Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes

Bardos, Jonah; Kwal, Jaclyn; Caswell, Wayne; Jahandideh, Samad; Stratton, Melissa; Tucker, Michael; DeCherney, Alan H.; Devine, Kae; Hill, Micah J.; O’Brien, Jeanne E.

doi:10.1016/j.fertnstert.2022.10.010

Cited by 20 publications

(4 citation statements)

References 13 publications

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“…There is significant variability in PGT-A results between labs and platforms, with no industry-wide standardization currently in place. 17 Factors like methods used for biopsy preparation and the interpretation of results by clinicians could influence PGT-A results, possibly leading to differing detection rates of single versus complex aneuploidy. 18 However, for the advancement of assistive reproductive technologies in IVF, the benchmark should be hastening the time to pregnancy and enhancing live birth outcomes.…”

Section: Discussionmentioning

confidence: 99%

Automatic Ploidy Prediction and Quality Assessment of Human Blastocyst Using Time-Lapse Imaging

Rajendran,

Brendel,

Barnes

et al. 2023

Preprint

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Assessing fertilized human embryos is crucial for in vitro-fertilization (IVF), a task being revolutionized by artificial intelligence and deep learning. Existing models used for embryo quality assessment and chromosomal abnormality (ploidy) detection could be significantly improved by effectively utilizing time-lapse imaging to identify critical developmental time points for maximizing prediction accuracy. Addressing this, we developed and compared various embryo ploidy status prediction models across distinct embryo development stages. We present BELA (Blastocyst Evaluation Learning Algorithm), a state-of-the-art ploidy prediction model surpassing previous image- and video-based models, without necessitating subjective input from embryologists. BELA uses multitask learning to predict quality scores that are used downstream to predict ploidy status. By achieving an AUC of 0.76 for discriminating between euploidy and aneuploidy embryos on the Weill Cornell dataset, BELA matches the performance of models trained on embryologists’ manual scores. While not a replacement for preimplantation genetic testing for aneuploidy (PGT-A), BELA exemplifies how such models can streamline the embryo evaluation process, reducing time and effort required by embryologists.

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Section: Discussionmentioning

confidence: 99%

Automatic Ploidy Prediction and Quality Assessment of Human Blastocyst Using Time-Lapse Imaging

Rajendran,

Brendel,

Barnes

et al. 2023

Preprint

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“…Currently, PGT refers to a broad range of techniques, including fluorescence in situ hybridization (FISH) and comprehensive molecular methodologies, such as array comparative genomic hybridization (aCGH), quantitative polymerase chain reaction (qPCR), single-nucleotide polymorphism (SNP) array, and next-generation sequencing (NGS). Alongside benefits, each type of testing has limitations that inevitably contribute to a certain subset of diagnostic errors [ 1 , 2 , 3 , 4 , 5 , 6 ]. Nevertheless, the evidence of the embryo genetic constitution obtained using these methods is decisive for uterine transfer.…”

Section: Introductionmentioning

confidence: 99%

Re-Examination of PGT-A Detected Genetic Pathology in Compartments of Human Blastocysts: A Series of 23 Cases

Tikhonov,

Krapivin,

Malysheva

et al. 2024

JCM

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Background: In recent years, preimplantation genetic testing for aneuploidies (PGT-A) has become widespread in assisted reproduction. However, contrary to expectations, PGT-A does not significantly improve the clinical outcomes of assisted reproductive technologies. One of the underlying reasons is the discordance between the PGT-A results and the true chromosomal constitution of the blastocyst. In this case series, we re-examined the PGT-A results in trophectoderm (TE) re-biopsies and in the two isolated blastocyst compartments—the TE and the inner cell mass (ICM). Methods: This study enrolled 23 human blastocysts from 17 couples who were referred for assisted reproduction. The blastocysts were unsuitable for uterine transfer due to the chromosomal imbalance revealed by PGT-A using array comparative genomic hybridization (aCGH) (n = 11) or next-generation sequencing (NGS) (n = 12). The re-examination of the PGT results involved two steps: (1) a TE re-biopsy with subsequent aCGH and (2) blastocyst separation into the TE and the ICM with a subsequent cell-by-cell analysis of each isolated compartment by fluorescence in situ hybridization (FISH) with the DNA probes to chromosomes 13, 16, 18, 21, and 22 as well as to the PGT-A detected imbalanced chromosomes. Results: In 8 out of 23 cases, the PGT-A results were concordant with both the re-biopsy and the isolated TE and ICM analyses. The latter included the diagnoses of full non-mosaic aneuploidies (five cases of trisomies and two cases of monosomies). In one case, the results of PGT-A, aCGH on the TE re-biopsy, and FISH on the isolated TE showed Xp tetrasomy, which contrasted with the FISH results on the isolated ICM, where this chromosomal pathology was not detected. This case was classified as a confined mosaicism. In 4 out of 23 cases, the results were partially discordant. The latter included one case of trisomy 12, which was detected as non-mosaic by PGT-A and the re-biopsy and as mosaic by FISH on the isolated TE and ICM. This case was classified as a true mosaicism with a false negative PGT-A result. In 11 out of 23 cases, the re-examination results were not concordant with the PGT-A results. In one of these discordant cases, non-mosaic tetraploidy was detected by FISH in the isolated TE and ICM, whereas the PGT-A and the TE re-biopsy failed to detect any abnormality, which advocated for their false negative result. In two cases, the re-examination did not confirm full aneuploidies. In eight cases, full or partial mosaic aneuploidies as well as chaotic mosacism were not confirmed in the isolated TE nor the isolated ICM. Thus, in 47.8% of cases, the PGT-A results did not reflect the true chromosomal constitution of a blastocyst. Conclusions: The PGT results may have different prognostic value in the characterization of the chromosomal constitution of a blastocyst. The detected non-mosaic aneuploidies have the highest prognostic value. In stark contrast, most PGT-identified mosaic aneuploidies fail to characterize the true chromosomal constitution of a blastocyst. Once detected, a differential diagnosis is needed.

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“…In the past, aneuploidy rates for embryos derived from donor oocytes were reported to be as high as 40%–50%, a number consistent with the observation of high loss rates in early studies. However, more recently, donor egg aneuploidy rates appear to be lower, perhaps closer to 25% ( 3 ). Other laboratories report rates closer to 20% (Progenesis, personal communication).…”

mentioning

confidence: 99%

Is preimplantation genetic testing for aneuploidy (PGT-A) getting better? How can we know and how do we counsel our patients?

Paulson

2023

F&S Reports

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Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes

Cited by 20 publications

References 13 publications

Automatic Ploidy Prediction and Quality Assessment of Human Blastocyst Using Time-Lapse Imaging

Automatic Ploidy Prediction and Quality Assessment of Human Blastocyst Using Time-Lapse Imaging

Re-Examination of PGT-A Detected Genetic Pathology in Compartments of Human Blastocysts: A Series of 23 Cases

Is preimplantation genetic testing for aneuploidy (PGT-A) getting better? How can we know and how do we counsel our patients?

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