Hostname: page-component-594f858ff7-7tp2g Total loading time: 0 Render date: 2023-06-08T04:40:33.027Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "corePageComponentUseShareaholicInsteadOfAddThis": true, "coreDisableSocialShare": false, "useRatesEcommerce": true } hasContentIssue false

Cell and Molecular Biological Challenges of ICSI: ART before Science?

Published online by Cambridge University Press:  01 January 2021


The general perception of how innovative assisted reproductive technologies (ART) are introduced is through a carefully controlled series of experiments in an animal model, such as the mouse. Only after the technique has been proven can one consider confirmatory studies on mammals closely related to humans, such as rhesus monkeys or other nonhuman primates. With this background of a peer-reviewed body of well-established published data, there is sufficient foundation and rationale to propose a clinical investigation to a responsible human subjects institutional review board (IRB). IRBs weigh the benefits and risks of the new methods to human subjects, and then consider the appropriate informed consent procedures for the particular case. Only after a large number of clinical studies are performed at multiple sites and are peer reviewed can the efficacy and safety of the innovative approach be clearly evaluated. At that time, the potential therapy can be responsibly offered to suitable beneficiaries.

Copyright © American Society of Law, Medicine and Ethics 1998

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


See Bonduelle, M., “Prospective Follow-Up Study of 55 Children Born after Subzonal Inseminations and Intracytoplasmic Sperm Injection,” Human Reproduction, 9 (1994): 1765–67.Google Scholar
See Palermo, G., “Pregnancies after Intracytoplasmic Sperm Injection of Single Spermatozoon into an Oocyte,” Lancet, 340 (1992): 17-18; Palermo, G., “Sperm Characteristics and Outcome of Human Assisted Fertilization by Subzonal Insemination and Intracytoplasmic Sperm Injection,” Fertility and Sterility, 59 (1993): 826-35; Devroey, P., “Normal Fertilization of Human Oocytes after Testicular Sperm Extraction and Intracytoplasmic Sperm Injection,” Fertility and Sterility, 62 (1994): 639-41; Devroey, P., “Pregnancies after Testicular Sperm Extraction and Intracytoplasmic Sperm Injection in Non-Obstructive Azoospermia,” Human Reproduction, 10 (1995): 1457-60; and Silber, S. “The Use of Epididymal Sperm in Assisted Reproduction,” in Tesarik, J., ed., Male Factor in Human Infertility (Rome: Ares-Serono Symposia, 1994): 335–68.Google Scholar
A few reports have noted an increased frequency of sex chromosome anomalies. These need to be confirmed, but do not raise cautionary warnings sufficient to undermine this most significant advance in the treatment of male infertility. See, for example, In't Veld, P., “Sex Chromosomal Abnormalities and Intracytoplasmic Sperm Injection,” Lancet, 773 (1995): 346; Bonduelle, M., “Comparative Follow-Up Study of 130 Children Born after ICSI and 130 Children Born after IVF,” Human Reproduction, 10 (1995): 3327-31; and Tournaye, H., “Intracytoplasmic Sperm Injection (ICSI): The Brussels Experience,” Reproduction, Fertility and Development, 7 (1995): 269–79.Google Scholar
See Palermo, G., “Evolution of Pregnancies and Initial Follow-Up of Newborns Delivered after Intracytoplasmic Sperm Injection,” JAMA, 276 (1996): 1893–97; and Tournaye, H. Van Steirteghem, A., “ICSI Concerns Do Not Outweigh Its Benefits,” Journal of NIH Research, 9 (1997): 3540.Google Scholar
See Schatten, G., “The Centrosome and Its Mode of Inheritance: The Reduction of the Centrosome During Gameto-genesis and Its Restoration During Fertilization,” Developmental Biology, 165 (1994): 299-335; and Simerly, C., “The Paternal Inheritance of the Centrosome, the Cell's Microtubule-Organizing Center, in Humans and the Implications for Infertility,” Nature Medicine, 1 (1995): 4753.Google Scholar
See Hewitson, L., “The Cell Biological Basis of Intracytoplasmic Sperm Injection: Microtubule, Chromatin and Membrane Dynamics,” Molecular Biology of the Cell, 7 (1996): 3717.Google Scholar
See Schatten, , supra note 4.Google Scholar
See Gard, D., “γ-tubulin Is Asymmetrically Distributed in the Cortex of Xenopus laevis Oocytes,” Developmental Biology, 161 (1994): 131–40.CrossRefGoogle Scholar
