Non-invasive embryo selection strategy for clinical IVF to avoid wastage of potentially competent embryos

Chen, Li; Li, Wen; Liu, Yuxiu; Peng, Zhihang; Lv, Cai; Zhang, Ningyuan; Xu, Jingtao; Wang, Liang; Teng, Xiaoming; Yao, Yingshui; Ma, Menglin; Liu, Jianqiao; Lü, Sijia; Sun, Haixiang; Yao, Bing

doi:10.1016/j.rbmo.2022.03.006

Cited by 12 publications

(13 citation statements)

References 38 publications

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“…The result of NiPGT enables one to judge the potential of embryo implantation and may be used as a reference factor for the order of embryo implantation, to avoid wasting embryos due to false positivity. In addition, this result is similar to the embryo selection strategy mentioned in a previous article [ 32 ]. In this article, Chen et al established an embryo selection strategy by evaluating the probability of euploidy using culture medium to avoid wasting embryos.…”

Section: Discussionsupporting

confidence: 87%

Non-invasive preimplantation genetic testing for conventional IVF blastocysts

Xie

Zhang

et al. 2022

J Transl Med

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Background Previous studies suggested that non-invasive preimplantation genetic testing (niPGT) for intracytoplasmic sperm injection (ICSI) blastocysts can be used to identify chromosomal ploidy and chromosomal abnormalities. Here, we report the feasibility and performance of niPGT for conventional in vitro fertilization (IVF) blastocysts. Methods This was a prospective observational study. In the preclinical stage, whole genome amplification and NGS were performed using the sperm spent culture medium (SCM). Then, trophectoderm (TE) biopsies and corresponding SCM derived from 27 conventional IVF monopronuclear embryos were collected. In the clinical stage, samples from 25 conventional IVF cycles and 37 ICSI cycles from April 2020–August 2021 were collected for performance evaluation. Results Preclinically, we confirmed failed sperm DNA amplification under the current amplification system. Subsequent niPGT from the 27 monopronuclear blastocysts showed 69.2% concordance with PGT results of corresponding TE biopsies. In the clinical stage, no paternal contamination was observed in any of the 161 SCM samples from conventional IVF. While maternal contamination was observed in 29.8% (48/161) SCM samples, only 2.5% (4/161) samples had a contamination ratio ≥ 50%. Compared with that of TE biopsy, the performances of NiPGT from 161 conventional IVF embryos and 122 ICSI embryos were not significantly different (P > 0.05), with ploidy concordance rates of 75% and 74.6% for IVF and ICSI methods, respectively. Finally, evaluation of the euploid probability of embryos with different types of niPGT results showed prediction probabilities of 82.8%, 77.8%, 62.5%, 50.0%, 40.9% and 18.4% for euploidy, sex-chromosome mosaics only, low-level mosaics, multiple abnormal chromosomes, high-level mosaics and aneuploidy, respectively. Conclusions Our research results preliminarily confirm that the niPGT approach using SCM from conventional IVF has comparable performance with ICSI and might broadening the application scope of niPGT.

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Section: Discussionsupporting

confidence: 87%

Non-invasive preimplantation genetic testing for conventional IVF blastocysts

Xie

Zhang

et al. 2022

J Transl Med

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“…Furthermore, morphokinetic parameters can aid in differentiating between euploid and aneuploid embryos, despite lacking sufficient accuracy to replace the PGT-A. Morphokinetic assessment, chromosomal screening, and AI [ 60 ] may help identify euploid embryos with the highest developmental potential. On day 5, embryos with the highest probability of implantation had a CC3 between 9.7 h and 21 h [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Validation of Non-Invasive Preimplantation Genetic Screening Using a Routine IVF Laboratory Workflow

