title: Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos.
abstract: Morphological assessments are the main way in which fertility clinics select in vitro generated embryo(s) for transfer to the uterus. However, it is widely acknowledged that the microscopic appearance of an embryo is only weakly correlated with its viability. Furthermore, the extent to which morphology is affected by aneuploidy, a genetic defect common in human preimplantation embryos, remains unclear. Aneuploidy is of great relevance to embryo selection as it represents one of the most important causes of implantation failure and miscarriage. The current study aimed to examine whether morphological appearance can assist in identifying embryos at risk of aneuploidy. Additionally, the data produced sheds light on how chromosomal anomalies impact development from the cleavage to the blastocyst stage. A total of 1213 embryos were examined. Comprehensive chromosome analysis was combined with well-established criteria for the assessment of embryo morphology. At the cleavage stage, chromosome abnormalities were common even amongst embryos assigned the best morphological scores, indicating that aneuploidy has little effect on microscopic appearance at fixed time points up until Day 3 of development. However, at the blastocyst stage aneuploidies were found to be significantly less common among embryos of optimal morphological quality, while such abnormalities were overrepresented amongst embryos considered to be of poor morphology. Despite the link between aneuploidy and blastocyst appearance, many chromosomally abnormal embryos were able to achieve the highest morphological scores. In particular, blastocysts affected by forms of aneuploidy with the greatest capacity to produce clinical pregnancies (e.g. trisomy 21) were indistinguishable from euploid embryos. The sex ratio was seen to be equal throughout preimplantation development. Interestingly, however, females were overrepresented amongst the fastest growing cleavage-stage embryos, whereas a sex-related skew in the opposite direction was noted for the most rapidly developing blastocysts. In summary, this study confirms that, at the cleavage stage, chromosome abnormalities have little if any effect on morphological scores assigned using traditional criteria. At the blastocyst stage some forms of aneuploidy begin to affect microscopic appearance, but in most instances the impact is subtle. In the case of the most clinically relevant aneuploidies (those capable of forming a pregnancy) there was no detectable effect on morphology at any preimplantation stage.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: E
authors.initials: E
authors.lastname: Fragouli
authors.forename: S
authors.initials: S
authors.lastname: Alfarawati
authors.forename: K
authors.initials: K
authors.lastname: Spath
authors.forename: D
authors.initials: D
authors.lastname: Wells
mesh_terms: D000782:Aneuploidy; D001755:Blastocyst / Q000378:metabolism / Q000473:pathology*; D002877:Chromosomes, Human / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008853:Microscopy; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D012107:Research Design
keywords: aCGH; aneuploidy; blastocyst stage; cleavage stage; embryo morphology