Comprehensive Chromosome Screening (CCS)
Comprehensive Chromosome Screening & IVF
PFC offers Comprehensive Chromosome Screening (CCS) as an option for patients undergoing in vitro fertilization (IVF). CCS is a treatment for women that wish to improve implantation rates, reduce miscarriage rates, and reduce the risk of multiples after IVF. This is one of the truly exciting technologies that sets apart modern fertility programs such as Pacific Fertility Center, and we are pleased to be able to offer CCS to our patients.
Providing high pregnancy rates with minimum risk after in vitro fertilization requires high quality embryos. But a problem remains in the IVF lab – which embryos are high quality? Embryos that look good under the microscope don’t always have what it takes to produce a pregnancy. Selecting high quality embryos, those with the highest pregnancy potential, can reduce the numbers of embryos transferred, avoiding miscarriage, increasing pregnancy rates, and improving the health of children born after IVF.
Women that can benefit from CCS include those with:
- Recurrent miscarriage
- Clinical aneuploidy (Downs’ Syndrome) risk
- Multiple pregnancy risk
- Sex-linked genetic illness risk
CCS Outcomes at Pacific Fertility Center
Pregnancy rates after CCS are very high. At Pacific Fertility Center 74.5% of women aged 40 and under that received an embryo selected with CCS conceived a clinical pregnancy (n=51 transfers in 2012); that is, 3 out of 4 embryo transfers resulted in a clinical pregnancy. Embryo implantation rates were over 70% per embryo transferred for each age group in women age 40 and under. One embryo screened with CCS produces very high pregnancy rates after transfer.
These "hot off the press" preliminary data are among the best rates we have yet seen after fertility therapy. Final pregnancy delivery data will be available next year and we anticipate continued high success rates, as we expect miscarriage rates to be very low in these pregnancies.
This is a true paradigm shift in the options that we can offer couples pursuing fertility treatment.
CCS – Choosing the best embryo
Comprehensive Chromosome Screening (CCS) is a technique that allows selection of the healthiest from a group of embryos. After in vitro fertilization, a few cells from each embryo are sent to the genetics lab and chromosomes are counted. The embryos with a normal number of chromosomes are selected from the group for transfer.
Embryo selection by conventional imaging techniques is not very selective. Abnormal embryos often look just like normal embryos under the microscope. Early cell division is to some extent independent of the number of chromosomes in the embryo, so an embryo with an abnormal number of chromosomes can look just like any other. To compensate, IVF programs may transfer more than one embryo, risking multiple pregnancy. When an abnormal embryo results in pregnancy, miscarriage is possible.
CCS refines embryo selection, offering a means of choosing the best embryos, the most likely to succeed, out of a group.
The biology behind Comprehensive Chromosome Screening
An embryo that contains a normal number of chromosomes is a ‘euploid’ embryo. An embryo that carries an abnormal number of chromosomes is ‘aneuploid’. Examples of aneuploid embryos include trisomy 18 and trisomy 21, otherwise known as Down Syndrome. Embryos can also be affected by complex combinations of abnormal chromosomes, and even contain an extra entire set of chromosomes (triploidy).
Aneuploidy is quite common and, more often than not, CCS testing will show that an embryo is aneuploid. Half or more (sometimes all) embryos in a particular IVF treatment cycle are aneuploid, and while we can’t prove this, we suspect that the majority of natural conceptions are affected by aneuploidy as well. The common clinical scenarios of age-related infertility, miscarriage, and Down Syndrome are all expressions of aneuploidy.
In the embryology lab, at the earliest days of embryo development, most of these aneuploid embryos don’t develop, and are never seen clinically. A few aneuploid embryos continue development and result in clinical problems. Miscarriage occurs in about a fourth of pregnancies – most of these are aneuploid. The rate of aneuploid embryos resulting in miscarriage increases dramatically with maternal age such that 50% or more of pregnancies after age 40 will miscarry. In milder forms of aneuploidy, embryos can survive longer, with a few continuing on into pregnancy, accounting for common problems like Down Syndrome.
