Genetic Laboratory

Innovators in Reproductive Genetics

Preimplantation Diagnosis for monogenic diseases

PGD ONE™

Experiencematters

PGD ONE™

cycles, average patient’s age: 36.5 ± 4.6 years

embryos without genetic load

embryos underwent diagnosis

diagnostic embryos tested

Pregnancy success rate

1,813 2,045

7,139 6,628 49,4%

* concerning number of PGD/PGS procedures conducted

According to the ESHRE PGD Consortium*

Autosomal dominant

Familial combined hyperlipidaemia

5.0

Familial hypercholsterolaemia

2.0

Dominant otosclerosis 1.0

Adult polycystic kidney disease

0.8

Multiple exostoses 0.5

Huntington's disease 0.5

Autosomal recessive

Cystic fibrosis 0.4

alpha-1-antitrypsin deficiency

0.2

Phenylketonuria 0.1

Congenital adrenal hyperplasia

0.1

Spinal muscular atrophy

0.1

Sickle cell anaemia 0.1

X-Linked recessive

Fragile X syndrome

0.5

Duchenne muscular dystrophy

0.3

X-linked ichthyosis 0.2

Haemophilia A 0.1

Becker muscular dystrophy

0.05

Haemophilia B 0.03

Genetic Disorder

Frequency per 1000 births.

Source: www.geneticalliance.org.uk

January 2005 – April 2015

PGD ONE™ is a preimplantation genetic diagnosis for monogenic diseases.

World’s

PGD Lab6th

Table 1. Approximate frequency of some of the most common Mendelian disorders in the UK population.

PGD ONE™ is a test that detects the genetic defects (mutations) inherited by a child from their parents. DNA material from embryos is analysed prior to transfer to the uterus, that is, before the woman actually becomes pregnant.

The test can be carried out on material collected by biopsy in the 3rd (blastomere) or 5th/6th (trophectoderm cells) day of the embryo culture. Because of the risk of misdiagnosis caused by the pollution of sperm when using standard in vitro fertilization, the ICSI procedure is recommended. Any diagnosis of PGD ONE™ is treated individually and preceded by an examination of the material from the prospective parents. Under the procedure, a frozen embryos transfer (FET) is required.

Possibility of diagnosing any known genetic-based monogenic disease at the embryo stage, and reducing the risk of its occurrence in your child

Possibility of conducting a PGS-NGS 360°™ (Preimplantation Genetic Screening) from a single sample (single biopsy) at the same time – reducing the risk of monogenic diseases and genetic defects resulting from an abnormal number of chromosomes

Free PGD BIOPSY KIT™ Free shipment Online access to results

People with a genetic test result confirming a clinical diagnosis of monogenic disease

People with a genetic test result confirming the presence of mutation carriers The presence of inherited genetic diseases or a history of specific mutation

in the family

What is PGD ONE™?

Why is it worth to perform PGD ONE™?

INVICTA Genetic Laboratory offers:

What are the indications for PGD ONE™?

NGSNext Generation Sequencing

Development of the diagnosis

Embryo biopsy

Completion of the biopsy report

Preparation of material for transport Preparation of shipping document

Shipment to the INVICTA Genetic Laboratory

Results available within 3 weeks

• Development of an individual preimplantation genetic diagnosis, based on the material collected from the patients and the subsequent genetic laboratory results.

• Upon request, INVICTA sends a SALIVA KIT for collection of biological material from the parents and relatives (if required).

• A sample is collected via biopsy of an embryo on the 3rd or 5/6th day of the culture.

• Blastomere or trophectoderm cells are used for testing.

• Until dispatch, the material sample is stored at -20°C.• For transportation, 3 cooling cartridges are used that

are also frozen to -20°C. The cartridges are placed around the test-tube rack inside the box.

• During transport, the biopsy material is kept cool, or preferably frozen.

• Transport duration depends on the time and place of shipment.

Cooperation step by step

NGS methodology

Shipping address: INVICTA Genetic LaboratoryGdańsk Science and Technology ParkTrzy Lipy 3, 80–172 GdańskE–mail: info@invictagenetics.comTel.: +48 784 373 593

Sample preparation

Libraries preparation with barcoding

Sequence preparation

Information read-out

Data analysis

PGD ONE™ is individually designed preimplantation genetic diagnosis for particular patients in order to exclude transmission to descendant a genetic feature proven to be a cause of disease by test results from genetic diagnostics laboratory. Performing PGD ONE™ does not exclude risk of genetic disease, which may be resulted from other factors, e.g. de novo mutations, undiagnosed mutations, or other genetic diseases.

Limitations

Ready–to–use universalINVICTA PGD BIOPSY KIT™

Diagnosis of

parents

Transport

Biopsy

Result

1

3

2

4

The world’s first use of NGS (Next Generation Sequencing) in the PGD ONE™ preimplantation diagnosis for monogenic diseases. INVICTA Genetic Laboratory: February 2015

Genetic disorder Gene/Locus

Cystic fibrosis (CF), Mucoviscidosis CFTR

Smith-Lemi-Opitz syndrome (SLOS) DHCR7

Muscular dystrophy (DMD) DMD

Deafness, autosomal recessive 1A (DFNB1A) GJB2

Huntington disease (HD) HD

Autosomal Dominant Polycystic Kidney Disease 1 (ADPKD1)

PKD

Spinal muscular atrophy SMN1

Adenylosuccinase Deficiency ADSL

Familial adenomatous polyposis 1 (FAP1) APC

Argininosuccinic aciduria ASL

Osteogenesis imperfecta, type IV (OI Type IV) COL1A1

Genetic disorder Gene/Locus

Haemophilia A F8

Facioscapulohumeral muscular dystophy 1 (FSHD1)

FSHD

Epidermolysis bullosa simplex (EBS) KRT14

Congenital disorder of glycosylation, type 1a (CDG1A)

PMM2

Pituitary hormone deficiency, combined, 2 (CPHD2)

PROP1

Cardioencephalomyopathy SCO2

Loeys-Dietz syndrome TGFBR

Tuberous sclerosis 1 (TSC1) TSC1

Wiskott-Aldrichsyndrome (WAS) WAS

Table 2. Twenty of the most routinely sought point mutations in a PGD ONE™ preimplantation diagnosis at the INVICTA Genetic Laboratory.