See Compton, D.A. Cleveland, D.W., “NuMA, a Nuclear Protein Involved in Mitosis and Nuclear Reformation,” Current Opinions in Cell Biology, 6 (1994): 343-46; and Cleveland, D.W., “NuMA: A Protein Involved in Nuclear Structure Spindle Assembly, and Nuclear Reformation,” Trends in Cell Biology, 5 (1995): 6064.Google Scholar
See Hewitson, L., “Chromatin and DNA Configurations after Intracytoplasmic Sperm Injection in the Rhesus Monkey: Failures and Successes,” Biology of Reproduction, 55 (1996): 271-80; and Sutovsky, P., “Intracytoplasmic Sperm Injection for Rhesus Monkey Fertilization Results in Unusual Chromatin, Cytoskeletal, and Membrane Events, but Eventually Leads to Pronuclear Development and Sperm Aster Assembly,” Human Reproduction, 11 (1996): 1703–12.Google Scholar
See Huszar, G., “Correlation Between Sperm Creatine Phosphokinase Activity and Sperm Concentrations in Normospermic and Oligospermic Men,” Gamete Research, 19 (1988): 67-75; and Huszar, G. Vigue, L., “Incomplete Development of Human Spermatozoa Is Associated with Increased Creatine Phosphokinase Concentrations and Abnormal Head Morphology,” Molecular Reproduction and Development, 34 (1993): 292–98.Google Scholar
See Huszar, G., “Sperm Creatine Kinase Activity in Fertile and Infertile Oligospermic Men,” Journal of Andrology, 11 (1990): 40-46; and Huszar, G., “Sperm Creatine Phosphokinase M-Isoform Ratios and Fertilizing Potential of Men: A Blinded Study of 84 Couples Treated with In Vitro Fertilization,” Fertility and Sterility, 57 (1992): 882–88.CrossRefGoogle Scholar
See Huszar, G., “Creatine Kinase (CK) Immunocy-tochemistry of Human Hemizona-sperm Complexes: Selective Binding of Sperm with Mature CK-Staining Pattern,” Fertility and Sterility, 61 (1994): 136–42.CrossRefGoogle Scholar
See Huszar, G., “Sperm Plasma Membrane Remodeling During Spermiogenetic Maturation in Men: Relationship among Plasma Membrane 1,4-Galactosyl-Transferase, Cytoplasmic Creatine Phosphokinase, and Creatine Phosphokinase Isoform Ratios,” Biology of Reproduction, 56 (1997): 1020–24.CrossRefGoogle Scholar
See Huszar, , supra note 12.Google Scholar
See Hiramoto, Y., “Microinjection of the Live Spermatozoa into Sea Urchin Egg,” Experimental Cell Research, 27 (1962): 416–26.CrossRefGoogle Scholar
See Markert, C. Petters, R., “Homozygous Mouse Embryos Produced by Microsurgery,” Journal of Experimental Zoology, 201 (1977): 295-302; Ron-El, R., “Intracytoplasmic Sperm Injection in the Mouse,” Human Reproduction, 8 (1993): 128-34; and Kimura, Y. Yanagimachi, R., “Intracytoplasmic Sperm Injection in the Mouse,” Biology of Reproduction, 52 (1995): 709–20.Google Scholar
See Schatten, G., “Microtubule Configurations During Fertilization, Mitosis and Early Development in the Mouse and the Requirement for Egg Microtubule-Mediated Motility During Mammalian Fertilization,” Proceedings of the National Academy of Sciences, USA, 82 (1985): 4152-56; Schatten, G. Schatten, H., “Behavior of Centrosomes During Fertilization and Cell Division in Mouse Oocytes and in Sea Urchin Eggs,” Proceedings of the National Academy of Sciences, USA, 83 (1986): 105-09; and Hewitson, L., “Microtubule Organization and Chromatin Configurations in Hamster Oocytes During Fertilization, Parthenogenetic Activation and After Insemination with Human Sperm,” Biology of Reproduction, 57 (1997): 967–75.Google Scholar
See Simerly, , supra note 4; and Wu, G., “Microtubule and Chromatin Configurations During Fertilization and Early Development in Rhesus Monkeys, and Regulation by Intracellular Calcium Ions,” Biology of Reproduction, 55 (1996): 269–71.Google Scholar
See Navara, C., “Microtubule Organization in the Cow During Fertilization, Polyspermy, Parthenogenesis, and Nuclear Transfer: The Role of the Sperm Aster,” Developmental Biology, 162 (1994): 2940.Google Scholar
See Breed, W., “Distribution of Microtubules in Eggs and Early Embryos of the Marsupial, Monodelphis domestica,” Developmental Biology, 164 (1994): 230–40.Google Scholar
See Hewitson, L., “Homologous and Heterologous Intracytoplasmic Sperm Injection (ICSI): Cytoplasmic Source Affects Sperm Decondensation and Microtubule Organization,” unpublished (1998).Google Scholar
