Mosaic pregnancy after transfer of a “euploid” blastocyst screened by DNA microarray

Abstract

BackgroundHigh proportions of human embryos produced by in vitro fertilization are aneuploidy and mosaic. DNA microarray is one of the most practical screening methods to select euploid embryos for transfer. However, mosaic pregnancy is still possible due to embryonic mosacism. Here we report a successful pregnancy after transfer of a mosaic blastocyst with euploid inner cell mass.MethodsA woman with a previous trisomy 13 pregnancy pursued infertility treatment with preimplantation genetic screening by a trophectoderm biopsy and DNA microarray. NimbleGen oligonucleotide DNA microarray was applied to biopsied samples from 13 blastocysts. A euploid blastocyst was transferred to the patient and subsequent prenatal cytogenetic tests were performed by FISH and/or G banding.ResultsFollowing DNA microarray, it was found that 5 blastocysts were euploid and 8 were aneuploidy. Transfer of one euploid blastocyst resulted in a clinical pregnancy. Prenatal cytogenetic tests of samples biopsied from chorionic villi sample showed both trisomy 21 (47 XX, +21) and euploid (46, XX) cells. Further prenatal cytogenetic test with a sample from amniotic fluid indicated that all cells were euploid (46, XX). The pregnancy was continued and a healthy girl was delivered after 41 weeks of gestation.ConclusionsThis is the first report to indicate a mosaic pregnancy after transfer of a “euploid” blastocyst that was screened by DNA microarray, and the case further confirms that mosaicism is present in human blastocysts produced by in vitro fertilization.

Human embryo mosaicism: did we drop the ball on chromosomal testing?

“…It has been found that in about 2 % of pregnancies, the fetus had normal chromosomes while the placenta had either a combination of normal and abnormal chromosomes or totally abnormal chromosomes [14][15][16][17]. Fetal/placental mosaicism is one type of potential mosaicism.…”

“…Such results may be due to either decreased mosaicism within TE and ICM cells at the blastocyst stage or to an increased likelihood that the ICM is euploid if the mosaic TE contains some euploid cells [18]. Some fetuses with normal chromosomes have a fully abnormal or mosaic chromosome complement within the placenta [15,16]. It has been estimated that approximately 2 % of viable pregnancies are affected by this type of mosaicism, termed Bconfined placental mosaicism^ [16].…”

“…They concluded that the use of PGS, particularly in poor prognosis patients, might actually reduce the chance of a normal pregnancy by limiting the transfer of viable embryos based on PGS results. Further complicating the picture of the relevance and impact of mosaicism are case reports like that from Haddad et al (2013) describing the transfer of a euploid, micro-array tested blastocyst that was later found to be mosaic (47 XX, +21; 46, XX) on prenatal CVS sampling. The pregnancy was continued, and a healthy girl was delivered at 41 weeks [15].…”

“…Further complicating the picture of the relevance and impact of mosaicism are case reports like that from Haddad et al (2013) describing the transfer of a euploid, micro-array tested blastocyst that was later found to be mosaic (47 XX, +21; 46, XX) on prenatal CVS sampling. The pregnancy was continued, and a healthy girl was delivered at 41 weeks [15]. The results of these studies, taken together, point to the potential for mosaicism and abnormal cell line segregation in the trophectoderm to impair the clinical accuracy of PGS results.…”

Technique to ‘Map' Chromosomal Mosaicism at the Blastocyst Stage

“…The examination of individual cells at the blastocyst stage is particularly important to gain insight into possible origins and mechanisms of mosaicism, such as non-disjunction, endoreduplication, anaphase lagging, uniparental disomy, and their prevalence during preimplantation development [Taylor et al, 2014a]. Indeed, mosaicism could be responsible both for false negative and false positive preimplantation genetic screening (PGS) diagnoses [Haddad et al, 2013;Wener et al, 2014].…”