Euploidy rates in donor egg cycles significantly differ between fertility centers

STUDY QUESTION: Do external factors affect euploidy in egg donor cycles? SUMMARY ANSWER: The study demonstrates that during human assisted reproduction, embryonic chromosome abnormalities may be partly iatrogenic. WHAT IS KNOWN ALREADY: Chromosome abnormalities have been linked in the past to culture conditions such as temperature and Ph variations, as well as hormonal stimulation. Those reports were performed with older screening techniques (FISH), or ART methods no longer in use, and the subjects studied were not a homogeneous group. STUDY DESIGN, SIZE, DURATION: A total of 1645 donor oocyte cycles and 13 282 blastocyst biopsies from 42 fertility clinics were included in this retrospective cohort study. Samples from donor cycles with PGS attempted between September 2011 and July 2015 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGS cycles from multiple fertility clinics referred to Reprogenetics (Livingston, NJ) that involved only oocyte donation were included in this study. Testing was performed by array comparative genomic hybridization (aCGH). Ploidy data were analyzed using Generalized Linear Mixed Models with logistic regression using a logit link function considering a number of variables that represent fixed and random effects. MAIN RESULTS AND THE ROLE OF CHANCE: Euploidy rate was associated with the referring center and independent of almost all the parameters examined except donor age and testing technology. Average euploidy rate per center ranged from 39.5 to 82.5%. The mean expected rate of euploidy was 68.4%, but there are variations in this rate associated with the center effect. LIMITATIONS, REASONS FOR CAUTION: Data set does not include details of the donor selection process, donor race or ethnic origin, ovarian reserve or ovarian responsiveness. Due to the retrospective nature of the study, associations are apparent, however, causality cannot be established. Discrepancies in regard to completeness and homogeneity of data exist due to data collection from over 40 different clinics. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to show a strong association between center-specific ART treatment practices and the incidence of chromosome abnormality in human embryos, although the meiotic or mitotic origin of these abnormalities could not be determined using these technologies. Given the widespread applications of ART in both subfertile and fertile populations, our findings should be of interest to the medical community in general as well as the ART community in particular. STUDY FUNDING/COMPETING INTEREST(S): No external funds were used for this study. S. Munne is a founding principle of Reprogenetics/current employee of Cooper Genomics. M Alikani’s spouse is a founding principle of Reprogenetics/current consultant for Cooper Genomics. The remaining authors have no conflicts to declare

PGS analysis of over 100,000 blastocysts using high resolution next generation sequencing

To determine the types and frequency of abnormalities in human blastocyst detected by high resolution next generation sequencing (hr-NGS) stratified by age and laboratory

Aneuploidy and recombination in the human preimplantation embryo. Copy number variation analysis and genome-wide polymorphism genotyping

Research question What are the incidence and patterns of meiotic trisomies and recombination separately and in relation to each other at the blastocyst stage via single nucleotide polymorphism genotyping combined with array comparative genomic hybridization. Design Single nucleotide polymorphism microarrays were carried out on a total of 1442 blastocyst stage embryos derived from 268 fertile couples undergoing preimplantation genetic diagnosis for the purposes of avoiding transmittance of known single gene disorders to their offspring; 24-chromosome aneuploidy screening via array comparative genomic hybridization was carried out in parallel. Results One hundred per cent of meiotic trisomies identified in these embryos were of maternal origin and their incidence increased significantly with advancing maternal age (P Conclusions This study yielded unique data concerning recombination and the origin of aneuploidies observed during the first few days of life and provides a novel insight into these important biological processes.</p

Detection of mosaicism at blastocyst stage with the use of high-resolution next-generation sequencing

A significant proportion of human preimplantation embryos produced during the course of in vitro fertilization (IVF) treatments contain two or more cytogenetically distinct cell lines. This phenomenon, known as chromosomal mosaicism, can involve the presence of cells with different types of aneuploidy in the absence of any normal cells or a mixture of euploid and abnormal cells. Although a high prevalence of mosaicism at the cleavage and blastocyst stages has been appreciated for two decades, the precise frequency of the phenomenon and its consequences for embryo viability have been difficult to quantify. Recent advances in genetic technologies, such as high-resolution next-generation sequencing, have allowed mosaicism to be detected with much greater sensitivity than earlier methods. The application of these techniques to trophectoderm biopsies, taken from embryos before transfer to the uterus, has provided insight into the clinical impact of mosaicism. Data from recent studies show that blastocysts associated with mosaic trophectoderm biopsy specimens implant less often than embryos with a chromosomally normal biopsy. In addition, the mosaic embryos that succeed in establishing a pregnancy are at a significantly higher risk of miscarriage. Because mosaic embryos are less likely to produce a viable pregnancy than their euploid counterparts, we suggest that they are given a lower priority for transfer to the uterus. However, because these embryos can sometimes produce successful pregnancies, it is important that they can be considered for transfer in the absence of fully euploid embryos and after appropriate patient counseling. Unlike aneuploidy of meiotic origin, mosaicism, which is caused by mitotic errors occurring after fertilization, does not increase with advancing maternal age. There may, however, be clinical, treatment, or patient-related factors that contribute to the risk of mosaicism occurring. This review discusses the validation of methods that permit the detection of chromosomal mosaicism in IVF embryos and findings of clinical relevance