The Role of Mitochondria from Mature Oocyte to Viable Blastocyst

Abstract

The oocyte requires a vast supply of energy after fertilization to support critical events such as spindle formation, chromatid separation, and cell division. Until blastocyst implantation, the developing zygote is dependent on the existing pool of mitochondria. That pool size within each cell decreases with each cell division. Mitochondria obtained from oocytes of women of advanced reproductive age harbor DNA deletions and nucleotide variations that impair function. The combination of lower number and increased frequency of mutations and deletions may result in inadequate mitochondrial activity necessary for continued embryo development and cause pregnancy failure. Previous reports suggested that mitochondrial activity within oocytes may be supplemented by donor cytoplasmic transfer at the time of intracytoplasmic sperm injection (ICSI). Those reports showed success; however, safety concerns arose due to the potential of two distinct populations of mitochondrial genomes in the offspring. Mitochondrial augmentation of oocytes is now reconsidered in light of our current understanding of mitochondrial function and the publication of a number of animal studies. With a better understanding of the role of this organelle in oocytes immediately after fertilization, blastocyst and offspring, mitochondrial augmentation may be reconsidered as a method to improve oocyte quality.

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

“…Although the outcome of IVF treatment may be improved by selecting euploid oocytes (Geraedts et al 2011), whether any interventions can be designed to rescue fertility in women who produce no euploid oocytes remains controversial. Procedures, such as oocyte cytoplasmic donation or mitochondrial augmentation of MII-arrested oocytes (Chappel 2013), have been proposed as a means of boosting fertility in older women. However, given the growing body of evidence that defects in centromeric cohesion are a major cause of aneuploidy in human oocytes from older women, it is difficult to envisage how interventions, such as mitochondrial augmentation, could prevent these from segregating randomly during anaphase II.…”

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…A reduced pool of mtDNA within the oocyte has been associated with a reduced fertilization potential (276) and also a reduced ovarian reserve (213). Furthermore, ageing is associated with an adverse effect on the mitochondria [reviewed by Schatten (297)], leading to an in increase in mtDNA damage and mutations with mtDNA, structural abnormalities with the mitochondria, a reduction in ATP synthesis, and an increase in ROS production (57,297). Putative methods to improve mitochondrial function are the oral administration of CoQ10 (32), an electron transporter involved in the transport of electrons within the respiratory chain within the mitochondria (32), to assist mitochondrial function or even to introduce donor ooplasm to "rejuvenate" an oocyte.…”

The AUGMENTSM Treatment: Physician Reported Outcomes of the Initial Global Patient Experience

“…Other causes of poor egg/embryo quality beyond age-related factors include medical conditions such as type II diabetes, obesity, polycystic ovary syndrome (PCOS), as well as other genetic and environmental factors [6,7]. Over the past 25 years, an increasing body of clinical and preclinical data has demonstrated that the decline in egg quality is largely due to a reduction in energy production [8][9][10][11]. In the 1990s, there were attempts at improving egg and embryo quality by injecting cytoplasm from young, healthy, donor eggs into the eggs of women with a history of reproductive failures [12][13][14].…”

“…The cytoplasm injection procedure involved the injection of third-party mitochondria obtained from younger donor eggs and resulted in the birth of approximately 50 seemingly healthy babies [12][13][14]. This groundbreaking work was not pursued as more study was required [11].…”