTROLLED OVARIAN STIMULATION AND ANTI-MULLERIAN HORMONE MEASUREMENTS: A CONTROLLED STUDY. A. A. Azim, E. R. Rauch, M. Ravich, S. Witkin, K. Oktay. Weill Medical Coll of Cornell Univ, New York, NY; Departemnt of Obstetrics & Gynecology New York Presbyterian Hospital, New York, NY. OBJECTIVE: Chemotherapy regimens containing alkylating agents result in primordial follicle death and premature ovarian failure. Depending on the age and the type/dose of chemotherapy, some women may continue to menstruate. Our aim was to ascertain the impact of chemotherapy on ovarian reserve in patients who previously received chemotherapy by response to controlled ovarian hyper stimulation (COH) and anti-mullerian hormone (AMH) levels. DESIGN: Prospective study with retrospective controls. MATERIALS AND METHODS: 45 cancer patients underwent controlled ovarian stimulation for IVF before (30 patients, 30 IVF cycles) or after (15 patients, 30 IVF cycles) chemotherapy. Patients with basal serum FSH ⬎13mIU/mL or E2⬎70pg/ml were excluded. AMH was measured on previously stored serum samples from the day of initiation of the ovarian stimulation. RESULTS: Mean ages and baseline FSH levels of pre- and postchemotherapy IVF patients were similar (36.8⫾0.91 vs. 36.3⫾1). The mean interval from completion of chemotherapy to IVF was 8.03⫾1.32 years (range 1-23). Of the 30 IVF cycles in post-chemotherapy patients, 22 received alkylating agents and 8 did not (table 1). There were no significant differences between the study and control cycles regarding day-2 estradiol (E2), length of stimulation, total gonadotropin dose, and E2 on hCG day (table 2). Cycle cancellation rate was 20% and 26.67% for pre and post-chemotherapy patients, respectively. The number of oocytes retrieved and fertilized were significantly higher in pre-chemotherapy group (p⬍0.0001). Two clinical pregnancies were achieved in the postchemotherapy group, one ending in spontaneous abortion and the other in the delivery of a healthy baby (6.67% clinical pregnancy rate and 3.33% delivery rate per attempted cycle). All fertilized oocytes in the control group were cryopreserved at 2-pronuclei stage. Baseline AMH levels were significantly lower in post chemotherapy IVF patients compared to those who underwent IVF prior to chemotherapy (0.270 ⫾0.077 vs. 0.84⫾0.27 ng/ml, p⫽0.03). In the pre-chemotherapy group
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there was a positive correlation between the AMH levels and the number of oocytes retrieved (r⫽0.663, p⫽0.004 ). This correlation was not detected in the post chemotherapy group (r⫽0.205).
M. M. Guarnaccia, M. V. Sauer, R. A. Lobo. Columbia Univ Coll of Physicians and Surgeons, New York, NY. OBJECTIVE: Patients older than 37 may be at risk for poor IVF outcome even when traditional baseline parameters such as FSH, LH and E2 are within normal limits. A more sensitive marker for predicting cycle cancellation in this group would be useful when other parameters appear nondiscriminatory. MIS has been validated as a sensitive marker of ovarian reserve in the general infertility population, with good correlation to ovarian response. We hypothesized that MIS could also be used as a discriminatory marker for IVF cycle cancellation in the group of older patients with otherwise normal baseline parameters. DESIGN: Retrospective case-control. MATERIALS AND METHODS: Archived day 2 serum samples from 25 patients aged 37 or older who experienced cycle cancellation due to poor response (Group 1) were assayed for MIS by ELISA (DSL, Webster TX). Cycles were cancelled if the patient did not have a total of at least 3 growing follicles by day 7 of stimulation. Fifty age-matched patients who successfully responded to gonadotropin stimulation were used as controls (Group 2). Baseline FSH, LH and E2 assays were performed by standard immunometric assays (Immunolite). Data were analyzed using SPSS for Windows 13.0. Results are reported as mean ⫹/- SEM. Mann Whitney U was used for comparisons of independent samples. ROC curves constructed to determine the predictive accuracy of the diagnostic parameters. Spearman