January 2008 News Following the controversy surrounding the Dutch and Belgian clinical trials of PGS in different patient groups, which featured in the late breaking session at last years ESHRE Annual Meeting in Lyon, incoming Chairman, Professor Joep Geraedts, has organised an ESHRE PGS Task Force. The main aim of the Task Force, which meets for the first time on January 26th, is to consider organising a multicentre randomised clinical trial and to get a consensus on appropriate indications and the protocols to be used, which has been widely criticised in previous trials. As a long term advocate of PGS for women at high risk, I am pleased to be part of the Task Force and look forward to working with our Bridge Genoma partners to make the trial a success. Professor Alan Handyside (Co-Director) © 2008 Bridge Genoma (ISO registered)

Since our launch in November 2006, we have successfully established a preimplantation genetic diagnosis (PGD) service with our partners, Genoma Laboratories in Rome, enabling us to offer test development for any couple with a known single gene disorder within 1-2 months. These bespoke tests are comparable to the most advanced available anywhere and include mutation detection by mini-sequencing, combined with linked markers wherever possible (so-called 'haplotyping'). Uniquely in the UK, we can also include markers for chromosomes 21, 18 and 13 in cases of advanced maternal age or where there may be a high risk of aneuploidy.

We are also committed to providing comprehensive support to enable patients to be treated at the clinic of their choice. These services include HFEA license preparation, professional genetic counselling and, if needed, locum biopsy practitioners to work with or support the clinic's own embryology team.

Chromosomal aneuploidy is a leading cause of embryo morbidity and pregnancy loss. Our Camden laboratory has a dedicated team for molecular cytogenetics including a state registered clinical cytogeneticist. For women of advanced maternal age, we currently offer preimplantation genetic screening for 8 chromosomes (now including chromosome 15) designed to significantly reduce the risk of transferring embryos with potentially viable but abnormal aneuploidies and other abnormalities frequently associated with miscarriage.

Other tests include PGD for chromosomal translocations, aneuploidy screening of sperm and pharmacogenetic testing of FSH receptor polymorphisms to optimise ovarian response.

Our laboratory was ISO 9001; 2000 registered in November, 2007 and we are proud to be working with several of the UK's most prominent IVF centres.

Alan Thornhill PhD, Director

* Research highlights *

Trend towards improved clinical outcomes in infertile patients following PGS

Most clinics offering preimplantation genetic screening (PGS) in the UK only recommend screening in poor prognosis patients or for women in their late 30s and 40s in which there is good evidence of a high incidence of aneuploidy and an increased rate of preclinical and clinical pregnancy loss.

Recently, a large scale multicentre randomised controlled trial of clinical outcome following PGS in all women over the age of 35 demonstrated a significant decrease in live birth rate with screening[1]. Although the methodology of this trial has been criticised[2], one explanation is that embryo biopsy and screening may be detrimental in patients at relatively low risk of aneuploidy i.e. patients at the lower end of this age range.

Mersereau et al[3] now report on the interim analysis of a prospective randomised controlled trial designed to evaluate the effect of PGS for chromosomes X, Y, 22, 21, 18, 16 and 13 on clinical outcome in infertile patients generally, without restricting screening to poor prognosis patients. Although there was no statistically significant improvement in live birth rates or implantation rates in this pilot study (see Table below), in contrast to the larger trial, there was a trend towards improved clinical outcomes. The authors therefore conclude that further multicentre randomised trials will be needed to resolve these conflicting results.

[1] Mastenbroek, S et al (2007) In vitro fertilisation with preimplantation genetic screening. New Engl J Med. 357(1):9-17

[2] Handyside, AH , Thornhill, AR (2007) In vitro fertilization with preimplantation genetic screening. N Engl J Med. 357(17):1770

[3] Mersereau, JE, Pergament, E, Xhang, X, Milad, MP (2007) Preimplantation genetic screening to improve in vitro fertilisation pregnancy rates: a prospective randomised trial. Fertility and Sterility [Epub ahead of print]

In future issues: Microarrays in PGD, Pharmacogenetics and response to ovarian stimulation, and advanced Y chromosome microdeletion testing.

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Bridge Genoma

London Bioscience Innovation Centre

2 Royal College Street, London, NW1 0NH

Tel: +44 (0) 20 7089 1443, Fax: +44 (0) 20 7691 2027

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Website: www.bridgegenoma.com