Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial

  • Richard T. Scott Jr.
    Correspondence
    Reprint requests: Richard T. Scott Jr., M.D., Reproductive Medicine Associates of New Jersey, 140 Allen Road, Basking Ridge, New Jersey 07920.
    Affiliations
    Reproductive Medicine Associates of New Jersey, Morristown, New Jersey

    Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
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  • Kathleen M. Upham
    Affiliations
    Reproductive Medicine Associates of New Jersey, Morristown, New Jersey
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  • Eric J. Forman
    Affiliations
    Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey
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  • Tian Zhao
    Affiliations
    Reproductive Medicine Associates of New Jersey, Morristown, New Jersey
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  • Nathan R. Treff
    Affiliations
    Reproductive Medicine Associates of New Jersey, Morristown, New Jersey

    Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey

    Department of Genetics, Rutgers–State University of New Jersey, Piscataway, New Jersey
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      Objective

      To determine if cleavage- or blastocyst-stage embryo biopsy affects reproductive competence.

      Design

      Paired randomized clinical trial.

      Setting

      Academic-assisted reproduction program.

      Patient(s)

      Attempting conception through IVF.

      Intervention(s)

      After selecting two embryos for transfer, one was randomized to biopsy and the other to control. Both were transferred within shortly thereafter. The biopsy was submitted for microarray analysis and single-nucleotide polymorphism (SNP) profiling. Buccal DNA obtained from the neonate after delivery had microarray analysis and SNP profile compared with that of the embryonic DNA. A match confirmed that the biopsied embryo implanted and developed to term, whereas a nonmatch indicated that the control embryo had led to the delivery.

      Main Outcome Measure(s)

      Paired analysis of the delivery rates of the transferred embryos. Either twin delivery or failure to deliver represents equivalent outcomes for the biopsied and control embryos. In contrast, singletons were determined to be from the biopsied or the control embryo.

      Result(s)

      Blastomere biopsy on day 3 of development resulted in a significant reduction in sustained implantation. Only 30% of biopsied embryos had sustained implantation and ultimately developed into live-born infants versus 50% of unbiopsied controls, a relative reduction of 39%. In contrast, sustained implantation rates were equivalent (51% vs. 54%) for biopsied and control blastocysts.

      Conclusion(s)

      Cleavage-stage biopsy markedly reduced embryonic reproductive potential. In contrast, trophectoderm biopsy had no measurable impact and may be used safely when embryo biopsy is indicated.

      Clinical Trial Registration Number

      Key Words

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