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Papers and podcasts

24 chromosome aneuploidy screening is rapidly evolving. The following is a list of the key publications in the field, literature involving 24sure and links to podcasts of interest.

Please also download our 24sure publication booklet, or contact us for a print version.

 

To help navigate through the publications please use the links below:

Aneuploidy PGS in polar body (24,21,13,12,2) or trophectoderm biopsy (19,6)

Translocation PGD in polar body (15,3), blastomere biopsy (23,20) or trophectoderm biopsy (25,15)

Validation of 24sure technology in polar body (11,10), blastomere biopsy (22,17,8,4) or trophectoderm biopsy (18,16,14,9,7,5)

 

Assessment of 19,803 paired chromosomes and clinical outcome from first 150 cycles using array CGH of the first polar body for embryo selection and transfer

Fishel S, Craig A, Lynch C, Dowell K, Ndukwe G, Jenner L, Cater E, Brown A, Gordon A, Thornton S, Campbell A, Berrisford K, Kellam L, Sedler M.

J Fertiliz In Vitro 2011 1:101

  • This paper from CARE Fertility group, led by Simon Fishel, presents their experience of using 24sure on polar bodies since 2008 when they first assessed arrayCGH aneuploidy screening and achieved a live birth following use of the technology, see below.
  • They conclude that arrayCGH was proven to generate robust chromosome information and to generate improved implantation rates in women with very poor prognosis.

 

A review of PGS for IVF was recently published, written by the CARE Fertility Group in Nottingham.

A new era of PGS for IVF - will it yield the anticipated improved efficiency?

Fishel, S., Thornton, S., Dowell, K.

J. Fertiliz In Vitro 2011, 1:1

 

There were a large number of presentations and posters that used 24sure at the ASRM 2011 meeting held in Orlando in October 2011. This collection of work really shows the impact on outcomes following aneuploidy screening. Abstracts from the meeting are published in Fertility and sterility. Some of these talks are available to view at www.cytochip.com/presentations (log in required).

[O-74] FISH reanalysis of inner cell mass and trophectoderm samples of previously arrayCGH screened blastocysts reveals high accuracy of diagnosis and no sign of mosaicism or preferential allocation. A. Capalbo et al.

[O-76] Significant decrease in miscarriages after preimplantation genetic diagnosis (PGD) for recurrent pregnancy loss using array comparative genome hybridization (arrayCGH). J. Grifo, et al.

[O-83] 24 chromsome analysis of products of conception specimens by arrayCGH allows for more results than conventional karyotyping and allows for simultaneous maternal cell contaminations analysis. J. Sanchez, et al.


[O-88] Are patients undergoing PGD for chromosome rearrangements at increased risk of aneuploidy affecting chromosomes unrelated to their rearrangement (interchromosomal effect)?
S. Alfarawati et al.

[O-183] Implantation of euploid blastocysts, assessed by array comparative genomic hybridization (aCGH), in unstimulated cycles is not correlated with maternal age.
G. Harton, et al.

[O-198] Efficiency of preimplantation genetic screening (PGS) using arrayCGH compared to matched control IVF patient populations with and without day 3 PGS FISH.
A. Capalbo, et al.

[O-205] Chromosome breakage in oocytes and embryos: assessment of frequency, origin and clinical relevance of genetic instability during preimplantation development
D. Wells, et al.

[O-209] The progress of chromosome abnormalities from meiosis to the blastocyst stage.
E. Fragouli, et al.


[P-396] PGD via array comparative genome hybridization (aCGH) can be used for any translocation to simultaneously detect unbalanced embryos and aneuploidy. P. Colls, et al.

[P-406] Chromosomal mosaicism in day 3 embryos from young, successful art patients as determined by array comparative genomic hybridization (CGH). L. J. Wilton, Preimplantation Genetics, Melbourne IVF

[P-473] Analysis of 4795 day 3 embryos by array comparative genome hybridization (aCGH): aneuploidy patterns. S. Munne, etal. Reprogenetics, Livingston, NJ

 

Two papers were recently published that included data from the ESHRE PGS taskforce proof of principle trial - currently free full text articles.

Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results

Geraedts J, Montag M, Magli MC, Repping S, Handyside A, Staessen C, Harper J, Schmutzler A, Collins J, Goossens V, van der Ven H, Vesela K, Gianaroli L.

Hum Reprod. 2011 Sep 15. [Epub ahead of print]

Polar body array CGH for prediction of the status of the corresponding oocyte. Part II: technical aspects.

