Journal of Assisted Reproduction and Genetics, Vol. 9, No. 5, 1992
GENETICS
Preimplantation Genetics Two First Steps
Preimplantation genetic diagnosis has been developed for couples at high genetic risk. It circumvents the need for prenatal diagnosis and subsequent termination of affected fetuses in order to avoid the birth of affected children. This promising diagnostic technique has therefore a great appeal for many couples. With publications from two different centers that reported births following preimplantation genetic diagnosis, the field of preimplantation genetics took, in the last 6 months, another two steps forward. Investigators at Cornell University reported the birth of a normal girl following preimplantation sexing of embryos from a carrier mother with the X-linked disorder hemophilia A (1). Workers in London, in collaboration with workers at Baylor, announced the first birth following the preimplantation genetic diagnosis for a single gene disorder. An unaffected girl was born following preimplantation diagnosis for cystic fibrosis (2). In both of these cases, the procedure of biastomere biopsy followed by single cell polymerase chain reaction (PCR) was used for genetic analysis. It is important to note that, as expected, the removal of a single blastocyst from a preimplantation embryo has led to no deleterious effects on the fetus. In addition, it is becoming clear that PCR, using the appropriate internal controls, is capable of accurately analyzing the genotype of a single cell. Concerns regarding the potential of genetic mosaicism in preimplantation embryos has not materialized as an important problem in preimplantation genetics. With respect to animal models for human preimplantation diagnosis, encouraging work has come from workers at the Eastern Virginia Medical School who performed an elegant series of experiments using preimplantation genetic analysis from mouse blastomeres for the X-linked recessive sparse fur
mutation (ornithine transcarbamylase) from a total of 168 blastomeres. This work demonstrated that in the mouse, blastomere biopsy followed by PCR analysis is both accurate and reliable (3). While Handyside and colleagues were developing the techniques of bfastomere biopsy, other groups have been working toward the development of alternative methods of human preimplantation diagnosis. This includes preconception genetic diagnosis by polar body removal (4), and blastocyst biopsy following embryo lavage (5,6). Progress in the field of human preimplantation genetics has been painfully slow. This is probably due to a combination of factors. The lack of funding by the United States National Institute of Health for any research involving human embryos (including assisted reproductive technologies) has certainly limited the number of centers able to institute a program of human preimplantation research. Current regulations make it impossible to perform preliminary experiments using human embryonic material in the United States (7). In addition, preimplantation genetics requires a dedicated team of fertility specialists, embryologists, and molecular geneticists who work in a strong cooperative effort. Third, current methods of in vitro fertilization and embryo transfer are expensive and are accompanied by significant discomfort to patients with no guarantee of immediate success. Despite these limitations, many couples are willing to participate in clinical trials of preimplantation diagnosis and teams of researchers are struggling to establish a potentially valuable diagnostic technique. The pioneering work of Dr. Handyside and his colleagues has taken preimplantation genetic diagnosis for Mendelian diseases from a feasible hypothesis to reality. Hopefully, this will encourage other groups to develop programs for preimplantation genetic diagnosis. Until several more centers begin actively pursuing these techniques, the progress in this exciting field will unfortunately remain painfully slow.
The opinions presented in this column are those of its author(s) and do not necessarily reflect those of the journal and its editors, publisher, and advertisers. 1058-0468/92/1000-042250&5010 © 1992 Plenum Publishing Corporation
422
PREIMPLANTATIONGENETICS
REFERENCES 1. Grifo JA, Tang YX, Cohen J, Gilbert F, Sanyal MK, Rosenwaks Z: Pregnancy after embryo biopsy and coamplification of DNA from X and Y chromosomes. JAMA 1992;268:727729 2. 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 Eng J Med 1992;327:905-909 3. Morsey M, Takeuchi K, Kaufmann R, Veeck I_, Hodgen GD, Beebe SJ: Preclinical models for human pre-embryo biopsy and genetic diagnosis II. Polymerase chain reaction amplification of DNA from single lymphoblasts and blastomeres with mutation detection. Fert Steril 1992;327:951-953 4. Verlinsky Y, Rechitsky S, Evisikov S, White M, Ciestak M, Lifchez A, Valle J, Moise J, Strom CM: Preconception and
Journal of Assisted Reproduction and Genetics, Vol. 9, No. 5, 1992
423 preimptantation diagnosis for cystic fibrosis. Prenat Diag 1992;12:130-110 5. Brambati B, Formigli L: Uterine lavage for preimplantation genetic diagnosis. In Preimplantation Genetics, Y Verlinsky, A Kuliev (eds). New York, Plenum Press, 1991, pp 165-174 6. Carson S: Biopsy of blastocyst. In Preimplantation Genetics, Y Verlinsky, A Kuliev (eds). New York, Plenum Press, 1991, pp 85-90 7. Simpson JL, Carson SA: Preimplantation genetic diagnosis (editorial). N Eng J Med 1992;327:951-953
Charles IVl. Strom Illinois Masonic Medical Center Department of Obstetrics and Gynecology
