Kylie A. de Boer

Blastocysts more commonly have a normal karyotype than cleavage-stage embryos do. Moreover, blastocysts have also made a metabolic transition from catabolism and recycling of the oocyte's reserves and resources, processes that fuel the first 3 days of cleavage. Although not all blastocysts are karyotypically equal, it is still to be determined to what extent a mosaic karyotype might be a normal feature among embryos, both at the cleavage stage and the blastocyst stage--and when looking for karyotypic abnormalities by embryo biopsy might help the chance of implantation rather than harm it. It is also still impractical to look at all the chromosomes that can, through their aneuploidy, stand in the way of successful embryonic and fetal development. We report a randomized clinical trial of blastocyst biopsy followed by preimplantation genetic screening (PGS) for aneuploidy using 5-colour FISH. The trial was suspended and then terminated early when we were unable to show an advantage for PGS. If we are correct in assuming that mitotic non-disjunction is common by the stage of the blastocyst (and that it is much less ominous than meiotic non-disjunction), then further studies of effective PGS of blastocysts for aneuploidy require methods of analysis that cover all the chromosomes and can differentiate the triallelic and monoallelic states of meiotically derived aneuploidies from the biallelic state of mitotic aneuploidies.

Abstract Objective Modern in vitro fertilization practices involve transfer of embryos as blastocysts, when anabolic metabolism is well established and pregnancy rates can be maintained while transferring embryos singly to avoid multiple pregnancies. Embryo biopsy for preimplantation genetic diagnosis (PGD), however, is generally performed on day 3, when the embryo comprises just 6 to 8 cells, one or two of which are removed for testing. Implantation rates and clinical pregnancy rates have remained relatively low and a harmful effect from losing one or more cells from such early embryos has not been excluded. Methods We performed a sequential study involving 399 egg retrievals and 1879 embryo biopsies for patients undergoing PGD to avoid a serious monogenic disease or an unbalanced chromosomal translocation. We compared implantation and viable pregnancy rates after biopsies taken on day 3 (cleavage‐stage biopsy) with biopsies delayed until day 5 or 6, when the embryo is a blastocyst and 5 or more cells can be sampled from the trophectoderm while the inner cell mass, from which the fetus develops, remains intact. All embryos were transferred as blastocysts. Results Despite fewer blastocysts than cleavage embryos biopsied and tested (3.6 compared to 6.6), implantation rates per embryo transferred were 43.4% if biopsied at the blastocyst stage and 25.6% if biopsied at the cleavage stage (P < 0.01), with ongoing or live‐birth pregnancy rates per egg retrieval of 34.2% (average transfer number 1.1) for blastocyst biopsies and 25.5% (transfer number 1.6) for cleavage stage biopsies (P < 0.05, 1‐tailed). The multiple pregnancy rate for monogenic disease exclusion fell from 16.7% to 2% (P = 0.04, 1‐tailed). Conclusions For exclusion of genetic disease, day 5‐6 blastocyst‐stage biopsies are more likely to be followed by implantation and singleton births than is the case after PGD performed on day 3. Copyright © 2008 John Wiley & Sons, Ltd.