Novel frozen embryo transfer approach involving pronuclear stage cryopreservation and blastocyst transfer.

Novel frozen embryo transfer approach involving pronuclear stage cryopreservation and blastocyst transfer.

and 7 second deliveries). From the subanalysis, the percentage of retrievals resulting in at least one delivery was 68.9%. The ratio of total deliveri...

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and 7 second deliveries). From the subanalysis, the percentage of retrievals resulting in at least one delivery was 68.9%. The ratio of total deliveries per oocyte retrieval was 0.767.

Group A implantation rates. Fresh Sacs/ preembryos transferred (%)

Thawed sacs/ preembryos transferred (%)

2/8 (25.0) 143/278 (51.4%)a 872/1956 (44.6%)b 612/1896 (32.3%)c 74/372 (9.9%)* 1703/4510 (37.8%)d

15/33 (45.5%) 34/200 (17.0%)a 94/498 (18.9%)b 135/796 (17.0%)c 132/1080 (12.2%)* 410/2607 (15.7%)d

No. Transferred

Table 1. Total number of retrievals Oocytes retrieved (mean ⫾ S.D.) Oocytes normally fertilized and frozen (mean ⫾ S.D.) Total number of frozen embryo transfers Embryos thawed (mean ⫾ S.D.) Embryos transferred (mean ⫾ S.D.) Clinical pregnancies Ongoing pregnancies (⬎12 wks.) Implantation rate (sacs)

103 16.1 ⫾ 6.6 10.2 ⫾ 4.7 184 3.3 ⫾ 0.8 2.9 ⫾ 0.7 96 (52.2% of transfers) 83 (45.1% of transfers) 27.7%

Conclusions: Oocyte donation can be efficiently performed with the exclusive use of embryos cryopreserved at the pronuclear stage. Advantages of this approach include greatly simplified donor-recipient synchronization, increased safeguarding of patient confidentiality, optimization of the recipient uterine environment, considerable opportunities for genetic siblings and the possibility of quarantining embryos and retesting donors for infectious diseases. Supported By: Mayo Foundation.

1 2 3 4 ⬎4 Total a,b,c,d

p ⫽ p ⬍ 0.0001; * p ⬍ 0.0005.

Conclusions: Cryopreserved and thawed conceptuses do not possess the same implantation potential as their non-cryopreserved siblings. In general, implantation rates are significantly reduced after cryopreservation procedures. Women with cryopreserved preembryos who fail to achieve pregnancy after fresh transfer are at particular risk for low implantation after thaw. Under these circumstances, consideration might be given to the replacement of one additional conceptus in subsequent thaw attempts. Supported By: The Center for Reproductive Medicine and Infertility.

Wednesday, October 24, 2001 4:45 P.M. O-226

Wednesday, October 24, 2001 4:30 P.M. O-225 Are implantation rates reduced after cryopreservation and thawing when compared to fresh transfers in the same patients? L. L. Veeck, R. Bodine, R. N. Clarke, J. Libraro, N. Zaninovic, Z. Rosenwaks. Weill Medical Coll of Cornell Univ, New York, NY. Objective: Cryopreservation procedures offer an effective means of preserving human conceptuses beyond those required for immediate intrauterine transfer. Pronuclear oocytes, cleaved preembryos, and day 5 and 6 blastocysts can be frozen successfully and stored for the reproductive lifetimes of consenting in vitro fertilization (IVF) patients. Because most programs report lower pregnancy rates in freeze/thaw cycles, the question arises as to whether thawed conceptuses possess the same reproductive potential of their non-cryopreserved siblings. Here, implantation rates in fresh and thawed cycles are compared. Design: Retrospective analysis of 1449 consecutive treatment cycles (April 1995–December 2000) with cryopreservation of one or more conceptuses. Fresh transfer was carried out in 1344 cycles (105 cycles had all conceptuses frozen); transfer after thaw was undertaken in 668 cycles. Materials/Methods: Three different methods were used to group data in an effort to control for confounding variables. Group A: all cycles with freezing were analyzed for implantation (sacs/number conceptuses transferred) and compared to all cycles within the same group returning for thaw (all cycles; possible bias against thawed cycles since successful fresh cycles were apt to delay returning for thaw); Group B: all cycles within Group A with both fresh and thawed transfer (cycles matched for transfer fresh and thawed; possible bias against fresh cycles because fresh failures were apt to return for thaw in a timely fashion); and, Group C: all cycles within Group A with clinical pregnancy with both fresh and thawed transfers. Chi-Square was used for statistical analysis. Results: Group A is shown in the table below. Significant differences were found for both clinical pregnancy (68% vs 41%; not shown) and implantation (38% vs 16%) in the group as a unit, and in most subgroups categorized by number of preembryos replaced. Similarly, Group B (589 cycles) demonstrated a significantly lower thaw implantation rate (396/2010 vs 355/2223; 20% vs 16%; p ⬍ 0.001) in matched fresh versus thaw transfers. Group C (117 cycles) showed a trend towards lower implantation in thawed cycles, but this difference did not reach significance (179/394 vs 177/447; 45% vs 40%).

