Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial

Verpoest, Willem; Staessen, Cathérine; Bossuyt, Patrick M.; Goossens, V.; Altarescu, Gheona; Bonduelle, M.; Devesa, Martha; Eldar‐Geva, Talia; Gianaroli, Luca; Griesinger, G.; Kakourou, Georgia; Kokkali, Georgia; Liebenthron, Jana; Magli, Maria-Cristina; Parriego, M; Schmutzler, A. G.; Tobler, Monica; Ven, Katrin van der; Geraedts, J. P. M.; Sermon, Karen

doi:10.1093/humrep/dey262

Cited by 128 publications

(73 citation statements)

References 37 publications

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“…ESTEEM involved 396 patients aged 36–40 years with good ovarian reserve and tested whether PGT‐A by PBB would improve the chances of a live birth within 1 year. Both groups achieved the same pregnancy rate (24%) and PGT‐A did not shorten the time to pregnancy . However, PGT‐A reduced miscarriage from 14% to 7% ( P = 0.02) and increased the number of SETs (19% vs 56%; P < 0.001) with a corresponding trend toward reduced twins …”

Section: Pgt‐a Outcomes By Intention‐to‐treat Analysesmentioning

confidence: 86%

“…More recently, results of the ESTEEM (the ESHRE Study into the Evaluation of oocyte Euploidy by Microarray analysis) trial based on polar body biopsy (PBB) were reported . ESTEEM was a multicentre trial involving nine centres in seven countries in Europe and Israel having experience in PBB . ESTEEM involved 396 patients aged 36–40 years with good ovarian reserve and tested whether PGT‐A by PBB would improve the chances of a live birth within 1 year.…”

Section: Pgt‐a Outcomes By Intention‐to‐treat Analysesmentioning

confidence: 99%

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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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Section: Pgt‐a Outcomes By Intention‐to‐treat Analysesmentioning

confidence: 86%

Section: Pgt‐a Outcomes By Intention‐to‐treat Analysesmentioning

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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“…However, fewer embryo transfers were required following aneuploidy screening, and fewer miscarriages occurred to achieve the same LBR as the control group. Of note, 24 % of patients in the PBB group had no fresh embryo transfer after ART while in the control group this figure was only 7 % [11].…”

Section: Introductionmentioning

confidence: 92%

An Economic Analysis of Aneuploidy Screening of Oocytes in Assisted Reproduction in Germany

Neumann

Griesinger

2020

Geburtshilfe Frauenheilkd

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ABSTR AC T Background The randomized ESTEEM trial reported that preimplantation genetic aneuploidy testing of oocytes by polar body biopsy (PGT-A) with array comparative genomic hybridization (aCGH) in women aged 36-40 years undergoing assisted reproduction treatment reduces the number of embryo transfers and the risk of miscarriage while not impacting the live birth rate.Method A decision tree model based on data from the ESTEEM trial was created and analyzed, using three cost scenarios for assisted reproduction treatment in Germany (statutory health insurance [GKV] = the deductible is 50 % of the standard medical costs; private medical insurance [PKV] = invoicing is based on the German medical fee schedule [GOÄ]; private medical insurance with a simple GOÄ factor [simple GOÄ factor] = invoicing is based on the standard medical fees multiplied by a linear GOÄ factor). The scenarios were compared for cost-effectiveness (cost per live birth), cost per prevented miscarriage and the threshold values for cost and effectiveness.Results PGT-A increased the costs per live birth in all scenarios (GKV: + 208 %; PKV: + 49 %; simple GOÄ factor: + 89 %). A threshold analysis showed a substantial cost discrepancy between the actual cost of the intervention based on GOÄ (€ 5801) vs. the theoretically tolerable PGT-A cost (GKV: € 561, PKV: € 1037, single GOÄ-factor: € 743). The incremental cost per one prevented miscarriage was approximately € 70 000-75 000 for all cost scenarios. Conclusion The use of PGT-A with aCGH in assisted reproduction cannot be recommended from a cost-effectiveness perspective. ZUSAMMENFASSUNG Hintergrund Die ESTEEM-Studie zeigte, dass eine Aneuploidieuntersuchung von Eizellen durch Polkörperbiopsie (PKD) und array comparative genomic hybridization (aCGH) Diagnostik im Rahmen einer assistierten Reproduktion bei Frauen im Alter von 36 bis 40 Jahren die Lebendgeburtsrate nicht steigert, jedoch die Anzahl von Behandlungszyklen mit Embryoübertragung und das Abortrisiko verringert.

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“…This largely results from the fact that the original trials did not report the cumulative live birth rate, but instead reported the live birth rate per fresh transfer. The recently published ESTEEM (The ESHRE study into the evaluation of oocyte euploidy by microarray analysis) trial selected embryos based on the PGT‐A results of a first and second polar biopsy using comprehensive chromosome screening, and showed that this method did not increase the cumulative live birth rate . Nevertheless, these embryo selection techniques have been used widely in clinical practice before solid evidence was available.…”

Section: Limitations Of the Evidence On Embryo Selection Techniquesmentioning

confidence: 99%

Single embryo transfer with frozen transfer of all remaining embryos without further embryonic testing should be the standard of care in IVF

Kemper

Wang

Vuong

et al. 2018

BJOG

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Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial

Abstract: 25 June 2012.

Cited by 128 publications

References 37 publications

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

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

An Economic Analysis of Aneuploidy Screening of Oocytes in Assisted Reproduction in Germany

Single embryo transfer with frozen transfer of all remaining embryos without further embryonic testing should be the standard of care in IVF

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