Technologies such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cannot overcome mitochondrial or mtDNA deficiency, as they are unable to provide the oocyte with the appropriate boost in mtDNA copy number required to support development. However, they are essential technologies for other oocyte deficiencies and sperm disorders, respectively. Furthermore, they do not affect the transmission of mtDNA, as the outcomes from these techniques are similar to natural conception where mtDNA is solely inherited from the oocyte (79).
Mitochondrial and mtDNA deficiency can be overcome by the use of mitochondrial intracytoplasmic sperm injection (mICSI) (Figure 9), which enables a small population of mitochondria to be introduced into the egg from the same mtDNA genetic source (10, 72). The importance of introducing the mitochondria at the time of fertilisation is that there is a mtDNA replication event that occurs between fertilisation and the 2-cell stage which is utilised by the donated mtDNA to increase mtDNA copy number to levels that are a prerequisite for fertilisation outcome (10). Not only does this aid the process of fertilisation outcome, it also ensures that these activities take place before embryonic genome activation and that gene expression patterns are normalised for mtDNA deficient eggs. Indeed, when mtDNA deficient eggs develop through to the blastocyst stage, an event that occurs infrequently, the resultant blastocysts exhibit gene expression pathways that are indicative of, amongst many other factors, severe metabolic disorders (10). A similar approach using mitochondria isolated from egg precursor cells, which are isolated from the cortex of the ovary, to supplement oocytes has resulted in the generation of healthy babies (80). Others have used mitochondria isolated from cumulus-Granulosa cell populations to generate healthy children (81). In each of these examples, genetically identical (autologous) populations of mitochondria were used.
However, it is essential to ensure that the population of mtDNA introduced into an oocyte is genetically identical (21, 40, 82). Indeed, supplementation of oocytes with genetically diverse populations of mtDNA (Figure 10), as is the case when cytoplasmic transfer is performed using donor oocytes, has led to cases of autism and XO syndrome in humans and severe respiratory and metabolic disorders in mice (83) (Figure 11). This creates a problem for those assisted reproductive technologies that allow carry over of mtDNA into a recipient oocyte from a donor source (21, 40, 82). This is the case for those assisted reproductive technologies, such as germinal vesicle (84), metaphase II, pronuclear (85, 86), and somatic cell nuclear transfer (87) where a small amount of mtDNA that is present in mitochondria attached to the karyoplast is introduced into the recipient oocyte (Figure 12). Consequently, this population of mtDNA can be preferentially selected for and become the majority population inherited by the individual; or be selected against. This arises, as the selection of mtDNA is very much a random process during development and is likely influenced by the frequent changes in mtDNA copy number at key stages of development. 
