- Email: [email protected]
Intercycle variability in antral follicle count and its effect upon stimulation quality in in vitro fertilization
cancelled patients (9.5 ⫾ 0.7 vs. 7.0 ⫾ 0.5 IU/L, p ⫽ 0.007). For completed cycles in groups A vs. B, no statistically significant differences were noted in peak E2 (1380 ⫾ 289 vs. 1810 ⫾ 365 pg/ml), mean number of follicles ⬎16 mm (4.0 vs. 3.5), mean number of stimulation days (9.8 ⫾ 0.4 vs. 10.0 ⫾ 0.8), mean number of ampules of FSH (35.9 ⫾ 2.6 vs. 35.1 ⫾ 3.5), mean number of ampules hMG (15.2 ⫾ 1.9 vs. 17.8 ⫾ 1.6), mean number of oocytes (8.8 ⫾ 1.1 vs. 8.8 ⫾ 1.6), fertilization rates (64.5% vs. 64.7%), mean number of embryos transferred (2.8 ⫾ 0.3 vs. 3.1 ⫾ 0.3) and ongoing pregnancy rate per embryo transfer (33.3% vs. 42.9%). Conclusions: GnRH antagonist utilization in poor responders appears to be as effective as the conventional microdose protocol in the treatment of poor responders. Unfortunately, cycle cancellation rates remain high in both treatment protocols. Supported by: An Unrestricted Educational Grant from Organon Pharmaceuticals, Inc. and in part by Ferring Pharmaceuticals.
Monday, October 14, 2002 2:30 P.M. O-51 Individual treatment using the GnRH antagonist Cetrotide(R): Optimization of treament. Michael Ludwig, Alexander Katalinic, Constanze Banz, Klaus Diedrich. Dept Gynecology and Obstetrics, Univ Clin Lu¨ beck, Lu¨ beck, Germany; Dept Social Medicine & Cancer Epidemiology, Medical Univ Lu¨ beck, Lu¨ beck, Germany. Objective: Use of the GnRH-antagonist has made ovarian stimulation easier, safer, and more comfortable for the patient. To avoid administration of the antagonist in a too early phase of follicular growth, it might be advantageous to delay administration in individual cases. Doing this, a sudden drop in gonadotrophins during a sensitive period of the follicular phase, with possible subsequent disturbance of follicular and endometrial growth, can be avoided. This individualisation should optimize treatment using a GnRH antagonist in ovarian stimulation. Design: Prospective, randomized controlled study. Materials/Methods: The study was approved by the ethical committee of the university hospital. Fifty-four patients were randomised to receive either the fixed multiple-dose antagonist protocol starting on day 6 of gonadotrophins with Cetrotide 0.25 mg (FIX) (cetrorelix; Serono International S.A., Geneva, Switzerland), or an individualised protocol with start of Cetrotide 0.25 mg when the leading follicle had a size of at least 14 mm (IND), or an individualised single dose protocol using Cetrotide 3 mg (SIN), administered according to follicle size (at least 14 mm). There were 18 patients in each group. Exclusively recombinant FSH (recFSH, Gonal F) was used, starting with 150 IU daily. HCG was given when the leading follicle had a size of at least 18 mm. Primary endpoint was number of Cetrotide ampoules and number of monitoring visits. Statistical power for these parameters was 80%. Results: Patients from the three groups were comparable with regard to important variables like age, number of previous cycles etc. FIX patients needed significantly more Cetrotide ampoules (6.81 ⫹/⫺ 1.61) as compared to IND patients (4.59 ⫹/⫺ 1.65; p ⬍0.01). Number of recFSH days was similar between FIX, IND, and SIN patients with 12.04 ⫹/⫺ 1.65, 11.66 ⫹/⫺ 2.15, and 12.53 ⫹/⫺ 1.92, but total IU of recFSH was significantly lower in IND patients (1838 ⫹/⫺ 576) as compared to FIX (2232 ⫹/⫺ 624; p ⬍0.05) or SIN patients (2350 ⫹/⫺ 618; p ⬍0.05). Mean number of monitoring visits was similar between the three groups and not statistically significant different (2.83 ⫹/⫺ 0.77 vs. 2.43 ⫹/⫺ 0.61 vs. 3.09 ⫹/⫺ 0.63). Number of retrieved oocytes was significantly higher in the individualised groups (IND: 10.97 ⫹/⫺ 7.07; SIN: 11.23 ⫹/⫺ 9.51) as compared to the fixed protocol group (6.15 ⫹/⫺ 4.18; p ⬍0.05). There were 3, 4, and 3 ongoing pregnancies (⬎12 weeks of gestation) in the FIX, IND, and SIN group, respectively. Conclusions: Administration of Cetrotide in an individualized fashion leads to a similiar necessity of monitoring visits. The number of oocytes retrieved is significantly increased, and the number of Cetrotide ampoules is significantly decreased in a multiple-dose protocol. Individualisation makes Cetrotide treatment less expensive and more efficient. Supported by: no financial support.
