Abstract
Purpose: To compare the frequency and the degree of mosaicism in human embryos from Robertsonian translocation (RT) t(13;14) carriers, with embryos from karyotypically normal IVF patients.
Methods: FISH analysis of embryos from PGD cycles for RT t(13;14), with probes for chromosomes 13, 14, and 18 (Group I) and of embryos from karyotypically normal IVF patients with probes for chromosomes 13, 18, 21, X, and Y (Group II).
Results: The incidence of abnormal mosaic embryos was significantly higher in group I (38/51) as compared with group II (6/45) (χ2: P < 0.01). Furthermore, in group I the percentage of diploid cells per embryo was lower for chromosome 13 and 14 in comparison with 18, while in group II no differences were observed between the five chromosomes analyzed.
Conclusions: RT induces a high frequency of mosaicism specifically for the chromosomes implicated in the translocation; the analysis by FISH of two blastomeres is strongly recommended for these patients.
Keywords: Human embryos, mosaicism, preimplantation genetic diagnosis, Robertsonian translocation
Full Text
The Full Text of this article is available as a PDF (595.6 KB).
References
- 1.Handyside AH, Kontogianni EH, Hardy K, Winston RML. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344:768–770. doi: 10.1038/344768a0. [DOI] [PubMed] [Google Scholar]
- 2.Lissens W, Sermon K. Preimplantation genetic Diagnosis: Current status and new developments. Hum Reprod. 1997;12:1756–1761. doi: 10.1093/humrep/12.8.1756. [DOI] [PubMed] [Google Scholar]
- 3.Geraedts J, Handyside A, Harper J, Libaers I, Sermon K, Staessen C, Thornhill A, Viville S, Wilton L. ESHRE Preimplantation Genetic Diagnosis Consortium (PGD): Preliminary assessment of data from January 1997 to September. Hum Reprod. 1998;14:3138–3148. doi: 10.1093/humrep/14.12.3138. [DOI] [PubMed] [Google Scholar]
- 4.Delhanty JDA, Harper JC, Ao A, Handyside AH, Winston RM. Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Hum Genet. 1997;99:755–760. doi: 10.1007/s004390050443. [DOI] [PubMed] [Google Scholar]
- 5.Conn CM, Harper JC, Winston RML, Delanthy JD. Infertile couples with Robertsonian translocations: Preimplantation genetic analysis of embryos reveals chaotic cleavage divisions. Hum. Genet. 1998;102:117–123. doi: 10.1007/s004390050663. [DOI] [PubMed] [Google Scholar]
- 6.Munné S, Grifo J, Cohen J, Weier HUG. Chromosome Abnormalities in Human Arrested Preimplantation Embryos: A multiple-probe FISH study. Am J Hum Genet. 1994;55:150–159. [PMC free article] [PubMed] [Google Scholar]
- 7.Munné S, Weier HUG, Grifo J, Cohen J. Chromosome mosaicism in human embryos. Biol Reprod. 1994;51:41–49. doi: 10.1095/biolreprod51.3.373. [DOI] [PubMed] [Google Scholar]
- 8.Evsikov S, Verlinsky Y. Mosaicism in the inner cell mass of human blastocysts. Hum Reprod. 1998;13:3151–3155. doi: 10.1093/humrep/13.11.3151. [DOI] [PubMed] [Google Scholar]
- 9.Veiga A, Gil Y, Boada M, Carrera M, Vidal F, Boiso I, Ménézo Y, Barri PN. Confirmation of diagnosis in preimplantation genetic diagnosis (PGD) through blastocyst culture: Preliminary experience. Prenat Diagn. 1999;19:1242–1247. [PubMed] [Google Scholar]
