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Progesterone elevation during GnRH antagonists cycles in IVF adversely affects pregnancy and implantation rates
effect accross all trials. The pooled results (odds ratio (OR) and crude aggregate pregnancy rates (PR)) and their confidence intervals (CI) are shown in the table. Conclusions: Although a trend towards higher singleton pregnancy rate was observed with recombinant hCG, the meta-analysis only had sufficient power (80%) to detect a difference of 10% in the singleton pregnancy rate over a control event rate of 16%. Smaller differences may exist but were undetectable with the sample size currently available. The upper confidence limit indicates that a clinically significant improvement in singleton pregnancy rate is possible and further RCTs will be required to test this hypothesis. In the absence of a deleterious effect on outcome, recombinant hCG is an attractive alternative to urinary hCG because of its purity. Supported by: None.
P-95 Comparison of intracytoplasmic sperm injection pregnancy rates in Eastern Indian and Caucasian women. Collin Smikle, Susan P. Willman, Denise Walker, Kristin Ivani. Reproductive Science Ctr of the San Francisco Bay Area, San Ramon, CA. Objective: To compare the outcome differences in East Indian and Caucasian women who were treated with Intracytoplasmic Sperm Injection. Design: Retrospective chart review of East Indian patients using case controls from the Caucasian patient population. Materials/Methods: Pregnancy rate was the main outcome variable assessed in a chart review of East Indian and Caucasian women undergoing in vitro fertilization and intracytoplasmic sperm injection from January 2000 to March 2002. Results: There were 41 East Indian and 328 Caucasian women ⬍35 years of age who underwent their first cycle of in vitro fertilization and intracytoplasmic sperm injection (ICSI) during this period. Treatment cycles evaluated were first IVF cycles with embryo transfer performed at 72 hours. Intracytoplasmic sperm injection was performed for oligoasthenospermia in 108 of 328 treatment cycles (32.9%) of the Caucasian group and 24 of 41 treatment cycle (58.5%) in the East Indian group; p ⫽.0491. Comparing only ICSI cycles using fresh ejaculate sperm, the pregnancy rates were 37% (40/108) in the Caucasian vs. 12.5%(3/24)in the East Indian group; p ⫽.02. There were no differences in the number of days of gonadotropin therapy, peak estradiol levels, number of oocytes recovered, fertilization rate, number of embryos transferred, nor embryo quality as assessed by morphology and cell division (cumulative embryo score (CES). Number of surplus embryos cryopreserved (cryo) was also evaluated as an indirect indicator of embryo quality and there was no difference. Conclusions: A higher incidence of male factor infertility requiring ICSI as an intervention was observed in the East Indian population. This study confirms an earlier observation that Eastern Indian women demonstrate a significantly lower clinical pregnancy rate as compared to Caucasian women undergoing ART. This lower pregnancy rate is not predicted by the age of the female partner, ovarian response, or embryo morphology. Further studies are needed to identify the factors that may contribute to the observed discrepancy. Supported by: Reproductive Science Center of the San Francisco Bay Area and IntegraMed.
February 2002 that had a serum E2, LH and P4 level on hCG injection day were included. No distinction was made between day 6 or 14 mm follicle criteria to start the antagonist. Premature luteinization was define as a P4 to E2 ratio ⱖ1 (P4 ng/ml ⫻ 1000/E2 pg/ml), as a P4 levelⱖ1 ng/ml and as a P4 level ⱖ1.2 ng/ml. Cycles with and without premature luteinization were compared for age, day 3 basal hormones, serum E2, p4 level and LH, and number of mature (ⱖ16 mm) follicles on hCG day, mature oocytes retrieved, total FSH dose, total HMG dose, days of antagonists use, days of ovarian stimulation and number of 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-Whiney test, logistic regression anaylisis and ROC curve as appropiate. Results: Ninety-two ART cycles were studied over a 5 month period. Ten cycles did not have embryos transferred. The incidence of premature luteinization, pregnancy and implantation rates are despicted in Table 1. No difference was found in age, day 3 basal hormones, LH on hCG day, number of mature folicle and number of mature oocyte retrieved. A statistically significant difference was found in the total FSH dose, total HMG dose, days of stimulation and in the days of antagonists use in all 3 cut-offs groups. No LH surges (ⱖ10 U) were noted in any cycle on hCG day. Logistic regression analysis showed the P4 level to be significantly correlated to the outcome (-1.283 p ⫽ 0.002). P4 level and P4/E2 ratio areas under the ROC curve were 0.695 and 0.601 with the difference been statistically different (p ⫽ 0.048) The ROC curve showed a P4 level of ⱖ1.2 ng/ml as the most efficient cut-off criteria to discriminated between the pregnant and no pregnant cycles with a 85.2% sensitivity, 47.3% specificity, 51.9% positive predictive value and 82.7% negative predictive value. Three criteria for premature luteinization and cycle outcome P4/E2 ratio
P4 level ng/ml
ⱖ1 ⱕ0.9 ⱖ1 ⱕ0.9 ⱖ1.2 ⱕ1.1 Cycles 19 No. of Transfers 16 Incidence 20.6 Pregnancy rate per transfer (%) 18.7 Implantation rate (%) 7.32
73 66
45 40 48.9 36.4 20 18.53 10.3
47 42
37 33 40.2 45.2* 18.2 22.3* 9.3
55 49 42.9* 21*
* p less than 0.05 Conclusions: Premature luteinization during GnRH antagonists IVF cycles is a frequent event and adversely affects the pregnancy and implantation rate basically disturbing endometrial receptivity. P4 elevations are not caused by LH escapes and reflects the mature granulosa cell response to continued and prolonged exogenous FSH exposure. A P4 level ⱖ1.2 ng/ml is the best cut-off criteria for an adverse outcome. A randomized trial is under way to confirm these results and to find the best approach in cases of premature luteinization. Supported by: IVI Valencia.
