Assisted reproductive technology is today considered a safe and reliable medical intervention, with healthy live births a reality for many IVF and ICSI treatment cycles. However, there are increasing numbers of published reports describing epigenetic/imprinting anomalies in children born as a result of these procedures. These anomalies have been attributed to methylation errors in embryo chromatin remodelling during in vitro culture. Here we re-visit three concepts: (1) the so-called ‘in vitro toxicity’ of ‘essential amino acids’ before the maternal to zygotic transition period; (2) the effect of hyperstimulation (controlled ovarian hyperstimulation) on homocysteine in the oocyte environment and the effect on methylation in the absence of essential amino acids; and (3) the fact/postulate that during the early stages of development the embryo undergoes a ‘global’ demethylation. Methylation processes require efficient protection against oxidative stress, which jeopardizes the correct acquisition of methylation marks as well as subsequent methylation maintenance. The universal precursor of methylation [by S-adenosyl methionine (SAM)], methionine, ‘an essential amino acid’, should be present in the culture. Polyamines, regulators of methylation, require SAM and arginine for their syntheses. Cystine, another ‘semi-essential amino acid’, is the precursor of the universal protective antioxidant molecule: glutathione. It protects methylation marks against some undue DNA demethylation processes through ten-eleven translocation (TET), after formation of hydroxymethyl cytosine. Early embryos are unable to convert homocysteine to cysteine as the cystathionine β-synthase pathway is not active. In this way, cysteine is a ‘real essential amino acid’. Most IVF culture medium do not maintain methylation/epigenetic processes, even in mouse assays. Essential amino acids should be present in human IVF medium to maintain adequate epigenetic marking in preimplantation embryos. Furthermore, morphological and morphometric data need to be re-evaluated, taking into account the basic biochemical processes involved in early life.

The aim of this study was to analyse the possible occurrence of the interchromosomal effect (ICE) in human preimplantation embryos obtained from Robertsonian and reciprocal translocation carriers focusing on ones with chromosome 10 rearrangements who were undergoing preimplantation genetic diagnosis (PGD) and to investigate whether offering aneuploidy screening would be beneficial to these patients. Cleavage stage embryos from translocation carriers undergoing PGD were biopsied. Multicolour fluorescence in situ hybridisation for the chromosomes involved in the translocation in addition to nine more chromosomes (13, 15, 16, 17, 18, 21, 22, X and Y) was used in the analysis. The control group involved embryos obtained from age-matched patients undergoing preimplantation genetic screening (PGS). Cumulative aneuploidy rate in embryos derived from both Robertsonian and reciprocal translocation carriers was found to be similar with the control group. Therefore no ICE was observed in cleavage stage embryos obtained from these carriers. More than half of the embryos with chromosome 10 rearrangements had aneuploidy for which an increased aneuploidy rate was more apparent in male carriers. Thus, it is possible that there is a risk of ICE in reciprocal carriers with chromosome 10 rearrangements. This study showed that there is no ICE in embryos derived from Robertsonian and reciprocal translocation carriers. However high rates of aneuploidy in structurally normal chromosomes were detected in embryos derived from these carriers and thus aneuploidy screening in addition to PGD may increase the pregnancy rates of these patients.