18例囊胚染色體異常鑲嵌化植入後有6例產出正常染色體新生兒
其餘12例未著床或著床後流產
本研究顯示囊胚染色體異常鑲嵌化在日後發育過程仍具自我修復染色體異常之能力
但植入囊胚染色體異常鑲嵌化之胚胎仍有產下染色體異常胎兒之風險，此仍須充分告知病患其承受風險之認知‧
Healthy Babies after Intrauterine Transfer of Mosaic Aneuploid Blastocysts
To the Editor:
Chromosomal aneuploidy is recognized as a factor that contributes to unsuccessful embryo implantation and spontaneous abortion. It provides an explanation for the relatively low success rate of in vitro fertilization (IVF) treatments. Preimplantation genetic screening is widely used to identify chromosomally normal (euploid) embryos and select them for intrauterine transfer in order to improve the clinical outcome of IVF.1
Chromosomal mosaicism is a relatively common finding in IVF-derived human embryos.2 Mosaic embryos, which are characterized by the presence of a mixture of diploid and aneuploid cell lines, are not usually transferred because they are deemed to be abnormal. Although the effect of mosaicism on implantation and the developmental potential of these embryos is not known, it is reasonable to assume that mosaicism reduces the likelihood of success of IVF.3
The low levels of mosaicism reported in prenatal specimens and the reduced incidence of mosaicism with increasing gestational age suggest that there exists a mechanism by which mosaic aneuploidy is corrected or by which aneuploid cells are “outcompeted” by euploid cells.4 To our knowledge, healthy live births after transfer of mosaic aneuploid blastocysts obtained by means of IVF have not been reported. However, a previous study in which the researchers were unaware of the results of genetic screening may have involved the transfer of mosaic embryos that resulted in clinical pregnancies.5
Between May 2013 and July 2014, we analyzed 3802 blastocysts by means of array-comparative genomic hybridization testing (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). We detected chromosomal mosaicism in 181 blastocysts (4.8%). The transfer of mosaic embryos was made available to a consecutive nonselected series of 18 women for whom IVF had resulted in no euploid embryos. We provided the results of the genetic screening to the women and counseled them on the potential consequences of transferring a mosaic embryo. We tailored the counseling according to the type of aneuploidy.
An institutional ethics committee approved the protocol (available at NEJM.org), and we obtained written informed consent from each woman before proceeding with embryo implantation. All the women elected to undergo implantation (only one mosaic blastocyst was available in each case). Eight clinical pregnancies (maternal serum positive for the beta subunit of human chorionic gonadotropin) ensued, of which six resulted in the birth of a singleton infant at term. All pregnancies that went to term were confirmed, by means of sampling of the chorionic villi, to have a normal karyotype (Table 1).
Our study shows that mosaic embryos can develop into healthy euploid newborns. These findings have implications for women who undergo IVF resulting in mosaic embryos but no euploid embryos.
We hypothesize that the extent and type of mosaicism affect the IVF success rate; our data were insufficient to test this hypothesis. Our study was small, and additional clinical data must be obtained before this approach can be evaluated for routine integration into preimplantation genetic screening programs in women undergoing IVF. Transfer of mosaic embryos with purportedly “viable” aneuploidies should be considered with
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