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Abstracts
Monday, October 14, 2002 2:45 P.M. O-52 Is rapid follicular development during controlled ovarian hyperstimulation (COH) for IVF and ICSI detrimental to success rate? Tarek Ghobara, Patrick Vandekerckhove, Richard Kennedy. Ctr for reproductive Medicine, Coventry and Warwickshire Univ Hosp, Coventry, UK. Objective: To determine whether a rapid follicular growth pattern and a short follicular phase (SFP) during COH in IVF and ICSI cycles is associated with certain clinical or biochemical characteristics of such women, and whether it has an effect on the outcome of such cycles. Design: Retrospective controlled study. Materials/Methods: All IVF and ICSI cycles performed between 1–11998 and 31–12–2001 were reviewed. Cycles in which ⬎⫽3 follicles had reached ⬎⫽17 mm diameter after only nine days of COH and on which oocytes retrieval was performed on day 11 of cycle were identified as cycles with rapid follicular development and SFP. This was the study group of interest. Cycles in which COH was initiated on the same day as each of SFP cycles and in which oocytes retrieval was performed on cycle day 14 or 15 served as the control group. Cycles using donated oocytes were excluded. All women underwent pituitary down regulation using a short acting GnRH agonist followed by follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG). Results: The study included 54 SFP cycles and 169 control cycles. Women age, type of infertility (primary or secondary) or order of IVF and ICSI cycles (first or repeat cycle) were not significantly different between SFP group and control group. Equally, basal FSH levels, treatment type (IVF or ICSI), total dose or type of used FSH or HMG were not significantly different. Male factor infertility was slightly more common in control group than in SFP group 92 (54%) vs. 20 (37%). There were no significant differences in other causes of infertility (tubal, anovulation, poor ovarian reserve, endometriosis and unexplained). The number of large size follicles (⬎⫽17mm) (5.4 vs. 5.1) or the total number of large and medium (14 – 16mm) size follicles (8.6 vs. 9.6) on ultrasound scan 48 hours prior to oocytes retrieval were not significantly different. There were less medium size follicles in SFP group (3.2 vs. 4.5, P ⬍0.01). The number of retrieved oocytes (8.1 vs. 9.6, p ⫽ 0.03) and the number of fertilized oocytes (5.3 vs. 6.7, P ⫽ 0.04) were less in the SFP group. However, there was no significant difference in fertilization rate (70% vs. 69.7%), number of transferred embryos (2.1 vs. 2.05) and number of frozen embryos (2.1 vs. 2.8). The clinical pregnancy rate [18 (33%) vs. 63 (37%)], ectopic pregnancy, miscarriage or live birth rates were not significantly different between the two groups. Conclusions: In our study a SFP was not associated with advanced women’s age or higher basal FSH levels. The smaller number of medium size follicles in the SFP group suggests that a second cohort of follicles did not have a chance to complete its development. This reflected itself in a smaller number of retrieved and fertilised oocytes. Nevertheless, the numbers of frozen embryos, clinical pregnancy, live birth rates were not different and the clinical significance of these differences is therefore doubtful. A SFP seems therefore to have no detrimental effect on oocyte quality, endometrial development or embryo implantation. Although a SFP in the spontaneous cycle has been found by some to be associated with reduced fertility, this appeared not to be the case during COH for IVF and ICSI. During COH the outcome of cycles with SFP is comparable to cycles with ‘normal’ follicular phase length. Supported by: Centre for Reproductive Medicine, Coventry, UK.
