Live Birth with or without Preimplantation Genetic Testing for Aneuploidy

Yan, Junhao; Qin, Yingying; Zhao, Han; Sun, Yun; Gong, Fei; Li, Rong; Sun, Xiaoxi; Ling, Xiufeng; Li, Hong; Hao, Cuifang; Tan, Jichun; Yang, Jing Bo; Zhu, Yi-Min; Li, Fenghua; Chen, Fan; Wei, Daimin; Lu, Juanjuan; Ni, Tianxiang; Zhou, Wei; Wu, Keliang; Gao, Yuan; Shi, Yuhua; Lu, Yao; Zhang, Ting; Wu, Wei; Ma, Xiang; Ma, Hailan; Fu, Jing; Zhang, Junqiang; Meng, Qingyu; Zhang, Heping; Legro, Richard S.; Chen, Zi‐Jiang

doi:10.1056/nejmoa2103613

Cited by 172 publications

(93 citation statements)

References 30 publications

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“…Moreover, 11 embryos (63.3%) were found to be euploid. Again, figure that is in agreement with both the STAR study [ 12 ] of patients' age 33.7 ± 3.59yrs, and the study by Yan et al [ 13 ] of patients' age 29.1 ± 3.6 yrs, with euploidy rate of good-quality blastocysts of 43.1%, and 69.8%, respectively.…”

Section: Discussionsupporting

confidence: 90%

“…These higher rates were explained and related to small sample size, and the delay between stopping to develop (Day 3) and the biopsy of the arrested embryos (Day 6), which might be the culprit of the DNA degeneration or damages. In the present study, euploidy rate in all the embryos and in the different subgroups (arrested and developing embryos) did not differ from those reported in the literature [ 12 , 13 ] in young patients, ranging between 43.1% and 69.8%. We might therefore speculate that the cause of developmental arrest is not the embryo genetic integrity, but rather other reasons, such as the culture conditions.…”

Section: Discussioncontrasting

confidence: 60%

See 1 more Smart Citation

Cleavage-stage human embryo arrest, is it embryo genetic composition or others?

Orvieto

Jonish-Grossman

Maydan

et al. 2022

Reprod Biol Endocrinol

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SummaryEmbryo transfer is a crucial step in IVF cycle, with increasing trend during the last decade of transferring a single embryo, preferably at the blastocyst stage. Despite increasing evidence supporting Day 5 blastocyst-stage transfer, the optimal day of embryo transfer remains controversial. The crucial questions are therefore, whether the mechanisms responsible to embryos arrest are embryo aneuploidy or others, and whether those embryos arrested in-vitro between the cleavage to the blastocyst stage would survive in-vivo if transferred on the cleavage-stage. We therefore aim to explore whether aneuploidy can directly contribute to embryo development to the blastocyst stage. Thirty Day-5 embryos, that their Day-3 blastomere biopsy revealed a single-gene defect, were donated by 10 couples undergoing preimplantation genetic testing treatment at our center. Affected high quality Day-3 embryos were cultured to Day-5, and were classified to those that developed to the blastocyst-stage and those that were arrested. Each embryo underwent whole genome amplification. Eighteen (60%) embryos were arrested, did not develop to the blastocyst stage and 12 (40%) have developed to the blastocyst stage. Nineteen embryos (63.3%) were found to be euploid. Of them, 12 (66.6%) were arrested embryos and 7 (58.3%) were those that developed to the blastocyst-stage. These figures were not statistically different (p = 0.644). Our observation demonstrated that the mechanism responsible to embryos arrest in vitro is not embryo aneuploidy, but rather other, such as culture conditions. If further studies will confirm that Day-5 blastocyst transfer might cause losses of embryos that would have been survived in vivo, cleavage-stage embryo transfer would be the preferred timing. This might reduce the cycle cancellations due to failure of embryo to develop to the blastocyst stage and will provide the best cumulative live birth-rate per started cycle.

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Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 60%

Cleavage-stage human embryo arrest, is it embryo genetic composition or others?

Orvieto

Jonish-Grossman

Maydan

et al. 2022

Reprod Biol Endocrinol

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“…With advances in molecular genetic techniques and improved embryo culture methods, preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS) may be a reliable method to improve embryo selection by identifying euploid embryos with normal chromosomes. However, controversy remains regarding the clinical effectiveness of PGT-A ( 5 – 7 ). A randomized controlled study suggested that PGT-A reduced the early pregnancy loss rate after the first embryo transfer ( 6 ), while a recent trial showed that PGT-A did not improve the frequency of cumulative live-birth ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Blastocyst Morphology and Developmental Rate on Euploidy and Live Birth Rates in Preimplantation Genetic Testing for Aneuploidy Cycles With Single-Embryo Transfer

Guan

Ren

et al. 2022

Front. Endocrinol.

