Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study

Abstract

Background Previous studies from this as well as other research groups suggested that non-invasive chromosome screening (NICS) with embryo culture medium can be used to identify chromosomal ploidy and chromosomal abnormalities. We here report a series of clinical cases utilizing the technology. Methods A total of 45 couples underwent in vitro fertilisation during a period between February 2016 and February 2017. Karyotyping revealed normal chromosomes in both partners in 23 couples, and chromosomal rearrangements in at least one partner in 22 couples. Intracytoplasmic sperm injection (ICSI) was used for fertilization. NICS was carried out using embryo culture medium at the blastocyst stage via multiple annealing and looping-based amplification cycles, whole-genome amplification and next-generation sequencing. Results A total of 413 embryos were obtained; 170 blastocysts were subjected to NICS. The screening showed euploidy in 79 embryos, aneuploidy in 52 embryos, and mosaic ploidy for 33 embryos. The rate of euploidy was comparable in couples with normal karyotype (50.7%; 38/75) vs. chromosomal rearrangement (43.2%; 41/95). A total of 52 euploid embryos (50 oocyte retrieval cycles) were transferred in 43 women. Biochemical pregnancy rate was 72.0% (36/50). Clinical pregnancy rate was 58.0% (29/50). The rate of spontaneous miscarriage was 3/29 (none with chromosomal aneuploidy). A total of 27 healthy babies were delivered. Conclusions NICS could identify embryo chromosomal abnormalities in couples either with or without chromosomal rearrangement, with satisfying clinical outcomes. Electronic supplementary material The online version of this article (10.1186/s12967-019-1827-1) contains supplementary material, which is available to authorized users.

Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy

“…While none of them provided encouraging results, two showed that TE-biopsy PGT-A was superior to niPGT-A (28,30). However, one very recent study in women <30 y reported 27 normal births following transfer of 50 embryos identified as euploid by niPGT-A (31). Moreover, in another report, when combining niPGT-A with blastocoel fluid DNA analysis, concordance was higher than PGT-A with TE biopsy alone (29).…”

Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review

“…Results were fully concordant when SCM-PGT was compared with pregnancies (Galluzzi et al, 2015) or live births . Moreover, a recent study reported 27 healthy births after SCM-PGT (Fang et al, 2019). Although encouraging, these results do not allow any conclusion to be reached because the number of cases is too low.…”

Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements

“…Only later studies revealed that maternal DNA contamination from the oocyte retrieval procedure is a significant concern, and the uninterrupted culture from zygote to blastocyst stage likely maximizes that problem. The same testing method, namely MALBAC amplification (Yikon Genomics) and NGS on a HiSeq 2500 instrument (Illumina), was used in a study by Fang and colleagues, this time washing embryos at Day 3 of culture and moving to new media drops until Day 5 or 6 [223]. The study reports a 97% amplification rate in the 170 samples analyzed.…”