Pregnancy outcomes from more than 1,800 in vitro fertilization cycles with the use of 24-chromosome single-nucleotide polymorphism–based preimplantation genetic testing for aneuploidy

Simon, Alexander L.; Kiehl, Michelle; Fischer, Erin; Proctor, J. Glenn; Bush, M.; Givens, C.; Rabinowitz, Matthew; Demko, Zachary

doi:10.1016/j.fertnstert.2018.03.026

Cited by 63 publications

(63 citation statements)

References 30 publications

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“…preimplantation genetic testing | noninvasive PGT-A | culture medium | ICSI | human blastocyst P reimplantation genetic testing for aneuploidy (PGT-A) using trophectoderm (TE) biopsy is currently the most widely used genetic test for identification of de novo aneuploidies in embryos in clinical in vitro fertilization (IVF). Despite the overall high implantation rates achieved following transfer of euploid embryos (1)(2)(3)(4), debate continues regarding the accuracy and the safety of this approach, as well as which patients and/or age groups may truly benefit with an increased probability of having a healthy live birth (5)(6)(7)(8).…”

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confidence: 99%

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

Huang

Bogale

Tang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

148

170

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Preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy is widely applied in in vitro fertilization (IVF) to identify aneuploid embryos. However, potential safety concerns regarding biopsy and restrictions to only those embryos suitable for biopsy pose limitations. In addition, embryo mosaicism gives rise to false positives and false negatives in PGT-A because the inner cell mass (ICM) cells, which give rise to the fetus, are not tested. Here, we report a critical examination of the efficacy of noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) in the spent culture media of human blastocysts by analyzing the cell-free DNA, which reflects ploidy of both the TE and ICM. Fifty-two frozen donated blastocysts with TE biopsy results were thawed; each of their spent culture medium was collected after 24-h culture and analyzed by next-generation sequencing (NGS). niPGT-A and TE-biopsy PGT-A results were compared with the sequencing results of the corresponding embryos, which were taken as true results for aneuploidy reporting. With removal of all corona-cumulus cells, the false-negative rate (FNR) for niPGT-A was found to be zero. By applying an appropriate threshold for mosaicism, both the positive predictive value (PPV) and specificity for niPGT-A were much higher than TE-biopsy PGT-A. Furthermore, the concordance rates for both embryo ploidy and chromosome copy numbers were higher for niPGT-A than TE-biopsy PGT-A. These results suggest that niPGT-A is less prone to errors associated with embryo mosaicism and is more reliable than TE-biopsy PGT-A.

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mentioning

confidence: 99%

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

Huang

Bogale

Tang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

148

170

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“…The molecular factors contributing to a developmentally competent human embryo are only beginning to be explored. It is known that even euploid embryos transferred into a normal uterus fail to implant 30%-50% of the time (Dahdouh et al 2015;Setton et al 2015;Whitehead et al 2017;Simon et al 2018). Although some of this may be because of the endometrium, other uterine pathology, and potential paternal factors, there is another possible explanation for this imperfect efficiency even when all available testing is confirmatory: the shroud of mystery surrounding the molecular events of preimplantation development, particularly those that establish embryo competence.…”

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confidence: 99%

RNA-seq as a tool for evaluating human embryo competence

et al. 2019

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The majority of embryos created through in vitro fertilization (IVF) do not implant. It seems plausible that rates of implantation would improve if we had a better understanding of molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer uses an ad hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing (RNA-seq) of embryos could yield high-dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Recent advances enabling the production of RNAseq libraries from single cells have facilitated the application of this technique to the study of transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to embryo selection procedures by generating RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for assessing embryo competence. Specifically, we show the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype and to identify candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.

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“…Simon et al reported LBR per transfer of 64.5% and per retrieval of 45.1% in 1621 non-donor frozen cycles with PGS in 2018. 29 Lee et al also reported LBR per initiated cycle of 46.3% in 82 cycles of RPL couples with PGS in 2019. 30 These data might be analysed by comprehensive chromosome testing (PGS2.0).…”

Section: Oftenmentioning

confidence: 97%

Comparison of PGS2.0 versus conventional embryo morphology evaluation for patients with recurrent pregnancy loss: a study protocol for a multicentre randomised trial

Chen

Sui

et al. 2020

BMJ Open

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IntroductionPregnancy loss (PL) is an adverse life event, and there is no proven effective treatment for recurrent PL (RPL). Preimplantation genetic screening (PGS) can be performed to reduce the risks of PL; however, there is still no solid scientific evidence that PGS improves outcomes for couples experiencing RPL. Comprehensive chromosome screening (PGS2.0) has become a routine practice in in vitro fertilisation (IVF) clinics. Previous studies based on PGS1.0 with a focus on RPL couples where the female is of advanced maternal age have reported contradictory results. Hence, a multicentre randomised trial is needed to provide evidence for the clinical benefits of PGS2.0 treatment for RPL couples.Methods and analysisOverall, 268 RPL couples undergoing IVF cycles will be enrolled. Couples will be randomised according to a unique grouping number generated by a random digital software into (1) PGS2.0 group and (2) non-PGS (conventional embryo morphology evaluation) group. This study aims to investigate whether the live birth rate (LBR) per initiated cycle after PGS2.0 is superior to the LBR per initiated cycle after conventional embryo evaluation (non-PGS group). Live birth will be defined as a live baby born after a gestation period of >28 weeks, with a birth weight of more than 1000 g. A multivariate logistic regression model will be used to adjust for confounding factors.Ethics and disseminationEthical approval has been granted by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University and the participating hospitals. Written informed consent will be obtained from each couple before any study procedure is performed. Data from this study will be stored in the Research Electronic Data Capture. The results of this trial will be presented and published via peer-reviewed publications and presentations at international conferences.Trial registration numberNCT03214185; Pre-results.

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Pregnancy outcomes from more than 1,800 in vitro fertilization cycles with the use of 24-chromosome single-nucleotide polymorphism–based preimplantation genetic testing for aneuploidy

Cited by 63 publications

References 30 publications

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

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

RNA-seq as a tool for evaluating human embryo competence

Comparison of PGS2.0 versus conventional embryo morphology evaluation for patients with recurrent pregnancy loss: a study protocol for a multicentre randomised trial

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