New chromosomal screening strategy shows promise in PGS

Dec 31 2009

A new strategy that researchers believe provides a more comprehensive screening of the entire chromosomal makeup of an embryo shows tremendous promise in the field of preimplantation genetic screening (PGS) according to a study published in the December issue of Fertility and Sterility.

Forty-five infertile couples participated in the study with an average age of 37.7 years. Using a novel screening approach, researchers biopsied several cells from embryos five days after fertilization, also known as the blastocyst stage. The patients underwent comparative genomic hybridization (CGH) screening, which researchers say allows for a more comprehensive look at the chromosomal health of the cell.

Results show successful biopsy in close to 100 percent of the embryos using CGH. Of these embryos, more than half (51.3 percent) were diagnosed as abnormal. The remaining embryos with normal chromosome counts were implanted and of the CGH group, 68.9 percent produced a fetus.

Reprogenetics, LLC, in Livingston, New Jersey, performed the genetic diagnosis. Its president, Santiago Munne, says the CGH screening results could provide the answers to challenges that IVF researchers have faced for years.

"One of the greatest challenges currently facing IVF practitioners is how to reduce the risk of multiple pregnancy while maintaining or improving pregnancy rates," says Dagan Wells, a senior scientist at Oxford University and one of the authors of the study. "The research suggests that CGH will be an extremely useful tool, allowing us to move IVF toward single embryo transfer." A reduction in the risks of miscarriage and Down syndrome are also predicted if embryos are screened using CGH.

Traditionally, PGS has been conducted to improve the success rate of in vitro fertilization (IVF) for women of advanced maternal age and repeat pregnancy loss. Research has shown that many times IVF fails because a majority of the embryos that are created in vitro are chromosomally abnormal. Embryos with a chromosome abnormality have very little chance of producing a baby. When performing IVF in conjunction with CGH, researchers are able to detect embryos with a healthy set of chromosomes and make sure they are given maximum priority for transfer to the womb.

Many IVF laboratories currently perform chromosome screening (PGS) at the 6-10 cell stage (3 days after fertilization). While this technique has been shown to improve IVF outcomes by some PGD laboratories, such as Reprogenetics, others have not been able to duplicate these results. This is, according to another recent publication in the same journal, due to the use of non-optimized methods, such as poor embryo biopsy technique. However, regardless of the method used, the standard technique only detects a fraction of chromosomes and by analyzing a single cell may have an intrinsic risk of misdiagnosis, which at Reprogenetics is about 6%.

CGH allows researchers to overcome both of these perceived obstacles. Biopsy is performed at the blastocyst stage, a full two days later than traditional PGS methods, where several cells can be safely sampled from a tissue that will not become fetus but placenta (the trophectoderm). As previous studies have shown, cells sampled during this stage are highly representative of the remainder of the embryo and thus the errors are minimized. In addition, CGH allows researchers to screen all chromosomes for abnormalities,

"The blastocyst-CGH approach shows enormous promise," states Dr. Wells. "Despite these encouraging results, we plan to follow up with a randomized trial to confirm the efficacy of this new procedure."

The CGH technique has been further improved since the submission of this work for publication, by allowing analyses of day 3 embryos in 24 hours, a new technique called array CGH.