P-97
ART: OVARIAN STIMULATION P-96 Progesterone elevation during GnRH antagonists cycles in IVF adversely affects pregnancy and implantation rates. Ivan Valencia, Ernesto Bosch, Carlos Simon, Carlos Troncoso, Jose´ Remohi, Antonio Pellicer. Inst Valenciano de Infertilidad, Valencia, Spain. Objective: Premature luteinization has always been controversial in IVF cycles. Subtle P4 elevations (ⱖ 0.9 ng/ml) have been recently described during the late follicular phase in GnRH antagonists cycles. Therefore, the objective of this study was to analize the incidence and effect of premature luteinization in GnRH antagonists cycles for IVF using the various definitions listed in the literature and to define cut-off values for clinical use. Design: Retrospective study. Materials/Methods: All GnRH antagonists cycles from October 2001 to
S148
Abstracts
Oocyte recruitment in IVF patients with limited ovarian reserve (LOR), maximizing quality of ooctyes and embryos. Douglas Chapman Daly, Cheryl L. Daly, David Mayo, Andrew Jacobs. Grand Rapids Fertility & IVF and the Dept of Ob/Gyn of Medical Education and Research Council of Grand Rapids and Michigan State Univ Coll of Human Medicine, Grand Rapids, MI; Grand Rapids Fertility & IVF, Grand Rapids, MI. Objective: Quality embryos derived from quality oocytes lead to pregnancy. Patients with LOR can not respond to FSH stimulation with large numbers of oocytes. Oocyte quality is more important in these patients. We wondered if the hormonal environment during the weeks pre-induction effected oocyte quality. We wished to evaluate an induction protocol utilizing 2mg estradiol(E2)in the luteal phase of the preparation cycle followed by FSH(300IU) starting cycle day(CD)2, and late follicular ganirelix acetate with 375IU FSH/150IU LH (E2/nat) versus our established protocol of pre-induction birth control pills followed by microdose leuprolide and 300IU FSH/75IU LH (BCP/micr).
Vol. 78, No. 3, Suppl. 1, September 2002
P-95 Comparison of intracytoplasmic sperm injection pregnancy rates in Eastern Indian and Caucasian women. Collin Smikle, Susan P. Willman, Denise Walker, Kristin Ivani. Reproductive Science Ctr of the San Francisco Bay Area, San Ramon, CA. Objective: To compare the outcome differences in East Indian and Caucasian women who were treated with Intracytoplasmic Sperm Injection. Design: Retrospective chart review of East Indian patients using case controls from the Caucasian patient population. Materials/Methods: Pregnancy rate was the main outcome variable assessed in a chart review of East Indian and Caucasian women undergoing in vitro fertilization and intracytoplasmic sperm injection from January 2000 to March 2002. Results: There were 41 East Indian and 328 Caucasian women ⬍35 years of age who underwent their first cycle of in vitro fertilization and intracytoplasmic sperm injection (ICSI) during this period. Treatment cycles evaluated were first IVF cycles with embryo transfer performed at 72 hours. Intracytoplasmic sperm injection was performed for oligoasthenospermia in 108 of 328 treatment cycles (32.9%) of the Caucasian group and 24 of 41 treatment cycle (58.5%) in the East Indian group; p ⫽.0491. Comparing only ICSI cycles using fresh ejaculate sperm, the pregnancy rates were 37% (40/108) in the Caucasian vs. 12.5%(3/24)in the East Indian group; p ⫽.02. There were no differences in the number of days of gonadotropin therapy, peak estradiol levels, number of oocytes recovered, fertilization rate, number of embryos transferred, nor embryo quality as assessed by morphology and cell division (cumulative embryo score (CES). Number of surplus embryos cryopreserved (cryo) was also evaluated as an indirect indicator of embryo quality and there was no difference. Conclusions: A higher incidence of male factor infertility requiring ICSI as an intervention was observed in the East Indian population. This study confirms an earlier observation that Eastern Indian women demonstrate a significantly lower clinical pregnancy rate as compared to Caucasian women undergoing ART. This lower pregnancy rate is not predicted by the age of the female partner, ovarian response, or embryo morphology. Further studies are needed to identify the factors that may contribute to the observed discrepancy. Supported by: Reproductive Science Center of the San Francisco Bay Area and IntegraMed.
