preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder. Fertil
Steril. 2012 Nov;98(5):1236-40.
Objective
To evaluate the utility of
trophectoderm biopsy for preimplantation genetic diagnosis (PGD) of
mitochondrial (mt) DNA mutation load.
Design
A PGD case and analysis of
blastocyst mosaicism.
Setting
Academic center for reproductive
medicine.
Patient(s)
A 30-year-old carrier of 35%
3243A>G mtDNA mutation load with a daughter affected by mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.
Intervention(s)
Blastocyst biopsy for PGD of
mutation load and gender.
Main
Outcome Measure(s)
Variation in mutation load within
and among embryos, and newborn mutation load after PGD-based selection.
Result(s)
Oocytes and embryos were found to
possess a variety of 3243A>G mutation loads from 9% to 90% in oocytes and 7%
to 91% in embryos, demonstrating that PGD would be a relevant procedure. Highly
consistent results were obtained within multiple biopsies of both cleavage- and
blastocyst-stage embryos. Importantly, mutation loads observed in trophectoderm
were predictive of the inner cell mass (r2 = 0.97). Transfer
of a male embryo, predicted to possess 12% mutation load by analysis of a
trophectoderm biopsy, resulted in the delivery of a boy with tissue-specific
mutation loads ranging from undetectable to 15%.
Conclusion(s)
This study represents the first
successful clinical application of PGD to reduce the transgenerational risk of
transmitting an mtDNA disorder and supports the applicability of blastocyst
trophectoderm PGD for carriers of mtDNA mutations attempting reproduction.
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