Monday, October 14, 2002 3:00 P.M. O-53 Intercycle variability in antral follicle count and its effect upon stimulation quality in in vitro fertilization. Karl R. Hansen, Jamie L. Morris, Michael R. Soules. Univ of Washington, Seattle, WA. Objective: The development of multiple follicles in response to gonadotropin treatment is critical to successful outcomes in assisted reproductive technologies (ART). The number of antral follicles (AFs) identified prior to
Vol. 78, No. 3, Suppl. 1, September 2002
stimulation in ART cycles has been shown to correlate well with multiple measures of in vitro fertilization (IVF) outcome. It is widely believed that the number of AFs correlates with the primordial follicle reserve. However, little is known about intercycle variability in antral follicle (AF) counts in patients undergoing IVF. Additionally the effect of these differences upon stimulation quality has not been investigated. Design: Retrospective study; university ART clinic. Materials/Methods: Patients experiencing two or more IVF cycles within a one-year interval between 2000 –2002 were included if AF counts were obtained during the pre-stimulation ultrasound. (In a separate group of normal women (n ⫽ 20) we found no significant change in AF count before and after treatment with a GnRH agonist.) Forty-seven patients (age 23– 45) having undergone a total of 101 IVF cycles were identified. To evaluate intercycle variability, means and percent change from the mean in AF counts were calculated and compared. Mean AF counts were also compared to means of parameters of IVF stimulation quality, including oocytes recovered, peak estradiol, length of stimulation, and gonadotropin dose. Comparisons of IVF stimulation quality were made between the low and high AF count cycle through a paired analysis. Comparisons were also made between the low and high AF count cycles and simulation quality in individuals with greater intercycle AF count variability (⬎50% change from the mean), and between individuals with greater vs. lesser intercycle variability. Statistical analysis included Wilcoxon signed-rank, Mann-Whitney (rank-sum) tests, and Spearman Correlation Coefficients. Results: AF count was positively correlated with the number of oocytes retrieved (r ⫽ 0.71, p ⫽ ⬍0.0001), peak estradiol (r ⫽ 0.50, p ⫽ 0.0007), and negatively correlated with gonadotropin dose (r ⫽ ⫺0.66, p ⫽ ⬍0.0001). Intercycle variability in AF number was greater at lower AF counts (r ⫽ ⫺0.31, p ⫽ 0.036), but was not correlated with age (p ⫽ NS). Paired analysis of stimulation quality between the low and high AF count cycle for each patient did not show a difference in oocytes retrieved, peak estradiol, gonadotropin dose, or biochemical and clinical pregnancy rates (p ⫽ NS). Stimulation quality was greater in individuals with lesser intercycle variability (p ⫽ 0.0036); however, no difference was detected in comparison of the lower to higher AF count cycle in individuals with greater intercycle variability. Conclusions: There is moderate intercycle variability in AF number, and this variability is greater in individuals with lower AF counts. Although AF count was well correlated with multiple parameters of IVF outcome; within an individual patient, higher AF count in a given cycle was not predictive of better stimulation quality compared to a lower count cycle. Therefore, it does not appear to be prudent to attempt to select an optimal cycle for stimulation in a particular patient. Greater intercycle variability is associated with decreased ovarian reserve. Supported by: The Division of Reproductive Endocrinology and Infertility, University of Washington.
