The relationship between trinucleotide repeat length and reproductive outcome in myotonic dystrophy type 1 (DM1)

OBJECTIVE: Myotonic dystrophy (DM1) is one of over 30 neurological disorders that attribute their pathogenesis and symptomatic status to extensions of trinucleotide repeats over a critical size. Whereas in male DM1 patients the relation between DM1 and poor spem quality secondary to gonadal atrophy has been established, no such relation has been demonstrated in DM1 affected females. This study aims to analyse the relationship between trinucleotide repeat length and reproductive outcome in a large cohort of DM1 patients undergoing ICSI and PGD.

DESIGN: Prospective observational study.

MATERIALS AND METHODS: The effect of trinucleotide repeat length on reproductive outcome per patient was analysed using bivariate analysis (T-test) and multivariate analysis using logistic regression for age, body mass index (BMI), basal FSH values, fertility status, parity and trinucleotide repeat length. The effect of these variables including trinucleotide repeat length on cumulative live birth rate was performed with Kaplan-Meier and Cox regression analysis. SPSS 16.0 for Windows (SPSS Inc, Chicago, Illinois) was used for statistical analysis.

RESULTS: Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The mean number of CTG repeats was not significantly different between the female affected group and the male affected group (419 (SD 299) vs 345 (SD 211); NS). The number of trinucleotide repeats does not have an influence on reproductive outcome when adjusted for age, BMI, basal FSH values, parity, infertility status and male or female affected status. Cox regression analysis indicates that cumulative live birth rate (overall observed cumulative live birth rate: 46%; overall expected cumulative live birth rate: 72%) is not influenced by the number of trinucleotide repeats. The only factor with a significant effect on reproductive outcome per cycle as well as cumulative reproductive outcome is age (p
CONCLUSIONS: This study shows that there is no evidence of any effect of trinucleotide repeat length on reproductive outcome in DM1 patients undergoing ICSI and PGD. Preconceptional assessment and counseling should however still consider trinucleotide repeat length analysis because of the relationship with the symptomatic status of the DM1 patient.