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The oocytes donation as a model to study the effect of estradiol level on oocytes quality.
Conclusions: 225 IU is more efficacious than 150 IU of Gonal-F® with respect to the number of oocytes retrieved, although this required a higher total dose of Gonal-F®. The high cancellation rate with 150 IU would suggest that this dose is insufficient in some patients to achieve the threshold for multiple follicular development. Increasing the dose in older patients (ⱖ33 y) did not result in higher oocyte numbers, suggesting that increasing the dose of rFSH does not compensate for the age-related decrease in ovarian reserve.
P-195 The oocytes donation as a model to study the effect of estradiol level on oocytes quality. F. Cano, J. Idrobo, M. Molla´, A. Ballesteros, J. Landeras, J. Remohı´. IVI Murcia, Murcia, Spain; IVI, Valencia, Spain. Objective: Although controversial, there is general agreement about the poor in-vitro fertilization (IVF) results in high responder patients. The detrimental effect on uterine receptivity of high serum estradiol concentration has been demonstrated, but the relationship between high levels of estradiol levels and diminished oocyte and embryo quality is to date under debate. This clinical study was undertaken to analyze the effect of estradiol levels on oocyte-embryo quality. Design: The reproductive outcome of oocytes recipients have been studied according to the estradiol levels of pure oocytes donor. Materials/Methods: 92 cycles of oocytes recipients were included in the analysis. The patients were divided into four groups, according to the estradiol level of the oocytes donors on the hCG day: 1000 –2000 pg/ml (21 oocytes recipients cycles); 2000 –3000 pg/ml (30); 3000 – 4000 pg/ml (19); ⬎4000 pg/ml (22). A long stimulation protocol was used for the oocyte donors, and steroid replacement was used in the oocyte recipients. Patients with ovarian function were desensitized with leuprolide acetate in the secretory phase of the previous cycle. Quality of the donated oocytes and transferred embryos, fertilization, implantation and pregnancy rates were analyzed. Results: The four groups were similar in age, estradiol levels at transference day, and number of days of hormonal replacement before the embryo transfer. Fertilization rate, quality and number of embryo transferred, pregnancy, implantation and miscarriage rates were not significantly different between the groups. Estradiol levels the hCG day(pg/ml) Oocytes Recipients Cycles Inseminated Oocytes Embryo Quality (No. Blast. ⫹ Frag. Degree) Fertilization rate Transferred Embryos Pregnancy rate Implantation rate Miscarriage rate
1000–2000 2001–3000 3001–4000
⬎4000
21
30
19
22
8.1 ⫾ 2.5 3.1 ⫾ 1.5
7.9 ⫾ 2.1 3.0 ⫾ 1.4
7.6 ⫾ 1.3 3.3 ⫾ 1.3
8.0 ⫾ 1.7 3.1 ⫾ 1.1
79.3 ⫾ 18.6 78.7 ⫾ 19.7 81.2 ⫾ 15.9 70.8 ⫾ 27.1 3.4 ⫾ 0.9 3.2 ⫾ 1.1 2.8 ⫾ 1.3 3.1 ⫾ 1.3 9/21 (42.8) 14/30 (46.6) 10/19 (52.6) 14/22 (63.6) 17.3 19.2 26.8 20.8 2/9 (22.2) 2/14 (14.2) 2/10 (20) 3/14 (21.4)
Conclusions: Estradiol level of oocytes donors does not affect the oocytes and embryo quality, and the outcome of the oocytes donation program is not altered by the high levels of estradiol in the oocytes donors. Supported by: IVI-MURCIA.
