There are a number of incidences where young patients may wish to protect and/or preserve their future fertility. Fertility preservation may, for example, be advocated in girls and adolescents undergoing surgical interventions where the ovaries must be removed as a consequence of abdominal trauma. For adolescents and young women who have a familial history of premature ovarian failure, it may be foolhardy to delay child-bearing (Conway 2001; Davis etal. 2000). These patients may elect to preserve their oocytes or ovarian tissue to prolong their reproductive lifespan. Girls with Turner Syndrome have a very high risk of premature menopause or, in the most severe cases, they may be permanently sterile. The former group of individuals may elect to cryopreserve their ovarian tissue during their pre-pubertal or early teenage years before their ovarian reserve is completely lost and menopause ensues (Hreinsson etal. 2002; Saenger etal. 2001).
The overwhelming application of fertility preservation techniques to date is to those patients who are at risk of temporarily or permanently losing their fertility as a result of cancer treatment. For this group of patients the documented late effects of pelvic irradiation, with or without treatment with alkylating chemotherapy agents,1 include reduced pregnancy rates in young women and a high risk of partial or total ovarian failure (Meirow 2000; Meirow and Nugent 2001). While the preservation of fertility in young cancer patients forms the main focus of this review, the biology surrounding the onset of early menopause and the methods used to preserve and restore the fertility of cancer patients can be applied to any young patient, regardless of diagnosis, who is at risk of premature loss of their ovarian function.
Irrespective of the diagnosis of a young patient it is clear that, in the ovary, the number of oocytes is limited, it is fixed since fetal life, and it cannot be regenerated (Faddy et al. 1992). When the reserve of the earliest staged primordial follicles and the primordial oocytes they contain has been exhausted (on average this would occur naturally in women around age 50) menopause occurs. Thus, surgical removal of ovarian tissue or exposure to radiation or alkylating agents and platinum compounds will permanently and prematurely deplete the ovarian reserve and so render young patients of any age temporarily or even permanently infertile (Bath etal. 2001; Meirow 2000; Wallace, Thomson and Kelsey 2003). Furthermore, it appears that the extent of gonadal damage induced by irradiation or chemotherapy depends on the patient's gender, age at the time of treatment, radiation dose and fractionation schedule and the total dose and nature of chemotherapy delivered (Grundy etal. 2001a). Partial or total loss of fertility is particularly relevant to young girls who, in the event of ovarian failure, are faced with the prospect of lifelong hormone replacement therapy - a regime that is not, in itself, risk free. Until such a time as medical treatments can be directly targeted to malignant cells, health care professionals are faced with the challenge of not only devising improved treatment strategies that protect the individual's well-being, but also of developing and implementing protocols that will protect and/or conserve the fertility of these young patients.
The options for preserving the fertility of young female patients range from no medical intervention at all to the use of invasive procedures to harvest tissues or isolated cells from the ovaries. Each method has its own advantages, disadvantages and risks. The approaches that can be used to protect the fertility of girls and adolescents can be divided into three broad categories: prediction of ovarian damage; protection of the ovaries; and preservation of oocytes (Table 5.1).
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