correlation coefficients were calculated for independent variables. RESULTS: Groups were statistically identical in terms of age (39.7 ⫹/0.39 vs 39.9 ⫹/- 0.21), FSH (9.5 ⫹/- 0.60 vs 9.2 ⫹/- 0.36 mIU/mL), LH (5.1⫹/-0.62 vs 4.5 ⫹/- 0.24 mIU/mL), E2 (31.1⫹/- 2.5 vs 29.8⫹/-1.7 pg/mL), and starting gonadotropin dose (523 ⫹/- 10 vs 502 IU/d). MIS was statistically lower in cancelled cycles compared to completed cycles (0.22 ⫹/- 0.05 vs 0.98 ⫹/- 0.18 ng/mL, p⬍.01). In relation to cycle cancellation, AUC of the ROC curve for MIS was the largest of all the examined markers at 0.882. In group 1, 20/25 (80%) of patients had an MIS ⬍0.3 ng/mL, whereas only 7/50 (14%) of patients in group 2 had an MIS ⬍0.3 ng/mL. Using 0.35 ng/mL as the threshold, 23/25 (92%) of patients in group 1 had MIS levels below this value, compared to 13/50 (26%) patients with normal response. Within the group of patients that successfully responded to gonadotropins, total number of oocytes retrieved correlated significantly with FSH (R⫽ -.499, p⬍.01) but more dramatically with MIS (R⫽.651, p⬍.01). FSH and MIS were weakly but significantly correlated (R⫽-.353, p⫽.002). CONCLUSION: MIS may be useful in identifying older patients with normal traditional parameters who have an increased risk for IVF failure. Compared to age, FSH, LH or E2, MIS appears to have the greatest diagnostic accuracy for predicting ovarian response. Accurate prediction of cycle cancellation could minimize the incidence of IVF failure and expedite the triage to alternative approaches to child bearing. Supported by: None.
Wednesday, October 25, 2006 4:15 pm O-289 DEHYDROEPIANDROSTERONE (DHEA) SUPPLEMENTATION AND PREGNANCY OUTCOME: EFFECT ON PREGNANCY RATE AND SPEED OF CONCEPTION. H. Brill, D. H. Barad, N. Gleicher. Center for Human Reproduction - NYC, New York City, NY. CONCLUSION: Ovarian reserve is significantly diminished in patients who previously received chemotherapy even if they have normal baseline FSH levels. Baseline AMH levels may be a better predictor of ovarian response than baseline FSH levels. Supported by: None.
Wednesday, October 25, 2006 4:00 pm O-288 MIS PREDICTS CYCLE CANCELLATION IN OLDER IVF PATIENTS WITH NORMAL FSH. N. Douglas, G. S. Nakhuda, J. G. Wang,
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Abstracts
OBJECTIVE: We, and other authors, previously reported on the beneficial effects of dehydroepiandrosterone (DHEA) supplementation on ovarian function in women with diminished ovarian reserve. Whether these beneficial effects, however, also translate into improved pregnancy rates has never before been investigated in controlled fashion. The objective of this study was, therefore, to investigate whether DHEA affects pregnancy rates. DESIGN: Historical Case-Control study. MATERIALS AND METHODS: DHEA treatment was initiated in June 2004. 88 consecutive women with a history of diminished ovarian reserve, evidenced by inadequately poor response to ovulation induction, who, in spite of prior recommendations to pursue egg donation, had decided to continue with IVF cycles, represented the DHEA study group. Historical controls were 101 consecutive women, treated at the same center before we began study of DHEA supplementation. The controls had maximal baseline
Vol. 86, Suppl 2, September 2006
CONCLUSION: In young IVF patients (⬍35 years old), currently used markers of ovarian reserve, such as AFC and FSH levels, do not predict oocyte quality as measured by IR. However, quantity may reflect quality, as demonstrated by the decreased IR in young women who have ⱕ6 oocytes retrieved. However, these younger patients should not be excluded from treatment as even with the lower number of oocytes retrieved, their IR exceeds that of older patients with higher oocyte numbers. This suggests that while there might be some decrease in quality (IR) with decreasing oocyte collection number (quantity), age may still be the primary determinant of IR and pregnancy rates and that quantity does not always predict quality. Younger patients should therefore not be excluded from IVF based on AFC or FSH levels. Supported by: None.
