Preimplantation genetic diagnosis for Myotonic Dystrophy Type 1

Aim: Myotonic dystrophy type 1 (MD1) is one of the major indications for preimplantation genetic diagnosis (PGD) for monogenic inherited disorders worldwide, but female MD1 carriers have a reduced PGD success rate compared to PGD for other indications. Aim of this study was to search for biomarkers predictive for favorable PGD outcome.

Material and methods: retrospectively evaluation of 202 polar body diagnosis (PBD) cycles for 95 families and 37 different monogenetic disorders at our center including 10 female MD1 carriers.

Results: Transfer of 38 embryos in 22/25 MD1 PBD cycles resulted in 4 clinical pregnancies (18.2% per ET), 2 abortions and 2 live births. Better results could be obtained in 84 PBD cycles for the other main indications with clinical pregnancy rates per transfer cycle and birth/ongoing pregnancies of 45.8%/41.6% (CFTR), 42.8%/28.6% (BMD/DMD), 21.4%/14.3% (FraX premutation) and 50%/30% (FraX full mutation). With a similar number of retrieved (9.7 vs. 10.6) or mature (9.6 vs. 8.1) per OR cycle we observed a reduced implantation rate of 13.1% for MD1 vs. 20.9% and birth rate of 8.0% vs. 25% (main indications) per PBD transfer cycle, correlated with decreased Anti-Mueller-Hormone levels.

Conclusion: Current functional data suggest aberrant splicing and RNA toxicity to cause the pleiotropic MD1 clinical manifestations. While the targets of this effect during ART remain unknown, our data point towards oocyte/embryo quality or endometrium receptivity and may guide the development of novel ART strategies. Currently, female MD1 carriers interested in PGD should be informed about their limited PGD success rates.