836 W. Wellington Chicago, Illinois 60657
GENETICS
Preimplantation Genetics Two First Steps
Preimplantation genetic diagnosis has been developed for couples at high genetic risk. It circumvents the need for prenatal diagnosis and subsequent termination of affected fetuses in order to avoid the birth of affected children. This promising diagnostic technique has therefore a great appeal for many couples. With publications from two different centers that reported births following preimplantation genetic diagnosis, the field of preimplantation genetics took, in the last 6 months, another two steps forward. Investigators at Cornell University reported the birth of a normal girl following preimplantation sexing of embryos from a carrier mother with the X-linked disorder hemophilia A (1). Workers in London, in collaboration with workers at Baylor, announced the first birth following the preimplantation genetic diagnosis for a single gene disorder. An unaffected girl was born following preimplantation diagnosis for cystic fibrosis (2). In both of these cases, the procedure of biastomere biopsy followed by single cell polymerase chain reaction (PCR) was used for genetic analysis. It is important to note that, as expected, the removal of a single blastocyst from a preimplantation embryo has led to no deleterious effects on the fetus. In addition, it is becoming clear that PCR, using the appropriate internal controls, is capable of accurately analyzing the genotype of a single cell. Concerns regarding the potential of genetic mosaicism in preimplantation embryos has not materialized as an important problem in preimplantation genetics. With respect to animal models for human preimplantation diagnosis, encouraging work has come from workers at the Eastern Virginia Medical School who performed an elegant series of experiments using preimplantation genetic analysis from mouse blastomeres for the X-linked recessive sparse fur
mutation (ornithine transcarbamylase) from a total of 168 blastomeres. This work demonstrated that in the mouse, blastomere biopsy followed by PCR analysis is both accurate and reliable (3). While Handyside and colleagues were developing the techniques of bfastomere biopsy, other groups have been working toward the development of alternative methods of human preimplantation diagnosis. This includes preconception genetic diagnosis by polar body removal (4), and blastocyst biopsy following embryo lavage (5,6). Progress in the field of human preimplantation genetics has been painfully slow. This is probably due to a combination of factors. The lack of funding by the United States National Institute of Health for any research involving human embryos (including assisted reproductive technologies) has certainly limited the number of centers able to institute a program of human preimplantation research. Current regulations make it impossible to perform preliminary experiments using human embryonic material in the United States (7). In addition, preimplantation genetics requires a dedicated team of fertility specialists, embryologists, and molecular geneticists who work in a strong cooperative effort. Third, current methods of in vitro fertilization and embryo transfer are expensive and are accompanied by significant discomfort to patients with no guarantee of immediate success. Despite these limitations, many couples are willing to participate in clinical trials of preimplantation diagnosis and teams of researchers are struggling to establish a potentially valuable diagnostic technique. The pioneering work of Dr. Handyside and his colleagues has taken preimplantation genetic diagnosis for Mendelian diseases from a feasible hypothesis to reality. Hopefully, this will encourage other groups to develop programs for preimplantation genetic diagnosis. Until several more centers begin actively pursuing these techniques, the progress in this exciting field will unfortunately remain painfully slow.
The opinions presented in this column are those of its author(s) and do not necessarily reflect those of the journal and its editors, publisher, and advertisers. 1058-0468/92/1000-042250&5010 © 1992 Plenum Publishing Corporation
422
PREIMPLANTATIONGENETICS
REFERENCES 1. Grifo JA, Tang YX, Cohen J, Gilbert F, Sanyal MK, Rosenwaks Z: Pregnancy after embryo biopsy and coamplification of DNA from X and Y chromosomes. JAMA 1992;268:727729 2. 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 Eng J Med 1992;327:905-909 3. Morsey M, Takeuchi K, Kaufmann R, Veeck I_, Hodgen GD, Beebe SJ: Preclinical models for human pre-embryo biopsy and genetic diagnosis II. Polymerase chain reaction amplification of DNA from single lymphoblasts and blastomeres with mutation detection. Fert Steril 1992;327:951-953 4. Verlinsky Y, Rechitsky S, Evisikov S, White M, Ciestak M, Lifchez A, Valle J, Moise J, Strom CM: Preconception and
Journal of Assisted Reproduction and Genetics, Vol. 9, No. 5, 1992
423 preimptantation diagnosis for cystic fibrosis. Prenat Diag 1992;12:130-110 5. Brambati B, Formigli L: Uterine lavage for preimplantation genetic diagnosis. In Preimplantation Genetics, Y Verlinsky, A Kuliev (eds). New York, Plenum Press, 1991, pp 165-174 6. Carson S: Biopsy of blastocyst. In Preimplantation Genetics, Y Verlinsky, A Kuliev (eds). New York, Plenum Press, 1991, pp 85-90 7. Simpson JL, Carson SA: Preimplantation genetic diagnosis (editorial). N Eng J Med 1992;327:951-953
Charles IVl. Strom Illinois Masonic Medical Center Department of Obstetrics and Gynecology
836 W. Wellington Chicago, Illinois 60657
