Impact of Maternal Age on Oocyte and Embryo Competence

Abstract

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences.

Keywords: IVF; aging; aneuploidies; oocyte competence; ovarian reserve.

Figure 1

Effect of advanced maternal age on oocyte/embryo competence and putative mechanisms impaired by aging. Aging in women causes both a reduction of the ovarian reserve and of the oocyte competence. All the processes impaired may result into a lower energy production/balance involving a small reduction of embryo developmental rate to the blastocyst stage, as well as a higher frequency of chromosome missegregation during maternal meiosis leading to a high increase in blastocyst aneuploidy rate (especially in women older than 35) [data adapted from Franasiak et al. (10) and Capalbo et al. (11)]. Ultimately, these mechanisms converge into a decreased fertility, an increased prevalence of vital chromosomal abnormalities, an increased miscarriage rate, as well as an increased prevalence of numerical chromosomal abnormalities in the newborns [data adapted from Hassold and Hunt (13) and Heffner (4)]. The aneuploidy rate is estimated per biopsied blastocyst; the fertility is estimated as number of babies born per 1,000 married women; the overall prevalence of vital aneuploidies is estimated per clinically recognized pregnancy; the miscarriage rate is estimated per clinical pregnancy; at last, the overall prevalence of numerical chromosomal abnormalities is estimated per number of newborns.