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Comparison of microdose and standard doses of GnRH analogue in flare protocols for controlled ovarian hyperstimulation in poor responders.
Group Group Group Group Group Group
A. 1st Cycle D5 (N ⫽ 38) A. 2nd Cycle D3 (N ⫽ 7) B. 1st Cycle D3 (N ⫽ 71) B. 2nd Cycle D5 (N ⫽ 9) B. 2nd Cycle D3 (N ⫽ 5)
# Emb. Trans.
% Pregnant
% Implanted
% Multiple
2.4 ⫾ 0.7 3.9 ⫾ 0.9 3.0 ⫾ 0.9 2.8 ⫾ 1.0 2.4 ⫾ 0.9
42% 57% 35% 67% 60%
27% 44% 19% 29% 25%
50% 60% 56% 50% 0%
Conclusions: In cases with previous failure to achieve optimal ovarian response and on-going pregnancies with the use of minidose protocol, microdose protocol provides higher levels of estradiol and increased number of high quality embryos. No matter which protocol was used, poor responders had lower pregnancy rates. Microdose GnRH analogue protocol is an alternative when minidose protocol results in poor ovarian response and no clinical pregnancy. P-338
Conclusions: These data support the proposal that an alternate day of embryo transfer may be considered for those patients who require repeat IVF cycles, since both D3 and D5 transfers provide comparable pregnancy rates. For both D3 and D5 ET, careful attention must be paid to the number of embryos transferred in order to reduce the risk of high order multiple gestations.
P-337 Comparison of microdose and standard doses of GnRH analogue in flare protocols for controlled ovarian hyperstimulation in poor responders. K. Yakin, S. Kahraman, F. Vanlioglu, Y. Kumtepe, N. Findikli. Istanbul Memorial Hosp, Istanbul, Turkey; Ataturk Univ Faculty of Medicine, Erzurum, Turkey. Objective: The purpose of the study was to compare the efficacy of two different regimens; microdose and standard doses for the use of GnRH analogue, in the management of poor responders. Design: A retrospective analysis was performed on the data obtained from the files of 137 women who demonstrated poor ovarian reserve and signed into assisted reproductive techniques (ART) with flare protocol. Materials/Methods: GnRH analogue was used as microdoses in 54 and as standard doses in 83 cycles for controlled ovarian hyperstimulation. In the microdose protocol, 40 micrograms leuprolide acetate b.i.d was started 3 days after the discontinuation of oral contraceptive usage for 21 days. In the standard dose flare-up regimen, 400 milligrams nafarelin was started on cycle day 2 in combination with gonadotropin and the dose is decreased to 200 milligrams per day on cycle day 6. In both groups, urinary FSH and HMG combination was started according to the body mass index and the dose is decreased in a step-down manner according to follicular growth. The laboratory and clinical results were compared in both groups. Results: In the microdose group, 8 cycles were cancelled (14.8%) due to inadequate follicular response. In the standard dose flare group, 16 cycles were cancelled (19.3%); 11 (13.2%) due to failed follicular growth and 5 (6.1%) due to premature LH surge. There was no statistically significant difference between two regimens in terms of age and basal FSH levels. The duration of induction was significantly longer and more gonadotropin ampules were used in the microdose regimen (p ⬍ 0.001). The peak estradiol level was higher with increased yield of M-II oocytes in the microdose group (p ⬍ 0.01 and p ⬍ 0.05, respectively). No premature LH surge was seen in the microdose regimen. For the microdose and co-flare regimens, the overall pregnancy rate per embryo transfer were 28% and 16%, respectively (p ⬍ 0.05). The comparison of clinical and laboratory results (mean ⫾ standard deviation.