FERTILITY & STERILITY威

Novel frozen embryo transfer approach involving pronuclear stage cryopreservation and blastocyst transfer. A. P. Singh, C. A. Sattler, D. G. Hammitt. Mayo Clin Scottsdale, Scottsdale, AZ. Objective: A successful embryo cryopreservation program is essential for optimizing ART outcomes. Cryopreservation can be performed at various stages of embryo development. Our ART program has traditionally cryopreserved embryos at the pronuclear (PN) stage with subsequent thaw and transfer at the cleavage stage. However, cleavage stage transfer has limitations including limited ability for embryo selection and the need to transfer multiple embryos. The purpose of this study was to compare results of our traditional frozen embryo transfer (FET) approach to a novel methodology of PN cryopreservation with subsequent thaw and transfer at the blastocyst stage. Design: Retrospective cohort analysis. Materials/Methods: From 4/20/99 to 12/31/00, 63 FET cycles were initiated in 51 patients. In over 90% of cycles embryos were cryopreserved at the PN stage. Endometrial preparation for transfers involved GnRHa down regulation and standard hormonal protocols. 47 transfers (49 thaws) were performed two days following thaw (standard FET). 8 transfers (9 thaws) were performed 4 days following thaw (blastocyst FET). Indications for blastocyst transfer included multiple pregnancy concerns, multiple prior failed cycles and poor embryo quality. Results: Results are presented in Table 1. Table 1. Standard FET versus blastocyst FET.

Parameter No. of cycles No. of thaws No. of transfers Age Mean No. thawed Mean No. transferred Pregnancy rate per thaw Pregnancy rate per transfer Ongoing rater per transfer Implantation rate per embryo

Standard FET

Blastocyst FET

P-value

54 49 47 36.1 ⫾ 5.8 4.3 ⫾ 1.3 3.4 ⫾ 0.79 19/49 (39%) 19/47 (40%) 19/47 (40%) 28/158 (18%)

9 9 8 37.9 ⫾ 2.8 8.7 ⫾ 3.2 2.3 ⫾ 0.89 5/9 (56%) 5/8 (63%) 5/8 (63%) 7/18 (39%)

NS† 0.000 0.001 NS NS NS 0.032

† NS ⫽ not significant. Conclusions: Pronuclear cryopreservation with thaw and blastocyst transfer is an effective approach to optimize ART outcomes. This methodology

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is particularly appealing as it combines two very successful techniques:PN freezing and blastocyst transfer. This approach may be applicable in patients with multiple failed IVF cycles, poor embryo quality, advanced maternal age, or at high risk for multiple pregnancy.

ART: OUTCOME STUDIES Wednesday, October 24, 2001 2:00 P.M. O-227 Assessment of early cleaving in vitro fertilized human embryos to the 2-cell stage prior to transfer improves embryo selection. D. Sakkas, G. B. Percival, Y. D’Arcy, K. Sharif, M. Afnan. Yale Univ Sch of Medicine, New Haven, CT; Assisted Conception Unit, Birmingham Women’s Hosp, Birmingham, UK; Birmingham Women’s Hosp, Birmingham, UK. Objective: To determine the most viable embryos for transfer after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Design: On the day of fertilization (day 1), two pronuclei embryos were checked at between 1500 and 1700 to see if early cleavage to the 2-cell stage had occurred or not. Early cleaving embryos were pre-selected for transfer on day 2. Study 1: Comparison of implantation and pregnancy rates in patients with early cleaving 2-cell embryos pre-selected for transfer and those without early cleaving 2-cell embryos. Study 2: Alternating weeks in which pre-selection was performed and not performed. Materials/Methods: The study was performed at the IVF program of the Birmingham Women’s Hospital, Birmingham, UK. All patients with fertilized embryos undergoing IVF or ICSI cycles with transfer on day 2 were included. The number of fertilized embryos cleaving to the 2-cell stage on day 1, embryo cell number and quality on day 2, implantation rates and pregnancy rates were assessed. Results: Study 1: Patients who had early cleaving 2-cell embryos had a significantly higher pregnancy and implantation rate [45/100 (45.0%) and 58/219 (25.5%), respectively] than patients without early cleaving 2-cell embryos [31/130 (23.8%) and 43/290 (14.8%), respectively]. In 65 patients who had two early cleaving embryos for transfer 50.7% of them achieved a pregnancy. Study 2: In weeks when pre-selection of early cleaving 2-cell embryos was performed the overall pregnancy and implantation rates [43/90 (47.7%) and 52/199 (26.1%), respectively] of the clinic were significantly improved compared to when no assessment of early cleavage was performed [24/77 (31.2%) and 29/168 (17.3%), respectively], and embryo selection was made at the time of transfer. In both studies the majority of patients (70%) had only 2 embryos transferred. Conclusions: The presence of early cleaving 2-cell embryos improves a patient’s chance of achieving pregnancy. The adoption of more stringent embryo selection criteria in the clinics day to day running can improve overall pregnancy rates. Supported By: ACU, Birmingham Women’s Hospital, Birmingham, UK.

