The importance of aneuploidy in human reproductive failure

Human reproduction is a remarkably inefficient process. On average, fertile couples attempting to conceive only succeed in achieving a clinical pregnancy one month out of every five. For infertile patients undergoing in vitro fertilization (IVF) pregnancy rates are similarly low. More than 80% of the embryos transferred to the uterus during IVF treatment fail to implant and two-thirds of cycles do not produce a child [1]. As a result, most IVF patients require two or more rounds of treatment to achieve a pregnancy. There are many potential reasons why an embryo might not establish a pregnancy; however, it is clear that one of the most important is chromosome abnormality. This is particularly true for embryos derived from women of advanced reproductive age. While it is not unusual for half of the blastocyst stage embryos produced by women in their early thirties to be chromosomally abnormal, this figure increases dramatically with age, such that an aneuploidy rate exceeding 75% is typical for blastocysts from women over the age of 40 [2]. The high prevalence of aneuploidy, coupled with its detrimental impact on development, explains the majority of embryo implantation failures and miscarriages. Evidence for the lethality of aneuploidy comes from the detection of chromosome imbalances in the majority of miscarriages [3, 4] and from blinded studies where embryos, later revealed to be chromosomally abnormal, had been transferred to patients [5].