- 10.Emiliani S, Gonzalez-Merino E, Van den Bergh M, Abramowicz M, Vassart G, Englrt Y, Delneste D. Re-analysis by fluorescence in situ hybridisation of spare embryos cultured until Day 5 after preimplantation genetic diagnosis for a 47, XYY infertile patient demonstrates a high incidence of diploid mosaic embryos: A case report. Prenat Diagn. 2000;20:1063–1066. [PubMed] [Google Scholar]
- 11.Sandalinas M, Sadowy S, Alikani M, Calderon G, Cohen J, Munné S. Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage. Hum Reprod. 2001;16:1954–1958. doi: 10.1093/humrep/16.9.1954. [DOI] [PubMed] [Google Scholar]
- 12.Bielanska M, Lin Tan S, Ao A. Chromosomal mosaicism throughout human preimplantation development in vitro: Incidence, type, and relevance to embryo outcome. Hum Reprod. 2002;17:413–419. doi: 10.1093/humrep/17.2.413. [DOI] [PubMed] [Google Scholar]
- 13.Scriven PN, Handyside AH, Mackie Ogilvie C. Chromosome translocations: Segregation modes and strategies for preimplantation genetic diagnosis. Prenat Diagn. 1998;18:1437–1449. [PubMed] [Google Scholar]
- 14.Conn CM, Harper JC, Winston RML, Delhanty JD. Infertile couples with Robertsonian translocations: Preimplantation genetic analysis of embryos reveals chaotic cleavage divisions. Hum Genet. 1998;102:117–123. doi: 10.1007/s004390050663. [DOI] [PubMed] [Google Scholar]
- 15.Munné S, Scott R, Sable D, Cohen J. First pregnancies after preconception diagnosis of translocations of maternal origin. Fertil Steril. 1998;69:675–681. doi: 10.1016/s0015-0282(97)00568-2. [DOI] [PubMed] [Google Scholar]
- 16.Evsikov S, Cleslak MLT, Verlinsky Y. Effect of chromosomal translocations on the development of preimplantation human embryos in vitro. Fertil Steril. 2000;74:672–677. doi: 10.1016/s0015-0282(00)01513-2. [DOI] [PubMed] [Google Scholar]
- 17.Escudero T, Lee M, Carrel D, Blanco J, Munne S. Analysis of chromosome abnormalities in sperm and embryos from two 45,XY,t(13;14) (q10;q10) carriers. Prenat Diagn. 2000;20:599–602. doi: 10.1002/1097-0223(200007)20:7<599::aid-pd883>3.3.co;2-h. [DOI] [PubMed] [Google Scholar]
- 18.Iwarsson E, Malmgren H, Inzunza J, Ahrlund-Richter L, Sjoblom P, Rosenlund B, Fridstrom M, Hovatta O, Nordenskjold M, Blennow F. Highly abnormal cleavage divisions in preimplantation embryos from translocation carriers. Prenat Diagn. 2000;20:1038–1047. [PubMed] [Google Scholar]
- 19.Coonen E, Dumoulin JCM, Ramaekers FCS, Hopman AH. Optimal preparation of preimplantation embryo interphase nuclei for analysis by fluorescence in-situ hybridization. Hum Reprod. 1994;9:533–537. doi: 10.1093/oxfordjournals.humrep.a138540. [DOI] [PubMed] [Google Scholar]
- 20.Staessen C, Van Assche E, Joris H, Bonduelle M, Vandervorst M, Liebaers I, Van Steirteghem AC. Clinical experience of sex determination by fluorescent in-situ hybridization for preimplantation genetic diagnosis. Mol Hum Reprod. 1999;5:382–389. doi: 10.1093/molehr/5.4.382. [DOI] [PubMed] [Google Scholar]
- 21.Hopman AH, Ramaekers FC, Raap AK, Beck JL, Devilee P, Van der Ploeg M, Vooijs GP. In situ hybridization as a tool to study numerical chromosome aberrations in solid bladder tumours. Histochemistry. 1998;89:307–316. doi: 10.1007/BF00500631. [DOI] [PubMed] [Google Scholar]
