Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder

Fertil Steril. 2012 Nov;98(5):1236-40. doi: 10.1016/j.fertnstert.2012.07.1119. Epub 2012 Aug 21.


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 (r(2) = 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.

Publication types

  • Case Reports
  • Video-Audio Media

MeSH terms

  • Adult
  • Biopsy
  • Blastocyst / chemistry*
  • Child, Preschool
  • DNA, Mitochondrial / analysis*
  • Embryo Transfer
  • Female
  • Fertilization in Vitro
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Heredity
  • Humans
  • Infant, Newborn
  • Lymphocytes / chemistry
  • MELAS Syndrome / diagnosis*
  • MELAS Syndrome / genetics
  • Male
  • Mosaicism
  • Mutation*
  • Oocytes / chemistry
  • Predictive Value of Tests
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Sex Determination Analysis


  • DNA, Mitochondrial