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Both day 3 and day 5 embryo morphology are highly predictive for the chromosomal status of the preimplantation embryo as analyzed by fluorescent in situ hybridization (FISH)
was augmented by evaluation of references cited in the reviewed articles. Moreover, we hand-searched pertinent articles published this past decade in Fertility and Sterility, Human Reproduction and the Journal of Assisted Reproduction and Genetics. Finally, we reviewed the work of various panels ⫺ including, the Human Embryo Research Panel, National Bioethics Advisory Commission, ASRM, HFEA, PCB and others ⫺ studying interrelated issues of embryo research, assisted reproduction and genetic testing. RESULTS: Indications for PGD can be conceptually divided into ten categories. In descending order of ethical defensibility and concomitant political palatability, they include: (1) debilitating genetic illness (2) moderate genetic illness (3) gender selection for disease prevention (4) recurrent pregnancy loss or IVF failure (5) advanced maternal age (6) late-onset disease (7) ulterior altruistic purposes such as sibling HLA-matching (8) genetic or disease predisposition (9) elective gender selection (10) selection of traits. Ethical scrutiny supports PGD performed for any of the first 8 indications. The potential avoidance of a substantial number of pregnancy terminations has not been sufficiently emphasized or optimally utilized to overcome the political gridlock confronting federal funding of preembryo research. Such sponsorship could positively impact upon public health concerns of multiple gestation and the safety of innovative procedures. Furthermore, the use of PGD to preclude costly genetic disease presents economic implications for insurance coverage of assisted reproduction. Finally, an overarching regulatory scheme modeled after HFEA is rejected. ASRM efforts to balance factors regarding elective gender selection is supported; eugenic trait selection is viewed as presently implausible and insufficient as a basis for more restrictive policies. CONCLUSION: PGD can be further sanctioned and promoted by focused ethical and policy analysis. This has repercussions for the practice of both PGD and assisted reproduction. Supported by: None.
P-324 Prevalence of male and female embryos in PGD for sex selection cycles. M. H. Fakih, K. Sakhel, M. Shmoury, I. Khan. IVF Michigan and Michigan State University, Rochester Hills, MI; IVF Michigan PC, Rochester Hills, MI. OBJECTIVE: To study the prevalence of male or female genotypes in the embryos of couples undergoing IVF with PGD for sex selection. DESIGN: Couples undergoing IVF with PGD for sex selection were followed up prospectively. MATERIALS AND METHODS: A total of 157 embryos from 14 patient cycles of IVF that were biopsied for PGD were included in the analysis. There were 2 cycles for female sex selection and 12 cycles for male sex selection. Following fertilization of the oocytes by ICSI, embryo biopsy was performed on day 3 and the diagnosis was determined using fluorescent in situ hybridization (FISH) for chromosomes 13, 16, 18, 21, 22, X and Y. Embryos were then transferred on day 5. RESULTS: Among 67 normal embryos, only 17(25.4%) were of the sex selected. In the male sex selection cycles out of 51 normal embryos 14 (27.5%) were male sex. In the female sex selection cycles there were 3 out of 16 normal embryos (18.8%) that were female. Of the 14 cycles of PGD for sex selection, 10 ended with a transfer of a total of 18 embryos achieving 40% pregnancy rate per transfer and 38.9% implantation rate. Table 1 summarizes the results of the study.
CONCLUSION: There is a decreased prevalence of embryos with the sex selected in PGD cycles for sex selection. This may be the result of a preponderance of X chromosome bearing spermatozoa in couples with female offsprings and similarly a preponderance of Y chromosome bearing spermatozoa in couples with male offsprings. Supported by: None.
