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Analysis of 50 frozen blastocyst transfers: pregnancy in prior fresh ART cycles does not predict outcome.
Fresh ART cycle outcomes of patients who subsequently underwent FBET.
Frozen blastocyst transfer results. 1 Embryo 2 Embryos 3 Embryos Total transferred transferred transferred transferred Mean patient age: Total cycles/embryos transferred Pregnancies (⫹hCG)/ongoing: Biochemical/miscarriages: Clinical/ongoing rate: Clinical sacs (1/2/3): Fetal hearts (0/1/2/3/4): Implantation rate:
36.6 22/22
35.5 119/238
36.3 12/36
35.6 153/296
7/5
60/38
6/3
73/46
2/0 16/6 3/0 21/6 22.7%/ 37.0%/ 25.0%/ 34.0%/ 22.7% 31.9% 25.0% 30.1% 5/0/0 36/8/0 2/1/0 43/9/0 0/5/0/0/0 2/34/8/0/0 1/1/1/0/0 3/40/9/0/0 22.7% 21.9% 11.1% 20.6%
Conclusions: Extended embryo culture prior to cryopreservation combined with transfer of only two embryos (or three in patients with extreme poor prognosis) prevented high order multiple gestation pregnancies. This strategy resulted in a good pregnancy rate (49 ongoing pregnancies/153 thaw cycles) with a relatively low twin gestation rate (9/49 ongoing pregnancies). This approach may be preferable to the traditional strategy of cryopreservation at the cleavage stage and transfer of greater numbers of embryos.
P-35 Analysis of 50 frozen blastocyst transfers: pregnancy in prior fresh ART cycles does not predict outcome. A. J. Levi, M. P. Leondires, J. H. Segars, J. L. McKeeby, L. A. Scott, R. J. Alvero. Combined Fed Program in Reproductive Endocrinology and the Pediatric & Reproductive Endocrinology Branch/NIH, Bethesda, MD; A R T Institute of Washington, Inc at Walter Reed Army Medical Ctr, Washington, DC. Objective: Reports indicate that the likelihood of success in cryopreserved cleaving embryo transfer (ET) cycles may be predicted by the fresh ART cycle from which those frozen embryos were derived. Whether performance in prior ART cycles can predict the outcome of subsequent frozen blastocyst embryo transfers (FBET) is unknown. To address this question, we compared data from fresh ART cycles to determine if FBET cycle outcome could be predicted by prior pregnancy. Design: A cohort analysis of 50 fresh ART cycles and 50 FBET cycles at a university based assisted reproductive science center from October 1998 to January 2001. Materials/Methods: All patients who underwent fresh ART cycles and had frozen blastocyst transfers with embryos derived from those cycles were included in this study. All infertility diagnoses were included. Patients were separated into two groups: patients with clinical pregnancies during FBET cycles (Group A), and patients who failed to achieve a clinical pregnancy in FBET cycles (Group B). Fresh cycle data from which the frozen blastocysts were derived were then compared. The primary outcome variable was implantation rate (IR). Secondary outcome variables included ampules of gonadotropins used, peak estradiol (E2), number of oocytes retrieved (OR), number of embryos transferred (ET), overall pregnancy rate (PR), clinical pregnancy rate per transfer (CPR/T), and spontaneous abortion (SAB) rate. Statistical analysis was performed using the Fisher exact test and unpaired t-test where appropriate. An alpha error of ⬍0.05 was considered significant. Results: Seventeen patients (17/50; 34.0%) achieved clinical pregnancies in FBET cycles (Group A), and 33 patients (33/50; 66.0%) did not (Group B). The mean age (33.6 ⫾ 3.1 vs. 32.6 ⫾ 4.4 years) and basal FSH concentrations (5.4 ⫾ 2.5 vs. 6.8 ⫾ 4.4 IU/L) did not differ between groups. The primary outcome variable, IR, was 20% higher in Group B compared to Group A. Peak E2, ampules of gonadotropins used, total OR, total ET, overall PR, CPR/T, and SAB rate did not differ significantly between groups. Based on the observed differences in the primary outcome variable between groups, a post-hoc analysis with a power of 80% and an alpha of 0.05 revealed that a study would require approximately 650 patients in each group to demonstrate a significant difference.
