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Research must continue on preimplantation genetic diagnosis methodologies
FERTILITY AND STERILITY威 VOL. 82, NO. 2, AUGUST 2004 Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Research must continue on preimplantation genetic diagnosis methodologies Alan Trounson, Ph.D. Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia
Further research is required to enable a larger pool of appropriate patients to benefit from preimplantation genetic diagnosis. (Fertil Steril威 2004;82:299. ©2004 by American Society for Reproductive Medicine.)
Progress on preimplantation genetic diagnosis (PGD) has been clinically welcomed, particularly by patients with inherited genetic disease. There are now options for couples who wish to avoid therapeutic abortion, which is necessary with conventional prenatal diagnosis. The application of highly accurate genomic diagnostic methodologies for simple cells is remarkable and a tribute to the innovation of molecular cell biologists. If the genomic mutation can be identified and confirmed to be present in the couple, it may be identified in the oocyte polar bodies or the individual cells of preimplantation embryos formed by IVF. Error rates are extremely small and well within the range of acceptance for patients since confirmation by prenatal testing is available. However, few IVF clinics throughout the world have the cell biopsy and molecular experience to provide this service.
Received September 17, 2003; revised and accepted September 17, 2003. Reprint requests: Jill McFadyean, Department of Physiology, Building 13F, Room FG29, Monash University, Wellington Road, Clayton, Victoria, Australia (FAX: 61-3-99055583; E-mail: jillian.mcfadyean@med. monash.edu.au). 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2003. 09.083
It is clear that aneuploidy and chromosome rearrangements are common in human embryos produced by IVF. Identification of these developmentally compromised embryos should increase the success rates for normal development of embryos transferred to patients, reduce the need for multiple embryos transferred in any one ovulatory cycle, and reduce the rate of miscarriage in IVF. Technology in this area has lagged, with identification of aneuploidy and rearrangements generally restricted to skilled individuals using multicolor fluorescence in situ hybridization (FISH) for a minority of chromosomes (usually 5–7). While it is evident that the miscarriage rate is decreased for the transferred embryos of IVF
patients examined for aneuploidy by FISH, there is no really compelling evidence that IVF pregnancy success rates are increased or that the number of embryos required for pregnancy is significantly decreased. The lack of wellcontrolled studies is commonly a lamentable characteristic of IVF clinical research. It is also claimed that assessment of fivecolor FISH in embryos is sufficient to identify the majority of aneuploid embryos, but there is a lack of confirmation using other techniques (e.g., fluorescent polymerase chain reaction) and there are problems in determining the mosaicism of chromosome numbers in cells of individual embryos. Despite these deficiencies, it is certainly important to continue research to increase the reliability of observations for embryos, automation of methodologies to remove subjective reading of FISH results, simplification of embryo biopsy methods, and continued development of alternative diagnostic techniques that can assess the majority of chromosomes and any potential rearrangements. The adoption of PGD worldwide has been relatively slow and restricted to a few clinics that are well resourced for molecular and cell biology capacity and for the necessary associated equipment. Until the technology is simplified and the evidence for improved IVF success rates is adequately demonstrated, PGD will remain a “boutique” option for IVF patients, an option that is available only under restricted circumstances. Further research is required to enable a larger pool of appropriate patients to benefit from PGD.
299
Research must continue on preimplantation genetic diagnosis methodologies Alan Trounson, Ph.D. Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia
Further research is required to enable a larger pool of appropriate patients to benefit from preimplantation genetic diagnosis. (Fertil Steril威 2004;82:299. ©2004 by American Society for Reproductive Medicine.)
Progress on preimplantation genetic diagnosis (PGD) has been clinically welcomed, particularly by patients with inherited genetic disease. There are now options for couples who wish to avoid therapeutic abortion, which is necessary with conventional prenatal diagnosis. The application of highly accurate genomic diagnostic methodologies for simple cells is remarkable and a tribute to the innovation of molecular cell biologists. If the genomic mutation can be identified and confirmed to be present in the couple, it may be identified in the oocyte polar bodies or the individual cells of preimplantation embryos formed by IVF. Error rates are extremely small and well within the range of acceptance for patients since confirmation by prenatal testing is available. However, few IVF clinics throughout the world have the cell biopsy and molecular experience to provide this service.
Received September 17, 2003; revised and accepted September 17, 2003. Reprint requests: Jill McFadyean, Department of Physiology, Building 13F, Room FG29, Monash University, Wellington Road, Clayton, Victoria, Australia (FAX: 61-3-99055583; E-mail: jillian.mcfadyean@med. monash.edu.au). 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2003. 09.083
It is clear that aneuploidy and chromosome rearrangements are common in human embryos produced by IVF. Identification of these developmentally compromised embryos should increase the success rates for normal development of embryos transferred to patients, reduce the need for multiple embryos transferred in any one ovulatory cycle, and reduce the rate of miscarriage in IVF. Technology in this area has lagged, with identification of aneuploidy and rearrangements generally restricted to skilled individuals using multicolor fluorescence in situ hybridization (FISH) for a minority of chromosomes (usually 5–7). While it is evident that the miscarriage rate is decreased for the transferred embryos of IVF
patients examined for aneuploidy by FISH, there is no really compelling evidence that IVF pregnancy success rates are increased or that the number of embryos required for pregnancy is significantly decreased. The lack of wellcontrolled studies is commonly a lamentable characteristic of IVF clinical research. It is also claimed that assessment of fivecolor FISH in embryos is sufficient to identify the majority of aneuploid embryos, but there is a lack of confirmation using other techniques (e.g., fluorescent polymerase chain reaction) and there are problems in determining the mosaicism of chromosome numbers in cells of individual embryos. Despite these deficiencies, it is certainly important to continue research to increase the reliability of observations for embryos, automation of methodologies to remove subjective reading of FISH results, simplification of embryo biopsy methods, and continued development of alternative diagnostic techniques that can assess the majority of chromosomes and any potential rearrangements. The adoption of PGD worldwide has been relatively slow and restricted to a few clinics that are well resourced for molecular and cell biology capacity and for the necessary associated equipment. Until the technology is simplified and the evidence for improved IVF success rates is adequately demonstrated, PGD will remain a “boutique” option for IVF patients, an option that is available only under restricted circumstances. Further research is required to enable a larger pool of appropriate patients to benefit from PGD.
299