Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew

Abstract

Purpose of review-The relationship between increasing maternal age and trisomy has been recognized for over 50 years and is one of the most important etiological factors associated with any human genetic disorder. Specifically, the risk of trisomy in a clinically recognized pregnancy rises from about 2-3% for women in their twenties to an astounding 30% or more for women in their forties. Thus, as women approach the end of their child-bearing years, errors of chromosome segregation represent the most important impediment to a successful pregnancy.Recent findings-Despite the clinical importance of this relationship, we do not understand how age affects the likelihood of producing a normal egg. Errors that affect chromosome segregation could occur at several stages during the development of the oocyte: in the fetal ovary, either during the mitotic proliferation of oogonia or the early stages of meiosis; in the "dictyate" oocyte, during the 10-50 year period of meiotic arrest; or during the final stages of oocyte growth and maturation, when meiosis resumes and the meiotic divisions take place. Recent evidence from studies of human oocytes and trisomic conceptions and from studies in model organisms implicates errors at each of these stages Summary-It seems likely that there are multiple causes of human age-related nondisjunction, complicating our efforts to understand -and, ultimately, to provide preventative measures for -errors associated with increasing maternal age.

Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies

“…A full chromosome complement is then restored upon fusion of the egg with a haploid sperm at fertilization, initiating embryogenesis. Unfortunately, the meiotic cell cycle becomes highly prone to errors with age, which often results in a much higher proportion of aneuploid oocytes ovulated by older women (38,39). One of the most widely known consequences of female reproductive aging is a dramatic rise in trisomy 21, which increases from around 2% of clinical pregnancies in women in their twenties to 30% or more of clinical pregnancies in women in their forties (2,39).…”

“…Unfortunately, the meiotic cell cycle becomes highly prone to errors with age, which often results in a much higher proportion of aneuploid oocytes ovulated by older women (38,39). One of the most widely known consequences of female reproductive aging is a dramatic rise in trisomy 21, which increases from around 2% of clinical pregnancies in women in their twenties to 30% or more of clinical pregnancies in women in their forties (2,39). Our understanding of this maternal age effect remains limited; however, analyses of human and mouse oocytes have shown that aging disrupts the ability of oocytes to assemble and maintain meiotic spindles, which tightly align homologous chromosomes for segregation at anaphase.…”

In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43

“…reason for the decrease of fertility in IVF [1][2][3]. For women over the age of 40 in the United States, roughly half of all clinical pregnancies established through IVF are lost, failing to result in live births (SART CORS Clinic Summary Report, 2012).…”

Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre

“…6 Aneuploidy is the most common abnormality found in embryos derived from in-vitro fertilisation (IVF), and leads to poor outcomes. [7][8][9][10][11][12][13] Morphological assessment of embryos or blastocysts alone, however, cannot negate the potential risk of replacing aneuploid embryos or blastocysts. 14 Preimplantation genetic screening (PGS) has been proposed to improve the IVF outcomes by screening for aneuploid embryos or blastocysts.…”