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Despite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and one inner cell mass [ICM] analyzed per blastocyst; n = 390), we determine the origin of the aneuploidy and the diagnostic predictive value of segmental aneuploidy detection in TE biopsies toward the ICM's chromosomal constitution. Contrary to the prevalent meiotic origin of whole-chromosome aneuploidies, we show that sub-chromosomal abnormalities in human blastocysts arise from mitotic errors in around 70% of cases. As a consequence, the positive-predictive value toward ICM configuration was significantly lower for segmental as compared to whole-chromosome aneuploidies (70.8% versus 97.18%, respectively). In order to enhance the clinical utility of reporting segmental findings in clinical TE biopsies, we have developed and clinically verified a risk stratification model based on a second TE biopsy confirmation and segmental length; this model can significantly improve the prediction of aneuploidy risk in the ICM in over 86% of clinical cases enrolled. In conclusion, we provide evidence of the predominant mitotic origin of segmental aneuploidies in preimplantation embryos and develop a risk stratification model that can help post-test genetic counseling and that facilitates the decision-making process on clinical utilization of these embryos.

Objective Breast and intestinal cancers chemoprevention would significantly impact on cancer care. Hence, we assessed the chemopreventive efficacy of the antioxidant lipoic acid (LA) in mice overexpressing a wild-type Her2/neu, as an animal model of breast cancer, and in APCmin mice for intestinal cancer. Methods Mice were randomised at weaning, and were treated with LA for lifetime. Tumour incidence, growth rate and histopathology were analysed on an individual tumour basis. Results LA efficiently chemoprevented tumour appearance in APCmin mice. Strikingly, though, LA doses, that were chemopreventive in APCmin mice (⩾300 μg/day), increased breast cancer growth in Her2/neu mice. Even in experimental groups, where LA overall reduced tumour risk (80 μg/day), LA consistently stimulated the growth rate of established breast tumours. Breast and colon tumours incidence was unaffected by LA, indicating no significant impact of LA on tumour initiation and no protection from mutations driving tumour progression. Conclusions Stimulation of breast cancer growth and inhibition of intestinal tumours by LA indicate that diverse growth control mechanisms are modulated by LA in different organs. Concern is raised about the use of LA for cancer chemoprevention.