NEXCCS Your guide to aneuploidy screening
GROWING FAMILIES What is comprehensive chromosome screening? Comprehensive chromosome screening (CCS), also known as preimplantation genetic screening (PGS) or aneuploidy screening, is designed to identify which embryos have the greatest potential to become a healthy pregnancy and baby. Embryos with the normal number of chromosomes, also called euploid embryos, have a greater chance of becoming a healthy pregnancy and baby. Euploid embryos have 46 chromosomes and are created when a sperm with 23 chromosomes fertilizes an egg with 23 chromosomes (see Fig. A). Sometimes embryos are created that do not have the usual number of chromosomes. These embryos, also called aneuploid embryos, are more likely to result in in vitro fertilization (IVF) failure. By transferring only euploid embryos, IVF teams and patients can improve the chances of success with IVF. Aneuploidy also contributes to miscarriage and can be associated with health problems during pregnancy or in the baby following delivery. One of the most common examples of aneuploidy is trisomy 21, also referred to as Down syndrome, which is caused by the presence of a third copy of chromosome 21. Fig. A Normal egg with 23 chromosomes Normal sperm with 23 chromosomes Family, like branches on a tree, we all grow in different directions yet our roots remain as one. Unknown Euploid embryo with 46 chromosomes Comprehensive chromosomal screening using NexCCS helps IVF teams and patients make better decisions about which embryos should be considered for IVF transfer based on their chromosomal makeup.
How common is aneuploidy? The chance for aneuploidy increases with maternal age and ranges from about 20% to greater than 90% at the time of fertilization. 100 Approximate Percent of Embryos Which Are Aneuploid 90 80 70 60 50 40 30 20 10 0 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45+ Maternal Age (yrs)
What is NexCCS? Before the development of aneuploidy screening, selecting embryos for IVF transfer was based largely on how an embryo looked; however, we now know that there is little connection between how an embryo appears on the outside and the number of chromosomes present within. 1 Current aneuploidy screening through the FEC uses next-generation sequencing (NGS) based comprehensive chromosome screening. NexCCS has been developed following extensive clinical trials and counts all 23 pairs of chromosomes at the molecular level for a comprehensive approach. Fig. B NEXCCS PROCESS STEP 1 Perform trophectoderm biopsy STEP 2 FEC receives embryo biopsy STEP 3 FEC analyzes biopsy What type of sample is needed for NexCCS? To begin aneuploidy screening with NexCCS, (see Fig. B) a sample is biopsied (safely removed) from an embryo. The method of biopsy used in NexCCS has been determined to be the safest available. 2 Approximately 5 cells are removed from a specific area of the embryo called the trophectoderm at a specific time in embryonic development. Unlike other methods of biopsy, a trophectoderm biopsy has no significant impact on the reproductive potential of the embryo and therefore maximizes the benefit of NexCCS. 2 STEP 4 Results made available to your clinical team Adding NexCCS testing to your IVF plan will increase your chances of a healthy pregnancy without any delays in your care. NexCCS allows for higher delivery rates and safer pregnancies. The biopsied cells are sent to the FEC, where they are analyzed. A report is sent to your IVF team, who will discuss the results of NexCCS with you. Explore other tests at FEClabs.org
What happens to my embryos during NexCCS? Your embryos never leave the care and security of your team s IVF laboratory. The NexCCS biopsy process requires only a few cells, which are safely removed and sent for analysis. The patient coordinators and laboratory technicians work closely with your IVF team to coordinate the sending and receiving of biopsy material. All required local, state, and national regulations are followed closely to ensure the safest and most effective handling of your samples. NexCCS is at least 98.7% accurate in screening for whole chromosome aneuploidy. 