Genetic Laboratory

Innovators in Reproductive Genetics

Genetic diagnosis of miscarriages

iMGE Test™

iMGE Test™ Identification of the causes of miscarriage

of 1000 pregnancies with chromosomal defects are miscarriedGenetic errors in a developing embryo may cause early pregnancy loss, death of the embryo/fetus or premature delivery occur in the vast majority of cases. Therefore, the incidence of live births of children with chromosomal defects amounts only to 3 of 1000 births.

Identification of the cause of miscarriage may help in planning an optimal course of treatment for couples who experienced pregnancy loss.

Over 60% of spontaneously miscarried embryos/fetuses have chromosomal defect*.

Conducted by INVICTA chromosome analysis identified causes of pregnancy loss in 62% of all miscarriages which in other cases would remain unexplained.

The majority of chromosomal defects in such cases are aneuploidies, i.e. chromosomal number abnormalities.

997

Without the chromosome analysis

Unexplained

Other significant factors80%

20%

With the chromosome analysis

Fetal chromosome abnormalities

Unexplained

Other significant factors

62%

20%

18%

With the chromosome analysis based on NGS technique

Remaining

Aneuploidies96%

4%

* Information on the page refers to the analysis of the situation of women aged 35 and older who have experienced recurrent miscarriages. The majority of chromosomal defects in such cases are aneuploidies, i.e. chromosomal number abnormalities (Marquard et al. FertilSteril. 2010 Sep;94(4):1473–7.).

Test which detects the presence of chromosomal defects and identifies sex of the miscarried fetus.

INVICTA Genetic Laboratory offers:

Miscarriage Genetic Evaluation Test (Genetic Diagnosis of Miscarriages) – iMGE Test™ is a group of analyses of the miscarriage material performed with molecular biology techniques which allow to obtain information on the presence of chromosomal defects and about the sex of the fetus.

In contrast to classical cytogenetic methods: the tests do not require in vitro cultivation prior to the analysis, the results are obtained from over 95% of tests conducted, the technique allows to avoid false positive results due to contamination with

mother cell material.

It allows to detect the most frequent chromosomal defects which may cause miscarriages

It allows quick and reliable determination of the fetus’ sex NGS method allows simultaneous analysis of numerical changes in all

chromosomes which are present in human body

If the genetic causes of miscarriage are identified, the following actions are recommended:

genetic consultation undertaking appropriate diagnosis and therapeutic steps Pre–implantation Diagnosis

Specialist collection kit Free transport Online access to the results

In the case of miscarriage, testing for genetic conditions should be routinely conducted in order to determine the probable cause of pregnancy loss.

iMGE Tests is recommended in particular if miscarriage occurs in:

women who decides to get pregnant after 35 years of age couples who were diagnosed as the carriers of chromosomal defects couples whose family presented with genetic defects (so–called positive genetic

history) women who have history of recurrent miscarriages couples whose in vitro programmes failed despite transferring embryos with normal

morphology couples who have been treated for idiopathic infertility for a long time

What is iMGE Test™?

Why is it worth to perform iMGE Test™?

What next?

Indications for iMGE Test™

Sample collection• Targeted biopsy during

the procedure typically performed by the physician after the miscarriage

Preparation of the sample• Place in the solution of

physiological saline

Filling the referral note

Preparation of the material fortransport• Transport at temperature of 2–8°C

Preparation of shipping document

Shipment to the INVICTAGenetic Laboratory• To be delivered within 48 hours

since the collection time• Until it is sent, store at temperature

of 2–8°C

Sample collection• Targeted biopsy during the

procedure typically performed by the physician after the miscarriage

• preparation of the paraffin block in the histopathological laboratory

Preparation of the sample• Place the block in the transport

container

Filling the referral note

Preparation of the material fortransport• Transport at room temperature

Preparation of shipping document

Shipment to the INVICTAGenetic Laboratory• To be delivered ANY time since

the collection

Cooperation step by step

NGS methodology

Shipping address: INVICTA Genetics LaboratoryGdańsk Science and Technology Parkul. Trzy Lipy 3, 80–172 GdańskE–mail: genetyka@invicta.pl • Tel.: +48 784 373 593

