It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development.

The use of genome wide single nucleotide polymorphism (SNP) arrays for high resolution molecular cytogenetic analysis using a combination of quantitative and genotype analysis is well established. This study demonstrates that by Mendelian analysis of the SNP genotypes of the parents and a sibling or other appropriate family member to establish phase, it is possible to identify informative loci for each of the four parental haplotypes across each chromosome and map the inheritance of these haplotypes and the position of any crossovers in the proband. The resulting 'karyomap', unlike a karyotype, identifies the parental and grandparental origin of each chromosome and chromosome segment and is unique for every individual being defined by the independent segregation of parental chromosomes and the pattern of non-recombinant and recombinant chromosomes. Karyomapping, therefore, enables both genome wide linkage based analysis of inheritance and detection of chromosome imbalance where either both haplotypes from one parent are present (trisomy) or neither are present (monosomy/deletion). The study also demonstrates that karyomapping is possible at the single cell level following whole genome amplification and, without any prior patient or disease specific test development, provides a universal linkage based methodology for preimplantation genetic diagnosis readily available worldwide.

Among the many educational materials produced by the European Society of Human Reproduction and Embryology (ESHRE) are guidelines. ESHRE guidelines may be developed for many reasons but their intent is always to promote best quality practices in reproductive medicine. In an era in which preimplantation genetic diagnosis (PGD) has become a reality, we must strive to maintain its efficacy and credibility by offering the safest and most effective treatment available. The dominant motivators for the development of current comprehensive guidelines for best PGD practice were (i) the absence of guidelines and/or regulation for PGD in many countries and (ii) the observation that no consensus exists on many of the clinical and technical aspects of PGD. As a consequence, the ESHRE PGD Consortium undertook to draw up guidelines aimed at giving information, support and guidance to potential, fledgling and established PGD centres. The success of a PGD treatment cycle is the result of great attention to detail. We have strived to provide a similar level of detail in this document and hope that it will assist staff in achieving the best clinical outcome for their patients.

Crossover recombination reshuffles genes and prevents errors in segregation that lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Here, we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses. Genotyping > 4 million informative single-nucleotide polymorphisms (SNPs) from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns of 529 chromosome pairs. We uncover a novel reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germline by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings reveal that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II.

This review provides an overview of studies performed to date on the effect of cryopreservation on the oocyte, sperm and embryos. Controversy of the reported data has highlighted the gaps in our knowledge not only for clinical studies, but also for basic research in human embryos. New perspectives for future research are proposed.

The European Society of Human Reproduction and Embryology PGD Consortium has collected data on PGD cycles and deliveries since 1997. From 15,158 cycles, 24 misdiagnoses and adverse outcomes have been reported; 12/2538 cycles after polymerase chain reaction and 12/12,620 cycles after fluorescence in situ hybridization. The causes of misdiagnosis include confusion of embryo and cell number, transfer of the wrong embryo, maternal or paternal contamination, allele dropout, use of incorrect and inappropriate probes or primers, probe or primer failure and chromosomal mosaicism. Unprotected sex has been mentioned as a cause of adverse outcome not related to technical and human errors. The majority of these causes can be prevented by using robust diagnostic methods within laboratories working to appropriate quality standards. However, diagnosis from a single cell remains a technically challenging procedure, and the risk of misdiagnosis cannot be eliminated.

SummaryDefects in segregation lead to missing or lacking chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Physical exchanges (crossovers) between homologous chromosomes are formed during foetal development and ensure that the pair remains tethered until their separation decades later in the meiotic divisions in adult oocytes. Here, we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses (embryo or oocytes and corresponding polar bodies). Genotyping > 4 million informative single-nucleotide polymorphisms (SNPs) from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns from 529 chromosome pairs.We uncover a novel reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germline by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings reveal that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II.3 Main text.Errors in chromosome segregation during the meiotic divisions in human female meiosis are a major cause of aneuploid conceptions, leading to implantation failure, pregnancy loss, and congenital disorders 1 . The incidence of human trisomies increases exponentially in women from ~ 35 years of age, but despite conservative estimates that 10-30% of natural conceptions are aneuploid 2 , the underlying causes and their relative contributions are still unclear. In addition to maternal age, one important factor that is hypothesized to predispose to missegregation in both sexes is altered recombination. Recombinant chromosomes in the offspring are the result of crossovers, the reciprocal exchange of DNA between homologous chromosomes (homologs). Together with sister chromatid cohesion, crossovers physically link the homolog pair together during the prophase stage of meiosis (Fig. 1a), which takes place during foetal development in females. The linkages have to be maintained for decades, because the two rounds of chromosome segregation only occur in the adult woman. By following the pattern of genetic markers such as single nucleotide polymorphisms (SNPs) on the two chromosomes inherited from the mother in trisomic conceptions, it has been inferred that some crossovers occur too close to centromeres 1,3-6 , where they may disrupt the cohesion between the two sister chromatids 7,8 . Other crossovers have been suggested to be too far from the centromeres to mediate correct attachment, or to be lacking altogether (non-exchange, E 0 ) 1,3-6 . If these inferences are correct, it follows that events that shape the recombination landscape in oocytes during foetal development of women affect their risk of having an aneuploid conception decades later in adult lif...

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