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Journal of Assisted Reproduction and Genetics
Erschienen in: Journal of Assisted Reproduction and Genetics 9-10/2009

01.10.2009 | Genetics

Quantitative decision-making in preimplantation genetic (aneuploidy) screening (PGS)

verfasst von: Michael C. Summers, Andrew D. Foland

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 9-10/2009

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Abstract

Purpose

To analyze using hypergeometric probability statistics the impact of performing preimplantation genetic screening (PGS) on a cohort of day 3 cleavage stage embryos.

Methods

Statistical mathematical modeling.

Results

We find the benefit of performing PGS is highly dependent on the number of day 3 embryos available for biopsy. Additional hidden variables that determine the outcome of PGS are the rates of aneuploidy and mosaicism, and the probability of a chromosomally mosaic embryo to test “normal”. If PGS is performed, our analysis shows that many combinations of the number of biopsiable embryos, and the rates of aneuploidy and mosaicism results in a marginal benefit from the intervention. Other combinations are detrimental if PGS is actually undertaken. Finally, increases in PGS error rates lead to a rapid loss in the ability of PGS to provide useful discriminatory information.

Conclusion

We set out the statistical framework to determine the limits of PGS when a specific number of day 3 preimplantation embryos are available for biopsy. In general, PGS cannot be recommended a priori for a specific clinical situation due to the statistical uncertainties associated with the different hidden variable quantitative parameters considered important to the clinical outcome.
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Literatur
1.
Munné S, Grifo J, Cohen J, Weier H. Chromosome abnormalities in human arrested preimplantation embryos: a multiple probe FISH study. Am J Hum Genet. 1994;55:150–9.PubMed
2.
Munné S, Daily T, Sultan KM, Cohen J. The use of fist polar bodies for preimplantation diagnosis of aneuploidy. Mol Hum Reprod. 1995;10:1014–20.
3.
Munné S, Marquez C, Reing A, Garrisi J, Alikani M. Chromosome abnormalities in embryos obtained after conventional in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 1998;69:904–8.CrossRefPubMed
4.
Munné S, Magli C, Bahce M, Fung J, Legator M, Morrison L, et al. Preimplantation diagnosis of the aneuploidies most commonly found in spontaneous abortions and live births: XY, 13, 14, 15, 16, 18, 21, 22. Prenat Diagn. 1998;18:1459–66.CrossRefPubMed
5.
Harper JC, Dawson K, Delhanty JDA, Winston RML. The use of fluorescent in-situ hybridization (FISH) for analysis of in-vitro fertilization embryos: a diagnostic tool for the infertile couple. Hum Reprod. 1995;10:3255–8.PubMed
6.
Magli MC, Gianaroli L, Ferraretti AP. Chromosomal abnormalities in embryos. Mol Cell Endocrinol. 2001;183:S29–34.CrossRefPubMed
7.
Abdelhadi I, Colls P, Sandalinas M, Escudero T, Munné S. Preimplantation genetic diagnosis of numerical abnormalities for 13 chromosomes. Repro Biomed Online. 2003;6:226–31.
8.
Fritz MA. Perspectives on the efficacy and indications for preimplantation screening: where are we now? Hum Reprod. 2008;23:2617–21.CrossRefPubMed
9.
Munné S, Lee A, Rozenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8:2185–91.PubMed
10.
Munné M, Magli C, Cohen J, Morton P, Sadowy S, Gianaroli L, et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod. 1999;14:2191–9.CrossRefPubMed
11.
Munné S, Mireia S, Escudero T, Velilla E, Walmsley R, Sadowy S, et al. Improved implantation after preimplantation genetic diagnosis of anueploidy. Repro Biomed Online. 2003;7:91–7.
12.
Gianaroli L, Magli C, Ferraretti AP, Munné S. Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed. Fertil Steril. 1999;72:837–44.CrossRefPubMed
13.
Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod. 2004;19:2849–58.CrossRefPubMed
14.
Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, et al. In vitro fertilization with preimplantation screening. N Engl J Med. 2007;357:9–17.CrossRefPubMed
