Britain’s First Array CGH Baby: A Commentary

You may have read recently of a baby born in the United Kingdom following the performance of Comparative Genomic Hybridization (CGH) to help identify the best embryo(s) for transfer to the uterus. In this report, a great deal was made of two factors. The first was that the fresh embryo(s) chosen for transfer to the recipient’s uterus was selected because it had been derived from an egg that was found to have all its chromosomes intact. The second was that the technique used was Array CGH (aCGH) which was touted as having the advantage of being so fast that it allowed for the embryo to be transferred to the recipient’s uterus in the same cycle that the in vitro fertilization (IVF) was performed. This was contrasted with the slightly slower metaphase CGH (mCGH) method (used by SIRM) which it was implied would require that the embryos be preserved (cryostored) for at least one full cycle before being transferred. We call this division of the IVF cycle into two separate stages, "Staggered IVF” (see postings on this subject elsewhere on this website).

As many of you who are familiar with our published research at SIRM are aware, we have been performing mCGH egg/embryo selection for nearly 5 years and have had in excess of 100 births. Moreover, in our initial report (in Fertility and Sterility-2007) we utilized mCGH for egg testing followed by the transfer of fresh embryos in the same cycle. Thus the inference that only aCGH (when performed on eggs) is fast enough to allow for same-cycle fresh embryo transfers is simply not true.

Some background: CGH is a genetic test performed on DNA extracted from one of the following: the egg’s polar body (PB), a single cell (blastomere) taken from the early cleaved embryo (3 days post-fertilization), or from multiple (5-7) cells biopsied from an advanced 5-6 day (>100cell) embryo (i.e. the blastocyst). There is little doubt that CGH provides the most reliable method by which to identify chromosomally normal eggs and embryos…these being the ones that are most likely to make healthy babies.

Following is a comparison of aCGH and mCGH:

1. Both evaluate ALL of the cell’s chromosomes and provide the same information.
2. It is possible to perform either mCGH or aCGH on eggs permitting results to be available in time to allow for the transfer of blastocysts (day-5 embryos) in the same cycle that the IVF was performed.
3. Metaphase CGH is more reliable than aCGH when it comes to testing a single cell (as is the case when testing the egg or the early embryo). Array CGH, on the other hand, is best suited for use on advanced embryos (blastocysts) This is because aCGH requires a larger amount of DNA (several cells) than mCGH to yield accurate results.
4. Since almost all blastocysts have some chromosomally abnormal cells mixed in with normal ones (mosaicism), the question arises as to what percentage of the blastocyst’s cells need to be chromosomally normal in order to insure development into a healthy baby. The truth is that presently, (with very few babies having been born following blastocyst aCGH), there is no way of knowing for sure! We are thus still in the “speculative phase” when it comes to the use and reliability of aCGH as performed on advanced embryos.

Thus, in spite of this interesting report in the British press, for the time being at least, mCGH analysis of the early (day-3) embryo is the preferred method for selecting the most competent embryos for transfer.