Preclinical Models for Human Pre-embryo Biopsy and Genetic Diagnosis. I. Efficiency and Normalcy of Mouse Pre-embryo Development After Different Biopsy Techniques

Objective: To compare the usefulness of three micromanipulative methods at two different stages of pre-embryo development and to assess possible effects on postbiopsy survival and development.

Design: Four-cell and eight-cell mouse pre-embryos were biopsied using enucleation, aspiration, or extrusion of single blastomeres. After biopsy, pre-embryos were observed for in vitro and in vivo development.

Setting: Laboratories of The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School.

Patients, Participants: Only mice were used.

Interventions: Pre-embryo biopsy, developmental normalcy and pre-embryo transfer were studied.

Main Outcome Measure(s): Few pre-embryos died as a result of biopsy trauma. High postbiopsy survival rates were associated with normal intrauterine and postnatal development.

Results: Expanded blastocyst formation rates from four-cell and eight-cell pre-embryos were 94.6%, 96.7% (controls); 80.7%, 89.1% (enucleation); 90.1%, 91.7% (aspiration); 83.1%, 91.5% (extrusion), respectively. Live birth rates at the four-cell stage were slightly lower in the enucleation group than in the blastomere aspiration and extrusion groups or controls (49.2% versus 58.8%, 56.3% and 66.7%, respectively). For the eight-cell stage, there were no differences between the groups. No developmental abnormalities were found in body or organ weights, in neonates or at 3 weeks of age, or in their subsequent ability to reproduce a second generation.

Conclusions: Biopsy of mouse pre-embryos produces only a small loss of viability because of trauma and permits normal prenatal and postnatal development among surviving pre-embryos.