Does First Polar Body Array CGH Analysis Correlate with a Cleavage Stage Embryo Biopsy in IVF-ICSI Cycles and Preimplantation Genetic Screening

Abstract

To correlate first polar body(PB1) biopsy array comparative genomic hybridization(aCGH) technology with cleavage stage(D3) biopsy results analyzed with either FISH or SNP array. Prospective clinical trial. 15 IVF patients underwent PB1 biopsy followed by a D3 biopsy. Between 09/11-04/12, 27 patients consented and 15 met the study's criteria and underwent PB1 biopsy and D3 biopsy. 11 patients completed their cycle with a total of 101 PB1 and corresponding D3 biopsies. All mature metaphase II (MII) oocytes were fertilized by ICSI 4-6 hours following oocyte retrieval. 2-4 hours later, PB1 biopsies were performed and frozen. D3 biopsy was then performed and analyzed using either 9-probe FISH(13,15,16,17,18,21,22,X,Y) or SNP 24 CGH(physician/patient preference). Clinical decisions were based solely on the results of D3 analysis.ET was performed on day-5. Concordance between PB1 and D3 results, as well as ongoing pregnancy rates and IVF cycle outcome. 83% of MII oocytes fertilized normally using ICSI. Concordance analysis of the first 96(5 embryos had incomplete results) PB1 and corresponding D3 revealed 67.33% partial or complete concordance and 32.7% discordance. When the 9-probes FISH was used partial concordance was expected. PB1 aCGH had a sensitivity of 82.8% and specificity of 55.7% compared to D3. The kappa statistics was 0.35. Implantation rate was 31% (average 2.3 embryos per transfer). 36% pregnancy rate per cycle started and 27% ongoing pregnancy rate (57% and 42%, respectively, in patients who had ET).Tabled 1PB1 biopsyBlastomere biopsy%NormalNormal28.71AbnormalAbnormal - identical6.93AbnormalAbnormal - partial concordance8.91AbnormalAbnormal - different17.82NormalAbnormal5.94AbnormalNormal26.73N/A4.95100%PB1-Clinically correct diagnosis67.33%PB1-Clinically incorrect diagnosis32.67% Open table in a new tab Tabled 1D3 biopsy + (Normal)D3 biopsy - (Abnormal)Polar body + (Normal)292756Polar body - (Abnormal)63440356196KAPPA = 0.35 (Fair agreement) with C.I. (0.14, 0.54) p value = 0.0001 Open table in a new tab KAPPA = 0.35 (Fair agreement) with C.I. (0.14, 0.54) p value = 0.0001 PB1 biopsy can not completely replace embryo biopsy for PGS as it doesn't appraise 2nd meiosis error and mitotic errors. Our study suggests, that PB1 aCGH can accurately predict oocyte chromosomal status in 2/3 of cases and completed within 12 hours. Aneuploidy(partly due to mosaicism) was the predominant cause of non-viability in our study group. PB1 biopsy should be used in certain clinical scenarios and selected patients.