See Keefer, C., “Cleavage Development of Bovine Oocytes Fertilized by Sperm Injection,” Molecular Reproduction and Development, 25 (1990): 281–85.CrossRefGoogle Scholar
See Goto, K., “Fertilization by Sperm Injection in Cattle,” Theriogenology, 33 (1990): 238.Google Scholar
See Goto, K., “Blastocyst Formation Following Intracytoplasmic Injection of In-Vitro-Derived Spermatids into Bovine Oocytes,” Human Reproduction, 11 (1996): 824–29.Google Scholar
See Catt, J.W. Rhodes, S.L., “Comparative Intracytoplasmic Sperm Injection (ICSI) in Human and Domestic Species,” Reproduction, Fertility and Development, 7 (1995): 161–67.Google Scholar
See Sutovsky, P., “Binding of Oocyte Microvilli to the Perinuclear Theca of Fertilizing Sperm and Subsequent Theca Removal Constitute a Previously Unrecognized Step in Mammalian Fertilization,” Developmental Biology, 188 (1997): 7584.Google Scholar
See Tatham, B., “Centrifugation of Bovine Oocytes for Nuclear Micromanipulation and Sperm Microinjection,” Human Reproduction, 11 (1996): 1499–503.Google Scholar
See Hewitson, , supra note 21.Google Scholar
See Hewitson, , supra note 9; and Sutovsky, , supra note 9; and Wu, , supra note 18.Google Scholar
See Palermo, , supra note 3; and Tournaye, Steirteghem, Van, supra note 3.Google Scholar
See Schoysman, R., “Pregnancy after Fertilization with Human Testicular Sperm,” Lancet, 342 (1993): 1327-30; Tesarik, J., “Viable Embryos from Injection of Round Spermatids into Oocytes,” N. Engl. J. Med., 333 (1995): 525; and Tesarik, J., “Spermatid Injection into Human Oocytes. II. Clinical Application in the Treatment of Infertility Due to Non-Obstructive Azoospermia,” Human Reproduction, 11 (1996): 780–83.Google Scholar
See Patrizio, P., “Intracytoplasmic Sperm Injection (ICSI): Potential Genetic Concerns,” Human Reproduction, 10 (1995): 2520-23; Reijo, R., “Diverse Spermatogenic Defects in Humans Caused by Y Chromosome Deletions Encompassing a Novel RNA Binding Protein Gene,” Nature Genetics, 10 (1995): 383-93; Reijo, R., “Severe Oligozoospermia Resulting from Deletions of Azoospermia Factor Gene on Y Chromosome,” Lancet, 347 (1996): 1290-93; and Menke, D., “Expression of DAZ, an Azoospermia Factor Candidate, in Human Spermatozoa,” American Journal of Human Genetics, 60 (1997): 237–41.Google Scholar
See Vogt, P., “Microdeletions in Interval 6 of the Y Chromosome of Males with Idiopathic Sterility Point to Disruption of AZF, a Human Spermatogenesis Gene,” Human Genetics, 89 (1992): 91-96; see Reijo, , supra note 32; Pryor, J., “Microdeletions in the Y-Chromosome of Infertile Men,” N. Engl. J. Med., 336 (1997): 534-39; and Mulhall, J., “Azoospermic Men with Deletions of the DAZ Cluster Gene Are Capable of Completing Spermatogenesis, Fertilization, Normal Embryonic Development and Pregnancy with Retrieved Testicular Spermatozoa and ICSI,” Human Reproduction, 12 (1997): 503–08.Google Scholar
See Kent-First, M., “The Incidence and Possible Relevance of Y-Linked Microdeletions in Babies Born after Intracytoplasmic Sperm Injection and Their Infertile Fathers,” Molecular Human Reproduction, 2 (1998): 943–50.CrossRefGoogle Scholar
See Sutovsky, , supra note 9.Google Scholar
See Tesarik, (1995), supra note 31; Antinori, S., “Fertilization with Human Testicular Spermatids: Four Successful Pregnancies,” Human Reproduction, 12 (1997): 286-91; and Fishel, S., “Human Fertilization with Round and Elongated Spermatids,” Human Reproduction, 12 (1997): 336–40.Google Scholar
See Green, R.M., “Parental Autonomy and the Obligation Not to Harm One's Child Genetically,” Journal of Law, Medicine & Ethics, 25 (1997): 515.CrossRefGoogle Scholar
See Moretti, E., “Relationship among Head Size, Morphology and Chromosome Structure in Human Spermatozoa,” in 53rd Annual Meeting for the American Society for Reproductive Medicine (Birmingham: American Society for Reproductive Medicine, 1997): P-138.Google Scholar
See Lalwani, S., “Biochemical Markers of the Early and Late Spermatogenesis: Relationship Between the Lactate Dehydrogenase-X and Creatine Kinase-M Isoform Concentrations in Human Spermatozoa,” Molecular Reproduction and Development, 43 (1996): 495502.Google Scholar
See Bonduelle, M., “Prospective Follow-Up Study of 1987 Children Born after Intracytoplasmic Sperm Injection (ICSI),” Treatment of Infertility: The New Frontiers (1998): At 42.Google Scholar