Abstract
BackgroundSingle embryo transfer (SET) has been utilized as a strategy to reduce the chance of multifetal gestations in in vitro fertilization (IVF) but lower pregnancy rate remains a concern. Recent studies showed that favorable outcome regarding SET can be achieved by selecting embryos with “more normal” genetic components. We explored the use of rapid array comparative genomic hybridization (aCGH) to select blastocysts for fresh SET and compared with the protocols adopting vitrified (ultrarapidly frozen) embryo transfer cycle. Validation of the rapid protocol of aCGH and comparison of the result with the regular protocol of aCGH and next generation sequencing (NGS) are also performed.ResultsFirst-time IVF patients with normal karyotype (n = 21) were enrolled for elective fresh SET cycle (n = 8; designated as fresh SET group) or vitrified embryo transfer cycle (n = 13; designated as vitrified ET group) coupling with comprehensive chromosomal screening by a 9-h rapid aCGH from Day 5 trophectoderm (TE) biopsy. In fresh SET group, 86 blastocysts (10.8 blastocysts/patient) were biopsied and analyzed. Aneuploidy was detected in 53.5 % (46/86) of the biopsied blastocysts. All patients had a single embryo transferred on the following day. The clinical pregnancy rate was 87.5 % (7/8) and the ongoing pregnancy rate was 62.5 % (5/8). In vitrified ET group, 58 blastocysts (4.5 blastocysts/patient) were biopsied and 56 blastocysts were analyzed. Aneuploidy was detected in 39.3 % (22/56) of biopsies. The patients accepted for SET or double embryos transfer (DET) in non-stimulated cycles. The clinical pregnancy rate and the ongoing pregnancy rate was 76.9 % (10/13) and 53.8 % (7/13) respectively. Spontaneous abortions occurred in both of the two patient groups. In the series of fresh SET group, no twin pregnancy was noted and at least one healthy baby had been born at gestational age (GA) 37+6 weeks when submission. The results of PGS by rapid aCGH, regular aCGH and NGS were comparable in most occasions.ConclusionThis study evaluates the use of rapid aCGH to select blastocysts for fresh SET and demonstrates its feasibility in a real clinical IVF program. A successful livebirth is achieved and the favorable outcome is superior to the protocol adopting vitrified ET cycle in our own setting. Additional studies are needed to verify this pilot data and validate its application in large randomized trials.
Highlights
Single embryo transfer (SET) has been utilized as a strategy to reduce the chance of multifetal gestations in in vitro fertilization (IVF) but lower pregnancy rate remains a concern
More and more recent studies had made us known that the ironic outcome revealed by that randomized study may be due to the limitations of the genetic tool used for Preimplantation genetic screening (PGS) itself (FISH), as well as the timing of the biopsy was set at the cleavage stage embryos (Day 3)
It is known that the biopsy timing will be better at Day 5/6 blastocyst stage instead of Day 3 cleavage-stage embryos in regard to the implantation potential [3], and this new finding creates an even more difficulty: the time span of analysis if we want to do it in fresh transfer will be shortened from days to 1 day, which rendered the analysis of array comparative genomic hybridization (aCGH)
Summary
Single embryo transfer (SET) has been utilized as a strategy to reduce the chance of multifetal gestations in in vitro fertilization (IVF) but lower pregnancy rate remains a concern. Preimplantation genetic screening (PGS) has been considered a feasible strategy, by reducing the probability of transferring the aneuploid embryos during in vitro fertilization (IVF), in improving the implantation rate as well as the livebirth rate in the practice of artificial reproductive technology (ART) for decades [1]. More and more recent studies had made us known that the ironic outcome revealed by that randomized study may be due to the limitations of the genetic tool used for PGS itself (FISH), as well as the timing of the biopsy was set at the cleavage stage embryos (Day 3). After 2007, since the emergence of many new technologies available for genetic investigation, researchers are keen to verify and validate the new tools when being used in PGS [5, 13,14,15]
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