The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening  Jason M. Franasiak, M.D., Eric J. Forman, M.D., Kathleen H. Hong, M.D., Marie D. Werner, M.D., Kathleen M. Upham, B.S., Nathan R. Treff, Ph.D., Richard T. Scott, M.D.  Fertility and Sterility  Volume 101, Issue 3, Pages 656-663.e1 (March 2014) DOI: 10.1016/j.fertnstert.2013.11.004 Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Case demographics. (A) The mean, median, minimum, and maximum number of blastocysts biopsied according to patient age. In nearly all age groups, the minimum number biopsied was one blastocyst, and the median number exceeded five blastocysts in only patients aged 22, 24, 28, and 30 years. (B) The number of blastocysts per individual case. In 50% of the cases, there were three or fewer blastocysts available for biopsy, and 20% of the patients had only a single blastocyst available for biopsy. Fertility and Sterility 2014 101, 656-663.e1DOI: (10.1016/j.fertnstert.2013.11.004) Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Prevalence of aneuploidy. (A) The prevalence of aneuploidy relative to the age of the female partner demonstrates the lowest risk in women from their middle to late twenties, with significantly higher rates in embryos obtained from both younger and older women (P<1*10−6). The relationship between age and the rate of aneuploidy is a best fit at the 5th degree polynomial (regression line shown). (B) The relationship between maternal age and the probability that no euploid blastocysts will be available within a single cohort demonstrates a uniformly low risk between the maternal ages of 26 and 37 years. Higher risks are present in younger and older patients (P<.0003 or less). Fertility and Sterility 2014 101, 656-663.e1DOI: (10.1016/j.fertnstert.2013.11.004) Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Nature of aneuploidy. (A) The complexity of the aneuploidies that occur (the number of aneuploid chromosomes in a given trophectoderm sample) is impacted by maternal age (P<1*10−6). Increasing age results not only in an increase in the proportion of embryos that are aneuploid but also an increase in the proportion of those aneuploid embryos that will have more than one aneuploid chromosome. (B) The ratio of trisomies to monosomies approximates 1 throughout reproductive life, and absolute variation is low at all ages. Some variation does exist with younger patients, who have disproportionally greater monosomies, and older patients, who have disproportionate trisomies (P<.009). Fertility and Sterility 2014 101, 656-663.e1DOI: (10.1016/j.fertnstert.2013.11.004) Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Indications for comprehensive chromosomal screening. The indications were categorized as family balancing, general infertility care, recurrent pregnancy loss, and single gene cases. Our center offers CCS as routine care, and thus this represented the overwhelming majority of cases in each age group as well as overall. Single-gene cases were higher in patients under age 26 years. Otherwise, the other indications represent a minority of cases, so these results are generalizable to the general IVF population. Fertility and Sterility 2014 101, 656-663.e1DOI: (10.1016/j.fertnstert.2013.11.004) Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions