Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres

Abstract

on behalf of the BruMaStra PGD working groupThis study provides an overview of 13 years of experience of preimplantation genetic diagnosis (PGD) for Huntington's disease (HD) at three European PGD centres in Brussels, Maastricht and Strasbourg. Information on all 331 PGD intakes for HD, couples' reproductive history, PGD approach, treatment cycles and outcomes between 1995 and 2008 were collected prospectively. Of 331 couples for intake, 68% requested direct testing and 32% exclusion testing (with a preponderance of French couples). At the time of PGD intake, 39% of women had experienced one or more pregnancies. A history of pregnancy termination after prenatal diagnosis was observed more frequently in the direct testing group (25%) than in the exclusion group (10%; P¼0.0027). PGD workup was based on two approaches: (1) direct testing of the CAG-triplet repeat and (2) linkage analysis using intragenic or flanking microsatellite markers of the HTT gene. In total, 257 couples had started workup and 174 couples (70% direct testing, 30% exclusion testing) completed at least one PGD cycle. In total, 389 cycles continued to oocyte retrieval (OR). The delivery rates per OR were 19.8%, and per embryo transfer 24.8%, resulting in 77 deliveries and the birth of 90 children. We conclude that PGD is a valuable and safe reproductive option for HD carriers and couples at risk of transmitting HD.

Guidelines for presymptomatic testing for Huntington's disease: Past, present and future in France

“…Interestingly, a higher number of women (57%) request PT, as is it the case in general, and this preponderance is much higher for PND (74% requested by women carrying the mutation). In contrast to this, the sex ratio of requests for preimplantation genetic diagnosis (PGD) is 50:50 [18]. Interestingly, for exclusion PGD, there are more at risk men than women who ask that their genetic status not be revealed.…”

Prenatal testing in Huntington disease: after the test, choices recommence

“…Success rates for having a child with this procedure are still low:~20%. 2 Sperm or egg donations are also possible. Some parents accept the risk of transmitting the disease, others may renounce to have a child.…”

Genetic counseling and testing for Huntington's disease: A historical review

“…The risk of serious adverse events after predictive testing is no more than 1 to 2% [Almqvist et al, 1999[Almqvist et al, , 2003. Miscarriage or failed pregnancy is no more common in couples seeking in vitro fertilization (IVF)/ preimplantation genetic diagnosis (PGD) because of HD than it is for any other indication for IVF [van Rij et al, 2012]. Patients who undergo predictive or prenatal/preimplantation testing are generally glad that they underwent testing, and those who do not are apparently equally content with their situation.…”