Day 3 embryos, having a mixture of normal and abnormal cells (mosaicism), undergo a previously undescribed normalization process called genomic normalization during differentiation to the blastocyst stage. This normalization may be due to the abnormal cells (aneuploid) undergoing degeneration (apoptosis) — studies are showing that there are genes within the embryo that initiate apoptosis in abnormal cells rather than cell division or mitosis. Abnormal cells divide less than normal cells, thus resulting in their marginalization within the embryos (possibly resulting in fragments seen within the embryo) and /or due to mechanisms within the embryo that are not yet understood.
Initially, Arizona Center for Fertility Studies suggested that all abnormal day 3 embryos detected by PGD/PGS 23-chromosome microarray that reached the blastocyst stage by day 5 or 6 and appeared developmentally normal should undergo trophectoderm (TE) biopsy (at no additional charge) and then cryopreserved. If the TE biopsy came back showing a normal chromosome competent, it can be assumed that the embryo had "self-corrected" or undergone normalization, and could be used for a future frozen embryo transfer (FET).
As a result of our experience over the last several years doing 23-chromosome microarray (and now what seems to be conclusive evidence that embryos can "self-correct"), Arizona Center for Fertility Studies strongly recommends only doing biopsies on day 5-6 embryos (blastocysts) using laser-directed TE (trophectoderm) biopsy. This means that after the blastocyst is biopsied, it will undergo cryopreservation and be transferred in a subsequent frozen embryo transfer (FET) the following cycle. Although this means that the couple will need to wait a cycle to do the transfer, there are several advantages to doing a TE biopsy as opposed to a day 3 biopsy:
In Arizona Center for Fertility Studies’ experience, all of these advantages collectively add up to higher success rates when using PGD/PGS, and is the reason Arizona Center for Fertility Studies now strongly recommends only doing TE biopsy, cryopreservation, and subsequent next cycle FET on patients undergoing PGD/PGS. The one exception is in our out of state patients, unless they can make a return trip. Our success rates are still very good with day 3 biopsy, but Arizona Center for Fertility Studies prefers day 5 TE biopsy.
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