Research article

Towards a better understanding of preimplantation genetic screening and cumulative reproductive outcome: transfer strategy, diagnostic accuracy and cost-effectiveness

  • Received: 27 June 2016 Accepted: 23 September 2016 Published: 28 September 2016
  • A decision model was constructed to compare genetic testing and not testing, for the transfer of all suitable embryos, one at a time, from a cycle with up to ten embryos, until a first live birth was achieved or there were no more embryos available (a full cycle). Two strategies were investigated: (i) a fresh transfer with subsequent serial warmed cryopreserved embryo replacement, and (ii) freeze-all prior to serial embryo replacement. Sensitivity analyses were performed to assess the effect of embryo warming survival and diagnostic accuracy on cumulative rates. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio for a live birth event, and a clinical miscarriage avoided. Reproductive outcome probabilities were obtained from published prospective non-selection studies, and costs from websites and publications.
    Given 100% embryo warming survival and no false abnormal genetic test results, the live birth rate for a full cycle was the same with and without testing for both transfer strategies. Compared to not testing, it was theoretically possible for testing to be favoured for live birth only for the fresh and frozen transfer strategy, where more than one embryo was available, and dependent on the efficiency of warming survival and the positive predictive value of the test; however, this was unlikely to be cost-effective from a society perspective without a substantial reduction in genetic testing costs. For both transfer strategies, when more than one embryo was available, testing was more likely to achieve a live birth event following the first attempt with fewer attempts required overall. Testing was likely to be effective to avoid a clinical miscarriage but also to be expensive from a society perspective compared to the cost of dilation and curettage.

    Citation: Paul N. Scriven. Towards a better understanding of preimplantation genetic screening and cumulative reproductive outcome: transfer strategy, diagnostic accuracy and cost-effectiveness[J]. AIMS Genetics, 2016, 3(3): 177-195. doi: 10.3934/genet.2016.3.177

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  • A decision model was constructed to compare genetic testing and not testing, for the transfer of all suitable embryos, one at a time, from a cycle with up to ten embryos, until a first live birth was achieved or there were no more embryos available (a full cycle). Two strategies were investigated: (i) a fresh transfer with subsequent serial warmed cryopreserved embryo replacement, and (ii) freeze-all prior to serial embryo replacement. Sensitivity analyses were performed to assess the effect of embryo warming survival and diagnostic accuracy on cumulative rates. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio for a live birth event, and a clinical miscarriage avoided. Reproductive outcome probabilities were obtained from published prospective non-selection studies, and costs from websites and publications.
    Given 100% embryo warming survival and no false abnormal genetic test results, the live birth rate for a full cycle was the same with and without testing for both transfer strategies. Compared to not testing, it was theoretically possible for testing to be favoured for live birth only for the fresh and frozen transfer strategy, where more than one embryo was available, and dependent on the efficiency of warming survival and the positive predictive value of the test; however, this was unlikely to be cost-effective from a society perspective without a substantial reduction in genetic testing costs. For both transfer strategies, when more than one embryo was available, testing was more likely to achieve a live birth event following the first attempt with fewer attempts required overall. Testing was likely to be effective to avoid a clinical miscarriage but also to be expensive from a society perspective compared to the cost of dilation and curettage.


