Preimplantation genetic diagnosis for adult-onset and susceptibility diseases: perspectives of reproductive endocrinologists

reported post aCGH, of 1 twin due to pregnancy complications, with the other baby born healthy. Data was split by translocations type and analysed by the gender of carrier and maternal age. A lower percentage of unbalanced embryos are produced by male translocation carriers (13% v 67% in robertsonian translocations and 23% v 53% in reciprocal translocations) but over all aneuploidy rates are similar.The worst prognosis group are females aged 36yr and over, with one partner having a reciprocal translocation, where 92% of embryos were aneuploid. CONCLUSION: aCGH can be successfully applied to PGD of chromosome rearrangements, offering a quicker treatment for patients. The size of the chromosome segments, the position of breakpoints and array coverage allows a probability of detection to be calculated. This initial data indicates that analysis of a single blastomere by aCGH is a better indicator for embryo selection than FISH analysis of the chromosome rearrangement. The low miscarriage rate with aCGH is encouraging for both clinics and patients. The data confirms a lower percentage of unbalanced embryos from male carriers but a similar aneuploidy rate. Maternal age is confirmed as the most important factor in terms of ploidy and pregnancy rates. P-187 Tuesday, October 15, 2013 THERE IS NO INTERCHROMOSOMAL EFFECT IN THE EMBRYOS DERIVED FROM YOUNG CARRIERS OF RECIPROCAL AND ROBERTSONIAN TRANSLOCATIONS. P. Tulay, M. Gultomruk, N. Findikli, M. Bahceci. Research and Development Molecular Biology and Genetics Lab, Bahceci IVF Centre, Istanbul, Turkey. OBJECTIVE: This study aimed to analyse ICE in human preimplantation embryos derived from both reciprocal and Robertsonian translocation carriers who were undergoing preimplantation genetic diagnosis (PGD). DESIGN: Eleven cycles of PGD for Robertsonian translocation and twelve cycles of PGD for reciprocal translocation outcomes were analysed retrospectively from August 2010 to February 2011 in Bahceci Assisted Reproductive Technology Centres. MATERIALS AND METHODS: PGD was performed for 200 cleavage stage embryos derived from translocation carriers in younger women (average maternal age of 33 for reciprocal and 30 for Robertsonian translocation carriers) using multicolour fluorescent in situ hybridisation (FISH). An additional aneuploidy screening was performed by multicolour FISH for nine chromosomes (13, 15, 16, 17, 18, 21, 22, X and Y). A further 214 cleavage stage embryos (average maternal age of 32) with no structural chromosomal abnormalities were analysed as a control group. RESULTS: PGD was performed for 86 cleavage stage embryos derived from 10 couples carrying Robertsonian translocations and 11 couples carrying reciprocal translocations. This study showed that the female carriers of both Robertsonian and reciprocal translocations have a similar chance of producing a balanced embryo with normal copy number of the seven chromosomes analysed (13, 15, 16, 17, 18, 21, 22, X and Y). The risk of having an aneuploidy in one of these nine chromosomes was higher in embryos carrying either Robertsonian and reciprocal translocations. CONCLUSION: This study shows that there is ICE in the unbalanced embryos derived from carriers of both reciprocal and Robertsonian translocation. Supported by: Alfarawati et al (2012). P-188 Tuesday, October 15, 2013 PREIMPLANTATION GENETIC DIAGNOSIS FOR ADULT-ONSET AND SUSCEPTIBILITY DISEASES: PERSPECTIVES OF REPRODUCTIVE ENDOCRINOLOGISTS. B. Freedman, G. Steffen, C. Wicklund, A. Besser, M. E. Pavone, J. Dungan. Northwestern University Graduate Program in Genetic Counseling, Chicago, IL. OBJECTIVE: This study assesses perspectives of reproductive endocrinologists (REIs) regarding the use of preimplantation genetic diagnosis (PGD) to select against embryos carrying mutations/variants associated with adult-onset/susceptibility diseases. DESIGN: A study-specific survey examined REI opinions regarding the acceptability of using PGD to select against embryos carrying various adult-onset/susceptibility diseases (Huntington disease (HD), Becker muscular dystrophy (BMD), hereditary breast and ovarian cancer syndrome (HBOC), late-onset familial Alzheimer disease (LOFAD), and familial atypical mole melanoma syndrome (FAMM)) and opinions regarding regulatory guidelines in PGD practice. MATERIALS AND METHODS: REI members of the American Society for Reproductive Endocrinology and the Chicago Association of Reproduc-

