Abstract
Purpose:Preimplantation genetic diagnosis of translocations has seldom been attempted. Recently, a genetic test based on analyzing polar bodies at the methaphase stage, following fluorescent in situ hybridization with commercially available whole-chromosome painting DNA probes has been presented. Here we report the use of this method in seven couples in whom the female was a carrier of one of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases), 46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2), 46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;;q11).
Methods:The original method was improved in two ways. First, centromeric probes for one or both chromosomes involved in the translocation were added to avoid misdiagnosis caused by possible confusion of first polar body monovalent chromosomes (with two chromatids each) with single chromatids. Second, for cases with terminal translocations where commercially available probes do not cover telomere sequences, a telomere probe labeling the translocated fragment was added.
Results:A total of 26 abnormal, 18 balanced, and 22 normal eggs was detected. Nine normal and seven balanced embryos were transferred, resulting in eight (50%) implanting, of which one spontaneously aborted. To date, the remainder have produced karyotypically normal or balanced babies and ongoing pregnancies. The rate of spontaneous abortions after preimplantation genetic diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural cycles in the same patients (95%).
Conclusions:With the above improvements, the test can characterize any translocation of maternal origin and produce a high pregnancy rate and an apparently low frequency of spontaneous abortion.
Keywords: 1:3 segregation, t(4;14), t(7;20), t(9;11), t(14;18), t(13;14), t(14;21)
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REFERENCES
- 1.Handyside AH, Kontogianni EH, Hardy K, Winston RML. Pregnancies from biopsied human pre-implantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344:768–770. doi: 10.1038/344768a0. [DOI] [PubMed] [Google Scholar]
- 2.Grifo JA, Tang YX, Cohen J, Gilbert F, Sanyal MK, Rosenwaks Z. Ongoing pregnancy in a hemophilia carrier by embryo biopsy and simultaneous amplification of X and Y chromosome specific DNA from single blastomeres. JAMA. 1992;6:727–729. [PubMed] [Google Scholar]
- 3.Handyside AH, Lesko JG, Tarin JJ, Winston RML, Hughes MR. Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N Engl J Med. 1992;327:594–598. doi: 10.1056/NEJM199209243271301. [DOI] [PubMed] [Google Scholar]
- 4.Munné S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates and maternal age are correlated with chromosome abnormalities. Fertil Steril. 1995;64:382–391. [PubMed] [Google Scholar]
- 5.Verlinsky Y, Cieslak J, Ivakhnenko V, Lifchez A, Strom C, Kuliev A. Preimplantation Genetic Group: Birth of healthy children after preimplantation diagnosis of common aneuploidies by polar body fluorescent in-situ hybridization analysis. Fertil Steril. 1996;66:126–129. doi: 10.1016/s0015-0282(16)58399-x. [DOI] [PubMed] [Google Scholar]
- 6.Munné S, Scott R, Sable D, Cohen J: Pregnancies after preconception testing of Robertsonian translocations of maternal origin. Fertil Steril 1998 (in press) [DOI] [PubMed]
- 7.Cassel MJ, Munné S, Fung J, Weier HUG. Carrier-specific breakpoint-spanning DNA probes: An approach to preimplantation genetic diagnosis in interphase cells. Hum Reprod. 1997;12:2019–2027. doi: 10.1093/humrep/12.9.2019. [DOI] [PubMed] [Google Scholar]
- 8.Fung J, Munné S, Duell T, Weier HUG: Rapid cloning of translocation breakpoints: From blood to YAC in 50 days. J Biochem Mol Biol Biophys 1998; 1 (in press)
- 9.Conn CM, Harper JC, Winston RML, Delhanty JDA: Infertility couples with Robertsonian translocations: Preimplantation genetic analysis of embryos reveals chaotic cleavage divisions. Hum Genet 1998 (in press) [DOI] [PubMed]
- 10.Cohen J, Alikani M, Trowbridge J, Rosenwaks Z. Implantation enhancement by selective assisted hatching using zona drilling of embryos with poor prognosis. Hum Reprod. 1992;7:685–916. doi: 10.1093/oxfordjournals.humrep.a137720. [DOI] [PubMed] [Google Scholar]
- 11.Verlinsky Y, Ginsberg N, Lifchez A, Valle J, Moise J, Strom CM. Analysis of the first polar body: preconception genetic diagnosis. Hum Reprod. 1990;5:826–829. doi: 10.1093/oxfordjournals.humrep.a137192. [DOI] [PubMed] [Google Scholar]
- 12.Munné S, Dailey T, Sultan KM, Grifo J, Cohen J. The use of first polar bodies for preimplantation diagnosis of aneuploidy. Hum Reprod. 1995;10:1015–1021. doi: 10.1093/oxfordjournals.humrep.a136027. [DOI] [PubMed] [Google Scholar]
- 13.Angell RR, Xian J, Keith J, Ledger W, Baird DT. First meiotic division abnormalities in human oocytes: Mechanisms of trisomy formation. Cytogenet Cell Genet. 1994;65:194–202. doi: 10.1159/000133631. [DOI] [PubMed] [Google Scholar]
- 14.Dailey T, Dale B, Cohen J, Munné S. Association between non-disjunction and maternal age in meiosis-II human oocytes detected by FISH analysis. Am J Hum Genet. 1996;59:176–184. [PMC free article] [PubMed] [Google Scholar]
- 15.Therman E, Susman M. Structure Behavior, and Effects. New York: Springer Verlag; 1993. Human Chromosomes. [Google Scholar]
- 16.Hamerton JL. Frequency of mosaicism, translocation and other variants of trisomy 21. In: De la Cruz F, Gerald B, editors. Trisomy 21 (Down Syndrome): Research Perspective. Baltimore: University Park Press; 1981. pp. 99–107. [Google Scholar]
- 17.Benadiva C, Kligman I, Grifo J, Munné S. Aneuploidy 16 in human embryos increases significantly with maternal age. Fertil Steril. 1996;66:248–255. [PubMed] [Google Scholar]
- 18.Márquez C, Cohen J, Munné S. 23-chromosome multi-color spectral karyotyping of human oocyte and polar bodies. Am J Hum Genet. 1997;61:A133. doi: 10.1159/000015040. [DOI] [PubMed] [Google Scholar]
- 19.Lindenbaum RH, Hulten M, McDermott A, Seabright M. The prevalence of translocations in parents of children with regular trisomy 21: A possible interchromosomal effect? J Med Genet. 1985;22:24–28. doi: 10.1136/jmg.22.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]