Monday, October 14, 2002 3:45 P.M. O-54 Maternal balanced translocation is a risk factor for poor response to ovarian stimulation. Serena H. Chen, Tomas Escudero, Natalie A. Cekleniak, David B. Sable, Margaret G. Garrisi, Santiago Munne. Saint Barnabas Institute for Reproductive Medicine and Science (IRMS), Livingston, NJ. Objective: To determine if maternal balanced translocation is a risk factor for poor ovarian response to controlled ovarian hyperstimulation. Design: A retrospective analysis of ovarian response to gonadotropin stimulation in patients undergoing in vitro fertilization (icsi and non-icsi) and preimplantation genetic diagnosis (IVF/PGD) at a single center. Materials/Methods: All cycles for couples with a balanced autosomal translocation in either partner performed at Saint Barnabas IRMS from 1995 through 2001 were analyzed: a total of 98 cycles in 76 women were completed. Stimulation and embryology outcomes were compared between two groups: 59 cycles in 44 women with balanced translocations (female carrier) compared to 39 cycles in 32 women whose male partner had a balanced translocation (male carrier). Average female age, female smoking history, day 3 FSH, day 3 estradiol levels, and pregnancy rates were similar in both groups. Statistical analysis was performed comparing stimulation protocols, estradiol level on day of hCG, and other cycle parameters.
FERTILITY & STERILITY威
Results: In couples undergoing IVF/PGD to avoid transmission of an unbalanced karyotype, a significantly higher proportion of women carrying balanced translocations (female carrier) responded very poorly (estradiol on the day of hCG less than 1000 pg/mL) to ovarian stimulation compared to women whose partner had a balanced translocation (male carrier) (0.220 vs 0.053, p ⬍0.02). These differences in response occurred despite the fact that there were a significantly higher proportion of patients in the female carrier group using aggressive stimulations, leading us to believe that the risk of poor ovarian response in this group may be underestimated by this data (0.356 vs 0.158, p ⬍0.039). Conclusions: In couples undergoing IVF/PGD for balanced translocation, the risk for poor response to ovarian stimulation is significantly increased when the female partner carries the balanced translocation compared to when the male partner carries the translocation. The reasons for this finding are unknown. In some male translocation patients, a higher incidence of germ cell death has been noted. A similar mechanism should be investigated in female translocation patients. Supported by: No sponsors or grants.
Monday, October 14, 2002 4:00 P.M. O-55 Premature luteinization during GnRH antagonists cycles in IVF adversely affects pregnancy and implantation rates. Ivan Valencia, Ernesto Bosch, Carlos Troncoso, Carlos Simon, Jose Remohi, Antonio Pellicer. Inst Valenciano de Infertilidad, Valencia, Spain; Inst Valenciano de Infertilidad and Dept of Pediatrics, Obstetrics and Gynecology, Valencia Univ Sch of Medicine, Valencia, Spain. Objective: The effect of premature luteinization has always been controversial in IVF cycles. A retrospective analysis of our data from antagonists cycles showed that a serum progesterone ⬎1.2 ng/ml was significantly associated with a worse outcome in terms of pregnancy and implantation rate. Therefore we wanted to clarify this conclusion in a prospective manner. Design: Prospective observational study. Materials/Methods: In October 2001 a prospective study was started comparing GnRH antagonists cycles in IVF. All patients had a serum estradiol, LH and progesterone determination on the day of hCG injection. Premature luteinization was defined as a progesterone level ⬎1.2 ng/ml. Cycles with and without premature luteinization were compared for age, serum estradiol, progesterone and LH level, number of oocytes retrieved and embryos transferred. Pregnancy was defined as the presence of a gestational sac with fetal hearbeat. Implantation rate was defined as the number of fetal heartbeats over the number of embryos transfered. Statistical analysis was done using the Fisher exact test, Mann-Whitney test, logistic regression analysis and ROC curve as appropriate. A p value ⬍0.05 was considered significant. Results: Fifty-two ART cycles were included. One embryo transfer was cancelled because of risk of OHSS and all zygotes were frozen. The incidence of premature luteinization, pregnancy and implantation rates are detailed in Table 1. Premature luteinization on hCG day ocurred in 24/52 cycles (46.2%). No difference was found in age, serum estradiol and LH level on hCG day, number of oocytes retrieved or in the number of embryos transferred between those cycles with and with-out premature luteinization group. A statistically significant difference was only found in the number of gestational sacs observed (0.28 vs 0.78 p ⫽ 0.0208). No LH surge (⬎10 U/L) was noted in any cycle on hCG day. Logistic regression analysis showed the progesterone level to be significantly correlated to cycle outcome ( ⫺1.417 p ⫽ 0.026). The progesterone level of 1.2 ng/ml area under the ROC curve was 0.721 with a 80% sensitivity, 55% specificity, 54% positive predictive value and a 80.4% negative predictive value assuming a 40% pregnancy rate in the no premature luteinization group. Conclusions: These preliminary data from this group of patients showed that premature luteinization during GnRH antagonists IVF cycles was a frequent event and adversely affected the pregnancy and implantation rate. Progesterone elevations were not related to serum LH levels and may reflect the mature granulosa cell response to exogenous FSH exposure. A progesterone level ⬎1.2 ng/ml is the best cut-off criteria for an adverse outcome. Probably GnRH antagonists cycles could benefit from additional routine progesterone monitoring.