Wednesday, October 25, 2006 3:30 pm O-286 DOES ANTRAL FOLLICLE COUNT PREDICT IVF OUTCOMES IN POOR RESPONDERS? A. E. Reh, G. Schattman, S. Spandorfer, T. Chicketano, Z. Rosenwaks. New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY. OBJECTIVE: To determine the predictive value of initial Antral Follicle Counts (AFC) and early follicular phase Follicle Stimulating Hormone (FSH) to the number of oocytes retrieved and the subsequent pregnancy outcome in patients with poor ovarian response undergoing non-suppressed In Vitro Fertilization (IVF) cycles. DESIGN: Retrospective Chart Analysis of Patients undergoing aggressive stimulation protocols. MATERIALS AND METHODS: Patients who underwent gonadotropin stimulation for IVF using a GnRH antagonist from 4/2003 through 12/2005 were included. Transvaginal ultrasounds and cycle day 2 (CD2) FSH, Estradiol (E2), and Luteinizing Hormone (LH) were performed prior to gonadotropin administration. Subjects were excluded if they had ultrasounds or blood work performed outside our institution (n⫽61), or were undergoing IVF for purposes of cryopreservation or preimplantation genetic diagnosis (n⫽14). The primary outcome was the number of oocytes retrieved. The secondary outcomes evaluated were rates of cycle cancellation, fertilization (2PN), implantation, and clinical (fetal heart) pregnancy. Differences in age, CD2 FSH and E2, body mass index (BMI), ultrasonographer, total ampules, and maximum E2 were analyzed. RESULTS: A total of 398 cycles were reviewed. Mean age of the patients was 39.1 ⫾ 4 years with mean CD2 FSH of 8.0 ⫾ 3 mIU/ml and an average AFC of 7.2 ⫾ 4. Embryos were transferred in 94.5% of cycles with an overall clinical pregnancy rate of 27.3%. There was a negative correlation between AFC and CD2 FSH levels, controlled for age (-0.15; p⫽0.005). An AFCⱕ5 was associated with a higher cycle cancellation rate, lower maximum E2, fewer oocytes retrieved, and fewer 2PN (p⬍0.0001). There was no difference in implantation or clinical pregnancy rates after controlling for age. Having either an AFCⱕ5 or elevated FSH or E2 was associated with a higher rate of cycle cancellation, lower maximum E2, with fewer oocytes
FERTILITY & STERILITY威
CONCLUSION: We present one of the largest retrospective series supporting the role of antral follicle counts together with baseline hormonal levels in predicting ovarian response in patients undergoing non-suppressed IVF cycles. Lower antral follicle counts are associated with a higher rate of cycle cancellation with fewer oocytes obtained, yet outcomes following embryo transfer were not affected. Prior studies with suppressed protocols may have had suboptimal ovarian stimulation and thus underestimated the significance of AFC in poor responders. Moreover, antral follicle counts can be used in conjunction with current endocrine markers in providing crucial prognostic information for the physician evaluating and counseling poor responders before IVF stimulation. Supported by: None.
