• Mito-nuclear mismatch could lead to an array of developmental problems, as well as infertility and cancer ("Risks inherent to mitochondrial replacement," Dowling et al., EMBO Reports and “Mitochondrial Replacement, Evolution, and the Clinic,” Reinhardt et al., Science)
   
• Preferential replication of even tiny amounts of carryover mutated mtDNA could cause the very mitochondrial diseases the techniques are designed to prevent (“mtDNA Segregation in Heteroplasmic Tissues Is Common In Vivo and Modulated by Haplotype Differences and Developmental Stage,” Burgstaller et al., Cell)
   
• Epigenetic harm due to nuclear transfer could also cause the mitochondrial diseases the techniques are designed to prevent, or disturb mito-nuclear cross-talk (“Report on the safety of ‘mitochondrial replacement’ techniques: epigenetic issues,” Human Genetics Alert)
   
• We are learning more about how mitochondria have an outsized impact on complex phenotypic traits i.e. they do not merely serve a metabolic (battery-like) function (“Three-parent babies: It's more messy than we thought,” Editorial, New Scientist; “A meta-analysis of the strength and nature of cytoplasmic genetic effects,” Journal of Evolutionary Biology; and "Cytoplasmic genetic variation and extensive cytonuclear interactions influence natural variation in the metabolome," Joseph et al., eLife, discussed here.)
   
• Malformations have been reported in some animal models (“Nuclear transfer to prevent mitochondrial DNA diseases,” Poulton et al., The Lancet)

The range of profound safety risks, as well as viable alternatives, are discussed further in the following news articles and commentaries:
 

• An early pioneer of the development of germline mitochondrial manipulation, David L. Keefe, MD, abandoned the techniques because he believes they are too dangerous for any resulting children. In a letter to the senior policy officer of the UK’s Human Fertilisation and Embryology Authority, Keefe, chair of Obstetrics and Gynecology at NYU Langone Medical Center, explains that preimplantation genetic diagnosis is a safer alternative for women who want to have a healthy, genetically related child. 
   
• “FDA raises concerns about three-parent embryo procedure,” Karen Weintraub, USA TODAY (Includes concerns raised by Evan Snyder, M.D., Ph.D., Professor of the Human Genetics Program at the Sanford Burnham Medical Research Institute and cell biologist Renee Reijo Pera, vice president for research and economic development at Montana State University.)
   
• “Open letter to UK Parliament: avoid historic mistake on rushing human genetic modification,” Paul Knoepfler Ph.D., Professor at UC Davis School of Medicine in the Department of Cell Biology and Human Anatomy, Knoepfler Lab Stem Cell Blog
   
• “Deceptive Labeling of a Radical Embryo Construction Technique” Stuart Newman Ph.D, Professor of Cell Biology and Anatomy at New York Medical College, Huffington Post
   
• “IVF expert fears 'carry-over' risk in three-parent baby technique”, Steve Connor, The Independent‎ [With concerns raised by Justin St. John, Ph.D., Director of the Centre for Genetics Diseases]
   
• "Three-parent babies could be at greater risk of cancer, warn scientists," Sarah Knapton, The Independent