Tsai

Chang

et al. 2022

Biomedicines

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Embryo selection is needed to optimize the chances of pregnancy in assisted reproduction technology. This study aimed to validate non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) using a routine IVF laboratory workflow. Can niPGT-A combined with time-lapse morphokinetics provide a better embryo-selection strategy? A total of 118 spent culture mediums (SCMs) from 32 couples were collected. A total of 40 SCMs and 40 corresponding trophectoderm (TE) biopsy samples (n = 29) or arrested embryos (n = 11) were assessed for concordance. All embryos were cultured to the blastocyst stage (day 5 or 6) in a single-embryo culture time-lapse incubator. The modified multiple annealing and looping-based amplification cycle (MALBAC) single-cell whole genome amplification method was used to amplify cell-free DNA (cfDNA) from the SCM, which was then sequenced on the Illumina MiSeq system. The majority of insemination methods were conventional IVF. Low cfDNA concentrations were noted in this study. The amplification niPGT-A and conventional PGT-A was 67.7%. Based on this study, performing niPGT-A without altering the daily laboratory procedures cannot provide a precise diagnosis. However, niPGT-A can be applied in clinical IVF, enabling the addition of blastocysts with a better prediction of euploidy for transfer.

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“…Blastocysts will be classified into three grades from A to C according to the NICS results, with euploid probabilities of ≥0.94, 0.7–0.94 and ≤0.7 for A, B and C, respectively. In the pilot study for this trail, 30 the embryos with no result for amplification failure or non-informative results were included in grade B. The outcomes of transferring B-grade embryos were worse than A-grade embryos and better than C-grade embryos.…”

Section: Methods and Analysismentioning

confidence: 99%

“…A single blastocyst will be thawed and transferred in the preference order of A>B>C. The grading system had an area under the curve value of 0.92 and a negative predictive value of 0.93. 30 If the patients have only one blastocyst, the ni-PGT result will not be able to provide a reference for embryo selection. So randomisation and allocation will be performed when couples have ≥2 blastocysts.…”

Section: Methods and Analysismentioning

confidence: 99%

“…Moreover, no or non-informative results were neither euploidy nor aneuploidy, so these embryos were not suitable to be graded as A or C. Therefore, embryos with no result for amplification failure or non-informative results are graded B. A single blastocyst will be thawed and transferred in the preference order of A>B>C. The grading system had an area under the curve value of 0.92 and a negative predictive value of 0.93 30. If the patients have only one blastocyst, the ni-PGT result will not be able to provide a reference for embryo selection.…”

Section: Methods and Analysismentioning

confidence: 99%

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Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media: a protocol for a multicentre, double-blind, randomised controlled trial

Huang

Zeng

et al. 2022

BMJ Open

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IntroductionMorphological evaluation is used to select embryos for in vitro fertilisation. However, it does not fully reflect the implantation potential. Preimplantation genetic testing for aneuploidies (PGT-A) can detect embryonic aneuploidy, but biopsy procedure is invasive. Currently, a non-invasive PGT (ni-PGT) approach using spent medium is being evaluated. However, the clinical benefit of ni-PGT has not been clearly demonstrated. A multicentre randomised trial is needed to verify whether ni-PGT can be an new effective tool for evaluating embryos.Methods and analysisOverall, 1148 couples aged 35~42 (women) receiving in vitro fertilization–intracytoplasmic sperm injection are planned to be enrolled. Couples will be digitally randomised to (1) ni-PGT and (2) conventional morphology groups at a 1:1 treatment ratio. The primary outcome will be the ongoing pregnancy rate related to the first transfer cycle within 6 months after oocyte retrieval.Ethics and disseminationThe study protocol is approved by the Ethics Committee of Peking University Third Hospital and the participating hospitals. The results will be disseminated through international conferences and scientific journals.Trial registration numberNCT04339166.

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Non-invasive embryo selection strategy for clinical IVF to avoid wastage of potentially competent embryos

Cited by 12 publications

References 38 publications

Non-invasive preimplantation genetic testing for conventional IVF blastocysts

Non-invasive preimplantation genetic testing for conventional IVF blastocysts

Validation of Non-Invasive Preimplantation Genetic Screening Using a Routine IVF Laboratory Workflow

Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media: a protocol for a multicentre, double-blind, randomised controlled trial

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