Pre-implantation Genetic Screening (PGS), also known as Comprehensive Chromosome Screening (CCS ) is a great advancement for those women at high risk of miscarriage, increased risk of having a baby with Down’s syndrome, or for those whom in the past would have had multiple embryos transferred resulting an increased risk of twins and triplets.
Women who are at low risk for miscarriage, low risk of Down’s Syndrome, and who are good candidates for a single embryo transfer, PGS may not be beneficial. At RSC, pregnancy rates in these patients are 65% – 75%, high enough that the additional costs, invasiveness and unknown long term outcomes are not proven to be justified.
PGS is an option for all RSC patients and we recommend discussing your particular case with your physician.
Genetic testing of embryos prior to embryo transfer into the uterus has been in place for over ten years. In the past three years however, advances in DNA technology and a change in approach to the timing of the embryo biopsy has resulted in an improvement in pregnancy rates with this technique.
Because of these improvements, the application of testing embryos has expanded and the term CCS has been used to market the routine testing for chromosome number in all embryos generated in an IVF cycle.
In the past, IVF treatments commonly involved the transfer of more than one embryo per transfer and success was a balance of risk versus benefit. Over time, the risk of multiple pregnancies has become an increasing concern and single embryo transfer to achieve a singleton pregnancy has been regarded as the most desirable outcome.
As women get older, the percent of embryos that have a normal (46) number of chromosomes decreases. If an embryo has an abnormal number of chromosomes (aneuploidy) that it will fail to implant, result in a miscarriage, or result in an abnormal pregnancy such as Down’s Syndrome. So, in the past as the woman’s age increased, the number of embryos transferred in an IVF cycle increased.
Physicians and patients accepted a calculated risk: pregnancy rates would be higher if more than one embryo was transferred because at least one could be normal. This had its risk of a multiple pregnancy and still the uncertainty of knowing if the embryos were normal. There was still the risk for miscarriage and Down’s syndrome, both greater risks for women over 40 years.
Relying on extended culture is one way to screen embryos non-invasively for genetic health. Research has demonstrated that embryos that have an abnormal number of chromosomes typically fail to grow to the blastocyst stage and those that are chromosomally normal are more likely to develop.
By allowing embryos to grow over time, the abnormal embryos will slow down in development and even stop growing. Waiting until the blastocyst stage for embryo selection allows for improved selection of the embryo for transfer.
At RSC, we have been utilizing extended culture for over ten years. For RSC patients who are under the age of 38, the pregnancy rate with a single embryo transfer at the day 5 stage without pre-implantation genetic screening is 65%. In IVF cycles using donor eggs, pregnancy rates are 75% for a single embryo transfer relying on blastocyst development alone.
The second advance is PGS. This involves growing embryos to the blastocyst stage, removing 5-6 cells from the trophectoderm (the outer layer of cells in the blastocyst), freezing the embryos and testing the cells for chromosome number. A single embryo transfer is then done in the future as a frozen embryo transfer treatment cycle.
At RSC, the pregnancy rate for this type of treatment is 75% with a single embryo transfer. Some patients however will not have any normal embryos and will not ever have a transfer. In the past, those patients would have had a transfer but may have had a negative pregnancy test or possibly, an early miscarriage.
The exciting news about PGS or CCS is that miscarriage rates are low, about 10%, and the risk of having a pregnancy complicated by Down’s syndrome is reduced. Once a woman has a positive pregnancy test after an IVF cycle with a PGS embryo, the chance of live birth is about 65%. Prenatal testing with amniocentesis or chorionic villus sampling is still recommended based on a woman’s age.
So far, no increase in birth defects is being reported. Long-term risks, such as childhood cancers, late childhood disease or adult medical disorders will not be known for several years. To date, there has not been any published study on the cost-effectiveness of CCS. But so far, this advancement is promising.
At RSC, we think PGS is a great advancement for those women at higher risk of miscarriage, at increased risk of Down’s syndrome or those whom in the past would have had a multiple embryo transfer resulting in an increased risk of multiple pregnancy. That means those women who are ≥38 years, who have had repeat miscarriages or who have a history or medical diagnosis that puts them at increased risk.
For women who are low risk of miscarriage, low risk of Down’s Syndrome, we would prefer to have more data on long-term outcome risks before recommending PGS.
Why PGD or PGS?