P-196 A drop in serum estradiol prior to the administration of human chorionic gonadotropin (hCG) is not predictive of pregnancy outcome following in vitro fertilization (IVF) cycles. A. K. Styer, K. V. Jackson, M. D. Hornstein, C. Racowsky, E. S. Ginsburg, A. R. Gargiulo. Brigham and Women’s Hosp, Harvard Medical Sch, Boston, MA. Objective: An estradiol drop during controlled ovarian hyperstimulation for purposes of IVF has been traditionally considered a potential indication
S178
Abstracts
for cycle cancellation. In fact, no study to date has addressed the issue of whether such an estradiol drop has any effect on pregnancy outcome. Therefore, this study was undertaken to analyze the effect of an unpredictable drop in serum estradiol prior to hCG administration on pregnancy outcomes in IVF cycles. Design: Case-control study. Materials/Methods: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 were retrospectively reviewed. Our current protocol empirically recommends cancellation of IVF cycles that show a ⬎30% drop in serum estradiol (E2) in the absence of complete withdrawal of gonadotropin administration (i.e. coasting). 65 cycles were identified in which an egg retrieval (ER) was performed following a drop in serum E2 level that was not associated with coasting. In 25 of these cycles, daily gonadotropin dose was decreased at some time during the stimulation cycle, and in 40 there was no gonadotropin dose reduction. The ongoing-delivered pregnancy rates and pregnancy loss rates (spontaneous abortion, chemical, and ectopic) in the study cycles were compared to age and stimulation patternmatched control cycles in which there was no drop in the serum E2 level prior to ER. Data were analyzed using Mann-Whitney U, Chi square and Fisher’s exact tests as appropriate, with P ⬍ 0.05 considered statistically significant. Results: The study group and controls did not differ for day 3 FSH, number of prior IVF cycles, number of oocytes retrieved, fertilization rates or number of embryos transferred. There was no significant difference between the study group and the controls for ongoing-delivered rates (32% vs. 38%, p ⫽ 0.46) or pregnancy loss rates (28% vs. 24%, p ⫽ 0.76). Furthermore, when comparing exclusively those study and control cycles with a reduction in gonadotropin administration, there was no difference in either ongoing-delivered rates (44% vs. 52%, p ⫽ 0.57) or pregnancy loss rates (21% vs. 28%, p ⫽ 0.68). Similarly, there was no difference in ongoing pregnancy rates (25% vs. 30%, p ⫽ 0.62) or pregnancy loss rates (33% vs. 20%, p ⫽ 0.41) in the absence of a reduction in gonadotropin dose. When the study group was further stratified by the magnitude of estradiol drop (10% and ⱖ10% of prior level), no significant difference was seen in ongoing pregnancy rates and pregnancy loss rates (29% vs. 37%, p ⫽ 0.59, and 35% vs. 17%, p ⫽ 0.41, respectively). These trends were observed regardless of any decrease in gonadotropin dose used. Conclusions: In the absence of coasting, a drop in serum estradiol level during controlled ovarian hyperstimulation for IVF is not associated with a decrease in ongoing pregnancy rate. Cycle cancellation, as routinely recommended in this clinical setting, may not be warranted in all cases. The present analysis justifies a prospective study where cycles exhibiting an estradiol drop are not cancelled in order to determine definitive estradiol drop cancellation criteria.