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    [1] Brezina PR, Kutteh WH (2015) Clinical applications of preimplantation genetic testing. BMJ 350: g7611.
    [2] Gardner DK, Meseguer M, Rubio C, et al. (2015) Diagnosis of human preimplantation embryo viability. Hum Reprod Update 21: 727-747. doi: 10.1093/humupd/dmu064
    [3] Capalbo A, Ubaldi FM, Cimadomo D, et al. (2016) MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment. Fertil Steril 105: 225-235. doi: 10.1016/j.fertnstert.2015.09.014
    [4] Diez-Juan A, Rubio C, Marin C, et al. (2015) Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril 104: 534-541. doi: 10.1016/j.fertnstert.2015.05.022
    [5] Fragouli E, Spath K, Alfarawati S, et al. (2015) Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet 11: e1005241. doi: 10.1371/journal.pgen.1005241
    [6] Tobler KJ, Zhao Y, Ross R, et al. (2015) Blastocoel fluid from differentiated blastocysts harbors embryonic genomic material capable of a whole-genome deoxyribonucleic acid amplification and comprehensive chromosome microarray analysis. Fertil Steril 104: 418-425. doi: 10.1016/j.fertnstert.2015.04.028
    [7] Mastenbroek S, van der Veen F, Aflatoonian, A, et al. (2011) Embryo selection in IVF. Hum Reprod 26: 964-966. doi: 10.1093/humrep/der050
    [8] Pelkonen S, Koivunen R, Gissler M, et al. (2010) Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995–2006. Hum Reprod 25: 914-923. doi: 10.1093/humrep/dep477
    [9] Wennerholm UB, Henningsen AKA, Romundstad LB, et al. (2013) Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod 28: 2545-2553. doi: 10.1093/humrep/det272
    [10] Roque M (2015) Freeze-all policy: is it time for that? J Assist Reprod Genet 32: 171-176. doi: 10.1007/s10815-014-0391-0
    [11] Wells D, Alfarawati S, Fragouli E. (2008) Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH. Mol Hum Reprod 14: 703-710. doi: 10.1093/molehr/gan062
    [12] Capalbo A, Bono S, Spizzichino L, et al. (2013) Sequential comprehensive chromosome analysis on polar bodies, blastomeres and trophoblast: insights into female meiotic errors and chromosomal segregation in the preimplantation window of embryo development. Hum Reprod 28: 509-518. doi: 10.1093/humrep/des394
    [13] Rubio C, Rodrigo L, Mir P, et al. (2013) Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results. Fertil Steril 99: 1044-1048. doi: 10.1016/j.fertnstert.2013.01.094
    [14] Scott RT Jr, Upham KM, Forman EJ, et al. (2013) Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril 100: 624-630. doi: 10.1016/j.fertnstert.2013.04.039
    [15] Gleicher N, Kushnir VA, Barad DH (2014) Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reprod Biol Endocrinol 12: 22. doi: 10.1186/1477-7827-12-22
    [16] Mastenbroek S, Repping S (2014) Preimplantation genetic screening: back to the future. Hum Reprod 29: 1846-1850. doi: 10.1093/humrep/deu163
    [17] Dahdouh EM, Balayla J, García-Velasco JA (2015) Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials. Reprod Biomed Online 30: 281-289. doi: 10.1016/j.rbmo.2014.11.015
    [18] Lee E, Illingworth P, Wilton L, et al. (2015) The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod 30: 473-483. doi: 10.1093/humrep/deu303
    [19] COGEN, Controversies in Preconception, Preimplantation and Prenatal Genetic Diagnosis: A Statement on the use of Preimplantation Genetic Screening (PGS) of chromosomes for IVF patients, 2015. Available from: http://www.ivf-worldwide.com/cogen/general/cogen-statement.html.
    [20] Scott RT Jr, Ferry K, Su J, et al. (2012) Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril 97: 870-875. doi: 10.1016/j.fertnstert.2012.01.104
    [21] Chang LJ, Huang CC, Tsai YY, et al. (2013) Blastocyst biopsy and vitrification are effective for preimplantation genetic diagnosis of monogenic diseases. Hum Reprod 28: 1435-1444. doi: 10.1093/humrep/det048
    [22] Yang Z, Liu J, Collins GS, et al. (2012) Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 5: 24. doi: 10.1186/1755-8166-5-24
    [23] Wolfson Clinic: The integrated test, 2016. Available from: http://www.wolfson.qmul.ac.uk/service-1/antenatal-screening/screening-tests/the-integrated-test.
    [24] Private Healthcare UK: Cost of private healthcare. Available from: http://www.privatehealth.co.uk/costs/.
    [25] Complete Fertility Price List, 2015. Available from: http://www.completefertility.co.uk/price_list/complete-fertility-price-list.pdf.
    [26] Bionews 825: Mitochondrial DNA test improves IVF success rates, 2016. Available from: http://www.bionews.org.uk/page.asp?obj_id=579694&PPID=580189&sid=878.
    [27] Morris S, Karlsen S, Chung N, et al. (2014) Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down’s syndrome using cell free fetal DNA in the UK National Health Service. PLoS One 9: e93559. doi: 10.1371/journal.pone.0093559
    [28] Office for National Statistics: Annual Survey of Hours and Earnings, 2014. Available from: http://www.ons.gov.uk/ons/dcp171778_385428.pdf.
    [29] NICE: Guide to the methods of technology appraisal, 2013. Available from: http://www.nice.org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-of-technology-appraisal-2013-pdf.
    [30] Uitenbroek DG: SISA-Two by two table, 2016. Available from: http://www.quantitativeskills.com/sisa/statistics/twoby2.htm.
    [31] Murugappan G, Ohno MS, Lathi RB (2015) Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss. Fertil Steril 103: 1215-1220. doi: 10.1016/j.fertnstert.2015.02.012
    [32] Maheshwari A, McLernon D, Bhattacharya S (2015) Cumulative livebirth rate: time for a consensus? Hum Reprod 30: 2703-2707.
    [33] Scriven PN, Bossuyt PM (2010) Diagnostic accuracy: theoretical models for preimplantation genetic testing of a single nucleus using the fluorescence in situ hybridization technique. Hum Reprod 25: 2622-2628.
    [34] Scriven PN, Ogilvie CM, Khalaf Y (2012) Embryo selection in IVF: is polar body array comparative genomic hybridization accurate enough? Hum Reprod 27: 951-53. doi: 10.1093/humrep/des017
    [35] Verberg MF, Eijkemans MJ, Heijnen EM, et al. (2008) Why do couples drop-out from IVF treatment? A prospective cohort study. Hum Reprod 23: 2050-2055.
    [36] McDowell S, Murray A (2011) Barriers to continuing in vitro fertilisation--why do patients exit fertility treatment? Aust N Z J Obstet Gynaecol 51: 84-90. doi: 10.1111/j.1479-828X.2010.01236.x
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  • © 2016 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
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