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Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study.

Yang Z, Lin J, Zhang J, Fong WI, Li P, Zhao R, Liu X, Podevin W, Kuang Y, Liu J - BMC Med Genomics (2015)

Bottom Line: The NGS results were then compared with those of aCGH.Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05).With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

View Article: PubMed Central - PubMed

Affiliation: ZytoGen Global Genetics Institute, Timonium, MD, USA. sunmiy31@hotmail.com.

ABSTRACT

Background: Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening.

Methods: This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups.

Results: NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05).

Conclusions: While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

No MeSH data available.


Related in: MedlinePlus

Comparison of morphokinetic parameters of the early stages of embryonic development between NGS (red) and aCGH (blue) groups. t2 = time from insemination to 2 cells; t3 = time from insemination to 3 cells; t5 = time from insemination to 5 cells; cc2 = time between division to 2 cells and division to 3 cells; s2 = time between division to 3 cells and subsequent division to 4 cells; hpi = hours post insemination. Morphokinetic data were presented as mean ± SD. There were no significant differences in each of the morphokinetic parameters between NGS and aCGH groups (p >0.05, by Mann–Whitney test)
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Fig5: Comparison of morphokinetic parameters of the early stages of embryonic development between NGS (red) and aCGH (blue) groups. t2 = time from insemination to 2 cells; t3 = time from insemination to 3 cells; t5 = time from insemination to 5 cells; cc2 = time between division to 2 cells and division to 3 cells; s2 = time between division to 3 cells and subsequent division to 4 cells; hpi = hours post insemination. Morphokinetic data were presented as mean ± SD. There were no significant differences in each of the morphokinetic parameters between NGS and aCGH groups (p >0.05, by Mann–Whitney test)

Mentions: The most predictive morphokinetic parameters that were highly correlated with implantation [50, 51] were compared between the two study groups (Fig. 5). There were no significant differences in the time from insemination to 5 cells (t5) between Group A and Group B (50.2 ± 4.5 hpi vs. 50.4 ± 4.7 hpi, respectively, p >0.05). The time between division to 2 cells and division to 3 cells (cc2) was similar in the two groups (11.3 ± 1.1 hpi vs. 11.2 ± 1.2 hpi, respectively, p >0.05). Moreover, the time between division to 3 cells and subsequent division to 4 cells (s2) was also comparable between the two study groups (0.78 ± 0.68 hpi vs. 0.77 ± 0.69 hpi, respectively, p >0.05).Fig. 5


Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study.

Yang Z, Lin J, Zhang J, Fong WI, Li P, Zhao R, Liu X, Podevin W, Kuang Y, Liu J - BMC Med Genomics (2015)

Comparison of morphokinetic parameters of the early stages of embryonic development between NGS (red) and aCGH (blue) groups. t2 = time from insemination to 2 cells; t3 = time from insemination to 3 cells; t5 = time from insemination to 5 cells; cc2 = time between division to 2 cells and division to 3 cells; s2 = time between division to 3 cells and subsequent division to 4 cells; hpi = hours post insemination. Morphokinetic data were presented as mean ± SD. There were no significant differences in each of the morphokinetic parameters between NGS and aCGH groups (p >0.05, by Mann–Whitney test)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4477308&req=5

Fig5: Comparison of morphokinetic parameters of the early stages of embryonic development between NGS (red) and aCGH (blue) groups. t2 = time from insemination to 2 cells; t3 = time from insemination to 3 cells; t5 = time from insemination to 5 cells; cc2 = time between division to 2 cells and division to 3 cells; s2 = time between division to 3 cells and subsequent division to 4 cells; hpi = hours post insemination. Morphokinetic data were presented as mean ± SD. There were no significant differences in each of the morphokinetic parameters between NGS and aCGH groups (p >0.05, by Mann–Whitney test)
Mentions: The most predictive morphokinetic parameters that were highly correlated with implantation [50, 51] were compared between the two study groups (Fig. 5). There were no significant differences in the time from insemination to 5 cells (t5) between Group A and Group B (50.2 ± 4.5 hpi vs. 50.4 ± 4.7 hpi, respectively, p >0.05). The time between division to 2 cells and division to 3 cells (cc2) was similar in the two groups (11.3 ± 1.1 hpi vs. 11.2 ± 1.2 hpi, respectively, p >0.05). Moreover, the time between division to 3 cells and subsequent division to 4 cells (s2) was also comparable between the two study groups (0.78 ± 0.68 hpi vs. 0.77 ± 0.69 hpi, respectively, p >0.05).Fig. 5

Bottom Line: The NGS results were then compared with those of aCGH.Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05).With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

View Article: PubMed Central - PubMed

Affiliation: ZytoGen Global Genetics Institute, Timonium, MD, USA. sunmiy31@hotmail.com.

ABSTRACT

Background: Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening.

Methods: This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups.

Results: NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05).

Conclusions: While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

No MeSH data available.


Related in: MedlinePlus