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ObjectiveThe aim of this study was to investigate whether blastocyst morphology and developmental rate are associated with euploidy and live birth rates (LBRs) in single euploid frozen–thawed embryo transfer (FET) cycles.DesignRetrospective cohort study.MethodsThis study included 431 preimplantation genetic testing for aneuploidy (PGT-A) cycles followed by 393 FET cycles performed at our center from June 2017 to March 2021. All cycles were analyzed for euploidy based on blastocyst morphology (good, average and poor), developmental stage (day 5 and 6) and maternal age (< 35 and ≥ 35 years old). Multivariate logistic analysis models were used to identify the independent effects of conventional blastocyst morphology, developmental rate and morphological parameters (degree of blastocoele expansion, and grade of inner cell mass and trophectoderm (TE)) on LBRs.ResultsIn the group of women aged < 35 years, compared with poor-quality blastocysts, good-quality blastocysts (62.90% vs. 32.46%; odds ratio (OR) 3.163, 95% confidence interval (CI) 2.247–4.451; P < 0.001) and average-quality blastocysts (46.70% vs. 32.46%; OR 1.665, 95% CI 1.287–2.154; P < 0.001) had significantly higher euploidy rates. Additionally, day 5 blastocysts were associated with higher euploidy rates than day 6 blastocysts (49.28% vs. 35.02%; OR 1.506, 95% CI 1.191–1.903; P= 0.001). In the group of women aged ≥ 35 years, euploidy rates were also associated with blastocyst morphology, with 41.86%, 45.65% and 24.39% of good, average and poor-quality embryos, respectively, exhibiting euploidy. However, no relationship was seen between euploidy and blastocyst developmental rate. Multiple logistic regression analysis show that overall blastocyst morphology of euploid embryos was not associated with LBR, only embryos with A-grade TE had significantly higher LBRs than those with C-grade TE (62.71% vs. 45.40%; OR 2.189, 95% CI 1.166–4.109; P=0.015). Similarly, LBRs were significantly higher when day 5 blastocysts were transferred than when day 6 blastocysts were transferred (57.75% vs. 41.67%; OR 2.132, 95% CI 1.370–3.318; P = 0.001).ConclusionPoor-quality embryos have reduced rates of euploidy. However, blastocyst developmental rate only significantly associates with euploidy rates in women aged younger than 35. Furthermore, only TE grade and blastocyst developmental rate are significantly associated with LBRs following FET cycles.

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“…These results suggest that this euploid prediction model despite having good performance may not be useful in accurately determining the aneuploidy (due to low specificity). However, a recent study has demonstrated a comparable cumulative live birth rate in women undergoing conventional IVF and PGT-A, indicating PGT-A may potentially encourage the waste of healthy embryos [ 26 ]. As the goal of PGT-A is to select the best quality embryos for transfer, the high sensitivity of selecting euploid will decrease embryo waste.…”

Section: Discussionmentioning

confidence: 99%

Nomogram based on clinical and laboratory characteristics of euploid embryos using the data in PGT-A: a euploid-prediction model

Liu

2022

BMC Pregnancy Childbirth

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Background The evaluation of embryo morphology may be inaccurate. A euploid prediction model is needed to provide the best and individualized counseling about embryo selection based on patients and embryo characteristics. Methods Our objective was to develop a euploid-prediction model for evaluating blastocyst embryos, based on data from a large cohort of patients undergoing pre-implantation genetic testing for aneuploidy (PGT-A). This retrospective, single-center cohort study included data from 1610 blastocysts which were performed PGT-A with known genetic outcomes. The study population was divided into the training and validation cohorts in a 3:1 ratio. The performance of the euploid-prediction model was quantified using the area under the receiver operating characteristic (ROC) curve (AUC). In addition, a nomogram was drawn to provide quantitative and convenient tools in predicting euploid. Results We developed a reliable euploid-prediction model and can directly assess the probability of euploid with the AUC (95%CI) of 0.859 (0.834,0.872) in the training cohort, and 0.852 (0.831,0.879) in the validation cohort, respectively. The euploid-prediction model showed sensitivities of 0.903 and specificities of 0.578. Conclusions The euploid-prediction model is a reliable prediction model and can directly assess the probability of euploid.

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Live Birth with or without Preimplantation Genetic Testing for Aneuploidy

Cited by 172 publications

References 30 publications

Cleavage-stage human embryo arrest, is it embryo genetic composition or others?

Cleavage-stage human embryo arrest, is it embryo genetic composition or others?

Effect of Blastocyst Morphology and Developmental Rate on Euploidy and Live Birth Rates in Preimplantation Genetic Testing for Aneuploidy Cycles With Single-Embryo Transfer

Nomogram based on clinical and laboratory characteristics of euploid embryos using the data in PGT-A: a euploid-prediction model

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