Age (years) Day 3 FSH (iu/l) Duration of induction (days) Gonadotropin ampules Peak estradiol (pg/ml) No. oocytes M-II oocytes 2PN Embryos transferred Pregnancy rate (%)
Microdose (n ⫽ 46)
Co-flare (n ⫽ 67)
p
37.2 ⫾ 4.1 8.1 ⫾ 3.3 12.1 ⫾ 2.3 64.0 ⫾ 19.6 1459 ⫾ 651 8.3 ⫾ 4.3 6.7 ⫾ 3.8 4.6 ⫾ 3.2 2.9 ⫾ 1.4 28
36.5 ⫾ 3.91 7.6 ⫾ 3.2 9.3 ⫾ 2.4 48.5 ⫾ 18.6 1095 ⫾ 555 6.2 ⫾ 4.3 4.9 ⫾ 3.6 3.4 ⫾ 2.6 2.5 ⫾ 1.4 16
NS NS ⬍0.001 ⬍0.001 ⬍0.01 ⬍0.05 ⬍0.05 ⬍0.05 NS NS
Chi-square test.
FERTILITY & STERILITY威
The use of long-acting forms of gonadotropin-releasing hormone analogs (GnRHa Depot) increase miscarriage rates in oocyte donation cycles. G. Vargas-Chavarria, C. Caligara, E. Bosch, C. Simon, J. Remohi, A. Pellicer. Inst Valenciano de Infertilidad and Dept of Obstetrics and Gynecology, Sch of Medicine, Univ of Valencia, Valencia, Spain. Objective: To evaluate whether or not long-acting forms of GnRHa have any effect on the outcome of oocyte donation cycles. Design: Retrospective analysis of oocyte donation cycles from January 1999 to December 2000, including women with ovarian function treated with GnRHa. The time lapse between GnRH-a injection and embryos transfer (ⱕ and ⬎40 days, considering that period sufficient for the washout of the drug) was compared to the outcome of oocyte donation. Materials/Methods: Women with ovarian function treated with a depot preparation of Leuprolide acetate or Triptorelin, as pituitary down–regulation before oestrogen substitutive therapy (oestrogen valerate was administrated in increasing doses up to 6 mgr/day). Patients were divided in two groups: Group A (n ⫽ 368) were women in whom embryo transfer was performed ⱕ40 days after GnRHa depot injection. Group B (n ⫽ 337) were patients in whom GnRHa depot was injected ⬎40 days before the actual date of embryo replacement. The main IVF parameters were compared. Results: Results are shown in Table 1. Table 1. Group A
Group B
P
Age* 39.1 ⫾ 4.8 39 ⫾ 5 NS Oocytes received per recipient* 8.7 ⫾ 2.3 8.1 ⫾ 1.9 NS Embryos transferred* 2.8 ⫾ 1.3 2.6 ⫾ 1.3 NS Blastomeres per embryo* 4.3 ⫾ 1.7 5 ⫾ 1.8 NS Implantation rate % 4.3 ⫾ 1.7 25.0 NS Clinical pregnancies % 193/368 (52.5) 166/337 (49.7) NS Miscarriages % 54/193 (28.0) 26/166 (15.7) 0.005 * Mean (⫾SD). Conclusions: These data suggest that embryos transferred in recipients while the GnRha depot is active, have increased risk of early pregnancy loss. A deleterious effect of these compounds has to be ruled out in prospective studies. P-339 Half dose of Depot Triptorelin in pituitary suppression for in vitro fertilization (IVF): preliminary results. L. Dal Prato, A. Borini, A. Maccolini, M. R. Trevisi, L. Bianchi, C. Flamigni. Tecnobios Procreazione, Ctr for Reproductive Health, Bologna, Italy; Dept of Obstetrics and Gynecology, Univ of Bologna, Bologna, Italy. Objective: To compare the efficacy of standard and half doses of depot GnRH agonist triptorelin in pituitary down regulation, in a long protocol, during ovarian stimulation for IVF. Design: A prospective randomized study. Materials/Methods: 70 patients aged ⱕ38 years were randomized in two treatment groups. Pituitary desensitization was obtained in group 1 (35 patients) with half dose (1.87 mg) of triptorelin depot (Decapeptyl 3.75, IPSEN) in a single i.m. injection in the mid-luteal phase, and in group 2 (35 patients) with the standard full dose (3.75 mg) of the same GnRH agonist. At the onset of menses both groups received 4 ampoules (300 IU) of FSH (Metrodin HP 75, SERONO) daily for 2 days and 2 ampoules (150 IU) daily for 4 days; then the dose was adjusted according to the individual response. Results: No premature LH surge or luteinization occurred in both groups.