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Monday, October 14, 2002 2:30 P.M. O-51 Individual treatment using the GnRH antagonist Cetrotide(R): Optimization of treament. Michael Ludwig, Alexander Katalinic, Constanze Banz, Klaus Diedrich. Dept Gynecology and Obstetrics, Univ Clin Lu¨ beck, Lu¨ beck, Germany; Dept Social Medicine & Cancer Epidemiology, Medical Univ Lu¨ beck, Lu¨ beck, Germany. Objective: Use of the GnRH-antagonist has made ovarian stimulation easier, safer, and more comfortable for the patient. To avoid administration of the antagonist in a too early phase of follicular growth, it might be advantageous to delay administration in individual cases. Doing this, a sudden drop in gonadotrophins during a sensitive period of the follicular phase, with possible subsequent disturbance of follicular and endometrial growth, can be avoided. This individualisation should optimize treatment using a GnRH antagonist in ovarian stimulation. Design: Prospective, randomized controlled study. Materials/Methods: The study was approved by the ethical committee of the university hospital. Fifty-four patients were randomised to receive either the fixed multiple-dose antagonist protocol starting on day 6 of gonadotrophins with Cetrotide 0.25 mg (FIX) (cetrorelix; Serono International S.A., Geneva, Switzerland), or an individualised protocol with start of Cetrotide 0.25 mg when the leading follicle had a size of at least 14 mm (IND), or an individualised single dose protocol using Cetrotide 3 mg (SIN), administered according to follicle size (at least 14 mm). There were 18 patients in each group. Exclusively recombinant FSH (recFSH, Gonal F) was used, starting with 150 IU daily. HCG was given when the leading follicle had a size of at least 18 mm. Primary endpoint was number of Cetrotide ampoules and number of monitoring visits. Statistical power for these parameters was 80%. Results: Patients from the three groups were comparable with regard to important variables like age, number of previous cycles etc. FIX patients needed significantly more Cetrotide ampoules (6.81 ⫹/⫺ 1.61) as compared to IND patients (4.59 ⫹/⫺ 1.65; p ⬍0.01). Number of recFSH days was similar between FIX, IND, and SIN patients with 12.04 ⫹/⫺ 1.65, 11.66 ⫹/⫺ 2.15, and 12.53 ⫹/⫺ 1.92, but total IU of recFSH was significantly lower in IND patients (1838 ⫹/⫺ 576) as compared to FIX (2232 ⫹/⫺ 624; p ⬍0.05) or SIN patients (2350 ⫹/⫺ 618; p ⬍0.05). Mean number of monitoring visits was similar between the three groups and not statistically significant different (2.83 ⫹/⫺ 0.77 vs. 2.43 ⫹/⫺ 0.61 vs. 3.09 ⫹/⫺ 0.63). Number of retrieved oocytes was significantly higher in the individualised groups (IND: 10.97 ⫹/⫺ 7.07; SIN: 11.23 ⫹/⫺ 9.51) as compared to the fixed protocol group (6.15 ⫹/⫺ 4.18; p ⬍0.05). There were 3, 4, and 3 ongoing pregnancies (⬎12 weeks of gestation) in the FIX, IND, and SIN group, respectively. Conclusions: Administration of Cetrotide in an individualized fashion leads to a similiar necessity of monitoring visits. The number of oocytes retrieved is significantly increased, and the number of Cetrotide ampoules is significantly decreased in a multiple-dose protocol. Individualisation makes Cetrotide treatment less expensive and more efficient. Supported by: no financial support.