S202

ASRM Abstracts

tive Endocrinology completed a survey. Statistical analyses utilized IBM SPSS Statistics 20. RESULTS: 153 REIs completed the survey. The majority felt it was acceptable or definitely acceptable to use PGD to select against embryos carrying an HD mutation (99.3%), a BMD mutation (88.8%), an HBOC mutation (80.8%), an LOFAD variant (52%), and an FAMM mutation (65.6%). Respondents demonstrated a lack of consensus in attitudes regarding the need for PGD regulation. However, the majority (60.1%) agreed that the decision to use PGD to select against-onset/susceptibility diseases should be left exclusively to the patient. CONCLUSION: REIs generally approve of PGD use for adult-onset/susceptibility diseases and entrust patients with decision-making authority regarding acceptable and unacceptable uses of PGD. However, REIs demonstrate wide variability in opinions regarding PGD regulation and may benefit from clinical guidelines to promote consistent attitudes and practices. Supported by: The project was funded by Northwestern University’s Graduate Program in Genetic Counseling and by a student scholarship from the Assisted Reproductive Technologies Special Interest Group of the National Society of Genetic Counselors. P-189 Tuesday, October 15, 2013 IMPLANTATION ABILITY OF BLASTOCYST FROM PREIMPLANTATION GENETIC DIAGNOSIS (PGD) DOES NOT DEPEND ON THE DEDREE OF EXPANSION AFTER THE INITATION OF CAVITATION. P. Buendia,a A. Mercader,a A. Delgado,a L. Escrich,a C. Rubio,b M. J. De los Santos.a aPreimplantational Genetic Diagnosis, IVI Valencia, Valencia, Spain; bPGD Molecular Ginogenetics, IVIOMICS, Paterna, Valencia, Spain. OBJECTIVE: Embryos biopsied on D3 undergo delayed compaction and alteration of hatching mechanism due to artificial hole in the zona pellucida. Therefore morphological grading system based on expansion degree and quality of inner cell mass (ICM) and trophoectoderm (TE) normally used for blastocyst selection might be not valid. The aim of this study was to establish each morphological parameter’s contribution to the implantation potential of a chromosomally normal blastocyst from D3 biopsied embryos, attending to degree of blastocoel expansion and hatching status, size and compactness of ICM and cohesiveness and number of TE cells. DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 448 cycles including 624 embryos with known implantation from our PGD program have been included (January 2010-December 2012). Biopsies were performed on D3 in Ca2+ and Mg2+ free medium (G-PGD, Vitrolife) using laser technology (OCTAX). For assessment of aneuploidy screening FISH was used to analyze chromosomes 13, 15, 16, 17, 18, 21, 22, X, Y (Vysis) or CGH array technology (BlueGenome). Blastocyst score was based on Gardner and Schoolcraft criteria. Statistical comparisons were performed using chi2-test, univariate and multivariate logistic regression to evaluate the effect of ICM and TE grades. RESULTS: With the exemption of slow developing embryos (morulas, early blastocysts), that had lower rates of implantation rates of 14.0%, blastocyst with different degree of blastocoel expansion cavitated, hatching and hatched did not differ in implantation ability (31.5%, 36.4%, 19.2%, respectively). Concerning ICM nor correlation was seen among a, b and c grades (39.6%, 36.4%, 28.8%). Regarding TE grade logistic regression analysis demonstrated that TE grade was highly correlated with implantation OR 2.1(1.3-3.5 of CI 95%). CONCLUSION: Chromosomally normal blastocysts generated from biopsied D3 embryos, do not relay on expansion degree for implantation. In contrast, TE seems to be a more predictive variable that ICM once blastocoel is formed. P-190 Tuesday, October 15, 2013 MULTIPLE FACTOR PGD - 7 CASE REPORTS INVOLVING TESTING FOR UP TO 4 INDICATION IN A SINGLE BLASTOMERE. C. Lynch,a N. Tee,a H. Forbes,a K. Shaut,b A. Gordon.a,b aGenesis Genetics Europe, Nottingham, Nottinghamshire, United Kingdom; bGenesis Genetics, Detroit, MI. OBJECTIVE: To assess the feasibility, in terms of data produced and cycle outcomes, of testing for multiple indications in a single blastomere. DESIGN: We present: 2 cases where testing was performed for a single gene disorder and aneuploidy 2 where testing was performed for 2 single gene disorders

Vol. 100, No. 3, Supplement, September 2013