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A. 1st Cycle D5 (N ⫽ 38) A. 2nd Cycle D3 (N ⫽ 7) B. 1st Cycle D3 (N ⫽ 71) B. 2nd Cycle D5 (N ⫽ 9) B. 2nd Cycle D3 (N ⫽ 5)
# Emb. Trans.
% Pregnant
% Implanted
% Multiple
2.4 ⫾ 0.7 3.9 ⫾ 0.9 3.0 ⫾ 0.9 2.8 ⫾ 1.0 2.4 ⫾ 0.9
42% 57% 35% 67% 60%
27% 44% 19% 29% 25%
50% 60% 56% 50% 0%
Conclusions: In cases with previous failure to achieve optimal ovarian response and on-going pregnancies with the use of minidose protocol, microdose protocol provides higher levels of estradiol and increased number of high quality embryos. No matter which protocol was used, poor responders had lower pregnancy rates. Microdose GnRH analogue protocol is an alternative when minidose protocol results in poor ovarian response and no clinical pregnancy. P-338
Conclusions: These data support the proposal that an alternate day of embryo transfer may be considered for those patients who require repeat IVF cycles, since both D3 and D5 transfers provide comparable pregnancy rates. For both D3 and D5 ET, careful attention must be paid to the number of embryos transferred in order to reduce the risk of high order multiple gestations.
P-337 Comparison of microdose and standard doses of GnRH analogue in flare protocols for controlled ovarian hyperstimulation in poor responders. K. Yakin, S. Kahraman, F. Vanlioglu, Y. Kumtepe, N. Findikli. Istanbul Memorial Hosp, Istanbul, Turkey; Ataturk Univ Faculty of Medicine, Erzurum, Turkey. Objective: The purpose of the study was to compare the efficacy of two different regimens; microdose and standard doses for the use of GnRH analogue, in the management of poor responders. Design: A retrospective analysis was performed on the data obtained from the files of 137 women who demonstrated poor ovarian reserve and signed into assisted reproductive techniques (ART) with flare protocol. Materials/Methods: GnRH analogue was used as microdoses in 54 and as standard doses in 83 cycles for controlled ovarian hyperstimulation. In the microdose protocol, 40 micrograms leuprolide acetate b.i.d was started 3 days after the discontinuation of oral contraceptive usage for 21 days. In the standard dose flare-up regimen, 400 milligrams nafarelin was started on cycle day 2 in combination with gonadotropin and the dose is decreased to 200 milligrams per day on cycle day 6. In both groups, urinary FSH and HMG combination was started according to the body mass index and the dose is decreased in a step-down manner according to follicular growth. The laboratory and clinical results were compared in both groups. Results: In the microdose group, 8 cycles were cancelled (14.8%) due to inadequate follicular response. In the standard dose flare group, 16 cycles were cancelled (19.3%); 11 (13.2%) due to failed follicular growth and 5 (6.1%) due to premature LH surge. There was no statistically significant difference between two regimens in terms of age and basal FSH levels. The duration of induction was significantly longer and more gonadotropin ampules were used in the microdose regimen (p ⬍ 0.001). The peak estradiol level was higher with increased yield of M-II oocytes in the microdose group (p ⬍ 0.01 and p ⬍ 0.05, respectively). No premature LH surge was seen in the microdose regimen. For the microdose and co-flare regimens, the overall pregnancy rate per embryo transfer were 28% and 16%, respectively (p ⬍ 0.05). The comparison of clinical and laboratory results (mean ⫾ standard deviation.
Age (years) Day 3 FSH (iu/l) Duration of induction (days) Gonadotropin ampules Peak estradiol (pg/ml) No. oocytes M-II oocytes 2PN Embryos transferred Pregnancy rate (%)
Microdose (n ⫽ 46)
Co-flare (n ⫽ 67)
p
37.2 ⫾ 4.1 8.1 ⫾ 3.3 12.1 ⫾ 2.3 64.0 ⫾ 19.6 1459 ⫾ 651 8.3 ⫾ 4.3 6.7 ⫾ 3.8 4.6 ⫾ 3.2 2.9 ⫾ 1.4 28
36.5 ⫾ 3.91 7.6 ⫾ 3.2 9.3 ⫾ 2.4 48.5 ⫾ 18.6 1095 ⫾ 555 6.2 ⫾ 4.3 4.9 ⫾ 3.6 3.4 ⫾ 2.6 2.5 ⫾ 1.4 16
NS NS ⬍0.001 ⬍0.001 ⬍0.01 ⬍0.05 ⬍0.05 ⬍0.05 NS NS
Chi-square test.
