1 Centre for Reproductive Biology, Clinica Villa Del Sole, Via Manzoni, 15, 80123 Naples, 2 Dipartimento Clinico di Emergenza Ostetrica e Ginecologica e Medicina della Riproduzione, Azienda Universitaria Policlinico, Università degli Studi `Federico II', Via S. Pansini, 5, 80131 Naples, 3 Clinica Ruesch, Via Maria Cristina Di Savoia, 39, 80123 Naples and 4 Istituto di Clinica Ginecologia, II Università di Napoli, Largo Madonna delle Grazie, 80128 Naples, Italy
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Abstract |
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Key words: apoptosis/cytoplasmic transfer/IVF/oocyte reconstruction/preimplantation embryo
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Introduction |
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A recently developed alternative to oocyte donation has been termed `cytoplasmic donation' (Cohen et al., 1997, 1998
). In this technique, a fraction of cytoplasm from a donor oocyte is injected into a recipient oocyte prior to fertilization with the intracytoplasmic sperm injection (ICSI) technique. The presence of extraneous cytoplasm appears to increase the quality of the recipient oocyte to the level where the embryo produced is viable, although a measurable improvement in embryo quality does not always occur after cytoplasmic transfer. The mechanism of action of the technique is unknown.
In this case report, we describe the application of cytoplasmic donation to a couple affected by highly fragmented embryos after ICSI. The donation of cytoplasm to the couple's oocytes appeared to result in a reduction in the level of embryo fragmentation and an increase in the number of blastomeres present in the embryo on day 3. The couple had attempted ICSI 3 times without success prior to the cycle of cytoplasmic donation. With the treatment, the couple achieved a pregnancy and the birth of healthy twins.
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Case report |
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Discussion |
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Idiopathic infertility is often characterized by poor embryo quality including high levels of embryo fragmentation and slow preimplantation development. The routine use of assisted hatching and fragment removal, although successful, often fails in patients severly affected by embryo fragmentation combined with poor embryo development (Cohen et al., 1992; Alikani et al., 1993
). In these cases, cytoplasmic donation appears to be a powerful alternative to the only other option presently available, donation of oocytes. It has been suggested that fragmentation of developing embryos occurs due to the activation of apoptosis in individual blastomeres (Juriscova et al., 1996
). It is not currently understood how this can occur, and current evidence suggests that this process is not a response to abnormalities in chromosome segregation during meiosis or mitosis (Munné et al., 1993
; Harper et al., 1995
; Delhanty et al., 1997; Munné and Cohen, 1998
). If embryo fragmentation is an aptotic mechanism, the expression of apoptosis in developing embryos may be due to the erroneous activation of the pathway during oogenesis or spermatogenesis (De Pol et al., 1997
; Brill et al., 1999
) and its consequent expression in the preimplantation embryo (Brenner et al., 1997
). It is not known whether low levels of fragmentation have any physiological function during preimplantation development, although hypotheses have been proposed (Antczak and Van Blerkom 1999
; Edwards and Beard, 1999
).
It is not currently understood how the donation of cytoplasm from one oocyte to another can raise the potential for the recipient to form embryos of sufficient quality to implant and give rise to healthy individuals. One current hypothesis is that the transfer of mitochondria from good quality oocytes to poor permits the increased production of energy, enabling the recipient oocyte to produce sufficient metabolic products for normal development (Van Blerkom et al., 1998; Wilding et al., 2001
). Although this hypothesis may be partially correct, the introduction of mitochondria may not be the only mechanism of action of donated cytoplasm. A second hypothesis is that the transfer of `good' quality cytoplasm inhibits the erroneous fragmentation by introducing inhibitory factors (proteins or RNAs). mRNAs of proteins involved in apoptosis have been found in human oocytes and embryos (Brenner et al., 1997
). However, the high level of functional redundancy in the induction of apoptosis (White, 1996
; Rao and White, 1997
) suggests that elucidation of the function of these proteins in preimplantation human embryos will not be an easy task.
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Acknowledgements |
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Notes |
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References |
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Submitted on May 30, 2000; accepted on March 14, 2001.