Towards a better understanding of preimplantation genetic screening for aneuploidy: insights from a virtual trial for women under the age of 40 when transferring embryos one at a time

Scriven, Paul N.

doi:10.1186/s12958-017-0269-y

Cited by 22 publications

(19 citation statements)

References 15 publications

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“…These findings are in line with a recent virtual trial and cost analysis, which postulated a significantly higher cost per live birth and high costs for the reduction of miscarriage by PGT-A. 20 The cost-savings associated with PGT-A will obviously be driven by the costs of frozen-thawed embryo transfer…”

Section: Main Findingssupporting

confidence: 84%

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age

Neumann

Sermon

Bossuyt

et al. 2020

BJOG

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Objective What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT‐A) by polar body biopsy and array‐based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT‐A for infertility treatment in women 36–40 years of age? Design Decision tree model. Population A randomised clinical trial on PGT‐A (ESTEEM study). Methods Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT‐A. Costs and effects were analysed with this model for four different cost scenarios: high‐, higher medium, lower medium and low‐cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost‐effectiveness implications of PGT‐A. Results PGT‐A increased the cost per live birth by approximately 15% in the high‐cost scenario to approximately 285% in the low‐cost scenario. Threshold analysis revealed that PGT‐A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high‐cost scenario) to US$4,888 (low‐cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT‐A using the base case assumptions was calculated to be US$34,427 (high‐cost scenario) to US$51,146 (low‐cost scenario). A probabilistic sensitivity analysis showed cost‐effectiveness for PGT‐A from 1.9% (high‐cost scenario) to 0.0% (low‐cost scenario) of calculated samples. Conclusions While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high‐cost implications of applying PGT‐A using aCGH on polar bodies. Tweetable abstract PGT‐A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.

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Section: Main Findingssupporting

confidence: 84%

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age

Neumann

Sermon

Bossuyt

et al. 2020

BJOG

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“…Moreover, no attempts to identify effectiveness thresholds for age and number of blastocysts were made. Scriven investigated the cost-effectiveness profile of PGT-A using a complex and intricate model and failed to show any benefit (15). However, the virtual population tested was young (median age of 33, range 22-39) and no strata analyses were performed.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, the burning debate on the role of PGT-A has given limited attention to costeffectiveness considerations (14,15). This is in contrast with the current strong global commitment for equity and sustainability (16).…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness of preimplantation genetic testing for aneuploidies

Somigliana

Busnelli

Paffoni

et al. 2019

Fertility and Sterility

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Objective: To evaluate the economical benefit of preimplantation genetic testing of aneuploidies (PGT-A) when applied in an extended culture and stringent elective Single Embryo Transfer (eSET) framework. Design: Theoretical cost-effectiveness studySetting: Center with established expertise in trophectoderm biopsy for preimplantation genetic testing of monogenic disorders. Patients/Animals: NoneIntervention: Comparison of the cost-effectiveness between two IVF treatment strategies: i) serial transfer of all available blastocysts without genetic testing (first fresh transfer and subsequent frozen-thawed transfer) and ii) systematic use of genetic testing (trophectoderm biopsy, freeze all and frozen-thawed transfers of euploid blastocysts). The costs considered for this analysis are based on regional public health system provider. Main Outcome Measure: Costs per live birthResults: Cost-effectiveness profile of PGT-A improves with female age and number of available blastocysts. Sensitivity analyses varying the costs of embryo transfer, the costs of genetic analyses, the magnitude of the detrimental impact of PGT-A on live birth rate and the crude live birth rates change to some extent the thresholds for effectiveness but generally confirm the notion that PGT-A can be economically advantageous in some specific subgroups. Conclusions:PGT-A can be cost-effective in specific clinical settings and population groups.Economical considerations deserve attention in the debate regarding the clinical utility of PGT-A.

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“…The Spanish RCT found that including PGT‐A increased costs required to achieve a live birth without increasing overall chances of having a live birth . A theoretical model that evaluated cost‐effectiveness based on UK practice concluded that adding PGT‐A was unlikely to benefit most women under 40 years …”

Section: Inter‐laboratory Variability and Financial Costsmentioning

confidence: 99%

Preimplantation genetic testing for aneuploidy (PGT‐A): The biology, the technology and the clinical outcomes

Homer

2019

Aust NZ J Obst Gynaeco

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Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify preimplantation embryos with a normal chromosome complement (euploid) during in vitro fertilisation (IVF). By sifting out embryos with abnormal chromosome numbers (aneuploid), PGT-A should theoretically improve pregnancy success.However, earlier versions of PGT-A were ineffective, and in some cases, detrimental, due to biopsy-induced trauma and because the technology at the time could analyse only a fraction of all chromosomes. More recently, the emergence of technologies enabling all chromosomes to be analysed and a switch to less traumatic blastocyst-stage biopsy have seen widespread uptake of PGT-A.Assessing the full impact of blastocyst biopsy PGT-A requires consideration of multiple factors, including embryonic mosaicism, sensitivity of the technological platform used, embryo loss during long-term in vitro culture, embryo cryopreservation and inter-clinic variability in expertise. Significantly, there hasn't yet been an appropriately designed randomised controlled trial (RCT) of blastocyst biopsy PGT-A analysed by intention-to-treat that accounts for all these parameters on a per-cycle basis. The three RCTs reporting benefits studied outcomes on a per-embryo transfer basis were small and underpowered and demonstrated benefits for a very select sub-group of good prognosis patients. The liberal use of this very expensive IVF add-on for other patient populationshas not yet been shown to be effective, or indeed, without harm. K E Y W O R D Saneuploidy, embryo, in vitro fertilisation, mosaicism, next generation sequencing, PGT-A THE TECHNOLOGY: NEW AND IMPROVED PGT-AEmbryonic aneuploidy, most often arising from meiotic errors in oocytes, is the major cause of early pregnancy wastage. 1,2 While the hypothesis that pregnancy success should increase by screening out aneuploid embryos is therefore entirely plausible, the previous iteration of preimplantation genetic testing for aneuploidy (PGT-A: so-called PGS 1.0) was unsuccessful. 3 Meta-analysis of 11 randomised controlled trials (RCTs) failed to demonstrate any benefit for PGS 1.0 and indeed, found that it was detrimental for older women. 4 PGS 1.0 had shortcomings, 3,5 for instance, it involved removal of 1-2 cells from 6-8-cell cleavage-stage embryos, leading to the loss of a large proportion of cell mass (Fig. 1). In one study, implantation rates of 53% for non-biopsied cleavagestage embryos decreased to 31% post-biopsy. 6 Furthermore,

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Towards a better understanding of preimplantation genetic screening for aneuploidy: insights from a virtual trial for women under the age of 40 when transferring embryos one at a time

Cited by 22 publications

References 15 publications

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age

Cost-effectiveness of preimplantation genetic testing for aneuploidies

Preimplantation genetic testing for aneuploidy (PGT‐A): The biology, the technology and the clinical outcomes

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