Sample preparation

Libraries preparation with barcoding

Sequence preparation

Information read-out

Data analysis

This test was designed to detect aneuploidies and imbalance resulting from Robertsonian translocations. It does not detect segmental aneuploidies, germline mosaicism related to aneuploidy, structural chromosome defects (e.g. deletion of the chromosome part, inversion, duplication), uniparental disomy, triploidy, tetraploidy

Limitations

Sample collection & preparation

Transport

Result

1

2

3

Fresh material Paraffin block

Ready–to–use universalINVICTA Collection Kit

Results available within 7-14 days Results available within 7-14 days

First in the world use of NGS (Next Generation Sequencing) in the genetic diagnosis of miscarriages.

INVICTA Genetics Laboratory, July 2014.

Performing iMGE 24 Test™ ensures accuracy of 99.999% (quality assessment of Q50 acc. to Phred Quality Scores – the most common metric used to assess accuracy of a sequencing platform).

iMGE XY Test™ iMGE+ Test™ iMGE 24 Test™

ScopeX, Y chromosomes(identification of sex)

chromosome 13, 15, 16, 18, 21, 22; X and Y chromosomes

allchromosomes

Method

PCRPolymerase chainreaction

QF–PCRQuantitative Fluorescence Polymerase Chain Reaction

NGSNext GenerationSequencing

Reading2 places of AMELY and SRY on X and Y chromosome

42 placeson 8 chromosomes

100,000 places onall chromosomes

99,999%

Options INVICTA’s genetic diagnosis of miscarriages

is currently the most up–to–date method of analysing DNA information in the world. It ensures exceptionally precise, reliable and comprehensive result to determine the causes of miscarriage.

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. Van den Berg MM, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta. 2012 Dec; 1822(12):1951–9.

2. Romero ST, Geiersbach KB, Paxton CN, Rose NC, Schisterman EF, Branch DW, Silver RM. Differentiation of genetic abnormalities in early pregnancy loss. Ultrasound Obstet Gynecol. 2015 Jan; 45(1):89–94.

3. Vaiman D. Genetic regulation of recurrent spontaneous abortion in humans. Biomed J. 2015 Jan–Feb;38(1):11–24.

4. Jenderny J. Chromosome aberrations in a large series of spontaneous miscarriages in the German population and review of the literature. Mol Cytogenet. 2014 Jun 5;7:38.

5. Robberecht C, Schuddinck V, Fryns JP, Vermeesch JR. Diagnosis of miscarriages by molecular karyotyping: benefits and pitfalls. Genet Med. 2009 Sep;11(9):646–54.

6. Menasha J1, Levy B, Hirschhorn K, Kardon NB. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12–year study. Genet Med. 2005 Apr;7(4):251–63.

7. Choi TY, Lee HM, Park WK, Jeong SY, Moon HS. Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases. Obstet Gynecol Sci. 2014 Nov;57(6):518–25.

8. Kim JW, Lyu SW, Sung SR, Park JE, Cha DH, Yoon TK, Ko JJ. Shim SH. Molecular analysis of miscarriage products using multiplex ligation–dependent probe amplification (MLPA): alternative to conventional karyotype analysis. Arch Gynecol Obstet. 2015 Feb;291(2):347–54.

9. Donaghue C, Mann K, Docherty Z, Mazzaschi R, Fear C, Ogilvie C. Combined QF–PCR and MLPA molecular analysis of miscarriage products: an efficient and robust alternative to karyotype analysis. Prenat Diagn. 2010 Feb;30(2):133–7.

10. Lathi RB, Gustin SL, Keller J, Maisenbacher MK, Sigurjonsson S, Tao R, Demko Z. Reliability of 46,XX results on miscarriage specimens: a review of 1,222 first–trimester miscarriage specimens. Fertil Steril. 2014 Jan;101(1):178–82.

11. Furtado LV, Jama MA, Paxton CN, Wilson AA, Gardiner AE, Lyon E, Geiersbach KB. Aneuploidy detection in paraffin embedded tissue from products of conception by mini–STR genotyping. Fetal Pediatr Pathol. 2013 Apr;32(2):133–50.

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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