P-197 Luteinizing hormone (LH) surge on ganirelix (Antagon) is related to increased body mass index (BMI). R. I. Hardy, I. S. Tummon, M. Hosseinzadeh, V. R. Cardone, M. Seibel, M. Lee. Fertility Ctr of New England, Topsfield, MA; Fertility Ctr of New England, Reading, MA. Objective: Initial phase III clinical trials of ganirelix in IVF patients did not report an effect of BMI on LH surges; however, the patient population was limited to a BMI between 18 and 29 kg/m2. This study examines the incidence of LH surge in IVF patients on ganirelix with a BMI ⬎29 kg/m2. Design: Retrospective analysis of IVF clinical data. Materials/Methods: Seventy-six infertility patients, ranging in age from 26 – 46, were enrolled in a ganirelix IVF protocol. Ovulation induction involved clomiphene citrate (100 mg cycle days 2– 6) with recombinant FSH (cycle day 2 until hCG Rx). Ganirelix was administered on cycle day 8 at a dose of 0.25 mg and continued daily until hCG Rx. Blood samples were obtained on cycle days 2,5, and daily from cycle day 8 until oocyte retrieval. Concentrations of 17 [Szlig]-estradiol, progesterone, and LH were analyzed with electrochemicoluminescence immunoassays. The intra-assay coefficient of variation for LH was 1.6%. An LH surge was defined as ⬎10 IU/L. BMI was calculated by measured height and weight. A scatterplot of BMI and LH was produced and incidence of LH surge compared by Student’s t-test. Results: LH surges while on ganirelix occurred in 6 of the 76 patients. Two of these cycles were cancelled. Oocytes were retrieved in the remaining 4 cycles. One of the four retrieved cycles resulted in an on-going pregnancy. The LH surges occurred with a BMI range of 19.8 to 44.8;
Vol. 76, No. 3, Suppl. 1, September 2001
P-195 The oocytes donation as a model to study the effect of estradiol level on oocytes quality. F. Cano, J. Idrobo, M. Molla´, A. Ballesteros, J. Landeras, J. Remohı´. IVI Murcia, Murcia, Spain; IVI, Valencia, Spain. Objective: Although controversial, there is general agreement about the poor in-vitro fertilization (IVF) results in high responder patients. The detrimental effect on uterine receptivity of high serum estradiol concentration has been demonstrated, but the relationship between high levels of estradiol levels and diminished oocyte and embryo quality is to date under debate. This clinical study was undertaken to analyze the effect of estradiol levels on oocyte-embryo quality. Design: The reproductive outcome of oocytes recipients have been studied according to the estradiol levels of pure oocytes donor. Materials/Methods: 92 cycles of oocytes recipients were included in the analysis. The patients were divided into four groups, according to the estradiol level of the oocytes donors on the hCG day: 1000 –2000 pg/ml (21 oocytes recipients cycles); 2000 –3000 pg/ml (30); 3000 – 4000 pg/ml (19); ⬎4000 pg/ml (22). A long stimulation protocol was used for the oocyte donors, and steroid replacement was used in the oocyte recipients. Patients with ovarian function were desensitized with leuprolide acetate in the secretory phase of the previous cycle. Quality of the donated oocytes and transferred embryos, fertilization, implantation and pregnancy rates were analyzed. Results: The four groups were similar in age, estradiol levels at transference day, and number of days of hormonal replacement before the embryo transfer. Fertilization rate, quality and number of embryo transferred, pregnancy, implantation and miscarriage rates were not significantly different between the groups. Estradiol levels the hCG day(pg/ml) Oocytes Recipients Cycles Inseminated Oocytes Embryo Quality (No. Blast. ⫹ Frag. Degree) Fertilization rate Transferred Embryos Pregnancy rate Implantation rate Miscarriage rate
1000–2000 2001–3000 3001–4000
⬎4000
21
30
19
22
8.1 ⫾ 2.5 3.1 ⫾ 1.5
7.9 ⫾ 2.1 3.0 ⫾ 1.4
7.6 ⫾ 1.3 3.3 ⫾ 1.3
8.0 ⫾ 1.7 3.1 ⫾ 1.1
79.3 ⫾ 18.6 78.7 ⫾ 19.7 81.2 ⫾ 15.9 70.8 ⫾ 27.1 3.4 ⫾ 0.9 3.2 ⫾ 1.1 2.8 ⫾ 1.3 3.1 ⫾ 1.3 9/21 (42.8) 14/30 (46.6) 10/19 (52.6) 14/22 (63.6) 17.3 19.2 26.8 20.8 2/9 (22.2) 2/14 (14.2) 2/10 (20) 3/14 (21.4)
Conclusions: Estradiol level of oocytes donors does not affect the oocytes and embryo quality, and the outcome of the oocytes donation program is not altered by the high levels of estradiol in the oocytes donors. Supported by: IVI-MURCIA.
