Does supplementation with mitochondria improve oocyte competence? A systematic review

Abstract

Mitochondrial supplementation was proposed as a complementary treatment to assisted reproductive technologies to improve oocyte competence and support post-fertilization development. This strategy is based on the fact that poor-quality/aged oocytes contain lower and dysfunctional mitochondria. However, the efficacy and safety of mitochondrial supplementation is still controversial. Therefore, this review summarizes the clinical/biological outcomes of mitochondrial supplementation, aiming to improve oocyte competence or explore the safety of this technique, and was based on an online search using PubMed and Web of Science, until September 2019. The studies included reported outcomes related to efficacy and safety of mitochondrial supplementation either in human or animal models (bovine, porcine and mouse). Extracted data were organized according to study objective, the mitochondrial source and the main outcomes: fertilization/pregnancy rates, embryo development and adverse outcomes. Clinical pregnancy was not improved in the only randomized controlled trial published, although an increase was demonstrated in other non-randomized studies. Fertilization rate and embryo development were not different from control groups in the majority of studies, although performed in different contexts and using diverse sources of mitochondria. The safety of mitochondria transfer is still a concern, however, the euploid rate and the absence of reported congenital malformation from the clinical studies are reassuring. In summary, mitochondrial supplementation does not seem to cause harm although the benefit of improving oocyte competence is still unclear due to the diversity of methodological approaches and low-quality of the data available. Analyzed data supports the need to investigate further, in both pre-clinical and clinical contexts.

Embryo and Its Mitochondria

“…In pigs, using competent oocytes as a source of mitochondrial transfer was shown to significantly improve oocyte competence [46]. In conclusion, and as has been recently highlighted [172], the ability of mitochondrial transfer to improve oocyte competence remains unclear, and further studies are required to confirm not only its efficiency, but also its safety.…”

Strategies to Improve the Efficiency of Somatic Cell Nuclear Transfer

“…Additional mtDNA led to an increase in the expression of genes involved in the glycolytic metabolism and embryonic development [81]. More studies on mitochondrial supplementation in combination with other assisted reproductive technologies have been recently reviewed by Ferreira et al [82].…”

An Interplay between Epigenetics and Translation in Oocyte Maturation and Embryo Development: Assisted Reproduction Perspective

“…To enhance the fertilization rate of aged oocytes, the technique of mitochondrial supplementation can be applied. For this purpose, it is possible to use the method of either partial or total cytoplasm transfer from donor to recipient oocyte [ 94 , 95 ].…”