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Abstracts
Monday, October 14, 2002 2:45 P.M. O-52 Is rapid follicular development during controlled ovarian hyperstimulation (COH) for IVF and ICSI detrimental to success rate? Tarek Ghobara, Patrick Vandekerckhove, Richard Kennedy. Ctr for reproductive Medicine, Coventry and Warwickshire Univ Hosp, Coventry, UK. Objective: To determine whether a rapid follicular growth pattern and a short follicular phase (SFP) during COH in IVF and ICSI cycles is associated with certain clinical or biochemical characteristics of such women, and whether it has an effect on the outcome of such cycles. Design: Retrospective controlled study. Materials/Methods: All IVF and ICSI cycles performed between 1–11998 and 31–12–2001 were reviewed. Cycles in which ⬎⫽3 follicles had reached ⬎⫽17 mm diameter after only nine days of COH and on which oocytes retrieval was performed on day 11 of cycle were identified as cycles with rapid follicular development and SFP. This was the study group of interest. Cycles in which COH was initiated on the same day as each of SFP cycles and in which oocytes retrieval was performed on cycle day 14 or 15 served as the control group. Cycles using donated oocytes were excluded. All women underwent pituitary down regulation using a short acting GnRH agonist followed by follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG). Results: The study included 54 SFP cycles and 169 control cycles. Women age, type of infertility (primary or secondary) or order of IVF and ICSI cycles (first or repeat cycle) were not significantly different between SFP group and control group. Equally, basal FSH levels, treatment type (IVF or ICSI), total dose or type of used FSH or HMG were not significantly different. Male factor infertility was slightly more common in control group than in SFP group 92 (54%) vs. 20 (37%). There were no significant differences in other causes of infertility (tubal, anovulation, poor ovarian reserve, endometriosis and unexplained). The number of large size follicles (⬎⫽17mm) (5.4 vs. 5.1) or the total number of large and medium (14 – 16mm) size follicles (8.6 vs. 9.6) on ultrasound scan 48 hours prior to oocytes retrieval were not significantly different. There were less medium size follicles in SFP group (3.2 vs. 4.5, P ⬍0.01). The number of retrieved oocytes (8.1 vs. 9.6, p ⫽ 0.03) and the number of fertilized oocytes (5.3 vs. 6.7, P ⫽ 0.04) were less in the SFP group. However, there was no significant difference in fertilization rate (70% vs. 69.7%), number of transferred embryos (2.1 vs. 2.05) and number of frozen embryos (2.1 vs. 2.8). The clinical pregnancy rate [18 (33%) vs. 63 (37%)], ectopic pregnancy, miscarriage or live birth rates were not significantly different between the two groups. Conclusions: In our study a SFP was not associated with advanced women’s age or higher basal FSH levels. The smaller number of medium size follicles in the SFP group suggests that a second cohort of follicles did not have a chance to complete its development. This reflected itself in a smaller number of retrieved and fertilised oocytes. Nevertheless, the numbers of frozen embryos, clinical pregnancy, live birth rates were not different and the clinical significance of these differences is therefore doubtful. A SFP seems therefore to have no detrimental effect on oocyte quality, endometrial development or embryo implantation. Although a SFP in the spontaneous cycle has been found by some to be associated with reduced fertility, this appeared not to be the case during COH for IVF and ICSI. During COH the outcome of cycles with SFP is comparable to cycles with ‘normal’ follicular phase length. Supported by: Centre for Reproductive Medicine, Coventry, UK.
