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Elective single embryo transfer in fresh cycles
exhaustive follow-up. Recent studies reporting worrying information on IVF children support the clear need for evaluation on large number. Supported by: Serono.
Tuesday, October 15, 2002 4:15 P.M.
Blastocyst development on day 5 - A relationship to clinical pregnancy rate? C. McCaffrey, A. Adler, A. S. Berkeley, J. Grifo, N. Noyes, L. C. Krey. Program for In Vitro Fertilization, Reproductive Surg and Infertility, NYU Sch of Medicine, New York, NY. Objective: Transfer of multiple embryos to the uterus often results in a high order multiple gestation. In an effort to reduce this risk while maximizing the pregnancy rate, we culture to Day 5 (D5) the embryos of those patients who meet our criteria and transfer an optimal number based on our evaluation of embryo quality; this enables us to replace fewer embryos than was previously done on Day 3 (D3). Pregnancy and implantation rates were analyzed relative to the developmental status of the lead embryo on D5. Design: Retrospective analysis of all cycles utilizing D5 embryo transfer (ET) from 1/2000 to 3/2002 at a large university-based IVF program. We examined the cycles of patients ⱕ37 (n⫽584) and 38 – 42 (n⫽185) years old. Materials/Methods: Following retrieval, oocytes were fertilized by insemination or ICSI. Patients having ⱖ3 good quality embryos on D3 were eligible for D5 ET. Embryos were cultured in various media systems (G media, IVF Scandinavia; P media, Irvine Scientific; and Quinns media, Sage Biopharma). Blastocyst developmental stage and quality were graded according to Gardner. Data were analyzed by Fisher Exact or 2 tests with p ⬍0.05. Results: Pregnancy (PR) and implantation (IR) rates were positively correlated to the developmental status of the lead blastocyst on D5 (see Table). When only morulae or stage 1 blastocysts were transferred, the pregnancy rates were significantly lower than those for advanced stage blastocysts. Although not presented, a similar pattern was also observed in oocyte donation cycles. Furthermore, analysis of the distribution of development stages on D5 revealed that significantly more of the embryos of young patients progressed to blastocyst stage 3 or greater than in the older age group (63% versus 53%, p ⬍0.001) suggesting a reduced developmental potential in the older patients. We routinely transfer 2 embryos to patients ⱕ37 years of age and 3 embryos to patients ⱖ38 years old. Based on the lower PR and IR when only morulae and stage 1 blastocysts were available, we often transfer an additional embryo when the lead embryo has not progressed beyond a morula or stage 1 blastocyst. To date, there have been 15 triplet(⫹FH) gestations out of 332 pregnancies (4%) in the young patients, a group especially at risk for high order multiples. However, 8 of these triplets were due to monozygotic twinning when only 2 embryos were transferred. Relationship of lead embryo stage at transfer to clinical pregnancy (PR, ⫹FH) and implantation rates (IR, sac). IVF patient Age
Stage Morula Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
Tuesday, October 15, 2002 4:30 P.M. O-125
O-124
ⱕ37 years old
Supported by: None.
