| Autor: |
Scriven PN; 1] Guy's & St Thomas' Centre for PGD, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK [2] Division of Genetics & Molecular Medicine, King's College London, School of Medicine at Guy's, King's College & St Thomas' Hospitals, London, UK., Bint SM; 1] Guy's & St Thomas' Centre for PGD, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK [2] Cytogenetics department, GSTS-Pathology, Guy's & St. Thomas' NHS Foundation Trust, London, UK., Davies AF; 1] Guy's & St Thomas' Centre for PGD, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK [2] Cytogenetics department, GSTS-Pathology, Guy's & St. Thomas' NHS Foundation Trust, London, UK., Ogilvie CM; 1] Guy's & St Thomas' Centre for PGD, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK [2] Division of Genetics & Molecular Medicine, King's College London, School of Medicine at Guy's, King's College & St Thomas' Hospitals, London, UK [3] Genetics Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK. |
| Abstrakt: |
Our study provides an analysis of the outcome of meiotic segregation of three-way translocations in cleavage-stage embryos and the accuracy and limitations of preimplantation genetic diagnosis (PGD) using the fluorescence in situ hybridization technique. We propose a general model for estimating reproductive risks for carriers of this class of complex chromosome rearrangement. The data presented describe six cycles for four couples where one partner has a three-way translocation. For male heterozygotes, 27.6% of embryos were consistent with 3:3 alternate segregation resulting in a normal or balanced translocation chromosome complement; 41.4% were consistent with 3:3 adjacent segregation of the translocations, comprising 6.9% reflecting adjacent-1 and 34.5% adjacent-2 segregation; 24.1% were consistent with 4:2 nondisjunction; none showed 5:1 or 6:0 segregation; the probable mode could not be ascertained for 6.9% of embryos due to complex mosaicism or nucleus fragmentation. The test accuracy for male heterozygotes was estimated to be 93.1% with 100% sensitivity and 75% specificity. With 72.4% prevalence, the predictive value was estimated to be 91.3% for an abnormal test result and 100% for a normal test result. Two of four couples had a healthy baby following PGD. The proportion of normal/balanced embryo could be significantly less for female heterozygotes, and our model indicates that this could be detrimental to the effectiveness of PGD. A 20% risk of live-born offspring with an unbalanced translocation is generally accepted, largely based on the obstetric history of female heterozygotes; we suggest that a 3% risk may be more appropriate for male carriers. |
