PGT for structural chromosomal rearrangements in 300 couples reveals specific risk factors but an interchromosomal effect is unlikely.

RESEARCH QUESTION: What factors affect the proportion of chromosomally balanced embryos in structural rearrangement carriers? Is there any evidence for an interchromosomal effect (ICE)? DESIGN: Preimplantation genetic testing outcomes of 300 couples (198 reciprocal, 60 Robertsonian, 31 inversion and 11 complex structural rearrangement carriers) were assessed retrospectively. Blastocysts were analysed either by array-comparative genomic hybridization or next-generation sequencing techniques. ICE was investigated using a matched control group and sophisticated statistical measurement of effect size (φ). RESULTS: 300 couples underwent 443 cycles; 1835 embryos were analysed and 23.8% were diagnosed as both normal/balanced and euploid. The overall cumulative clinical pregnancy and live birth rates were 69.5% and 55.8%, respectively. Complex translocations and female age (≥35) were found to be risk factors associated with lower chance of having a transferable embryo (P < 0.001). Based on analysis of 5237 embryos, the cumulative de-novo aneuploidy rate was lower in carriers compared to controls (45.6% versus 53.4%, P < 0.001) but this was a 'negligible' association (φ < 0.1). A further assessment of 117,033 chromosomal pairs revealed a higher individual chromosome error rate in embryos of carriers compared to controls (5.3% versus 4.9%), which was also a 'negligible' association (φ < 0.1), despite a P-value of 0.007. CONCLUSIONS: These findings suggest that rearrangement type, female age and sex of the carrier have significant impacts on the proportion of transferable embryos. Careful examination of structural rearrangement carriers and controls indicated little or no evidence for an ICE. This study helps to provide a statistical model for investigating ICE and an improved personalized reproductive genetics assessment for structural rearrangement carriers.

Is there a correlation between follicle size and gene expression in cumulus cells and is gene expression an indicator of embryo development?

BACKGROUND: In an article published in 2017, we discussed the results of the first part of our study into the morphokinetic development of embryos in relation to follicle diameter and homogeneity of follicular development. Our findings showed that embryos coming from small follicles in heterogeneous cycles had significantly higher rates of arrest or failure to reach blastocyst than embryos coming from large follicles in homogenous cycles. The aim of this further study was to investigate the relationship between follicular size and gene expression of cumulus cells (CCs) and evaluate whether gene expression could be an indicator of embryo development. METHODS: This study was based on 2495 COCs from 184 patients. CC expressions of five genes (TNFAIP6, PTGS2, HAS2, PTX3 and GDF9) were studied by generalized linear mixed models (GLMMs) regarding follicular size. CC expressions were then separately analysed regarding patient-specific variables (age, BMI, AMH and follicular size) in relation to embryos reaching blastocyst (eRB) or top or good quality blastocysts (TQ + GQ) using GLMMs with logit link. RESULTS: Follicular size significantly correlated with the potential of an oocyte to develop into a blastocyst: oocytes developing from large follicles were more than twice as likely to develop into an eRB than oocytes from small follicles (p < 0.001). Gene expression of HAS2 and GDF9 correlated with blastocyst quality when separately evaluated with follicular size and the patient specific variables of age, BMI and AMH. However, no such correlation was found in other gene expressions studied. CONCLUSIONS: Our findings suggest that differences in the expression of genes studied could be related to follicular size rather than to embryo quality. Although gene expression of HAS2 and GDF9 correlated with blastocyst quality, the only variable correlating with eRB and TQ and GQ blastocysts for each of these five models was follicular size. TRIAL REGISTRATION: This prospective cohort study was registered at clinicaltrials.gov (NCT02230449).