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Predictive value of sperm chromosome analysis on the outcome of PGD for translocations.

2001; Elsevier BV; Volume: 76; Issue: 3 Linguagem: Inglês

10.1016/s0015-0282(01)02252-x

1556-5653

T. Escudero, Iman Abdelhadi, M. Sandalinas, S. Munné,

Genomic variations and chromosomal abnormalities

Objective: Carriers of translocations are at high risk of infertility, recurrent miscarriages, and chromosomally abnormal offspring. PGD of translocations has been demonstrated to be an effective method to reduce those risks. Often, however, most of the embryos analyzed by PGD are abnormal and no normal or balanced embryos are left for replacement. The objective of this study was to determine the predictive value of chromosome sperm analysis to foresee which patients will have a good prognosis of pregnancy after PGD for translocations.Design: Prospective study comparing chromosome abnormalities in sperm and in embryos after PGD analysis in carriers of reciprocal translocations.Materials/Methods: PGD was performed in 11 males carriers of translocations using a using a three-color scheme combination of two telomeric probes and a centromeric probe, or two centromeric probes and a telomeric one, for the chromosomes involved in the translocation. The same probes were previously used to analyze the sperm chromosome constitution of at least 1000 spermatozoa per patient. Embryo biopsy was performed in all embryos with more than 3 cells on day 3 of development. Only one cell was biopsied, and only normal or balanced embryos were replaced.Results: The frequency of unbalanced sperm cells ranged from 21% to 73%, with an average of 65%. The frequency of abnormal embryos detected after PGD ranged from 42% to 100%, with an average of 72%. There was good coincidence between sperm and PGD results in most patients. Substantial differences between sperm and PGD results were due to the presence other chromosome abnormalities in embryos (mosaicism, polyploidy, haploidy). Although we analyzed only 11 patients a very clear trend was observed in that patients with more than 65% abnormal sperm or 70% abnormal embryos did not achieved any successful pregnancy.Predictive value of chromosome sperm analysis. Tabled 1Translocation% Abnormal spermPGD cycles% Abnormal embryos# embryoscycle outcome46,XY,t(11;22)78.2181.811not pregnant46,XY,t(6;9)76.5180.05spontaneous abortion46,XY,t(08;22)76.2175.04not pregnant46,XY,t(3;4)76.1188.217not pregnant46,XY,t(1;18)70.9180.05not pregnant46,XY,t(02;18)69.0187.58not pregnant46,XY,t(1;13)63.0164.514ongoingmos46,XY,t(03;12)/46,XY58.7170.010ongoing46,XY,t(5;15)54.1141.712ongoing45,XY,t(13;14)26.4665.9412 delivered, 1 on-going, 3 not pregnant Open table in a new tab Conclusions: As published before there is a 20-30% baseline of chromosome abnormalities in human embryos produced in vitro. If that baseline is combined with the rate of chromosome abnormalities detected in sperm of translocation carriers, the result is very close to the frequency of chromosome abnormalities observed after PGD. Therefore sperm chromosome analysis seems to be a very good predictor of chromosome abnormalities and pregnancy outcome in translocation carriers. Males with more than 65% chromosomally abnormal sperm will have problems conceiving after PGD, and patients with much higher rates of abnormalities should maybe consider sperm donation.Supported By: The Institute for Reproductive Medicine and Science of saint Barnabas, NJ-07052; Vysis Inc., Downers Grove IL 60515, USA. Objective: Carriers of translocations are at high risk of infertility, recurrent miscarriages, and chromosomally abnormal offspring. PGD of translocations has been demonstrated to be an effective method to reduce those risks. Often, however, most of the embryos analyzed by PGD are abnormal and no normal or balanced embryos are left for replacement. The objective of this study was to determine the predictive value of chromosome sperm analysis to foresee which patients will have a good prognosis of pregnancy after PGD for translocations. Design: Prospective study comparing chromosome abnormalities in sperm and in embryos after PGD analysis in carriers of reciprocal translocations. Materials/Methods: PGD was performed in 11 males carriers of translocations using a using a three-color scheme combination of two telomeric probes and a centromeric probe, or two centromeric probes and a telomeric one, for the chromosomes involved in the translocation. The same probes were previously used to analyze the sperm chromosome constitution of at least 1000 spermatozoa per patient. Embryo biopsy was performed in all embryos with more than 3 cells on day 3 of development. Only one cell was biopsied, and only normal or balanced embryos were replaced. Results: The frequency of unbalanced sperm cells ranged from 21% to 73%, with an average of 65%. The frequency of abnormal embryos detected after PGD ranged from 42% to 100%, with an average of 72%. There was good coincidence between sperm and PGD results in most patients. Substantial differences between sperm and PGD results were due to the presence other chromosome abnormalities in embryos (mosaicism, polyploidy, haploidy). Although we analyzed only 11 patients a very clear trend was observed in that patients with more than 65% abnormal sperm or 70% abnormal embryos did not achieved any successful pregnancy. Predictive value of chromosome sperm analysis. Tabled 1Translocation% Abnormal spermPGD cycles% Abnormal embryos# embryoscycle outcome46,XY,t(11;22)78.2181.811not pregnant46,XY,t(6;9)76.5180.05spontaneous abortion46,XY,t(08;22)76.2175.04not pregnant46,XY,t(3;4)76.1188.217not pregnant46,XY,t(1;18)70.9180.05not pregnant46,XY,t(02;18)69.0187.58not pregnant46,XY,t(1;13)63.0164.514ongoingmos46,XY,t(03;12)/46,XY58.7170.010ongoing46,XY,t(5;15)54.1141.712ongoing45,XY,t(13;14)26.4665.9412 delivered, 1 on-going, 3 not pregnant Open table in a new tab Conclusions: As published before there is a 20-30% baseline of chromosome abnormalities in human embryos produced in vitro. If that baseline is combined with the rate of chromosome abnormalities detected in sperm of translocation carriers, the result is very close to the frequency of chromosome abnormalities observed after PGD. Therefore sperm chromosome analysis seems to be a very good predictor of chromosome abnormalities and pregnancy outcome in translocation carriers. Males with more than 65% chromosomally abnormal sperm will have problems conceiving after PGD, and patients with much higher rates of abnormalities should maybe consider sperm donation. Supported By: The Institute for Reproductive Medicine and Science of saint Barnabas, NJ-07052; Vysis Inc., Downers Grove IL 60515, USA.