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The Evolution Of CGH-Egg And Embryo Testing
by Geoffrey Sher, M.D.
Three problems restricted the growth of IVF in the U.S: 1) Cost of service and lack of insurance reimbursement, 2) Ignorance of the fact that IVF is far more efficacious than other infertility treatment and, 3) OB-Gyn’s and/or Reproductive Endocrinologists (RE’s) that do not have the necessary expertise required to optimize ART outcome. Since most insurance providers do not cover IVF services, most IVF costs have to be shouldered by the consumer. The reason why insurance providers have been reluctant to cover IVF are: a) absence of a verifiable reporting system on IVF outcomes, b) poor IVF success rates per embryo transfer and, c) an alarming incidence of high-order multiple pregnancies.
A “competent egg” is one that in most cases upon fertilization will propagate a chromosomally normal embryo and, a “competent embryo” is one that is karyotypically normal and which upon reaching a receptive uterus is most likely to spawn a viable pregnancy. Hitherto, the lack of reliably in identifying “competent eggs/embryos” has led to an inability to select the best embryo(s) for transfer. As a consequence implantation rates have been low (averaging at 15-25% per embryo in young women). In an attempt to improve I VF results many RE’s have tended to transfer several embryos at a time, which fact explains the virtual explosion in the IVF-induced high-order multiple birth (triplets or greater) rate in the U.S and reluctance on the part of most insurance companies to cover IVF services.
There is a profound lack of correlation between the microscopic appearance (grading) of embryos and embryo “competency”. Moreover Preimplantation Genetic Diagnosis/Sampling (PGD/S of human eggs and embryos for their chromosomal integrity, using Fluorescence in-situ Hybridization (FISH) is only fractionally more reliable. The reason is that FISH cannot fully access all the chromosomes….in fact only about 1/2 of them. Thus even when FISH reveals that all the accessed chromosomes are normal, there still remains more than a 45% chance of chromosomal aneuploidy involving those chromosomes not targeted by the test…and the incidence increases to about 60% by the time the woman reaches her forties. This constitutes a serious draw back when it comes to attempting to select the most “competent” eggs or embryos for dispensation in ART.
In 2007 we reported in the journal, “Fertility and Sterility” on a study where we fully karyotyped mature eggs (M2 oocytes) using metaphase comparative genomic hybridization (mCGH) rather than FISH.