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P-325 Both day 3 and day 5 embryo morphology are highly predictive for the chromosomal status of the preimplantation embryo as analyzed by fluorescent in situ hybridization (FISH). A. Jones, S. Patel, S. M. Slayden, D. B. Shapiro, H. I. Kort, Z. P. Nagy. Reproductive Biology Associates, Atlanta, GA; Agnes Scott College, Atlanta, GA. OBJECTIVE: Preimplantation genetic diagnosis (PGD) is increasingly used for aneuploidy screening of embryos both for diagnostic and for treatment purposes preventing the transfer of cytogenetically abnormal embryos, which is suggested to result in lowered abortion rates. It is however a concern that the biopsy procedure may negatively impact embryo viability and thus may impair chances of pregnancy. Therefore, determining which patients are suitable candidates for PGD is an important and complicated task. While the affect of maternal age on embryonic aneuploidy rates has been well established it is largely unknown whether embryo development and quality are correlated with aneuploidy. Thus, the objective of the present study was to analyze day 3 and day 5 embryonic data with respect to aneuploidy rates. DESIGN: Data collection and evaluation on 411 embryos from 53 IVF patients who underwent IVF treatment in the year of 2003. MATERIALS AND METHODS: Biopsy, fixation and FISH procedures were performed as standard, using 7 chromosomal probes (X, Y, 13, 16, 18, 21 and 22). Embryos were cultured until day 5 and embryo parameters were recorded each day. RESULTS: Mean female age was 39.0 ⫾3.1 (S.D.). 62.5% of embryos presented aneuploidy, 34.8% was normal and 2.6% provided no results. 38.5% of the anomalies were restricted to a single chromosome and 61.5% showed multiple alterations. 33.2% of the abnormal cases were monosomies, 51.5% were trisomies and 15.3% of them were combined. According to cell stage on day 3; ⬍6, 6, 7, 8, 9, ⬎9, the incidence of chromosomal abnormalities was as follows: 81%, 70%, 62%, 52%, 57% and 69% respectively (P⬍0.01). Any other day 3 embryonic feature (including fragmentation) presented a much weaker correlation with incidence of aneuploidy. Proportion of good, medium and poor quality blastocysts on day 5 were 27.3%, 50.7% and 22.0% with the following incidence of abnormalities: 54.6%, 69.1% and 80.5% respectively (P⬍0.01). CONCLUSION: The results of the present study demonstrate that embryo parameters both on day 3 and day 5 are very strongly correlated with the incidence of aneuploidy in an IVF patient population of advanced reproductive age. Cleavage stage proved to be the most reliable parameter on day 3 predicting chromosomal status of the embryo showing 8-cell stage as being optimal. Blastocyst quality was also strongly correlated with the chromosomal status of the embryo. Furthermore, it was also established that aneuploidy involving monosomies is 50% more frequent than trisomies, suggesting that chromosomal disparity causes an altered pattern in the actin rich cortical region of the oocytes organizing PB extrusion. Based on the outcome of the present study, it is recommended that embryo parameters, particularly day 3 cell stage, are considered in conjunction with age and embryo number when PGD for aneuploidy is being considered as a treatment option. Supported by: None.
P-326 Comparison of computer assisted infrared laser with acid tyrode solution in zona drilling for embryo biopsy. M. Li, C. Marin Deugarte, M. Surrey, H. Danzer, A. Decherney, D. Hill. ART Reproductive Center, Beverly Hills, CA; OBGYN, UCLA Medical Center, Los Angeles, CA; Cider-Sinai Medical Center, Los Angeles, CA; Cedar-Sinai Medical Center, Los Angeles, CA. OBJECTIVE: Zona drilling by Computer Assisted Infrared Laser is easy and precise. However the safety of laser used in IVF laboratory is still a concern. This study aims to evaluate the embryo biopsy procedure and to compare two different biopsy techniques: the Computer Assisted Infrared Laser (CAIL), using the Hamilton Thorn-Zilos-tk laser and the Acid Tyrode’s Solution (ATS). DESIGN: Retrospective MATERIALS AND METHODS: A total of 233 patients that underwent PGD for aneuploidy screening between 04/01/03 to 3/15/2004 were included in the study. The laboratory environment including the culture
Vol. 82, Suppl. 2, September 2004
P-324 Prevalence of male and female embryos in PGD for sex selection cycles. M. H. Fakih, K. Sakhel, M. Shmoury, I. Khan. IVF Michigan and Michigan State University, Rochester Hills, MI; IVF Michigan PC, Rochester Hills, MI. OBJECTIVE: To study the prevalence of male or female genotypes in the embryos of couples undergoing IVF with PGD for sex selection. DESIGN: Couples undergoing IVF with PGD for sex selection were followed up prospectively. MATERIALS AND METHODS: A total of 157 embryos from 14 patient cycles of IVF that were biopsied for PGD were included in the analysis. There were 2 cycles for female sex selection and 12 cycles for male sex selection. Following fertilization of the oocytes by ICSI, embryo biopsy was performed on day 3 and the diagnosis was determined using fluorescent in situ hybridization (FISH) for chromosomes 13, 16, 18, 21, 22, X and Y. Embryos were then transferred on day 5. RESULTS: Among 67 normal embryos, only 17(25.4%) were of the sex selected. In the male sex selection cycles out of 51 normal embryos 14 (27.5%) were male sex. In the female sex selection cycles there were 3 out of 16 normal embryos (18.8%) that were female. Of the 14 cycles of PGD for sex selection, 10 ended with a transfer of a total of 18 embryos achieving 40% pregnancy rate per transfer and 38.9% implantation rate. Table 1 summarizes the results of the study.