FERTILITY & STERILITY威
The use of long-acting forms of gonadotropin-releasing hormone analogs (GnRHa Depot) increase miscarriage rates in oocyte donation cycles. G. Vargas-Chavarria, C. Caligara, E. Bosch, C. Simon, J. Remohi, A. Pellicer. Inst Valenciano de Infertilidad and Dept of Obstetrics and Gynecology, Sch of Medicine, Univ of Valencia, Valencia, Spain. Objective: To evaluate whether or not long-acting forms of GnRHa have any effect on the outcome of oocyte donation cycles. Design: Retrospective analysis of oocyte donation cycles from January 1999 to December 2000, including women with ovarian function treated with GnRHa. The time lapse between GnRH-a injection and embryos transfer (ⱕ and ⬎40 days, considering that period sufficient for the washout of the drug) was compared to the outcome of oocyte donation. Materials/Methods: Women with ovarian function treated with a depot preparation of Leuprolide acetate or Triptorelin, as pituitary down–regulation before oestrogen substitutive therapy (oestrogen valerate was administrated in increasing doses up to 6 mgr/day). Patients were divided in two groups: Group A (n ⫽ 368) were women in whom embryo transfer was performed ⱕ40 days after GnRHa depot injection. Group B (n ⫽ 337) were patients in whom GnRHa depot was injected ⬎40 days before the actual date of embryo replacement. The main IVF parameters were compared. Results: Results are shown in Table 1. Table 1. Group A
Group B
P
Age* 39.1 ⫾ 4.8 39 ⫾ 5 NS Oocytes received per recipient* 8.7 ⫾ 2.3 8.1 ⫾ 1.9 NS Embryos transferred* 2.8 ⫾ 1.3 2.6 ⫾ 1.3 NS Blastomeres per embryo* 4.3 ⫾ 1.7 5 ⫾ 1.8 NS Implantation rate % 4.3 ⫾ 1.7 25.0 NS Clinical pregnancies % 193/368 (52.5) 166/337 (49.7) NS Miscarriages % 54/193 (28.0) 26/166 (15.7) 0.005 * Mean (⫾SD). Conclusions: These data suggest that embryos transferred in recipients while the GnRha depot is active, have increased risk of early pregnancy loss. A deleterious effect of these compounds has to be ruled out in prospective studies. P-339 Half dose of Depot Triptorelin in pituitary suppression for in vitro fertilization (IVF): preliminary results. L. Dal Prato, A. Borini, A. Maccolini, M. R. Trevisi, L. Bianchi, C. Flamigni. Tecnobios Procreazione, Ctr for Reproductive Health, Bologna, Italy; Dept of Obstetrics and Gynecology, Univ of Bologna, Bologna, Italy. Objective: To compare the efficacy of standard and half doses of depot GnRH agonist triptorelin in pituitary down regulation, in a long protocol, during ovarian stimulation for IVF. Design: A prospective randomized study. Materials/Methods: 70 patients aged ⱕ38 years were randomized in two treatment groups. Pituitary desensitization was obtained in group 1 (35 patients) with half dose (1.87 mg) of triptorelin depot (Decapeptyl 3.75, IPSEN) in a single i.m. injection in the mid-luteal phase, and in group 2 (35 patients) with the standard full dose (3.75 mg) of the same GnRH agonist. At the onset of menses both groups received 4 ampoules (300 IU) of FSH (Metrodin HP 75, SERONO) daily for 2 days and 2 ampoules (150 IU) daily for 4 days; then the dose was adjusted according to the individual response. Results: No premature LH surge or luteinization occurred in both groups.
S223