Successful Selection of Normal Embryos Using PGD in a Patient with Spinocerebellar Ataxia Type 3
Gayane Ambartsumyan MD1, Catherine Marin DeUgarte MD1, Man Li MD PhD2, Yury Verlinsky PhD3, David Hill PhD2, Alan H. DeCherney MD1.
1- Dept of OB/Gyn, UCLA Medical Center, Los Angeles, CA 90024 USA
2- ART Reproductive Center, Beverly Hills, Ca 90210 USA
3- Reproductive Genetics Institute, Chicago, IL 60657
Objective: To select for normal embryos using preimplantation genetic diagnosis (PGD) and in vitro fertilization in a woman with Spinocerebellar Ataxia Type 3, an autosomal dominant disease.
Design: Case report
Materials and Methods: Spinocerebellar Ataxia Type 3 (SCA3) is characterized by progressive cerebellar ataxia and variable findings including a dystonic-rigid syndrome, a Parkinsonian syndrome or a combined syndrome of dystonia and peripheral neuropathy. It is inherited in an autosomal dominant manner.
The diagnosis of SCA3 rests upon the use of DNA-based testing to detect an abnormal CAG trinucleotide repeat expansion of the Machado-Joseph disease (MJD) gene. Our patient’s mother and other family members had developed SCA3, so DNA-based testing was performed on the patient revealing 73 CAG repeats on one of the alleles of the MJD gene confirming the diagnosis of SCA3.
In an effort to avoid passing the rare gene to her offsprings, PGD analysis followed by IVF was performed specifically selecting for SCA3 on the MJD gene. Routine methods of ovulation induction and oocyte retrievals were used. Following aspiration of follicles, oocytes were evaluated and the mature oocytes were selected for Intracytoplasmic Sperm Injection (ICSI). Subsequently, PGD analysis was performed for the single gene disorder SCA3 through polar body biopsy and aneuploidy screening by Day 3 biopsy and FISH analysis. Finally, normal embryos were transferred on day 6 in a usual fashion.
Results: Two IVF cycles with PGD were performed. In the first cycle, 11 oocytes were aspirated with ICSI being performed on 6 that appeared mature. After PGD analysis, 2 oocytes yielded inconclusive results, 3 embryos were affected with SCA3, 1 embryo was not affected with SCA3 but it displayed monosomy 22. Therefore, no normal embryos were identified on the first cycle. In the second cycle, 18 oocytes were aspirated, 10 of which appeared mature for ICSI. Of these, 5 were affected, 3 were inconclusive and 2 were normal after PGD analysis. These 2 embryos were subsequently transferred on day 6. Pregnancy was confirmed 10 days after the transfer using serum beta hCG. Several weeks later, a sonogram revealed a twin gestation that is currently ongoing.
Conclusions: This case is an example of PGD and its ability to help a family that is affected by an autosomal dominant disease through helping to achieve healthy babies. The SCA3 disease transmission to offspring is therefore prevented in our patient.