38–42 years old
PR (%)
IR (%)
PR (%)
IR (%)
19/65 (29) 18/52 (35) 53/100 (53) 101/160 (63) 127/188 (67) 14/19 (74)
30/174 (17) 28/134 (21) 95/251 (38) 162/349 (46) 218/388 (56) 22/38 (58)
4/21 (19) 8/25 (32) 21/41 (51) 24/47 (51) 24/44 (55) 3/7 (43)
8/77 (10) 12/91 (13) 35/137 (26) 35/149 (23) 47/128 (37) 5/19 (26)
Elective single embryo transfer in fresh cycles. Del Marek, Martin Langley, Anna C. Nackley, Kathy M. Doody, Kevin J. Doody. Ctr for Assisted Reproduction, Bedford, TX. Objective: Previous reports have indicated that transfer of one single embryo may result in a reduction of multiple gestations with consistent high implantation and pregnancy rates. The purpose of this study is to evaluate pregnancy and implantation rates resulting from transfer of one blastocyst embryo derived from fresh cycles. Design: A retrospective analysis of single embryo transfer results from January 1, 1998 through March 31, 2002. Materials/Methods: Patients underwent down regulation with controlled ovarian hyper-stimulation. Oocyte retrieval occurred 36 –39 hours post Human Chorionic Gonadotropin (hCG) administration. Insemination was performed 38 – 42 hours post hCG using co-incubation of sperm with oocytes or sperm injection. Oocytes were individually placed in 100 l micro-drops of sequential media (S1, G1.2, IVF Science) under oil (Squibb) and cultured overnight in 5% CO2 and air at 37o C. Fertilization was evaluated 18 –20 hours after insemination. Fertilized oocytes were placed into fresh 100 l micro-drops of sequential media (S1, G1.2) and cultured in groups of two under oil to Day 3. Multi-cell embryos were moved to new 100 l micro-drops of sequential media (S2, G2.2, CCM, IVF Science) under oil for culture to Day 5 or 6 and subsequent blastocyst embryo transfer. An abdominal ultrasound (5 MHz) was utilized to assist intrauterine placement of the embryo transfer catheter (Wallace; Cook). A sonogram to determine total gestational sacs and fetal hearts was performed at 4 – 6 weeks post positive hCG. If cardiac activity was not documented at the initial sonogram, a follow-up sonogram was performed 1 week later. Results: Please refer to the table. Single Embryo Transfer Results.
Total Cycles: Mean Patient Age: Pregnancies (⫹hCG)/Ongoing: Biochemical/Miscarriages: Pregnancy Rate (⫹hCG): Clinical Pregnancy Rate: Ongoing Pregnancy Rate: Clinical Sacs (1/2/3): Implantation Rate: †
P ⬍ .001;
S48
Abstracts
Non-Elective Transfer
20 35.5 15/8 5/2 75.0%† 50.0%‡ 40.0%¶ 10/0/0 50.0%䉫
76 35.1 23/13 6/4 30.3% 22.4% 17.1% 17/0/0 22.4%
P ⬍ .05 (vs. non-elective transfer using Fisher’s Exact).
Conclusions: Of the 96 single fresh embryo transfers, 20(20.8%) patients requested to transfer one embryo and have their additional embryos cryopreserved. The remaining fresh cycle patients were forced to transfer only one embryo due to the limited availability of supernumerary embryos for transfer. As the selection of patients for single embryo transfer was generally based on the non-availability of additional embryos rather than patient choice, the low rate of blastulation does not seem to predict poor embryo quality in the embryos that continue to develop and evident in the pregnancy and implantation rates. No multiple gestations were noted. Supported by: Not Applicable.
Tuesday, October 15, 2002 4:45 P.M.
(ba, p ⬍ 0.05, dc, p ⬍ 0.05). Conclusions: Because the developmental stage of the lead blastocyst on D5 can predict pregnancy outcome, it may be used to determine a number of embryos for transfer that maintains a high pregnancy rate but minimizes the potential for a high order multiple gestation. This includes limiting transfers to 2 embryos when the lead BL is stage 3 or higher and increasing the number of embryos when the lead BL is grade 1 or a morula. Patients eligible for a 3 embryo transfer on D5 should be aggressively counseled about the possibility of a triplet outcome.
‡¶䉫
Elective Transfer
O-126 Influence of embryo transfer depth on pregnancy rate: Fear the fundus. C. S. Pope, E. K. D. Cook, M. Arny, A. Novak, D. R. Grow. Baystate Medical Ctr, Springfield, MA; Dept of Biostatistics and Epidemiology, Univ of MA, Amherst, MA. Objective: Though critically important, embryo transfer (ET) is perhaps the least studied step of Assisted Reproductive Technology. A well-de-
Vol. 78, No. 3, Suppl. 1, September 2002
Tuesday, October 15, 2002 4:15 P.M.
