Preimplantation genetic diagnosis for fragile Xa syndrome: difficult but not impossible

BACKGROUND: In this paper, we review our clinical preimplantation genetic diagnosis (PGD) programme for fragile Xa syndrome, analysing if PGD for these couples is still a valuable option, as it is particularly difficult for two reasons. First, the couples have to be informative (the number of triplet repeats on the healthy FMR-1 allele of the mother has to be different from the number of repeats on the healthy FMR-1 allele of the father) and second, women with a premutation are at increased risk of premature ovarian failure. METHODS: A total of 34 couples attended our genetics department between December 1998 and July 2001, requesting information about PGD for fragile Xa syndrome. RESULTS: Eight couples decided not to go further with the procedure and of the 26 remaining couples, 16 were informative (61.5%). Four couples have so far not started ovarian stimulation, one patient was totally refractive to stimulation and 11 couples have had a total of 19 oocyte retrievals. From these, there have been 13 embryo transfers with a clinical pregnancy rate per embryo transfer of 23%; the implantation rate was 13.6% and the live birth rate per couple was 27.3%. CONCLUSIONS: PGD for fragile Xa is feasible for a number of couples. A pre-PGD work-up should include a determination of the premutation or mutation carrier status, the maternal or paternal origin of the premutation and an estimation of the ovarian reserve of the patient. Fragile Xa premutation carriers should be advised not to postpone reproduction for too long.