FERTILITY & STERILITY威
Peak E2 (pg/ml)
Total OR
Overall CPR/T IR Total ET PR (%) (%) (%)
Group A 3087 ⫾ 1328 24.6 ⫾ 8.8 2.6 ⫾ 1.1 (n ⫽ 17) Group 8 3120 ⫾ 1426 23.2 ⫾ 10.2 2.2 ⫾ 0.7 (n ⫽ 33)
56.3
43.8
17.9
59.4
43.8
21.7
Conclusions: In contrast to reports of frozen cleaving ETs, prior pregnancy in fresh ART cycles from which frozen blastocysts were derived did not predict outcome in subsequent FBET cycles. The 34% CPR/T for FBETs in this study was two-fold higher than the published rates of frozen cleaving ETs but lower than the observed 61.6% CPR/T for fresh blastocysts at our program. The overall excellent prognosis for pregnancy in patients undergoing fresh blastocyst transfers may obscure factors that predict subsequent FBET outcome.
P-36 The impact of cryopreservation and subsequent embryo transfer on the outcome of IVF in patients at high risk for ovarian hyperstimulation syndrome: a controlled study. Z. Wiener-Megnazi, M. Dirnfeld, E. Rothschild, A. Lissak, Z. Silman, H. Abramovici. Carmel Medical Ctr, Haifa, Israel. Objective: To evaluate the outcome of IVF cycles with high risk for the development of ovarian hyperstimulation syndrome, in which preventive cryopreservation of all embryos was performed, and embryo transfer was postponed. Design: Case controlled retrospective analysis. Materials/Methods: Seventy three patients undergoing seventy three IVF treatment cycles in Carmel Medical Center during the period 1998 –2000 were analyzed. In thirty seven cycles, embryonic cryopreservation was performed, because of high risk for ovarian hyperstimulation syndrome, and embryos were transferred later. All embryos were frozen at either 48 or 72 hours. In thirty-six cycles, patients underwent transfer of fresh embryos. Controls were selected based on patients’ age, date of oocyte retrieval, and number of transferred embryos. Results: There were no significant differences in the two groups regarding mean age, gravidity, parity, the proportion of IVF vs. ICSI cycles, fertilization and cleavage rates, and number and quality of transferred embryos. A greater percentage of patients in the cryopreservation group were diagnosed as anovulatory than in the group with fresh embryo transfer (37.8% vs 8.5%). Patients in the cryopreservation group needed a lower number of gonadotropin ampules for ovarian stimulation than the group with fresh embryo transfer (27.2 vs. 36.5). The levels of E2 and P on the day of hCG administration were higher in the cryopreservation group than in the group with fresh embryo transfer (10,147.6 pmol/l vs. 4,412.7 pmol/l, P ⬍ 0.001 and 5.6 nmol/l vs. 4.3 nmol/l, P ⬍ 0.024, respectively). Patients in the cryopreservation group had a higher number of ovarian follicles on transvaginal sonography, aspirated oocytes and embryos than patients with the fresh embryo transfer (17.4 vs. 11.9, P ⬍ 0.001, 23.2 vs. 12.1, P ⬍ 0.001 and 10.4 vs. 5.5, P ⬍ 0.01, respectively). Pregnancy rates for first embryo transfer cycle were 34.3% for the cryopreservation group and 20.0% for the fresh embryo transfer group (P ⫽ 0.141; NS). Cumulative pregnancy rates were 43.2% in the cryopreservation group vs. 22.2% in the group with fresh embryo transfer (P ⬍ 0.04). There was one case of OHSS that developed in the study group and none in the control group. Conclusions: Cryopreservation of all embryos, as a protective measure in patients with high risk for the development of ovarian hyperstimulation syndrome yields high pregnancy rates and offers a safe and viable option. Furthermore, our results from the first cycle of embryo transfer indicate that the benefits of preventive cryopreservation are independent of the total number of embryos. We recommend preventive cryopreservation of all embryos as the preferred approach in the management of all patients at risk for developing OHSS.
