Presentation is loading. Please wait.

Presentation is loading. Please wait.

Preimplantation genetic diagnosis (PGD) in couples with reciprocal and Robertsonian translocations – limitations and results Mardesic,T., Kosarova,M.,

Similar presentations


Presentation on theme: "Preimplantation genetic diagnosis (PGD) in couples with reciprocal and Robertsonian translocations – limitations and results Mardesic,T., Kosarova,M.,"— Presentation transcript:

1 Preimplantation genetic diagnosis (PGD) in couples with reciprocal and Robertsonian translocations – limitations and results Mardesic,T., Kosarova,M., Zudova,D.,Jelinkova,L., Voboril,J., Sobotka,V. Institute Pronatal, Prague Antalya 2011

2 Chromosome translocation is a structural chromosomal abnormity caused by rearrangement of parts between nonhomologous chromosomes. Translocations can be balanced (in an even exchange of material with no genetic information extra or missing) or unbalanced (where the exchange of chromosome material is unequal resulting in extra or missing genes). Genetic examination of preimplantation embryos (PGD) can select chromosomal normal (or balanced) embryos suitable for embryotransfer

3 Carriers of translocations have reduced fertility and are at risk of recurrent miscarriages and unbalanced offspring. Translocations - reciprocal - Robertsonian

4 In couples with recurrent miscarriage the incidence of either of the partners being a carrier of a structural chromosomal abnormity is 3-4%, mainly consisting of reciprocal translocations (61%) and Robertsonian translocations (16%) Clifford et al., Hum Reprod, 1994 Franssen et al., BMJ, 2005

5 Reciprocal translocations exchange of material between nonhomologous chromosomes

6 Robertsonian translocations rearrangement involving centromeric fusion of two acrocentric chromosome with loss of the short arms. Karyotype leaves only 45 chromosomes since two chromosomes have fused together The most common translocation in human involves chromosomes 13 and 14 Risks: Infertility (unbalanced gametes) Repeated abortions Cancer (acute and chronic myelogenous leukemia) Chr.14 Chr.13 Chr.14 Chr.13

7 Material and methods 94 couples (first IVF-PGD cycles) with chromosomal translocation treated in Institute Pronatal Robertsonian translocation : 44x Reciprocal translocation: 50x PGD method: FISH on interphase blastomere nucleus

8 Material (Robertsonian translocations) Most frequent: t(13;14) – 70%

9 Material (reciprocal translocations) 50 couples Chromosomes affected: 1, 2, 3, 4, 5, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 21

10 Methods Biopsy of 1 blastomere (72 h) Nucleus fixation Genetic analysis (translocated chromosomes + 13, 18, 21, X, Y) ET max. 2 blastocysts (120 h) with normal chromosomal arrangement or with balanced translocation

11 Genetic examination – testing of probes before PGD Robertsonian translocation: DNA probes for subtelomeric regions of translocated chromosomes (Cytocell, Kreatech Biotechnology) Reciprocal translocations: 2 DNA probes for regions distal to breaks+ 1 DNA probe for proximal part (or vice versa), optimum are 2 distal and 2 proximal probes (Vysis, Cytocell, Kreatech Biotechnology)

12 Results (1) Translocation Mean age No. of fixed blastomeres per couple No. of diagnosed embryos per couple (%) Robertsonian33,27,47,2 (97,4) Reciprocal32,86,76,3 (97,0)

13 Results (2) Translocation No. cycles Cycles with ET (%) No. embryos with biopsy No. norm. embryos (%) Robertsonian4430 (68,2)27068 (25,2) Reciprocal5027 (54,0)35958 (16,4) Total9457 (60,6) (21,9)

14 Results (3) Translocation CPR/ started cycle (%) CPR/ ET (%) Robertsonian15 (34,1)15 (50,0) Reciprocal9 (18,0)9 (33,0) Total24 (25,5)24 (42,1)

15 Results (4) TranslocationPregnantAb. (%)BTHR % Robertsonian151 (6,7)93,3 Reciprocal91 (11,1)88,9 Total242 (8,3)91,7

16 Discussion – summary results No. cyclesCycles with ET (%) CPR / ET (%) Pronatal 9457 (60,6)24 (42,1) Verlinsky RBMonline (68,9)45 (35,7) ESHRE PGD Consortium (64,5) 357 (24,4)

17 Discussion – results according to the type of translocation TranslocationNo.of cycles Cycles with ET (%) No. of diagnosed embryos No of normal embryos (%) Robertsonian Pronatal ESHRE PGD Consortium (68,2) 565 (73,8) (25,2) 1457 (34,6) Reciprocal Pronatal ESHRE PGD Consortium (54) 900 (59,8) (16,4) 1974 (20,1)

18 Discussion – baby take home rate BTHR% before PGD BTHR % after PGD Pronatal-91,7 Verlinsky ,681,4 Munné ,5%87

19 Discussion Preimplantation analysis of interphase blastomere nucleus using FISH cannot discriminate between normal (with normal chromosomal arrangement) and balanced blastomeres (with balanced translocation)

20 Discussion – results according to the type of translocation in couples with reciprocal translocations more abnormal gametes (and embryos) are created compared to couples with Robertsonian translocation Couples with Robertsonian translocation have a higher chance for succesful treatment (PR/cycle) compared to couples with reciprocal translocations

21 Robertsonian translocation Chr.13 Chr.14 Chr.13 Chr.14 NormalBalanced translocation Trisomy chr.13 Trisomy chr.14 Monosomy chr.13 Monosomy chr.14

22 normal balanced U n b a l a n c e d 16 blastomeres gametes Chromosomal segregation in gametes in a carrier of reciprocal balanced translocation

23 Conclusion (1) PGD can benefit translocation carrier couples with a history of infertility or repeated pregnancy losses to conceive and deliver a healthy child in a short period of time

24 Conclusion (2) Couples with Robertsonian translocation have a higher chance for succesful treatment (PR/cycle) compared to couples with reciprocal translocations

25 Acknowledgement J.Vobořil J.Slámová D.Kult R.Středa T.Mardešić V.Sobotka L.Jelínková Š. Vilímová J.Mádrová M.Mašata I.Hamplová D.Hlinka Gynaecology EmbryologyGenetics M.Kosařová D. Zudová T. Brachtlová E. Bürgerová K. Slabá V. Gregor

26


Download ppt "Preimplantation genetic diagnosis (PGD) in couples with reciprocal and Robertsonian translocations – limitations and results Mardesic,T., Kosarova,M.,"

Similar presentations


Ads by Google