Telomere length in human blastocysts.

This is a retrospective study aiming to assess telomere length in human embryos 4 days post fertilization and to determine whether it is correlated to chromosomal ploidy, embryo developmental rate and patient age. Embryos were donated from patients undergoing treatment in the assisted conception unit. Seven couples took part, generating 35 embryos consisting of 1130 cells.

The origins of genetic variation between individual human oocytes and embryos: implications for infertility.

Human fertility is low in comparison with that seen in other well-studied mammals. The main reason for this state of affairs seems to be the frequent occurrence and persistence of chromosomal errors in the human conceptus. Evidence obtained over the past two decades shows that the exceptionally high incidence of chromosomal anomalies seen in human preimplantation embryos is the result of errors that may occur at various stages during gamete and embryo formation.

Preimplantation genetic diagnosis: recent triumphs and remaining challenges.

Over the last 20 years, preimplantation genetic diagnosis (PGD) has changed from being an experimental procedure to one that is carried out in specialized diagnostic centers worldwide. Genetic awareness and the rapid identification of germline mutations or chromosomal abnormalities enable individuals to know their risk of transmitting a genetic disease before they have children. This has created a demand for PGD from couples who wish to avoid terminations of affected pregnancies.

Is the polar body approach best for pre-implantation genetic screening?

Pre-implantation genetic screening is carried out with the aim of selecting oocytes or embryos that have the optimal chance of producing an ongoing pregnancy by eliminating those that have a detectable chromosomal anomaly. A variety of cells may be chosen for testing; the first polar body, with or without the corresponding second polar body, a single blastomere from a cleavage stage embryo or a group of cells from the trophectoderm at the blastocyst stage. This paper explains the different stages when aneuploidy may arise during oocyte development and the contribution made by post-zygotic aneuploidy to the overall burden as a basis for understanding the arguments for and against selecting polar bodies as the cells of choice for pre-implantation screening.

Preimplantation genetic diagnosis for myotonic dystrophy type 1 in the UK.

Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder caused by expansion of a trinucleotide repeat in a non-coding region of DMPK. Prenatal diagnosis (PND) is available; however, the decision to terminate affected pregnancies is difficult as the extent of disability is hard to predict from the size of the expansion. In preimplantation genetic diagnosis (PGD) genetic analysis is carried out before the establishment of pregnancy.

Complete cytogenetic investigation of oocytes from a young cancer patient with the use of comparative genomic hybridisation reveals meiotic errors.

Objectives: The complete cytogenetic investigation of human oocytes and the corresponding first polar bodies (PBs) derived from an 18-year old female cancer patient.

Methods: A whole-genome amplification method combined with comparative genomic hybridisation (CGH) was employed for the analysis of 14 oocytes and their corresponding first PBs.

Results: Chromosome abnormalities were detected in two oocyte-PB complexes.

Genetics of gametes and embryos.

Chromosome analysis of oocytes, sperm and embryos has mainly relied on fluorescent in situ hybridisation (FISH) and karyotyping. FISH studies have been performed on sperm from fertile and infertile men as well as men carrying known chromosomal translocations. Molecular DNA analyses has aided in the identification and treatment of men with Y chromosome deletions.

Cytogenetic and Y chromosome microdeletion screening of a random group of infertile males.

Objective: To assess whether to perform routine cytogenetic and Y chromosome microdeletion screening on all infertile male patients.

Design: A cytogenetic and Y microdeletion study of a random group of infertile men.

Setting: University department.

First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy.

Objective: To develop a preimplantation genetic diagnosis (PGD) protocol that allows any form of chromosome imbalance to be detected.

Design: Case report employing a method based on whole-genome amplification and comparative genomic hybridization (CGH).

Setting: Clinical IVF laboratory.

Preimplantation genetic diagnosis for single gene disorders: experience with five single gene disorders.

We report our experience of 14 preimplantation genetic diagnosis (PGD) cycles in eight couples carrying five different single gene disorders, during the last 18 months. Diagnoses were performed for myotonic dystrophy (DM), cystic fibrosis (CF) [Delta F508 and exon 4 (621+1 G>T)], fragile X and CF simultaneously, and two disorders for which PGD had not been previously attempted, namely neurofibromatosis type 2 (NF2) and Crouzon syndrome. Diagnoses for single gene disorders were carried out on ideally two blastomeres biopsied from Day 3 embryos.

A novel, de novo germline TP53 mutation in a rare presentation of the Li-Fraumeni syndrome in the maxilla.

We undertook the genetic analysis of a classic Li-Fraumeni syndrome (LFS) family with clustering of primary tumours including two maxillary sarcomas, a rare LFS site of tumour occurrence. Our aim was to investigate the presence of a specific type of TP53 mutation that could be associated with this unusual predilection of site for cancer occurrence. Mutational screening of the coding region of TP53 revealed an A>T transversion in codon 144 of exon 5 (CAG>CTG, Gln>Leu) in the germline of one of the three affected members, with loss of heterozygosity (LOH) in the tumour tissue.