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Frozen blastocyst transfer results. 1 Embryo 2 Embryos 3 Embryos Total transferred transferred transferred transferred Mean patient age: Total cycles/embryos transferred Pregnancies (⫹hCG)/ongoing: Biochemical/miscarriages: Clinical/ongoing rate: Clinical sacs (1/2/3): Fetal hearts (0/1/2/3/4): Implantation rate:
36.6 22/22
35.5 119/238
36.3 12/36
35.6 153/296
7/5
60/38
6/3
73/46
2/0 16/6 3/0 21/6 22.7%/ 37.0%/ 25.0%/ 34.0%/ 22.7% 31.9% 25.0% 30.1% 5/0/0 36/8/0 2/1/0 43/9/0 0/5/0/0/0 2/34/8/0/0 1/1/1/0/0 3/40/9/0/0 22.7% 21.9% 11.1% 20.6%
Conclusions: Extended embryo culture prior to cryopreservation combined with transfer of only two embryos (or three in patients with extreme poor prognosis) prevented high order multiple gestation pregnancies. This strategy resulted in a good pregnancy rate (49 ongoing pregnancies/153 thaw cycles) with a relatively low twin gestation rate (9/49 ongoing pregnancies). This approach may be preferable to the traditional strategy of cryopreservation at the cleavage stage and transfer of greater numbers of embryos.
P-35 Analysis of 50 frozen blastocyst transfers: pregnancy in prior fresh ART cycles does not predict outcome. A. J. Levi, M. P. Leondires, J. H. Segars, J. L. McKeeby, L. A. Scott, R. J. Alvero. Combined Fed Program in Reproductive Endocrinology and the Pediatric & Reproductive Endocrinology Branch/NIH, Bethesda, MD; A R T Institute of Washington, Inc at Walter Reed Army Medical Ctr, Washington, DC. Objective: Reports indicate that the likelihood of success in cryopreserved cleaving embryo transfer (ET) cycles may be predicted by the fresh ART cycle from which those frozen embryos were derived. Whether performance in prior ART cycles can predict the outcome of subsequent frozen blastocyst embryo transfers (FBET) is unknown. To address this question, we compared data from fresh ART cycles to determine if FBET cycle outcome could be predicted by prior pregnancy. Design: A cohort analysis of 50 fresh ART cycles and 50 FBET cycles at a university based assisted reproductive science center from October 1998 to January 2001. Materials/Methods: All patients who underwent fresh ART cycles and had frozen blastocyst transfers with embryos derived from those cycles were included in this study. All infertility diagnoses were included. Patients were separated into two groups: patients with clinical pregnancies during FBET cycles (Group A), and patients who failed to achieve a clinical pregnancy in FBET cycles (Group B). Fresh cycle data from which the frozen blastocysts were derived were then compared. The primary outcome variable was implantation rate (IR). Secondary outcome variables included ampules of gonadotropins used, peak estradiol (E2), number of oocytes retrieved (OR), number of embryos transferred (ET), overall pregnancy rate (PR), clinical pregnancy rate per transfer (CPR/T), and spontaneous abortion (SAB) rate. Statistical analysis was performed using the Fisher exact test and unpaired t-test where appropriate. An alpha error of ⬍0.05 was considered significant. Results: Seventeen patients (17/50; 34.0%) achieved clinical pregnancies in FBET cycles (Group A), and 33 patients (33/50; 66.0%) did not (Group B). The mean age (33.6 ⫾ 3.1 vs. 32.6 ⫾ 4.4 years) and basal FSH concentrations (5.4 ⫾ 2.5 vs. 6.8 ⫾ 4.4 IU/L) did not differ between groups. The primary outcome variable, IR, was 20% higher in Group B compared to Group A. Peak E2, ampules of gonadotropins used, total OR, total ET, overall PR, CPR/T, and SAB rate did not differ significantly between groups. Based on the observed differences in the primary outcome variable between groups, a post-hoc analysis with a power of 80% and an alpha of 0.05 revealed that a study would require approximately 650 patients in each group to demonstrate a significant difference.