Monday, October 14, 2002 3:00 P.M. O-53 Intercycle variability in antral follicle count and its effect upon stimulation quality in in vitro fertilization. Karl R. Hansen, Jamie L. Morris, Michael R. Soules. Univ of Washington, Seattle, WA. Objective: The development of multiple follicles in response to gonadotropin treatment is critical to successful outcomes in assisted reproductive technologies (ART). The number of antral follicles (AFs) identified prior to
Vol. 78, No. 3, Suppl. 1, September 2002
stimulation in ART cycles has been shown to correlate well with multiple measures of in vitro fertilization (IVF) outcome. It is widely believed that the number of AFs correlates with the primordial follicle reserve. However, little is known about intercycle variability in antral follicle (AF) counts in patients undergoing IVF. Additionally the effect of these differences upon stimulation quality has not been investigated. Design: Retrospective study; university ART clinic. Materials/Methods: Patients experiencing two or more IVF cycles within a one-year interval between 2000 –2002 were included if AF counts were obtained during the pre-stimulation ultrasound. (In a separate group of normal women (n ⫽ 20) we found no significant change in AF count before and after treatment with a GnRH agonist.) Forty-seven patients (age 23– 45) having undergone a total of 101 IVF cycles were identified. To evaluate intercycle variability, means and percent change from the mean in AF counts were calculated and compared. Mean AF counts were also compared to means of parameters of IVF stimulation quality, including oocytes recovered, peak estradiol, length of stimulation, and gonadotropin dose. Comparisons of IVF stimulation quality were made between the low and high AF count cycle through a paired analysis. Comparisons were also made between the low and high AF count cycles and simulation quality in individuals with greater intercycle AF count variability (⬎50% change from the mean), and between individuals with greater vs. lesser intercycle variability. Statistical analysis included Wilcoxon signed-rank, Mann-Whitney (rank-sum) tests, and Spearman Correlation Coefficients. Results: AF count was positively correlated with the number of oocytes retrieved (r ⫽ 0.71, p ⫽ ⬍0.0001), peak estradiol (r ⫽ 0.50, p ⫽ 0.0007), and negatively correlated with gonadotropin dose (r ⫽ ⫺0.66, p ⫽ ⬍0.0001). Intercycle variability in AF number was greater at lower AF counts (r ⫽ ⫺0.31, p ⫽ 0.036), but was not correlated with age (p ⫽ NS). Paired analysis of stimulation quality between the low and high AF count cycle for each patient did not show a difference in oocytes retrieved, peak estradiol, gonadotropin dose, or biochemical and clinical pregnancy rates (p ⫽ NS). Stimulation quality was greater in individuals with lesser intercycle variability (p ⫽ 0.0036); however, no difference was detected in comparison of the lower to higher AF count cycle in individuals with greater intercycle variability. Conclusions: There is moderate intercycle variability in AF number, and this variability is greater in individuals with lower AF counts. Although AF count was well correlated with multiple parameters of IVF outcome; within an individual patient, higher AF count in a given cycle was not predictive of better stimulation quality compared to a lower count cycle. Therefore, it does not appear to be prudent to attempt to select an optimal cycle for stimulation in a particular patient. Greater intercycle variability is associated with decreased ovarian reserve. Supported by: The Division of Reproductive Endocrinology and Infertility, University of Washington.
Monday, October 14, 2002 3:45 P.M. O-54 Maternal balanced translocation is a risk factor for poor response to ovarian stimulation. Serena H. Chen, Tomas Escudero, Natalie A. Cekleniak, David B. Sable, Margaret G. Garrisi, Santiago Munne. Saint Barnabas Institute for Reproductive Medicine and Science (IRMS), Livingston, NJ. Objective: To determine if maternal balanced translocation is a risk factor for poor ovarian response to controlled ovarian hyperstimulation. Design: A retrospective analysis of ovarian response to gonadotropin stimulation in patients undergoing in vitro fertilization (icsi and non-icsi) and preimplantation genetic diagnosis (IVF/PGD) at a single center. Materials/Methods: All cycles for couples with a balanced autosomal translocation in either partner performed at Saint Barnabas IRMS from 1995 through 2001 were analyzed: a total of 98 cycles in 76 women were completed. Stimulation and embryology outcomes were compared between two groups: 59 cycles in 44 women with balanced translocations (female carrier) compared to 39 cycles in 32 women whose male partner had a balanced translocation (male carrier). Average female age, female smoking history, day 3 FSH, day 3 estradiol levels, and pregnancy rates were similar in both groups. Statistical analysis was performed comparing stimulation protocols, estradiol level on day of hCG, and other cycle parameters.