Magli MC, Montag M, Köster M, Muzi L, Geraedts J, Collins J, Goossens V, Handyside AH, Harper J, Repping S, Schmutzler A, Vesela K, Gianaroli L.

Hum Reprod. 2011 Sep 9. [Epub ahead of print]

 

ESHRE's publication 'Focus on Reproduction', September issue, is an interesting read with a number of references to the upcoming polar body arrayCGH RCT trial and 24sure. Click here to download the issue, check out pages 12,32 and 34.

 

A number of abstracts and posters presented at the recent ESHRE 2011 conference in Stockholm used 24sure and 24sure related products. The abstract book is available for download from the ESHRE website.

O-250 PGD for translocations using array comparative genome hybridization. P. Colls et al., Reprogenetcs, Livingston, USA.

P-407 Maternal meiosis 1 errors detected by array comparative genomic hybridisation of first polar bodies correlate with poor embryo quality. C.S. Ottolini et al., University of Kent, University of Leeds and The Bridge Centre, London, UK.

P-430 Clinical application of array comparative genomic hybridization in preimplantation genetic diagnosis for reciprocal and robertsonian translocations. F. Fiorentino et al., Genoma, Rome, Italy

P-432 Successful clinical application of arrayCGH for 24 chromosome aneuploidy on day 3 preimplantation embryos: high efficiency and reliability. L. Rodrigo et al., Institut Universitari - IVI Valencia, Spain.

 

Array comparative genomic hybridisation on first polar bodies suggests that non-disjunction is not the predominant mechanism leading to aneuploidy in humans

Gabriel AS, Thornhill AR, Ottolini CS, Gordon A, Brown AP, Taylor J, Bennett K, Handyside A, Griffin DK

J Med Genet. 2011 Jul;48(7):433-7. Epub 2011 May 26.

  • Here the question of whether aneuploidy arises from non-disjunction (whole chromosome segregation errors) or through precocious separation (sister chromatid segregation errors) is addressed with the use of 24sure. 
  • They conclude that most anueploidy arises from sister chromatid separation errors (92% vs 8%). 
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PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization

Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L, Ubaldi FM, Iammarrone E, Gordon A, Pantos K.

Hum Reprod. 2011 Jul;26(7):1925-35. Epub 2011 Apr 12

  • This paper uses 24sure+ to detect translocations in day 3 embryos, balanced embryos were then selected for transfer on day 5 of the same cycle. Of 200 embryos analysed from 24 couples, 93.5% were successfully diagnosed. 16% of embryos were found to be normal/balanced for all chromosomes, 17.1% had the translocation and normal for aneuploidy on other chromosomes, 39.6% had the translocation and anueploidy, 27.3% were normal or balanced for the expected translocation, but had aneuploidy on other chromosomes.
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  • Embryos suitable for transfer were identified in 17 cycles (60.7%). 12 couples achieved clinical pregnancy (70.6% per embryo transfer) with a total of 14 embryos implanted (63.6% per transferred embryo).
    •

 

A number of abstracts and posters presented at the recent PCRS conference in Palm Springs used 24sure and 24sure related products. Abstracts from the meeting are published by Fertility and Sterility (vol 94(4) S1).

O-6 Implantation and miscarriage rates following arrayCGH analysis at the cleavage and blastocyst stages. G. Harton et al.

P-35 Reanalysis of monosomic embryos at the blastocyst stage following day 3 biopsy and array comparative genomic hybridization (aCGH). P. Colls et al.

P-36 Aneuploidy patterns in 3143 day-3 embryos analyzed by array CGH. S. Munne et al.

P-42 Trophectoderm cells derived from blastocyst biopsy are suitable for array CGH analysis of 24 chromosomes. Z. Yang et al.

 

First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis

Alfarawati S, Fragouli E, Colls P, Wells D.

Human Reprod. 2011 Jun;26(6):1560-74. Epub 2011 Mar 29

  • Conventional CGH and arrayCGH was applied to polar bodies, cleavage-stage embryos and blastocysts to assess the chromosomes of embryos from 16 patients known to be carriers of reciprocal or Robertsonian translocations or inversions. Results were obtained for 121 out of 132 samples (91.7%), 48.8% were found to carry abnormalities associated with the known rearrangement, sometimes together with other aneuploidies, 28.9% were balanced/normal for the rearrangement but contained other chromosomal aneuploidies, only 22.3% were chromosmally normal.