FERTILITY & STERILITY威
Peak E2 (pg/ml)
Total OR
Overall CPR/T IR Total ET PR (%) (%) (%)
Group A 3087 ⫾ 1328 24.6 ⫾ 8.8 2.6 ⫾ 1.1 (n ⫽ 17) Group 8 3120 ⫾ 1426 23.2 ⫾ 10.2 2.2 ⫾ 0.7 (n ⫽ 33)
56.3
43.8
17.9
59.4
43.8
21.7
Conclusions: In contrast to reports of frozen cleaving ETs, prior pregnancy in fresh ART cycles from which frozen blastocysts were derived did not predict outcome in subsequent FBET cycles. The 34% CPR/T for FBETs in this study was two-fold higher than the published rates of frozen cleaving ETs but lower than the observed 61.6% CPR/T for fresh blastocysts at our program. The overall excellent prognosis for pregnancy in patients undergoing fresh blastocyst transfers may obscure factors that predict subsequent FBET outcome.
P-36 The impact of cryopreservation and subsequent embryo transfer on the outcome of IVF in patients at high risk for ovarian hyperstimulation syndrome: a controlled study. Z. Wiener-Megnazi, M. Dirnfeld, E. Rothschild, A. Lissak, Z. Silman, H. Abramovici. Carmel Medical Ctr, Haifa, Israel. Objective: To evaluate the outcome of IVF cycles with high risk for the development of ovarian hyperstimulation syndrome, in which preventive cryopreservation of all embryos was performed, and embryo transfer was postponed. Design: Case controlled retrospective analysis. Materials/Methods: Seventy three patients undergoing seventy three IVF treatment cycles in Carmel Medical Center during the period 1998 –2000 were analyzed. In thirty seven cycles, embryonic cryopreservation was performed, because of high risk for ovarian hyperstimulation syndrome, and embryos were transferred later. All embryos were frozen at either 48 or 72 hours. In thirty-six cycles, patients underwent transfer of fresh embryos. Controls were selected based on patients’ age, date of oocyte retrieval, and number of transferred embryos. Results: There were no significant differences in the two groups regarding mean age, gravidity, parity, the proportion of IVF vs. ICSI cycles, fertilization and cleavage rates, and number and quality of transferred embryos. A greater percentage of patients in the cryopreservation group were diagnosed as anovulatory than in the group with fresh embryo transfer (37.8% vs 8.5%). Patients in the cryopreservation group needed a lower number of gonadotropin ampules for ovarian stimulation than the group with fresh embryo transfer (27.2 vs. 36.5). The levels of E2 and P on the day of hCG administration were higher in the cryopreservation group than in the group with fresh embryo transfer (10,147.6 pmol/l vs. 4,412.7 pmol/l, P ⬍ 0.001 and 5.6 nmol/l vs. 4.3 nmol/l, P ⬍ 0.024, respectively). Patients in the cryopreservation group had a higher number of ovarian follicles on transvaginal sonography, aspirated oocytes and embryos than patients with the fresh embryo transfer (17.4 vs. 11.9, P ⬍ 0.001, 23.2 vs. 12.1, P ⬍ 0.001 and 10.4 vs. 5.5, P ⬍ 0.01, respectively). Pregnancy rates for first embryo transfer cycle were 34.3% for the cryopreservation group and 20.0% for the fresh embryo transfer group (P ⫽ 0.141; NS). Cumulative pregnancy rates were 43.2% in the cryopreservation group vs. 22.2% in the group with fresh embryo transfer (P ⬍ 0.04). There was one case of OHSS that developed in the study group and none in the control group. Conclusions: Cryopreservation of all embryos, as a protective measure in patients with high risk for the development of ovarian hyperstimulation syndrome yields high pregnancy rates and offers a safe and viable option. Furthermore, our results from the first cycle of embryo transfer indicate that the benefits of preventive cryopreservation are independent of the total number of embryos. We recommend preventive cryopreservation of all embryos as the preferred approach in the management of all patients at risk for developing OHSS.
S123