Objective: To report the data from couples who were referred for preimplantation-genetic diagnostics (PGD) and treatment due to a significantly increased risk of offspring with a serious genetic disorder.
Design: Descriptive, prospective.
Method: Data were collected from couples that underwent PGD in the period 1993/'03 at Maastricht University Hospital. Embryos produced by means of in-vitro fertilisation (IVF) were subjected to genetic tests several days after fertilisation. Subsequently 1 or 2 unaffected embryos were transferred to the uterus. Where there was an increased risk of a male with an X-linked genetic disorder, the gender was determined using fluorescence in-situ hybridisation (FISH). This method was also used to detect structural chromosomal abnormalities. The polymerase chain reaction (PCR) method was used for mutation detection and/or marker analysis of monogenetic disorders.
Results: A total of 691 couples were referred for PGD. The most frequent indications were X-linked disorders (30%), in particular Fragile-X syndrome, Duchenne/Becker muscular dystrophy and haemophilia A/B. This was followed by autosomal dominant disorders (26%), such as Huntington's disease and myotonic dystrophy, and then structural chromosomal abnormalities (24%). A total of 120 women underwent 260 PGD cycles. An embryo transfer was possible in 158 of the cycles and this resulted in 45 successful pregnancies. The pregnancy rate was 17% per cycle initiated and 28% per cycle with embryo transfer. Up until december 2003 29 singletons, 8 sets of twins and 1 set of triplets were born. There were no misdiagnoses and none of the babies had congenital abnormalities.
Conclusion: PGD was a reliable and successful method, with pregnancy rates similar to those of IVF or intracytoplasmatic sperm injection. PGD should be stated as an alternative during the preconception counselling of couples with an increased genetic risk, especially for disorders where PGD can be routinely applied, such as Huntington's disease, myotonic dystrophy, cystic fibrosis, spinal muscular atrophy, Fragile-X syndrome and structural chromosomal abnormalities.