3 What kinds of results could be expected following NexCCS? NexCCS is designed to detect whole chromosome aneuploidy, meaning there is at least one additional or missing chromosome, leaving an abnormal or incorrect number. In addition, NexCCS also has the ability to detect some cases of segmental aneuploidy and mosaicism. Segmental aneuploidy means that a piece (or segment) of extra or missing chromosome material is detected in an embryo. Mosaicism refers to a single embryo that has a combination of cells with the usual number of chromosomes (euploid) and cells with extra or missing chromosomes (aneuploid). While the clinical significance of both segmental aneuploidy and mosaicism can vary, these findings increase the risk for implantation failure, miscarriage, and poor outcome. What is the clinical impact of segmental aneuploidy? Segmental aneuploidy refers to a segment of duplicated or deleted chromosome material detected in an embryo biopsy. Although the clinical significance of segmental aneuploidies can vary, deletions and duplications are associated with a significant risk of poor outcome. If transferred, these embryos have an approximate 50% reduction in the probability of progressing to a live-born infant. What is the clinical impact of mosaicism? Mosaicism refers to a combination of euploid and aneuploid cells in a single embryo. Embryo biopsies in this category have at least one chromosome that falls into a mosaic range. The risk for implantation failure, miscarriage, and poor outcome is increased in these embryos. Sustained implantation rates are reduced by approximately half for embryos with mosaic range results. If an embryo with mosaic range results does implant, the risk for obstetrical/ neonatal complications or ongoing health issues is not known. While a number of healthy infants have been reported following PGS with mosaic results, currently there is no long-term follow-up data. How often is a result of segmental aneuploidy or mosaicism expected? Segmental abnormalities impact 5% to 10% of all embryos. The presence of at least one chromosome in a mosaic range in an otherwise euploid embryo occurs in about 5% of samples.
How are results prioritized? A normal result indicates that the usual number of chromosomes was detected and that no whole chromosome abnormalities, mosaicism, or segmental aneuploidy was detected. These embryos have the highest priority for transfer. An abnormal result indicates that at least one whole chromosome aneuploidy was detected and the embryo should not be considered for transfer. If the result indicates segmental aneuploidy and/or mosaicism, the result is categorized as aneuploid with undetermined safety or reproductive potential. These results are considered the lowest priority for transfer, and genetic counseling is recommended to review if transfer of one of these embryos is being considered. How long before results are available? NexCCS results will generally be ready about a week after the FEC receives the biopsies. An in-depth report is sent directly to your IVF team, who will discuss the results of NexCCS with you. What does NexCCS cost? Speak with your IVF team about the costs and benefits of NexCCS. Typically, genetic screening of embryos for IVF is not covered by insurance plans, and most patients will have to cover some or all of the expense. Billing information is required prior to the start of your cycle; however, payment will not be processed until we receive your samples for testing. How accurate is NexCCS? NexCCS is at least 98.7% accurate in screening for whole chromosome aneuploidy, a dramatic improvement over other forms of aneuploidy testing. 3 This means that in over 98 out of 100 cases, NexCCS will correctly predict the number of chromosomes from the cells obtained in an embryo biopsy. However, there is a low chance for a false negative or false positive result. Therefore, as with any test, it is important that you speak to your physician to discuss the benefits and limitations of this test. Talk with your doctor or genetic counselor to determine if NexCCS is right for you. References: 1. Forman EJ, Upham KM, Cheng M, et al. Comprehensive chromosome screening alters traditional morphology-based embryo selection: a prospective study of 100 consecutive cycles of planned fresh euploid blastocyst transfer. Fertil Steril. 2013;100(3):718-724. 2. Scott RT Jr, Upham KM, Forman EJ, Zhao T, Treff NR. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril. 2013;100(3):624-630. 3. Data on file. The Foundation for Embryonic Competence. 2016.
ABOUT THE FEC The Foundation for Embryonic Competence (FEC) is a nonprofit organization dedicated to advancing knowledge and enhancing outcomes in embryonic research, diagnosis, and education. NexCCS and IdentifySGD are owned and operated by the FEC. All proceeds from NexCCS and IdentifySGD are used to support research and education. See our story at FEClabs.org 140 Allen Road, Suite 300, Basking Ridge, NJ 07920 908.580.1200 contact@feclabs.org 2017 The Foundation for Embryonic Competence