Introduction
Advanced maternal age (AMA) is a term commonly used to describe women who will be 35 years or older at their estimated date of confinement. This distinction has been made given the observation of increased adverse reproductive outcomes in this age group. It should be noted, however, that the adverse changes associated with advancing age occur gradually and are not necessarily an “all or none” effect. Over the last several decades there has been an increase in AMA, given a trend towards delayed child bearing among women living in industrialized nations. This delay has been attributed to multiple factors including, most notably, a greater emphasis on professional development among women. Increasing levels of education, delayed marriage, increasing second marriages, and improved contraceptive options also play a role in delayed child bearing.
The mean maternal age at the birth of a first child in women living in the United States increased from 21.4 years old to 24.9 years old from the 1970s to the 2000s. Similar increases in industrialized European and Asian countries have been reported. Furthermore, the proportion of women giving birth between the ages of 40 and 44 years has also increased from 3.8 to 7.4 per 1000 livebirths between 1981 and 1999. The proportion of women 45 years and older giving birth has increased from 0.2 to 0.4 per 1000 livebirths over the same time period. Much of this increase in maternal age has also been facilitated by assisted reproductive technologies. Finally, not only is the mean maternal age at first birth increasing, but also the overall number of children per family is decreasing.
Although the reproductive outcomes in women of AMA are generally acceptable, difficulties with conception as well as antepartum and intrapartum complications are more common in this obstetric group.
With advancing maternal age, fecundity decreases and the time to conception increases. This change is most notable in women older than 35 years of age. This prolongation in conception time is due to poorer oocyte quality and a decrease in the overall number of oocytes (ovarian reserve). Ovulatory dysfunction is also more common with advancing maternal age and contributes to difficulties with conception. Although ovarian factors are most highly associated with decreased fecundity in the AMA group, these women are also more likely to have tubal disease due to either endometriosis or a history of pelvic infections, and are more likely to have fibroids or polyps, which may distort the uterine cavity.
Treatment options for infertility are beyond the scope of this review but include expectant management, ovulation induction, intrauterine insemination, oocyte donation, and assisted reproductive technologies such as in vitro fertilization. Of note, maternal age remains the most important prognostic factor in women undergoing in vitro fertilization. Pregnancies achieved with the aid of assisted reproductive technologies more often result in multiple gestations and have also been associated with a higher rate of adverse perinatal outcomes, which will be discussed in further detail below.
Given the decline in oocyte quality as well as a potentially suboptimal hormonal and/or physical intrauterine environment, it is not surprising that the risk of spontaneous abortion increases with advancing maternal age. This increased risk of miscarriage is also correlated with the increased proportion of aneuploidies found in the embryos of these women. A large European study examining the reproductive outcomes of over one million pregnancies confirmed this positive correlation between advancing maternal age and the rate of spontaneous abortion. The overall pregnancy loss rate was 13.5% but when stratified by age, women 20–24 years old had a spontaneous abortion rate of 8.9% while women 45 years and older had a rate of 74.7%. Similarly, there was an increasing risk of ectopic pregnancy with advancing maternal age. The overall ectopic rate was 2.3%, with a risk of 1.4% in women aged 21 years at the time of conception versus a risk of 6.9% in women aged 44 years or more at the time of conception.
The risk of aneuploidy increases steadily with advancing maternal age and especially after the age of 35 years. Shuttleworth first described the association between advanced maternal age and trisomy 21, or Down’s syndrome, in 1909. This increase is thought to be the result of more common nondisjunction during meiosis, thus leading to oocytes with an abnormal number of chromosomes.
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