Most eggs, and most embryos, do not have what it takes to produce a viable pregnancy. On average, about 10 eggs are required to produce a euploid embryo. It works like this: two-thirds of eggs fertilize and form an embryo. Half of the embryos develop to the blastocyst stage at day 5, and about half of the day 5 embryos will be euploid. In other words, 10 eggs can produce 1-2 euploid embryos. 3 out of 4 of these euploid embryos will implant on average (75 percent implantation rate), with high pregnancy rates per transfer.
Age is the best predictor of aneuploidy and a major factor to consider when thinking about aneuploidy. In a woman under age 30, half of embryos are aneuploid. At age 42, 80% of embryos are aneuploid. On occasion, especially in older age groups, all embryos are aneuploid.
It is difficult to predict for an individual how many of the embryos will be aneuploid. In the extremes, we have seen circumstances where every embryo is euploid. Unfortunately somewhat more common is the opposite, all embryos aneuploid. Full aneuploidy is unusual under age 30, but afflicts a third of cycles over age 40. The only way to tell if an embryo is aneuploid is to test.
The technology of CCS
In CCS, a few cells are sampled from the embryo and chromosomes counted. Those that test normal can be transferred back to the mother to achieve pregnancy. CCS allows for selection of the highest quality embryos out of a group for transfer.
The technique of CCS after conventional in vitro fertilization is to grow embryos to day 5, the blastocyst stage. The embryo is hatched in the IVF lab, and a few cells sampled from the early placenta. The embryo is then vitrified (an advanced technique of embryo freezing), and stored for later transfer back to the uterus. The cell samples are sent to a genetics lab for a count of the chromosomes.
Embryos are stored after sampling, since genetic testing takes about a week. We are finding that almost all embryos do well with the freezing-thawing process, with >97% of embryos surviving vitrification and thaw. It appears that implantation rates actually improve with a delayed transfer in a cycle after the retrieval cycle. This is likely due to the effects of ovarian stimulation on the endometrial lining, making it a bit resistant to implantation in a fresh cycle. In a later natural cycle, the normal endometrial lining is restored with normal implantation rates.
Pacific Fertility Center uses the genetic lab Natera for its genetic testing. Natera uses a SNP microarray from Ilumina with a proprietary technology called Parental Support™, which tests all 24 chromosomes and delivers results that are typically >99% accurate.
Expectations are that on average about 1/10 eggs produces a chromosomally normal embryo, for example, starting with 10 eggs yields on average 7 embryos that on CCS testing will yield 1-3 with normal chromosomes.
The rate of chromosomally normal embryos varies between women especially with age. As women age, the chance of a chromosomally normal embryo declines. Under age 30, roughly half of embryos will be normal, and most young women find multiple euploid embryos after testing. Over age 40, 1/3 to 1/2 of all women will not find a viable embryo after CCS testing.
CCS Pros and Cons
Pros of CCS include:
- Improved selection of healthy embryos
- Reduction in aneuploidy
- Reduction in miscarriage rate
- Improved implantation rate
- Reduced multiple pregnancy risk
- Identification of gender
- Rare errors in test results
- Mosaicism (in 4% of cases, not all the sampled cells are genetically identical)
- Lack of randomized prospective trials
- Data on safety incomplete
- Data on delivered child outcomes is incomplete and under study
Despite the fact that there are a lack of randomized trials and data on outcomes is limited, we have enough experience with pre-implantation genetic diagnosis to feel confident that this is a safe and highly accurate procedure.
CCS is now an option for patients
Comprehensive Chromosome Screening (CCS) is a new way of selecting high quality embryos, with high implantation and pregnancy rates. Transferring one embryo and delivering one healthy child from each embryo transfer is a goal that at last is within reach. Treatment of illness related to chromosome count and quality is now possible.
PFC offers CCS as an option for patients undergoing in vitro fertilization (IVF), as a treatment for recurrent miscarriage, prevention of aneuploidy in pregnancy, and for women that wish to improve implantation rates, reduce miscarriage rates, and reduce the risk of multiple pregnancy after IVF. This is one of the truly exciting technologies that modern fertility care makes available, and we pleased to be able to offer this pioneering work to our patients.
CCS is another way that we are working for the benefit of our patients: “As a unified team, guided by the highest ethical standards, we provide our patients with individualized and compassionate fertility care.”