Blastocyst development on day 5 - A relationship to clinical pregnancy rate? C. McCaffrey, A. Adler, A. S. Berkeley, J. Grifo, N. Noyes, L. C. Krey. Program for In Vitro Fertilization, Reproductive Surg and Infertility, NYU Sch of Medicine, New York, NY. Objective: Transfer of multiple embryos to the uterus often results in a high order multiple gestation. In an effort to reduce this risk while maximizing the pregnancy rate, we culture to Day 5 (D5) the embryos of those patients who meet our criteria and transfer an optimal number based on our evaluation of embryo quality; this enables us to replace fewer embryos than was previously done on Day 3 (D3). Pregnancy and implantation rates were analyzed relative to the developmental status of the lead embryo on D5. Design: Retrospective analysis of all cycles utilizing D5 embryo transfer (ET) from 1/2000 to 3/2002 at a large university-based IVF program. We examined the cycles of patients ⱕ37 (n⫽584) and 38 – 42 (n⫽185) years old. Materials/Methods: Following retrieval, oocytes were fertilized by insemination or ICSI. Patients having ⱖ3 good quality embryos on D3 were eligible for D5 ET. Embryos were cultured in various media systems (G media, IVF Scandinavia; P media, Irvine Scientific; and Quinns media, Sage Biopharma). Blastocyst developmental stage and quality were graded according to Gardner. Data were analyzed by Fisher Exact or 2 tests with p ⬍0.05. Results: Pregnancy (PR) and implantation (IR) rates were positively correlated to the developmental status of the lead blastocyst on D5 (see Table). When only morulae or stage 1 blastocysts were transferred, the pregnancy rates were significantly lower than those for advanced stage blastocysts. Although not presented, a similar pattern was also observed in oocyte donation cycles. Furthermore, analysis of the distribution of development stages on D5 revealed that significantly more of the embryos of young patients progressed to blastocyst stage 3 or greater than in the older age group (63% versus 53%, p ⬍0.001) suggesting a reduced developmental potential in the older patients. We routinely transfer 2 embryos to patients ⱕ37 years of age and 3 embryos to patients ⱖ38 years old. Based on the lower PR and IR when only morulae and stage 1 blastocysts were available, we often transfer an additional embryo when the lead embryo has not progressed beyond a morula or stage 1 blastocyst. To date, there have been 15 triplet(⫹FH) gestations out of 332 pregnancies (4%) in the young patients, a group especially at risk for high order multiples. However, 8 of these triplets were due to monozygotic twinning when only 2 embryos were transferred. Relationship of lead embryo stage at transfer to clinical pregnancy (PR, ⫹FH) and implantation rates (IR, sac). IVF patient Age
Stage Morula Stage 1 Stage 2 Stage 3 Stage 4 Stage 5
Tuesday, October 15, 2002 4:30 P.M. O-125
O-124
ⱕ37 years old
Supported by: None.
