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SNP microarray-based PGS significantly improves the clinical outcome for translocation carriers

ABSTRACT: This was a retrospective comparison study of SNP-based preimplantation genetic screening (SNP-PGS) and FISH-based preimplantation genetic diagnosis (FISH-PGD) for 575 couples in total with chromosome translocations, including 169 couples treated by SNP-PGS between October 2011 and August 2012, and 406 couples treated by FISH- PGD between January 2005 and October 2011. In total, 773 blastocysts obtained from 169 couples were biopsied and frozen, embryo transfer was carried out on the balanced embryos. The PGS results and pregnancy outcomes were compared with those of FISH-PGD for 406 translocation carriers with 3,968 embryos biopsied on day 3. Of the 773 biopsied blastocysts, reliable SNP-PGS results were obtained for 717 (92.76%). For Robertsonian translocation carriers, the rate of normal/balanced embryos, embryos with translocation-related abnormalities, and embryos with abnormalities unrelated to a translocation were 57.80%, 23.39% and 18.81%, respectively. In reciprocal translocation carriers, the rate of normal/balanced embryos, embryos with translocation-related abnormalities and embryos with abnormalities unrelated to translocation were 35.47%, 52.10% and 12.42%, respectively. There was no significant differences in patient age, basal endocrine level and the average number of retrieved oocytes and good quality day 3 embryos before biopsy in the SNP-PGS group compared with the FISH-PGD group. The number of embryos biopsied in the FISH-PGD group was higher than in the SNP-PGS group. However, the pregnancy rate with successful delivery per oocyte retrieval and the implantation rate were both lower in the FISH-PGD group than in the SNP-PGS group. The spontaneous abortion rate was higher in the FISH-PGD group than in the SNP-PGS group.

ORGANISM(S): Homo sapiens

PROVIDER: GSE44994 | GEO | 2013/03/11

SECONDARY ACCESSION(S): PRJNA192801

REPOSITORIES: GEO

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Project description:Preimplantation genetic diagnosis (PGD) of aneuploidy by fluorescence in situ hybridisation (FISH) has not delivered the expected clinical benefit. Many previous re-analysis studies of embryos deemed aneuploid by FISH on day 3 have found a high degree of chromosomal normalcy at the blastocyst stage. While most have interpreted this as âself correction,â there remains a lack of evidence for such a phenomenon. A more comprehensive technique for 24 chromosome aneuploidy screening was utilised here to re-evaluate blastocysts previously diagnosed as abnormal by FISH and investigate possible self correction mechanisms, including extrusion or duplication of aneuploid chromosomes resulting in uniparental isodisomy (UPID), and preferential segregation of aneuploidy to the trophectoderm (TE). Embryos that developed to a morphologically normal blastocyst after an aneuploidy diagnosis by cleavage stage FISH were biopsed into 4 sections, 3 TE and 1 inner cell mass (ICM), and randomised for evaluation by single nucleotide polymorphism (SNP) microarray based 24 chromosome aneuploidy screening (MA-PGD). Fifty-eight percent of blastocysts were euploid for all 24 chromosomes despite an aneuploid FISH result on day 3. Only 18% were consistent with the original FISH diagnosis, while the remaining 24% identified abnormalities that were different from the original FISH diagnosis. Abnormalities did not preferentially segregate to the TE and aneuploid chromosome extrusion or duplication resulting in UPID did not occur. Cleavage stage FISH is poorly predictive of aneuploidy in an embryo that develops into a morphologically normal blastocyst. Clinicians should consider re-evaluating embryos diagnosed as aneuploid by FISH that form morphologically normal blastocysts using a validated comprehensive 24 chromosome aneuploidy screening method. Affymetrix SNP arrays were processed according to the manufacturer's directions on DNA extracted from 50 cryopreserved blastocysts that were biopsied into 3 sections of trophectoderm and 1 inner cell mass section. Affymetrix SNP array analysis was successfully completed on 145 trophectoderm samples and 47 ICM samples from embryos, 8 lymphocyte samples from cell lines and 6 mixed male and female samples.

Project description:Many studies estimate that chromosomal mosaicism within the cleavage stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism is overestimated due to technical inconsistency rather than biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques.Thirteen arrested cleavage stage embryos were studied. Each was biopsied into individual cells (n=160). The cells from each embryo were randomized into two groups. Those destined for FISH based aneuploidy screening (n=75) were fixed, 1 cell per slide. Cells for SNP microarray based aneuploidy screening (n=85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P=0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (4 of 13 embryos; 31%) than by FISH (13 of 13 embryos; 100%)(P=0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2+0.2) than microarray (1.3+0.2)(P<0.0001). This is the first prospective, randomized, blinded, and paired comparison between microarray and FISH based aneuploidy screening. Aneuploidy and mosaicism were less common with microarray. While evaluating a smaller number of chromosomes with a proportionally smaller opportunity for finding mosaicism, FISH still had a dramatically higher level of inter-cell variation in diagnosis. SNP microarray based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. Affymetrix SNP arrays were processed according to the manufacturer's directions on DNA extracted from 13 arrested cleavage stage embryos and biopsied into individual blastomere cells. Individual blastomeres were randomized and blinded for SNP microarray analysis (n = 85). Afflymetrix SNP array analysis was successfully completed on 82 blastomeres.

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SNP microarray-based PGS significantly improves the clinical outcome for translocation carriers

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