Wednesday, October 25, 2006 3:45 pm O-287 OVARIAN RESERVE IS IMPAIRED IN CANCER PATIENTS WITH NORMAL BASELINE FSH WHO PREVIOUSLY RECEIVED CHEMOTHERAPY AS DETERMINED BY RESPONSE TO CONTROLLED OVARIAN STIMULATION AND ANTI-MULLERIAN HORMONE MEASUREMENTS: A CONTROLLED STUDY. A. A. Azim, E. R. Rauch, M. Ravich, S. Witkin, K. Oktay. Weill Medical Coll of Cornell Univ, New York, NY; Departemnt of Obstetrics & Gynecology New York Presbyterian Hospital, New York, NY. OBJECTIVE: Chemotherapy regimens containing alkylating agents result in primordial follicle death and premature ovarian failure. Depending on the age and the type/dose of chemotherapy, some women may continue to menstruate. Our aim was to ascertain the impact of chemotherapy on ovarian reserve in patients who previously received chemotherapy by response to controlled ovarian hyper stimulation (COH) and anti-mullerian hormone (AMH) levels. DESIGN: Prospective study with retrospective controls. MATERIALS AND METHODS: 45 cancer patients underwent controlled ovarian stimulation for IVF before (30 patients, 30 IVF cycles) or after (15 patients, 30 IVF cycles) chemotherapy. Patients with basal serum FSH ⬎13mIU/mL or E2⬎70pg/ml were excluded. AMH was measured on previously stored serum samples from the day of initiation of the ovarian stimulation. RESULTS: Mean ages and baseline FSH levels of pre- and postchemotherapy IVF patients were similar (36.8⫾0.91 vs. 36.3⫾1). The mean interval from completion of chemotherapy to IVF was 8.03⫾1.32 years (range 1-23). Of the 30 IVF cycles in post-chemotherapy patients, 22 received alkylating agents and 8 did not (table 1). There were no significant differences between the study and control cycles regarding day-2 estradiol (E2), length of stimulation, total gonadotropin dose, and E2 on hCG day (table 2). Cycle cancellation rate was 20% and 26.67% for pre and post-chemotherapy patients, respectively. The number of oocytes retrieved and fertilized were significantly higher in pre-chemotherapy group (p⬍0.0001). Two clinical pregnancies were achieved in the postchemotherapy group, one ending in spontaneous abortion and the other in the delivery of a healthy baby (6.67% clinical pregnancy rate and 3.33% delivery rate per attempted cycle). All fertilized oocytes in the control group were cryopreserved at 2-pronuclei stage. Baseline AMH levels were significantly lower in post chemotherapy IVF patients compared to those who underwent IVF prior to chemotherapy (0.270 ⫾0.077 vs. 0.84⫾0.27 ng/ml, p⫽0.03). In the pre-chemotherapy group
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there was a positive correlation between the AMH levels and the number of oocytes retrieved (r⫽0.663, p⫽0.004 ). This correlation was not detected in the post chemotherapy group (r⫽0.205).