38–42 years old
PR (%)
IR (%)
PR (%)
IR (%)
19/65 (29) 18/52 (35) 53/100 (53) 101/160 (63) 127/188 (67) 14/19 (74)
30/174 (17) 28/134 (21) 95/251 (38) 162/349 (46) 218/388 (56) 22/38 (58)
4/21 (19) 8/25 (32) 21/41 (51) 24/47 (51) 24/44 (55) 3/7 (43)
8/77 (10) 12/91 (13) 35/137 (26) 35/149 (23) 47/128 (37) 5/19 (26)
Elective single embryo transfer in fresh cycles. Del Marek, Martin Langley, Anna C. Nackley, Kathy M. Doody, Kevin J. Doody. Ctr for Assisted Reproduction, Bedford, TX. Objective: Previous reports have indicated that transfer of one single embryo may result in a reduction of multiple gestations with consistent high implantation and pregnancy rates. The purpose of this study is to evaluate pregnancy and implantation rates resulting from transfer of one blastocyst embryo derived from fresh cycles. Design: A retrospective analysis of single embryo transfer results from January 1, 1998 through March 31, 2002. Materials/Methods: Patients underwent down regulation with controlled ovarian hyper-stimulation. Oocyte retrieval occurred 36 –39 hours post Human Chorionic Gonadotropin (hCG) administration. Insemination was performed 38 – 42 hours post hCG using co-incubation of sperm with oocytes or sperm injection. Oocytes were individually placed in 100 l micro-drops of sequential media (S1, G1.2, IVF Science) under oil (Squibb) and cultured overnight in 5% CO2 and air at 37o C. Fertilization was evaluated 18 –20 hours after insemination. Fertilized oocytes were placed into fresh 100 l micro-drops of sequential media (S1, G1.2) and cultured in groups of two under oil to Day 3. Multi-cell embryos were moved to new 100 l micro-drops of sequential media (S2, G2.2, CCM, IVF Science) under oil for culture to Day 5 or 6 and subsequent blastocyst embryo transfer. An abdominal ultrasound (5 MHz) was utilized to assist intrauterine placement of the embryo transfer catheter (Wallace; Cook). A sonogram to determine total gestational sacs and fetal hearts was performed at 4 – 6 weeks post positive hCG. If cardiac activity was not documented at the initial sonogram, a follow-up sonogram was performed 1 week later. Results: Please refer to the table. Single Embryo Transfer Results.
Total Cycles: Mean Patient Age: Pregnancies (⫹hCG)/Ongoing: Biochemical/Miscarriages: Pregnancy Rate (⫹hCG): Clinical Pregnancy Rate: Ongoing Pregnancy Rate: Clinical Sacs (1/2/3): Implantation Rate: †
P ⬍ .001;
S48
Abstracts
Non-Elective Transfer
20 35.5 15/8 5/2 75.0%† 50.0%‡ 40.0%¶ 10/0/0 50.0%䉫
76 35.1 23/13 6/4 30.3% 22.4% 17.1% 17/0/0 22.4%
P ⬍ .05 (vs. non-elective transfer using Fisher’s Exact).
Conclusions: Of the 96 single fresh embryo transfers, 20(20.8%) patients requested to transfer one embryo and have their additional embryos cryopreserved. The remaining fresh cycle patients were forced to transfer only one embryo due to the limited availability of supernumerary embryos for transfer. As the selection of patients for single embryo transfer was generally based on the non-availability of additional embryos rather than patient choice, the low rate of blastulation does not seem to predict poor embryo quality in the embryos that continue to develop and evident in the pregnancy and implantation rates. No multiple gestations were noted. Supported by: Not Applicable.
Tuesday, October 15, 2002 4:45 P.M.
(ba, p ⬍ 0.05, dc, p ⬍ 0.05). Conclusions: Because the developmental stage of the lead blastocyst on D5 can predict pregnancy outcome, it may be used to determine a number of embryos for transfer that maintains a high pregnancy rate but minimizes the potential for a high order multiple gestation. This includes limiting transfers to 2 embryos when the lead BL is stage 3 or higher and increasing the number of embryos when the lead BL is grade 1 or a morula. Patients eligible for a 3 embryo transfer on D5 should be aggressively counseled about the possibility of a triplet outcome.
‡¶䉫
Elective Transfer
O-126 Influence of embryo transfer depth on pregnancy rate: Fear the fundus. C. S. Pope, E. K. D. Cook, M. Arny, A. Novak, D. R. Grow. Baystate Medical Ctr, Springfield, MA; Dept of Biostatistics and Epidemiology, Univ of MA, Amherst, MA. Objective: Though critically important, embryo transfer (ET) is perhaps the least studied step of Assisted Reproductive Technology. A well-de-
Vol. 78, No. 3, Suppl. 1, September 2002