Comprehensive Chromosome Screening (CCS):
New Technologies Screen for all 23 Pairs of Human Chromosomes
The Colorado Center for Reproductive Medicine (CCRM) is conducting a clinical trial screening for all 23 pairs of human chromosomes prior to embryo transfer. The new analytical technology, microarray analysis, allows for the evaluation of all 23 pairs of human chromosomes on a single cell. This comprehensive chromosome screening becomes particularly important to patients over 40 who are prone to chromosomal errors in their eggs, as well as those patients with a history of recurrent pregnancy losses with an otherwise normal evaluation or who have had multiple failed IVF cycles.
In IVF, ideally, a fresh embryo transfer is performed once the embryo reaches day 5, the blastocyst stage. Preimplantation genetic screening (PGS) of day 5 blastocysts allows a window of only 6 hours for the analysis prior to a fresh embryo transfer. These new technologies are both comprehensive and labor-intensive with results taking longer than 6 hours to complete.
During this wait for results, embryos are in a suspended state of development using a new method of cryopreservation, quick-freezing called vitrification. Different from the former methods of slow freezing, vitrification allows the embryos to be flash frozen in a matter of seconds. This technique may assist in increasing the chances of implantation. Embryo survival after vitrification has significantly improved to 98% from approximately 70% observed after slow freezing. Fewer potentially damaging ice crystals form on the embryos during vitrification.
Waiting for the comprehensive chromosomal analysis has an added benefit to the patient. It offers some time for the patient’s body to return to a normal hormonal state after ovarian stimulation during an IVF cycle. A variety of studies have shown that replacing embryos into the uterus in a more natural hormonal state enhances the likelihood of implantation.
Potential CCS Advantages
The more traditional technique of performing PGS employs fluorescent in situ hybridization (FISH). FISH analysis on a single cell is limited to analysis of 5-10 chromosome pairs out of the 23 pairs of chromosomes. Since aneuploidy (chromosomal abnormalities) can affect any chromosome, it would be beneficial to expand PGS to include screening of all 23 pairs of chromosomes. In fact, several research studies have shown that performing PGS with FISH techniques on the day 3 embryo does not improve outcomes. Analysis of the entire chromosome complement of the embryo or oocyte, combined with further improvements in technology, could potentially further increase the likelihood of implantation and decrease the chance of miscarriage for patients and potentially decrease the number of embryos necessary for transfer. Performing a biopsy on the blastocyst stage embryo also allows us to obtain several cells, as opposed to current practice, which allows removal of only a single cell from the less advanced day 3 cleavage stage embryos.
This is a clinical study, but CCRM believes Comprehensive Chromosome Screening (CCS) could be a promising and beneficial PGS procedure for patients seeking to increase their chances of implantation and a live birth. We are delighted to announce ongoing healthy babies born from this approach making CCRM the only program in Colorado and the first in the US to have demonstrated success with this exciting new technology.
CCRM Results as of 11/1/2009
Thus far, a total of 114 patients in the CCS study have had egg
retrieval and subsequent frozen blastocyst transfer. Indications for
the testing include advanced maternal age, previous IVF failure(s), and
a history of multiple miscarriage(s). After the blastocyst embryos are
biopsied, they are cryopreserved using vitrification, which has resulted in a 97% blastocyst survival rate.
The uterus is then prepared for a frozen embryo transfer after the
woman’s body is allowed to naturally rid itself of the ovarian
stimulation drugs required during an IVF cycle. Eighty-eight of the 114
patients in the study (77%) have ongoing clinical pregnancies,
including 41 healthy deliveries to date. The first baby conceived with
this procedure was born in June 2008.
Why PGS?
An estimated 60% of all early miscarriages are associated with a chromosomal abnormality in the fetus. The purpose of PGS is to select and transfer only embryos that do not have numerical abnormalities for the chromosomes tested in order to achieve higher implantation rates and fewer pregnancy losses.
Research has shown chromosomal abnormalities in embryos may increase the risk of spontaneous miscarriage or the development of a genetically abnormal fetus in IVF pregnancies from the following indications: women 35 or older, couples with multiple-failed IVF cycles or implantation failure, and couples with repeated miscarriages.
Only embryos identified after screening as euploid are transferred. This should theoretically reduce the likelihood of implantation failure, miscarriage and/or aneuploid offspring.
Preimplantation genetic screening does have inherent false positives and negatives due to the limited number of cells available for testing. An inherent 10% error rate means that there is no guarantee of a healthy baby. If a pregnancy is established, traditional prenatal diagnosis like chorionic villus sampling or amniocentesis is highly recommended.