M. M. Guarnaccia, M. V. Sauer, R. A. Lobo. Columbia Univ Coll of Physicians and Surgeons, New York, NY. OBJECTIVE: Patients older than 37 may be at risk for poor IVF outcome even when traditional baseline parameters such as FSH, LH and E2 are within normal limits. A more sensitive marker for predicting cycle cancellation in this group would be useful when other parameters appear nondiscriminatory. MIS has been validated as a sensitive marker of ovarian reserve in the general infertility population, with good correlation to ovarian response. We hypothesized that MIS could also be used as a discriminatory marker for IVF cycle cancellation in the group of older patients with otherwise normal baseline parameters. DESIGN: Retrospective case-control. MATERIALS AND METHODS: Archived day 2 serum samples from 25 patients aged 37 or older who experienced cycle cancellation due to poor response (Group 1) were assayed for MIS by ELISA (DSL, Webster TX). Cycles were cancelled if the patient did not have a total of at least 3 growing follicles by day 7 of stimulation. Fifty age-matched patients who successfully responded to gonadotropin stimulation were used as controls (Group 2). Baseline FSH, LH and E2 assays were performed by standard immunometric assays (Immunolite). Data were analyzed using SPSS for Windows 13.0. Results are reported as mean ⫹/- SEM. Mann Whitney U was used for comparisons of independent samples. ROC curves constructed to determine the predictive accuracy of the diagnostic parameters. Spearman correlation coefficients were calculated for independent variables. RESULTS: Groups were statistically identical in terms of age (39.7 ⫹/0.39 vs 39.9 ⫹/- 0.21), FSH (9.5 ⫹/- 0.60 vs 9.2 ⫹/- 0.36 mIU/mL), LH (5.1⫹/-0.62 vs 4.5 ⫹/- 0.24 mIU/mL), E2 (31.1⫹/- 2.5 vs 29.8⫹/-1.7 pg/mL), and starting gonadotropin dose (523 ⫹/- 10 vs 502 IU/d). MIS was statistically lower in cancelled cycles compared to completed cycles (0.22 ⫹/- 0.05 vs 0.98 ⫹/- 0.18 ng/mL, p⬍.01). In relation to cycle cancellation, AUC of the ROC curve for MIS was the largest of all the examined markers at 0.882. In group 1, 20/25 (80%) of patients had an MIS ⬍0.3 ng/mL, whereas only 7/50 (14%) of patients in group 2 had an MIS ⬍0.3 ng/mL. Using 0.35 ng/mL as the threshold, 23/25 (92%) of patients in group 1 had MIS levels below this value, compared to 13/50 (26%) patients with normal response. Within the group of patients that successfully responded to gonadotropins, total number of oocytes retrieved correlated significantly with FSH (R⫽ -.499, p⬍.01) but more dramatically with MIS (R⫽.651, p⬍.01). FSH and MIS were weakly but significantly correlated (R⫽-.353, p⫽.002). CONCLUSION: MIS may be useful in identifying older patients with normal traditional parameters who have an increased risk for IVF failure. Compared to age, FSH, LH or E2, MIS appears to have the greatest diagnostic accuracy for predicting ovarian response. Accurate prediction of cycle cancellation could minimize the incidence of IVF failure and expedite the triage to alternative approaches to child bearing. Supported by: None.
Wednesday, October 25, 2006 4:15 pm O-289 DEHYDROEPIANDROSTERONE (DHEA) SUPPLEMENTATION AND PREGNANCY OUTCOME: EFFECT ON PREGNANCY RATE AND SPEED OF CONCEPTION. H. Brill, D. H. Barad, N. Gleicher. Center for Human Reproduction - NYC, New York City, NY. CONCLUSION: Ovarian reserve is significantly diminished in patients who previously received chemotherapy even if they have normal baseline FSH levels. Baseline AMH levels may be a better predictor of ovarian response than baseline FSH levels. Supported by: None.
Wednesday, October 25, 2006 4:00 pm O-288 MIS PREDICTS CYCLE CANCELLATION IN OLDER IVF PATIENTS WITH NORMAL FSH. N. Douglas, G. S. Nakhuda, J. G. Wang,
S124
Abstracts
OBJECTIVE: We, and other authors, previously reported on the beneficial effects of dehydroepiandrosterone (DHEA) supplementation on ovarian function in women with diminished ovarian reserve. Whether these beneficial effects, however, also translate into improved pregnancy rates has never before been investigated in controlled fashion. The objective of this study was, therefore, to investigate whether DHEA affects pregnancy rates. DESIGN: Historical Case-Control study. MATERIALS AND METHODS: DHEA treatment was initiated in June 2004. 88 consecutive women with a history of diminished ovarian reserve, evidenced by inadequately poor response to ovulation induction, who, in spite of prior recommendations to pursue egg donation, had decided to continue with IVF cycles, represented the DHEA study group. Historical controls were 101 consecutive women, treated at the same center before we began study of DHEA supplementation. The controls had maximal baseline
Vol. 86, Suppl 2, September 2006