It has been known for many years that a woman's response to gonadotropin stimulation relates to the number of oocytes retrieved and the chance of pregnancy. This response typically declines as age increases, but is often seen unexpectedly in younger women. Often these women have had sub optimal tests of ovarian reserve, however.
In the woman whose IVF stimulation has been cancelled due to poor response, or the poor responder who has completed the cycle but failed to conceive, several strategies have been offered to enhance the response to stimulation. The standard IVF stimulation includes initiating a GnRH agonist in the luteal phase of the preceding cycle, then starting gonadotropin stimulation in the early follicular phase while continuing the GnRH agonist.
Protocols which have been used with some success in poor responders include discontinuation of the GnRH agonist when the gonadotropin therapy is started, a "flare" or "microflare" protocol in which both the GnRH agonist and gonadotropin are started in the early follicular phase, and the use of a new GnRH antagonist rather than an agonist. Although some programs have used human growth hormone, most authorities feel there is no therapeutic benefit.
Favorable results have been reported with the use of each of these regimens, however they are less promising in the women with high early follicular phase FSH levels and in older women. In those groups, as well as those that fail to respond to a change in the stimulation protocol, oocyte donation should be considered.
Poor oocyte or embryo quality
The most direct assessment of oocyte quality occurs in the IVF laboratory after oocyte retrieval. Microscopic examination of the oocyte may detect abnormalities such as vacuolization, cytoplasmic inclusions, and clustering of organelles. These oocytes will have a poor likelihood of yielding embryos of normal potential. It is known that oocytes may have nuclear or cytoplasmic abnormalities that are not visible in the clinical setting by light microscopy. The most common genetic oocyte abnormality results from an error in chromatid segregation in the first meiotic division.
The only sign of poor oocyte quality that is apparent in the IVF laboratory may be seen in subsequent development of the embryo. An embryo that is developing slowly or is highly fragmented is likely to be the result of oocyte abnormalities. Advancing age has been associated with lower cytoplasmic levels of ATP and poor embryo development. Recent data has shown that oocytes have a fundamental polarization during development, continuing into embryonic development. Lack of normal polarization has been shown to be related to developmental potential of the embryo. The location of cellular fragmentation related to this polarization in the embryo is likely to be of critical prognostic significance.
Although oocyte and embryo abnormalities in one cohort may not be predictive of the quality of oocytes and embryos in a subsequent IVF cycle, they are often seen repetitively in the same woman, especially in older women, women with abnormal tests of ovarian reserve, and in couples with unexplained infertility. In those cases, strong consideration should be given to oocyte donation rather than a repeat standard IVF attempt.
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