Wednesday, October 24, 2001 2:15 P.M. O-228 Choice of fresh homologous or fresh donor embryo transfer is determined primarily by availability of insurance-mandated in vitro fertilization (IVF) coverage and university versus private practice. S. Feigenbaum. The Permanente Medical Group and Univ of CA, San Francisco, San Francisco, CA. Objective: Choices among advanced infertility therapies are widely thought to be influenced by patient emotions and ability to pay. To determine to what extent third-party reimbursement may drive decision-making in ART, the questions asked were 1) whether state-mandated insurance coverage for IVF-ET was a major influence in ART service selection, 2) whether the converse was also true, i.e., whether practices in states without mandated IVF coverage steered patients towards different services, and 3) would University-based programs, whether in IVF-mandated or non-mandated states demonstrate different approaches to these challenging decisions.

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Abstracts

Design: Descriptive study. Materials/Methods: The numbers and percentage of fresh homologous vs. donor egg transfers in women ⬎40 years old was ascertained from the recently published 1998 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports, published jointly by the CDC, ASRM, SART and RESOLVE. Representative states were selected. For IVF-mandated coverage—Massachusetts and Maryland. For comparison, two states with similar demographics but with no mandated IVF coverage were selected, New Jersey and Washington. Public University IVF programs in these states were examined as a comparison group. Only programs performing both IVF and donor oocyte transfers were included. Results: The percent of fresh donor egg embryo transfers compared to total fresh (donor plus homologous) embryo transfers in women ⬎40 years old in the states of Massachusetts, Maryland, New Jersey and Washington State was 16%, 17%, 30% and 46%, respectively. Analysis of 1998 National Summary data from all reporting clinics yielded 29% donor total transfers. In public University programs, the summary figure of donor to all transfers was 46%. This figure was not ascertainable for Massachusetts (and some other IVF mandate states, e.g., Illinois), where public University programs are largely administered by private clinics. In general, for most states without IVF-mandates, the difference between University and private clinics was not significantly different, e.g., Washington: 46% vs. 48%, New Jersey: 30% and 30%. The differences in homologous vs. donor transfers in IVF-mandate states could not be explained by success rates since, for the median practice, there was no difference in the success rates between private and University practices. Conclusions: The most recently published ART data suggest that both patients and insurance agencies were most vulnerable to prevailing economic incentives for performing homologous IVF-ET in that state. The higher donor:total fresh embryo transfer ratio in public University-based practices demonstrate that Universities were more insulated from this incentive than were their private practice peers. Outside of IVF-mandated states, however, there was less difference in the type of cycle an older reproductive-aged woman was likely to have received. As there were no clear differences between private and University success rates, the motive for steering patients to largely unproductive, expensive cycles seems clearly economic. These data and their interpretation raise ethical and economic concerns for our professional organizations.

Wednesday, October 24, 2001 2:30 P.M. O-229 Impact of failed IVF attempts: a strong negative predictor of subsequent outcome. S. D. Spandorfer, L. Burmeister, M. Yih, D. Chen, Z. Rosenwaks. Cornell Univ Medical Ctr, New York, NY. Objective: Recent work has suggested that multiple failed cycles of IVF-ET are not associated with a diminished chance of success in a subsequent attempt (Fertil Steril 1998;69:1005). This report was from a compilation of SART data involving multiple IVF-ET centers. Given the inherent difficulties in evaluating pregnancy rates from multiple centers, we sought to analyze pregnancy outcome from a single center in a large cohort of patients undergoing IVF-ET specifically evaluating the impact of previous failed attempts. Design: Prospective cohort outcome analysis of patients undergoing their first IVF over a 3-year period with followup for a total of 6 years. Only patients with all IVF cycles at our institution were included. Materials/Methods: 1292 consecutive women from 1995–1997 were included. These women all underwent their first ever cycle of IVF-ET at our center during the study period. The clinical rates of those patients with a second and third attempt(s) after failed cycle(s) were compared to the groups’ first ever attempt in an age dependent fashion. Clinical pregnancy was defined as the presence of a fetal heart beat at a seven-week sonogram. Results: The table demonstrates the results. Clinical pregnancy rates significantly decline after failed IVF attempts.

Vol. 76, No. 3, Suppl. 1, September 2001