15.
16.
Wilton LJ. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:1770.PubMed
17.
Handyside A, Thornhill AR. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:1770.PubMed
18.
Cohen J, Wells D, Munné S. Removal of 2 cells from cleavage stage embryos is likely to reduce the efficacy of chromosomal tests that are used to enhance implantation rates. Fertil Steril. 2007;87:496–503.CrossRefPubMed
19.
Munné S, Cohen J, Simpson JL. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:1769–70.CrossRefPubMed
20.
Munné S, Gianaroli L, Tur-Kaspa I, Magli C, Sandalinas M, Grifo J, et al. Substandard application of preimplantation genetic screening may interfere with its clinical success. Fertil Steril. 2007;88:781–4.CrossRefPubMed
21.
Munné S, Wells D, Cohen J. Technology requirements for preimplantation genetic diagnosis to improve assisted reproduction outcomes. Fertil Steril. 2009; Article in press.
22.
Simpson JL. What next for preimplantation genetic screening? Randomized clinical trial in assessing PGS: necessary but not sufficient. Hum Reprod. 2008;23:2179–81.CrossRefPubMed
23.
Hadarson T, Hanson C, Lundin K, Hillensjo T, Nilsson L, Stevic J, et al. Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate. Hum Reprod. 2008;23:2806–12.CrossRef
24.
Staessen C, Verpoest W, Donoso P, Haentjens P, Van der Elst J, Liebaers I, et al. Pre-implantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer. Hum Reprod. 2008;23:2818–25.CrossRefPubMed
25.
Jansen RPS, Bowman MC, de Boer KA, Leigh DA, Lieberman DB, McArthur SJ. What next for preimplantation genetic screening (PGS)? Experience with blastocyst biopsy and testing for aneuploidy. Hum Reprod. 2008;23:1476–8.CrossRefPubMed
26.
Mersereau JE, Pergament E, Xhang X, Milad MP. Preimplantation genetic screening to improve in vitro fertilization pregnancy rates: a prospective randomized controlled trial. Fertil Steril. 2008;90:1287–9.CrossRefPubMed
27.
Shahine LK, Cedars MI. Preimplantation genetic diagnosis does not increase pregnancy rates in patients at risk for aneuploidy. Fertil Steril. 2006;85:51–6.CrossRefPubMed
28.
Donoso P, Staessen C, Fauser BCLM, Devroey P. Current value of preimplantation genetic aneuploidy screening in IVF. Hum Reprod Update. 2007;13:15–25.CrossRefPubMed
29.
Gleicher N, Weghofer A, Barad D. Preimplantation genetic screening: “established” and ready for prime time? Fertil Steril. 2008;89:780–8.CrossRefPubMed
30.
Yakin K, Urman B. What next for preimplantation genetic screening? A clinician’s perspective. Hum Reprod. 2008;23:1686–90.CrossRefPubMed
31.
Goossens V, Harton G, Moutou PN, Traeger-Synodinos J, Sermon K, Harper JC. ESHRE PGD Consortium data collection VIII: cycles from January to December 2005 with pregnancy follow-up to October 2006. Hum Reprod. 2008;23:2629–45.CrossRefPubMed
32.
Harper JC, Sermon K, Geraedts J, Vesela K, Harton G, Thornhill A, et al. What next for preimplantation genetic screening? Hum Reprod. 2008;23:478–80.CrossRefPubMed
33.
Fauser BCJM. Preimplantation genetic screening: the end of an affair? Hum Reprod. 2008;23:2622–5.CrossRefPubMed
34.
Mastenbroek S, Scriven P, Twisk M, Vivelle S, Van der Veen F, Repping S. What next for preimplantation screening? More randomized controlled trials needed? Hum Reprod. 2008;23:2626–8.CrossRefPubMed
35.
Hodges JL, Lehman EL. Basic concepts of probability and statistics. Philadelphia: Society for Industrial and Applied Mathematics; 2004. p. 173–7.
36.
Alikani M, Calderon G, Tomkin G. Cleavage anomalies in early human embryos and survival after prolonged culture in vitro. Hum Reprod. 2000;15:2634–43.CrossRefPubMed
37.
Racowsky C, Jackson KV, Cekleniak NA, Fox JH, Hornstein MD, Ginsburg AS. The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer. Fertil Steril. 2000;73:558–64.CrossRefPubMed
38.
Racowsky C, Combelles CMH, Nureddin A, Pan Y, Finn A, Miles L, et al. Day 3 and day 5 morphologic predictors of embryo viability. Repro Biomed Online. 2003;6:323–31.
39.