PGD ONE™ can now diagnose any known genetic-based monogenic disease.

NGS provides accuracy of 99.999% (Q50 quality assessment by Phred Quality Scores – indicator developed for evaluation of DNA sequence analysis methods).

99,999%

used in the PGD ONE™ is currently the most up-to-date method of DNA analysis in the world. It provides exceptionally accurate, reliable and comprehensive results, from which it is possible to reduce the risk of monogenic diseases in babies.

NGS Next Generation Sequencing

Literature

Prof. Krzysztof Łukaszuk MD, Ph. D.Medical Directorof INVICTA Fertility Clinics

Bożena Maj M. Sc.Director of INVICTAMedical Laboratories

Sebastian Pukszta Ph.D.INVICTA Genetic LaboratoryDeputy Laboratory Managerfor Molecular Biology

Joanna Liss Ph.DDirector of INVICTAIVF Laboratory

Team

1. Lukaszuk K, Kalwak K, Pukszta S, Liss J, Jakiel G, Woclawek-Potocka I, Galvao A, Wasniewski T. Preimplantation genetic diagnosis of human leukocyte antigen for X-linked immunoproliferative syndrome caused by SAP mutation.

2. Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:252-3. doi: 10.1016/j.ejogrb.2014.09.034. Epub 2014 Sep 28.

3. Treff NR, Fedick A, Tao X, [et.al.]. Evaluation of targeted next-generation sequencing-based preimplantation genetic diagnosis of monogenic disease. Fertil Steril. 2013, 99(5),1377-1384.

4. Corrales I, Catarino S, Ayats J, Arteta D, Altisent C, Parra R, et al. High-throughput molecular diagnosis of von Willebrand disease by next generation sequencing methods. Haematologica 2012;97:1003

5. Rechitsky S, Pakhalchuk T, San Ramos G, Goodman A, Zlatopolsky Z, Kuliev A.First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing. Fertil Steril. 2015 Feb;103(2):503-12. doi: 10.1016/j.fertnstert.2014.11.007. Epub 2014 Dec 13.

6. Berger VK, Baker VL. Preimplantation diagnosis for single gene disorders. Semen Reprod Med. 2014 Mar;32(2):107-13. doi: 10.1055/s-0033-1363552. Epub 2014 Feb 10.

7. Daina G, Ramos L, Obradors A, Rius M, Martinez-Pasarell O, Polo A, Del Rey J, Obradors J, Benet J, Navarro J. First successful double-factor PGD for Lynch syndrome: monogenic analysis and comprehensive aneuploidy screening. Clin Genet. 2013 Jul;84(1):70-3. doi: 10.1111/cge.12025. Epub 2012 Oct 17.

8. Chang LJ, Chen SU, Tsai YY, Hung CC, Fang MY, Su YN, Yang YS. An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening. Clin Exp Reprod Med. 2011 Sep;38(3):126-34. doi: 10.5653/cerm.2011.38.3.126. Epub 2011 Sep 30.

9. Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, Pehlivan Budak T, Renwick P, De Rycke M, Geraedts JP, Harton G. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012 May-Jun;18(3):234-47. doi: 10.1093/humupd/dmr052. Epub 2012 Feb 16. Review.

10. Field PD, Martin NJ. CFTR mutation screening in an assisted reproductive clinic. Aust N Z J Obstet Gynaecol. 2011 Dec;51(6):536-9. doi: 10.1111/j.1479-828X.2011.01348.x. Epub 2011 Aug 22.

11. Preimplantation genetic diagnosis: state of the art 2011. Harper JC, Sengupta SB. Hum Genet. 2012 Feb;131(2):175-86. doi: 10.1007/s00439-011-1056-z. Epub 2011 Jul 12. Review.

12. Peyvandi F, Garagiola I, Mortarino M.Prenatal diagnosis and preimplantation genetic diagnosis: novel technologies and state of the art of PGD in different regions of the world. Haemophilia. 2011 Jul;17 Suppl 1:14-7. doi: 10.1111/j.1365-2516.2011.02559.x.

13. Simpson JL. Preimplantation genetic diagnosis at 20 years. Prenat Diagn. 2010 Jul;30(7):682-95. doi: 10.1002/pd.2552. Review.

14. Basille C, Frydman R, El Aly A, Hesters L, Fanchin R, Tachdjian G, Steffann J, LeLorc’h M, Achour-Frydman N. Preimplantation genetic diagnosis: state of the art. Eur J Obstet Gynecol Reprod Biol. 2009 Jul;145(1):9-13. doi: 10.1016/j.ejogrb.2009.04.004. Epub 2009 May 2.

15. Gutiérrez-Mateo C, Sánchez-García JF, Fischer J, Tormasi S, Cohen J, Munné S, Wells D. Preimplantation genetic diagnosis of single-gene disorders: experience with more than 200 cycles conducted by a reference laboratory in the United States. Fertil Steril. 2009 Nov;92(5):1544-56. doi: 10.1016/j.fertnstert.2008.08.111. Epub 2008 Oct 19.

INVICTA Genetic Laboratory

Gdańsk Science and Technology ParkTrzy Lipy 3, 80–172 GdańskT: +48 58 58 58 804

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Customer Service

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