P-196 A drop in serum estradiol prior to the administration of human chorionic gonadotropin (hCG) is not predictive of pregnancy outcome following in vitro fertilization (IVF) cycles. A. K. Styer, K. V. Jackson, M. D. Hornstein, C. Racowsky, E. S. Ginsburg, A. R. Gargiulo. Brigham and Women’s Hosp, Harvard Medical Sch, Boston, MA. Objective: An estradiol drop during controlled ovarian hyperstimulation for purposes of IVF has been traditionally considered a potential indication
S178
Abstracts
for cycle cancellation. In fact, no study to date has addressed the issue of whether such an estradiol drop has any effect on pregnancy outcome. Therefore, this study was undertaken to analyze the effect of an unpredictable drop in serum estradiol prior to hCG administration on pregnancy outcomes in IVF cycles. Design: Case-control study. Materials/Methods: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 were retrospectively reviewed. Our current protocol empirically recommends cancellation of IVF cycles that show a ⬎30% drop in serum estradiol (E2) in the absence of complete withdrawal of gonadotropin administration (i.e. coasting). 65 cycles were identified in which an egg retrieval (ER) was performed following a drop in serum E2 level that was not associated with coasting. In 25 of these cycles, daily gonadotropin dose was decreased at some time during the stimulation cycle, and in 40 there was no gonadotropin dose reduction. The ongoing-delivered pregnancy rates and pregnancy loss rates (spontaneous abortion, chemical, and ectopic) in the study cycles were compared to age and stimulation patternmatched control cycles in which there was no drop in the serum E2 level prior to ER. Data were analyzed using Mann-Whitney U, Chi square and Fisher’s exact tests as appropriate, with P ⬍ 0.05 considered statistically significant. Results: The study group and controls did not differ for day 3 FSH, number of prior IVF cycles, number of oocytes retrieved, fertilization rates or number of embryos transferred. There was no significant difference between the study group and the controls for ongoing-delivered rates (32% vs. 38%, p ⫽ 0.46) or pregnancy loss rates (28% vs. 24%, p ⫽ 0.76). Furthermore, when comparing exclusively those study and control cycles with a reduction in gonadotropin administration, there was no difference in either ongoing-delivered rates (44% vs. 52%, p ⫽ 0.57) or pregnancy loss rates (21% vs. 28%, p ⫽ 0.68). Similarly, there was no difference in ongoing pregnancy rates (25% vs. 30%, p ⫽ 0.62) or pregnancy loss rates (33% vs. 20%, p ⫽ 0.41) in the absence of a reduction in gonadotropin dose. When the study group was further stratified by the magnitude of estradiol drop (10% and ⱖ10% of prior level), no significant difference was seen in ongoing pregnancy rates and pregnancy loss rates (29% vs. 37%, p ⫽ 0.59, and 35% vs. 17%, p ⫽ 0.41, respectively). These trends were observed regardless of any decrease in gonadotropin dose used. Conclusions: In the absence of coasting, a drop in serum estradiol level during controlled ovarian hyperstimulation for IVF is not associated with a decrease in ongoing pregnancy rate. Cycle cancellation, as routinely recommended in this clinical setting, may not be warranted in all cases. The present analysis justifies a prospective study where cycles exhibiting an estradiol drop are not cancelled in order to determine definitive estradiol drop cancellation criteria.
P-197 Luteinizing hormone (LH) surge on ganirelix (Antagon) is related to increased body mass index (BMI). R. I. Hardy, I. S. Tummon, M. Hosseinzadeh, V. R. Cardone, M. Seibel, M. Lee. Fertility Ctr of New England, Topsfield, MA; Fertility Ctr of New England, Reading, MA. Objective: Initial phase III clinical trials of ganirelix in IVF patients did not report an effect of BMI on LH surges; however, the patient population was limited to a BMI between 18 and 29 kg/m2. This study examines the incidence of LH surge in IVF patients on ganirelix with a BMI ⬎29 kg/m2. Design: Retrospective analysis of IVF clinical data. Materials/Methods: Seventy-six infertility patients, ranging in age from 26 – 46, were enrolled in a ganirelix IVF protocol. Ovulation induction involved clomiphene citrate (100 mg cycle days 2– 6) with recombinant FSH (cycle day 2 until hCG Rx). Ganirelix was administered on cycle day 8 at a dose of 0.25 mg and continued daily until hCG Rx. Blood samples were obtained on cycle days 2,5, and daily from cycle day 8 until oocyte retrieval. Concentrations of 17 [Szlig]-estradiol, progesterone, and LH were analyzed with electrochemicoluminescence immunoassays. The intra-assay coefficient of variation for LH was 1.6%. An LH surge was defined as ⬎10 IU/L. BMI was calculated by measured height and weight. A scatterplot of BMI and LH was produced and incidence of LH surge compared by Student’s t-test. Results: LH surges while on ganirelix occurred in 6 of the 76 patients. Two of these cycles were cancelled. Oocytes were retrieved in the remaining 4 cycles. One of the four retrieved cycles resulted in an on-going pregnancy. The LH surges occurred with a BMI range of 19.8 to 44.8;
Vol. 76, No. 3, Suppl. 1, September 2001