CONCLUSION: There is a decreased prevalence of embryos with the sex selected in PGD cycles for sex selection. This may be the result of a preponderance of X chromosome bearing spermatozoa in couples with female offsprings and similarly a preponderance of Y chromosome bearing spermatozoa in couples with male offsprings. Supported by: None.
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P-325 Both day 3 and day 5 embryo morphology are highly predictive for the chromosomal status of the preimplantation embryo as analyzed by fluorescent in situ hybridization (FISH). A. Jones, S. Patel, S. M. Slayden, D. B. Shapiro, H. I. Kort, Z. P. Nagy. Reproductive Biology Associates, Atlanta, GA; Agnes Scott College, Atlanta, GA. OBJECTIVE: Preimplantation genetic diagnosis (PGD) is increasingly used for aneuploidy screening of embryos both for diagnostic and for treatment purposes preventing the transfer of cytogenetically abnormal embryos, which is suggested to result in lowered abortion rates. It is however a concern that the biopsy procedure may negatively impact embryo viability and thus may impair chances of pregnancy. Therefore, determining which patients are suitable candidates for PGD is an important and complicated task. While the affect of maternal age on embryonic aneuploidy rates has been well established it is largely unknown whether embryo development and quality are correlated with aneuploidy. Thus, the objective of the present study was to analyze day 3 and day 5 embryonic data with respect to aneuploidy rates. DESIGN: Data collection and evaluation on 411 embryos from 53 IVF patients who underwent IVF treatment in the year of 2003. MATERIALS AND METHODS: Biopsy, fixation and FISH procedures were performed as standard, using 7 chromosomal probes (X, Y, 13, 16, 18, 21 and 22). Embryos were cultured until day 5 and embryo parameters were recorded each day. RESULTS: Mean female age was 39.0 ⫾3.1 (S.D.). 62.5% of embryos presented aneuploidy, 34.8% was normal and 2.6% provided no results. 38.5% of the anomalies were restricted to a single chromosome and 61.5% showed multiple alterations. 33.2% of the abnormal cases were monosomies, 51.5% were trisomies and 15.3% of them were combined. According to cell stage on day 3; ⬍6, 6, 7, 8, 9, ⬎9, the incidence of chromosomal abnormalities was as follows: 81%, 70%, 62%, 52%, 57% and 69% respectively (P⬍0.01). Any other day 3 embryonic feature (including fragmentation) presented a much weaker correlation with incidence of aneuploidy. Proportion of good, medium and poor quality blastocysts on day 5 were 27.3%, 50.7% and 22.0% with the following incidence of abnormalities: 54.6%, 69.1% and 80.5% respectively (P⬍0.01). CONCLUSION: The results of the present study demonstrate that embryo parameters both on day 3 and day 5 are very strongly correlated with the incidence of aneuploidy in an IVF patient population of advanced reproductive age. Cleavage stage proved to be the most reliable parameter on day 3 predicting chromosomal status of the embryo showing 8-cell stage as being optimal. Blastocyst quality was also strongly correlated with the chromosomal status of the embryo. Furthermore, it was also established that aneuploidy involving monosomies is 50% more frequent than trisomies, suggesting that chromosomal disparity causes an altered pattern in the actin rich cortical region of the oocytes organizing PB extrusion. Based on the outcome of the present study, it is recommended that embryo parameters, particularly day 3 cell stage, are considered in conjunction with age and embryo number when PGD for aneuploidy is being considered as a treatment option. Supported by: None.
P-326 Comparison of computer assisted infrared laser with acid tyrode solution in zona drilling for embryo biopsy. M. Li, C. Marin Deugarte, M. Surrey, H. Danzer, A. Decherney, D. Hill. ART Reproductive Center, Beverly Hills, CA; OBGYN, UCLA Medical Center, Los Angeles, CA; Cider-Sinai Medical Center, Los Angeles, CA; Cedar-Sinai Medical Center, Los Angeles, CA. OBJECTIVE: Zona drilling by Computer Assisted Infrared Laser is easy and precise. However the safety of laser used in IVF laboratory is still a concern. This study aims to evaluate the embryo biopsy procedure and to compare two different biopsy techniques: the Computer Assisted Infrared Laser (CAIL), using the Hamilton Thorn-Zilos-tk laser and the Acid Tyrode’s Solution (ATS). DESIGN: Retrospective MATERIALS AND METHODS: A total of 233 patients that underwent PGD for aneuploidy screening between 04/01/03 to 3/15/2004 were included in the study. The laboratory environment including the culture
Vol. 82, Suppl. 2, September 2004