Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss

The goal of this retrospective study was to determine the rate of miscarriage in in vitro fertilization (IVF) pregnancies after sonographic confirmation of cardiac activity at 7 weeks gestation. The study included 2014 consecutive IVF pregnancies, from the years 1991 to 1996, in which fetal cardiac activity was documented. Standard ovulation induction protocols were used to prepare for IVF-embryo transfer. Selected embryos were transferred into the uterine cavity approximately 72 hours after being retrieved. The number of embryos transferred increased with advancing age, up to 5 for women more than 40 years of age. Pregnancy loss (spontaneous abortion [SAB]) occurred in 233 patients, 11.6% of the total. Losses clearly increased with advancing age, from 5.3% in women 30 years of age and younger to 22.2% in those aged 40 and older. Pregnancy loss was more likely in women with singleton pregnancies compared with those with multiple gestations (16.1% vs. 5.4%), but the former women were significantly older. More than one fourth of women aged 40 years and older failed to deliver a live-born infant. An age effect was also noted in women with SAB, but the SAB rate for multiple gestations was lower than in singleton pregnancies for all age groups. Cytogenetic analysis was carried out in 74 pregnancy losses and an abnormal karyotype was identified in 52 of them (71.2%). The rate of chromosomal aneuploidy was 82% in women aged 40 and older and 65% in those less than 40 years of age (odds ratio, 3.35). Approximately 4 in every 5 fetuses with an abnormal karyotype had trisomies, most frequently in chromosomes 21, 16, 22, 15, and 18 (in descending order). These data are from a single institution, and fetal age was precisely documented in all cases. A significant risk of pregnancy loss must be taken into account when counseling women about how many embryos will be transferred after IVF. Chromosomal aneuploidy appears to be the major underlying cause of these losses.