 

This poster from MGZ in Munich uses 24sure and 24sure+ and was presented at the GfH meeting in Regensburg March 2011.

Preimplantation genetic diagnosis - Array-CGH of pluripotent trophoblast cells after trophectoderm biopsy. Koehler et al.

 

A number of abstracts and posters presented at the recent Fertility conference in Dublin used 24sure and 24sure related products.

Can first polar body array CGH results predict developmental potential. Cater et al, CARE fertility

Developmental potential of embryos derived from oocytes found to have a single aneuploidy in the first polar body. Cater et al, CARE fertility

Oocyte chromosome complement does not appear to be a factor in fertilisation– a comparison of first polar body analysis of fertilised and unfertilised metaphase II oocytes. Lynch et al, CARE fertility

Application of aCGH for preimplantation genetic diagnosis of chromosome rearrangements and additional unrelated chromosome aneuploidy. Lynch et al, CARE fertilty

Trophectoderm biopsy and array CGH to detect unbalanced forms of t(9;15)(q22.2;q11.1) after failed FISH. Lynch et al, CARE fertility

Multiple Factor PGD – Diagnosis of chromosome aneuploidy and translocation status, HLA type and Fanconi Anaemia Type A in a single blastomere. Lynch et al, CARE fertilty

Comprehensive characterization of chromosome abnormalities in human blastocysts. Alfarawati et al, Reprogenetics, UK

High implantation, pregnancy and birth rates after comprehensive chromosomal screening of blastocysts. Wells et al, Reprogenetics, UK

Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation

Fragouli E, Alfarawati S, Daphnis DD, Goodall N, Mania A, Griffiths T, Gordon A, Wells D.

Human Reproduction. 2011 Feb;26(2):480-90. Epub 2010 Dec 8

  • This paper investigates whether the use of cells from the trophectoderm of blastocyst stage embryos offers an optimal strategy for PGS. High rates of mosaicism in blastocysts has previously been reported as a problem that can lead to misdiagnosis. Here it is concluded that most mosaic blastocysts contained no normal cells, as such trophectoderm aCGH analysis is an appropriate tool for determining blastocyst anueploidy.

 

www.ivfpodcasts.com

IVF podcasts is an excellent website that has a collection of short audio and video presentations, including interviews, demonstrations and lectures.

The embryo biopsy technique demonstration is particularly enlightening.

 

Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos.

Gutiérrez-Mateo C, Colls P, Sánchez-García J, Escudero T, Prates R, Ketterson K, Wells D, Munné S.

Fertil Steril. 2011 Mar 1;95(3):953-8. Epub 2010 Oct 25

  • This study shows 24sure to be highly robust, specific and able to provide results within 24 hours. In addition SurePlex is compared with an alternative DNA amplification method. A distinct advantage of SurePlex is evident through failed amplifications and misdiagnoses with the alternative method. The study also shows arrayCGH can detect 42% more abnormalities than the standard 12-probe FISH approach.

 

New ESHRE PGD guidelines

ESHRE PGD consortium

Hum Reprod. 2010 Oct 21

Four guidelines include one outlining PGD centre organisation and three relating to the methods used: amplification-based testing, fluorescence in situ hybridisation (FISH)-based testing and polar body/embryo biopsy.

 

Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes

Handyside AH, Harton GL, Mariani B, Thornhill AR, Affara N, Shaw MA, Griffin DK

J Med Genet. 2010 Oct;47(10):651-8. Epub 2009 Oct 25

  • This paper describes a method that uses SNP arrays for genome wide preimplantation genetic diagnosis which could remove the need to develop individual gene specific tests.

 

Combined Translocation and Aneuploidy-Screening after Polar Body Biopsy and Array-CGH

Kombinierte Translokations- und Aneuploidieuntersuchungen nach Polkörperbiopsie und array-Comparative Genomic Hybridisation

Montag M, Köster K, van der Ven K, Bohlen U, Bender F
van der Ven H

J. Reproduktionsmed. Endokrinol 2010; 7 (6), 498-502

  • This german article uses 24sure to analyse polar bodies and clearly detects translocations (nice profiles). The abstract is in english!

 

Preimplantation genetic diagnosis after 20 years

Alan H Handyside

Reprod Biomed Online. 2010 Sep;21(3):280-2. Epub 2010 Jul 21

  • This commentary piece from Alan Handyside discusses the technical advances in PGD over the last 20 years.

 

Technology requirements for preimplantation genetic diagnosis to improve assisted reproduction outcomes

Munné S, Wells D, Cohen J.

