Infertility Clinical Trial
Official title:
Oocytes Cryopreservation: The Impact of Cryopreservation on the Meiotic Spindle and Mitochondria of Human Oocytes.
Our aims is to document the possible effect of cryo- preservation at the meiotic spindle and mitochondrial levels.
The cryopreservation of oocytes (OC) has broad applications in the field of reproductive
endocrinology for the management of clinical problems in both fertile and infertile
patients. For example, young fertile women who are diagnosed with malignancies may freeze
their oocytes before initiating potentially toxic radiation or chemical cancer therapy which
may render them sterile.
Using the OC technology, we have established a frozen oocyte bank using healthy, compensated
egg donors who have been pre- screened using FDA criteria. Following an appropriate
quarantine time, oocytes can be thawed and offered to women diagnosed with premature ovarian
failure or diminished ovarian reserve. This application of OC has already shown promise by
eliminating the logistical and clinical complications associated with traditional oocyte
donation using fresh oocytes from donors.
From the societal perspective, cryopreservation of surplus oocytes in an IVF cycle may
remove some of the social and moral objections surrounding embryo cryopreservation.
Currently, our frozen oocyte pregnancy rate (56%) is equivalent to our frozen embryo
pregnancy rate (45%). Patients, who have completed their families, find it easier to discard
oocytes versus embryos.
Finally, women who make a personal choice to delay childbearing may be offered the option to
preserve their oocytes with the potential for later use.
The two distinct techniques currently being used for oocyte cryopreservation are: 1)
controlled-rate freezing and 2) vitrification. Controlled-rate freezing shares some
similarities with the basic technology employed for embryo cryopreservation in nearly every
IVF program. The technique involves the slow freezing of embryos in cryoprotectant
solutions, often combined with a computer-controlled freezer to regulate temperature
changes. Attempts to improve our understanding of oocyte cryobiology have been mostly
empirical using trial and error. Only limited experience has been gained by adopting
scientific models able to predict the effect of "cryo" stress imposed on oocytes using
various freezing methods (Fuller and Paynter, 2004; Paynter, 2005). In the absence of
properly designed studies, advances in clinical experience with oocyte freezing have been
very limited. One of the major obstacles to the implementation of oocyte freezing had been
the inability to achieve reproducible high survival rates owing to an important effect on
the intracellular organelles. For example, due to its sensitivity at low temperature, the
metaphase II spindle has always been considered susceptible to structural alterations which
potentially might interfere with normal chromosome segregation at meiosis II. Additionally,
the essential role of mitochondria in normal cell function, fertilization and early embryo
development has previously been described (Jones et al., 2004).
Our recently developed modified freeze-thaw protocol has consistently shown high recovery
rates, leading to optimism that oocyte storage could at last become available in clinical
practice. But it remains to be demonstrated that excellent post-thaw survival coincides with
cellular integrity and unaltered developmental competence. Therefore, prior to recommending
the adoption of oocyte cryopreservation, one of our aims is to document the possible effect
of cryo- preservation at the meiotic spindle and mitochondrial levels. An important aim of
our study is to assess the post-thaw viability and organelle integrity of oocytes using: 1)
a conservative technique [PolScope analysis of meiotic spindle] and 2) a non-conservative
technique [Fluorescence microscopy analysis of the meiotic spindle and mitochondria] using
our oocyte cryopreservation protocol.
Continuing development in freezing technology is occurring rapidly. It can be anticipated
that in the near future, egg freezing will become as successful as embryo cryopreservation.
Finally, as more clinical experience with egg freezing accumulates, acceptable outcome data
will determine the future of egg freezing. Until then, oocyte cryopreservation should be
used in carefully selected clinical cases with full disclosure to the patient regarding
risks and limited success rates.
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