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The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial. With the initial dose of GnRHa, the pituitary gland releases endogenous gonadotropins. This initial follicle stimulating hormone (FSH) release stimulates the ovary. After continued GnRHa exposure, further FSH release is prevented. Gonadotropin-releasing hormone analogues can be administered in many formulations with different durations of action. The most common side effects of GnRH analogues are related to the subsequent estrogen deprivation. Vasomotor symptoms, hot flushes, night sweats, vaginal dryness and headaches can occur. Cotherapy of a GnRHa during chemotherapy has been under investigation since the mid 1990s. If prolonged GnRHa administration decreases ovarian blood flow, then less chemotherapy may reach the ovary. Direct effects of GnRHa or FSH on ovarian tissue may influence ovarian response to chemotherapy. For GnRHa to be of benefit to fertility preservation, they would likely need to spare both oocyte quantity and quality.
The ovaries are very sensitive to cytotoxic treatment, especially to alkylating agents. It is clear that high doses of alkylating agents, irradiation, and advancing age all increase the risk of gonadal damage. This chapter presents the oncological indications for ovarian tissue cryopreservation. Cryopreservation of oocytes can be performed in postpubertal patients who are able to undergo a stimulation cycle, but the effectiveness of this technique is still low, with delivery rates from 1 to 5% for frozen-thawed oocytes using the slow-cooling techniques. The main drawback of ovarian tissue cryopreservation followed by avascular transplantation is that the graft is completely dependent on neovascularization and, as a result, a large proportion of follicles are lost during the initial ischemia occurring after transplantation. Reducing the ischemic interval between transplantation and revascularization is, therefore, essential to maintaining the follicular reserve and extending the lifespan and function of the graft.
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