Goossens V, De Ryke D, De Vos A, Staessen C, Michiels A, Verpoest W, et al. Diagnostic efficiency, embryonic development and clinical outcome after the biopsy of one or two blastomeres for preimplantation genetic diagnosis. Hum Reprod. 2008;23:481–92.CrossRefPubMed
40.
Debrock S, Melotte C, Spiessens C, Peeraer K, Vanneste E, Meeuwis L, et al. Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at last 35 years: a prospective randomized trial. Fertil Steril. 2009; Article in press.
41.
Schoolcraft WB, Katz-Jaffe MG, Stevens J, Rawlins M, Munné S. Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial. Fertil Steril. 2009;92:157–62.CrossRefPubMed
42.
Miller KA, Li X, Lambrese K, Su J, Treff N, Scott RT. Blastocyst formation rates in chromosomally normal versus abnormal embryos as analyzed by 24 chromosome microarray-based aneuploidy screening (MPGD). Fertil Steril. 2008;90(suppl 1):S346.CrossRef
43.
Papanikolaou EG, D’haeseleer E, Verheyen G, Van de Velde H, Camus M, Van Steirteghem A, et al. Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day of embryo culture. A randomized prospective study. Hum Reprod. 2005;20:3198–203.CrossRefPubMed
44.
Delhanty JDA. Mechanisms of aneuploidy induction in human oogenesis in early development. Cytogenet Genome Res. 2005;111:237–44.CrossRefPubMed
45.
Wells D, Delhanty JDA. Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization. Mol Hum Reprod. 2000;6:1055–62.CrossRefPubMed
46.
Voullaire L, Slater H, Williamson R, Wilton L. Chromosome analysis of blastomeres from human embryos by using comparative genomic hybridization. Hum Genet. 2000;106:210–7.CrossRefPubMed
47.
The Preimplantation Genetic Diagnosis International Society (PGDIS). Guidelines for good practice PGD: programme requirements and laboratory quality assurance. Repro Biomed Online. 2008;16:134–47.CrossRef
48.
Los JF, Van Opstal D, van der Berg C. The development of cytogenetically normal, abnormal and mosaic embryos: a theoretical model. Hum Reprod Update. 2004;10:79–94.CrossRefPubMed
49.
Delhanty JDA, Handyside A. The origin of genetic defects in man and their detection in the preimplantation embryo. Hum Reprod Update. 1995;1:201–15.CrossRefPubMed
50.
Handyside A, Delhanty JDA. Preimplantation genetic diagnosis: strategies and surprises. Trends Genet. 1997;13:270–5.CrossRefPubMed
51.
Delhanty JDA, Harper JC, Ao A, Handyside A, Winston RML. Multi-colour FISH detects chromosomal mosaicism and chaotic division in normal pre-implantation embryos from fertile patients. Hum Genet. 1997;99:755–60.CrossRefPubMed
52.
Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Chromosome mosaicism in day 3 embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15:1781–6.CrossRefPubMed
53.
Bielanska M, Tan SL, Ao A. Chromosomal mosaicism throughout human preimplantation development in vitro: incidence, type and relevance to embryo outcome. Hum Reprod. 2002;17:413–9.CrossRefPubMed
54.
Sandalinas M, Sadowy S, Alikani M, Calderon G, Cohen J, Munné S. Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage. Hum Reprod. 2001;16:1954–8.CrossRefPubMed
55.
Fragouli E, Lenzi M, Ross R, Katz-Jaffe M, Schoolcraft WB, Wells D. Comprehensive molecular analysis of the human blastocyst stage. Hum Reprod. 2008;23:2596–608.CrossRefPubMed
56.
Hernandez ER. What next for preimplantation genetic screening? Beyond aneuploidy. Hum Reprod. 2009;24:1538–41.CrossRefPubMed
57.
Huang A, Adusumalli J, Patel S, Liem J, Williams J, Pisarska MD. Prevalence of chromosomal mosaicism in pregnancies with infertility. Fertil Steril. 2009;91:2355–1260.CrossRefPubMed
58.
The Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine. Preimplantation genetic testing: a practice committee opinion. Fertil Steril. 2007;88:1497–504.CrossRef
Metadaten
Titel
Quantitative decision-making in preimplantation genetic (aneuploidy) screening (PGS)
verfasst von
Michael C. Summers
Andrew D. Foland
Publikationsdatum
01.10.2009
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 9-10/2009
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-009-9352-4

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