February 2002 that had a serum E2, LH and P4 level on hCG injection day were included. No distinction was made between day 6 or 14 mm follicle criteria to start the antagonist. Premature luteinization was define as a P4 to E2 ratio ⱖ1 (P4 ng/ml ⫻ 1000/E2 pg/ml), as a P4 levelⱖ1 ng/ml and as a P4 level ⱖ1.2 ng/ml. Cycles with and without premature luteinization were compared for age, day 3 basal hormones, serum E2, p4 level and LH, and number of mature (ⱖ16 mm) follicles on hCG day, mature oocytes retrieved, total FSH dose, total HMG dose, days of antagonists use, days of ovarian stimulation and number of 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-Whiney test, logistic regression anaylisis and ROC curve as appropiate. Results: Ninety-two ART cycles were studied over a 5 month period. Ten cycles did not have embryos transferred. The incidence of premature luteinization, pregnancy and implantation rates are despicted in Table 1. No difference was found in age, day 3 basal hormones, LH on hCG day, number of mature folicle and number of mature oocyte retrieved. A statistically significant difference was found in the total FSH dose, total HMG dose, days of stimulation and in the days of antagonists use in all 3 cut-offs groups. No LH surges (ⱖ10 U) were noted in any cycle on hCG day. Logistic regression analysis showed the P4 level to be significantly correlated to the outcome (-1.283 p ⫽ 0.002). P4 level and P4/E2 ratio areas under the ROC curve were 0.695 and 0.601 with the difference been statistically different (p ⫽ 0.048) The ROC curve showed a P4 level of ⱖ1.2 ng/ml as the most efficient cut-off criteria to discriminated between the pregnant and no pregnant cycles with a 85.2% sensitivity, 47.3% specificity, 51.9% positive predictive value and 82.7% negative predictive value. Three criteria for premature luteinization and cycle outcome P4/E2 ratio
P4 level ng/ml
ⱖ1 ⱕ0.9 ⱖ1 ⱕ0.9 ⱖ1.2 ⱕ1.1 Cycles 19 No. of Transfers 16 Incidence 20.6 Pregnancy rate per transfer (%) 18.7 Implantation rate (%) 7.32
73 66
45 40 48.9 36.4 20 18.53 10.3
47 42
37 33 40.2 45.2* 18.2 22.3* 9.3
55 49 42.9* 21*
* p less than 0.05 Conclusions: Premature luteinization during GnRH antagonists IVF cycles is a frequent event and adversely affects the pregnancy and implantation rate basically disturbing endometrial receptivity. P4 elevations are not caused by LH escapes and reflects the mature granulosa cell response to continued and prolonged exogenous FSH exposure. A P4 level ⱖ1.2 ng/ml is the best cut-off criteria for an adverse outcome. A randomized trial is under way to confirm these results and to find the best approach in cases of premature luteinization. Supported by: IVI Valencia.
P-97
ART: OVARIAN STIMULATION P-96 Progesterone elevation during GnRH antagonists cycles in IVF adversely affects pregnancy and implantation rates. Ivan Valencia, Ernesto Bosch, Carlos Simon, Carlos Troncoso, Jose´ Remohi, Antonio Pellicer. Inst Valenciano de Infertilidad, Valencia, Spain. Objective: Premature luteinization has always been controversial in IVF cycles. Subtle P4 elevations (ⱖ 0.9 ng/ml) have been recently described during the late follicular phase in GnRH antagonists cycles. Therefore, the objective of this study was to analize the incidence and effect of premature luteinization in GnRH antagonists cycles for IVF using the various definitions listed in the literature and to define cut-off values for clinical use. Design: Retrospective study. Materials/Methods: All GnRH antagonists cycles from October 2001 to
S148
Abstracts
Oocyte recruitment in IVF patients with limited ovarian reserve (LOR), maximizing quality of ooctyes and embryos. Douglas Chapman Daly, Cheryl L. Daly, David Mayo, Andrew Jacobs. Grand Rapids Fertility & IVF and the Dept of Ob/Gyn of Medical Education and Research Council of Grand Rapids and Michigan State Univ Coll of Human Medicine, Grand Rapids, MI; Grand Rapids Fertility & IVF, Grand Rapids, MI. Objective: Quality embryos derived from quality oocytes lead to pregnancy. Patients with LOR can not respond to FSH stimulation with large numbers of oocytes. Oocyte quality is more important in these patients. We wondered if the hormonal environment during the weeks pre-induction effected oocyte quality. We wished to evaluate an induction protocol utilizing 2mg estradiol(E2)in the luteal phase of the preparation cycle followed by FSH(300IU) starting cycle day(CD)2, and late follicular ganirelix acetate with 375IU FSH/150IU LH (E2/nat) versus our established protocol of pre-induction birth control pills followed by microdose leuprolide and 300IU FSH/75IU LH (BCP/micr).
Vol. 78, No. 3, Suppl. 1, September 2002