FERTILITY & STERILITY威
Results: In couples undergoing IVF/PGD to avoid transmission of an unbalanced karyotype, a significantly higher proportion of women carrying balanced translocations (female carrier) responded very poorly (estradiol on the day of hCG less than 1000 pg/mL) to ovarian stimulation compared to women whose partner had a balanced translocation (male carrier) (0.220 vs 0.053, p ⬍0.02). These differences in response occurred despite the fact that there were a significantly higher proportion of patients in the female carrier group using aggressive stimulations, leading us to believe that the risk of poor ovarian response in this group may be underestimated by this data (0.356 vs 0.158, p ⬍0.039). Conclusions: In couples undergoing IVF/PGD for balanced translocation, the risk for poor response to ovarian stimulation is significantly increased when the female partner carries the balanced translocation compared to when the male partner carries the translocation. The reasons for this finding are unknown. In some male translocation patients, a higher incidence of germ cell death has been noted. A similar mechanism should be investigated in female translocation patients. Supported by: No sponsors or grants.
Monday, October 14, 2002 4:00 P.M. O-55 Premature luteinization during GnRH antagonists cycles in IVF adversely affects pregnancy and implantation rates. Ivan Valencia, Ernesto Bosch, Carlos Troncoso, Carlos Simon, Jose Remohi, Antonio Pellicer. Inst Valenciano de Infertilidad, Valencia, Spain; Inst Valenciano de Infertilidad and Dept of Pediatrics, Obstetrics and Gynecology, Valencia Univ Sch of Medicine, Valencia, Spain. Objective: The effect of premature luteinization has always been controversial in IVF cycles. A retrospective analysis of our data from antagonists cycles showed that a serum progesterone ⬎1.2 ng/ml was significantly associated with a worse outcome in terms of pregnancy and implantation rate. Therefore we wanted to clarify this conclusion in a prospective manner. Design: Prospective observational study. Materials/Methods: In October 2001 a prospective study was started comparing GnRH antagonists cycles in IVF. All patients had a serum estradiol, LH and progesterone determination on the day of hCG injection. Premature luteinization was defined as a progesterone level ⬎1.2 ng/ml. Cycles with and without premature luteinization were compared for age, serum estradiol, progesterone and LH level, number of oocytes retrieved and embryos transferred. Pregnancy was defined as the presence of a gestational sac with fetal hearbeat. Implantation rate was defined as the number of fetal heartbeats over the number of embryos transfered. Statistical analysis was done using the Fisher exact test, Mann-Whitney test, logistic regression analysis and ROC curve as appropriate. A p value ⬍0.05 was considered significant. Results: Fifty-two ART cycles were included. One embryo transfer was cancelled because of risk of OHSS and all zygotes were frozen. The incidence of premature luteinization, pregnancy and implantation rates are detailed in Table 1. Premature luteinization on hCG day ocurred in 24/52 cycles (46.2%). No difference was found in age, serum estradiol and LH level on hCG day, number of oocytes retrieved or in the number of embryos transferred between those cycles with and with-out premature luteinization group. A statistically significant difference was only found in the number of gestational sacs observed (0.28 vs 0.78 p ⫽ 0.0208). No LH surge (⬎10 U/L) was noted in any cycle on hCG day. Logistic regression analysis showed the progesterone level to be significantly correlated to cycle outcome ( ⫺1.417 p ⫽ 0.026). The progesterone level of 1.2 ng/ml area under the ROC curve was 0.721 with a 80% sensitivity, 55% specificity, 54% positive predictive value and a 80.4% negative predictive value assuming a 40% pregnancy rate in the no premature luteinization group. Conclusions: These preliminary data from this group of patients showed that premature luteinization during GnRH antagonists IVF cycles was a frequent event and adversely affected the pregnancy and implantation rate. Progesterone elevations were not related to serum LH levels and may reflect the mature granulosa cell response to exogenous FSH exposure. A progesterone level ⬎1.2 ng/ml is the best cut-off criteria for an adverse outcome. Probably GnRH antagonists cycles could benefit from additional routine progesterone monitoring.
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