- 22.Munné S, Marquez C, Magli C, Morton P, Morrison L. Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X, Y, 13, 16, 18 and 21. Mol Hum Reprod. 1998;4:863–870. doi: 10.1093/molehr/4.9.863. [DOI] [PubMed] [Google Scholar]
- 23.Munné S, Magli C, Adler A, Wright G, De Boer K., Mortimer D, Tucker M, Cohen J, Gianaroli L. Treatment-related chromosome abnormalities in human embryos. Hum Reprod. 1997;12:780–784. doi: 10.1093/humrep/12.4.780. [DOI] [PubMed] [Google Scholar]
- 24.Harrison RH, Kuo HC, Scriven PN, Handyside AH, MakkieOgilvie C. Lack of cell cycle check points in human cleavage stage embryos revealed by a clonal pattern of chromosomal mosaicism analyzed by sequential multicolour FISH. Zygote. 2000;8:217–224. doi: 10.1017/s0967199400001015. [DOI] [PubMed] [Google Scholar]
- 25.Hardy K, Spanos S, Becker D, Iannelli P, Winston RM, Stark J. From cell death to embryo arrest: Mathematical models of human preimplantation embryo development. Proc Natl Acad Sci USA. 2001;13:1655–1660. doi: 10.1073/pnas.98.4.1655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Chen HW, Jang WS, Tzeng CR. Nitric oxide as a regulator in preimplantation embryo development and apoptosis. Fertil Steril. 2001;75:1163–1171. doi: 10.1016/s0015-0282(01)01780-0. [DOI] [PubMed] [Google Scholar]
- 27.Munné S, Dailey T, Finkelstein M, Weier HUG. Reduction in signal overlap results in increased FISH efficiency: Implications for preimplantation genetic diagnosis. J Assist Reprod Genet. 1996;13:149–156. doi: 10.1007/BF02072537. [DOI] [PubMed] [Google Scholar]
- 28.Ruangvutilert P, Delhanty JDA, Serhal P, Simopolou M, Rodeck CH, Harper JC. FISH analysis on day 5 post-insemination of human arrested and blastocyst stage embryos. Prenat Diagn. 2000;20:552–560. doi: 10.1002/1097-0223(200007)20:7<552::aid-pd871>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- 29.ESHREPGD Consortium Steering Committee Consortium Steering Committee: ESHRE Preimplantation Genetic Diagnosis Consortium: Data collection III (May 2001) Hum Reprod. 2002;17:233–246. doi: 10.1093/humrep/17.1.233. [DOI] [PubMed] [Google Scholar]
- 30.Vande Velde H, De Vos A, Sermon K, Staessen C, De Rycke M, Van Asshe E, Lissens W, Vandervorst M, Van Ranst H, Libaerts L, Van Steirteghem A. Embryo implantation after biopsy of one or two cells from cleavage-stage embryos with a view to preimplantation genetic diagnosis. Prenat Diagn. 2000;20:1030–1037. doi: 10.1002/1097-0223(200012)20:13<1030::aid-pd977>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- 31.Munné S, Escudero T, Sandalinas M, Sable D, Cohen J. Gamete segregation in female carriers of Robertsonian translocations. Cytogenet Cell Genet. 2000;90:303–308. doi: 10.1159/000056793. [DOI] [PubMed] [Google Scholar]
- 32.Munné S, Sandalinas M, Escudero T, Fung J, Gianaroli L, Cohen J. Outcome of preimplantation genetic diagnosis of translocations. Fertil Steril. 2000;73:1209–1218. doi: 10.1016/s0015-0282(00)00495-7. [DOI] [PubMed] [Google Scholar]
- 33.Munné S. Preimplantation genetic diagnosis of structural abnormalities. Mol Cell Endocrinol. 2001;183(Suppl1):S55–58. doi: 10.1016/s0303-7207(01)00578-0. [DOI] [PubMed] [Google Scholar]