Fertil Steril. 2010 Jul; 94(2):408-30. Epub 2009 May 5

  • A detailed discussion of the requirements for PGD - mostly regarding FISH applications. Important technical issues raised and discussion of previous trials, although not much discussion of array CGH.

 

What next for preimplantation genetic screening (PGS)? A position statement from the ESHRE PGD Consortium Steering Committee.

Harper J, Coonen E, De Rycke M, Fiorentino F, Geraedts J, Goossens V, Harton G, Moutou C, Pehlivan Budak T, Renwick P, Sengupta S, Traeger-Synodinos J, Vesela K.

Hum Reprod. 2010 Apr;25(4):821-3.

  •  Discussion of prior PGS trial data and outline the setting up of ESHRE trial using polar body biopsy and arrayCGH.

 

What next for preimplantation genetic screening? A polar body approach!

Geraedts J, Collins J, Gianaroli L, Goossens V, Handyside A, Harper J, Montag M, Repping S, Schmutzler A.

Hum Reprod.  2010 Mar;25(3):575-7.

  •  Outline of the proof of principle study by the ESHRE PGS Task Force to determine whether chromosome analysis of first and second polar bodies by arrayCGH enable timely identification of the chromosomal status of an oocyte.

 

Live birth after polar body array comparative genomic hybridization prediction of embryo ploidy-the future of IVF?

Fishel S, Gordon A, Lynch C, Dowell K, Ndukwe G, Kelada E, Thornton S, Jenner L, Cater E, Brown A, Garcia-Bernardo J.

Fertil Steril. 2010 Feb;93(3):1006.e7-1006.e10. Epub 2009 Nov 25.

  • A case report of a 41 year old lady who had previously had 13 cycles of failed IVF. This case uses 24sure with polar body biopsy and is the first reported case of a live birth after arrayCGH diagnosis of a polar body.

 

Genetic analysis of human embryos by metaphase comparative genomic hybridization (mCGH) improves efficiency of IVF by increasing embryo implantation rate and reducing multiple pregnancies and spontaneous miscarriages.

Sher G, Keskintepe L, Keskintepe M, Maassarani G, Tortoriello D, Brody S.

Fertil Steril. 2009 Dec;92(6):1886-94. Epub 2009 Jan 9.

  • This paper uses conventional CGH karyotyping (not arrays) to analyse all chromosomes in blastomeres derived from cleavage stage embryos. The study reports improved improved implantation and birth rates concurrent with reduced miscarriage.

 

Clinical application of comprehensive chromosomal screening at the blastocyst stage.

Schoolcraft WB, Fragouli E, Stevens J, Munne S, Katz-Jaffe MG, Wells D.

Fertil Steril. 2010 Oct;94(5):1700-6. Epub 2009 Nov 25.

  •  This paper uses conventional CGH to analyse all chromosomes in trophectoderm biopsies. Implantation rates were 50% higher with PGS than equivalent cycles from the same clinic.

 

Polar Body Diagnosis – A Step in the Right Direction?

Katrin van der Ven, Markus Montag, and Hans van der Ven.

Deutsches Ärzteblatt International, March 2008 105(11): 190-196

  • An explanation of the use of polar bodies in preimplantation genetic diagnosis. With discussion of German regulations.

 

Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH

Dagan Wells, Samer Alfarawati and Elpida Fragouli

Molecular Human Reproduction Vol.14, No.12 pp. 703–710, 2008

  • This review offers a really good overview of comprehensive chromosome screening and embryo viability. It also refers to many important papers published up to this time.

 

Successful pregnancies after application of array-comparative genomic hybridization in PGS-aneuploidy screening

Ali Hellani, Khaled Abu-Amero, Joseph Azouri, Siham El-Akoum

Vol 17 No 6. 2008 841-847 Reproductive BioMedicine Online

  •  ArrayCGH PGS using an oligo platform and compared to FISH panels. The first report to show a pregnancy following preimplantation genetic screening using arrayCGH.

 

Single-cell chromosomal imbalances detection by array CGH

Le Caignec C, Spits C, Sermon K, De Rycke M, Thienpont B, Debrock S, Staessen C, Moreau Y, Fryns JP, Van Steirteghem A, Liebaers I, Vermeesch JR

Vol 34 No 9. May 2006 e68 Nucleic Acids Res.

  •  Paper demonstrating the feasibility of arrayCGH detecting chromosome imbalance in single cells (inc. blastomeres).