The greatly improved survival of children and adolescents with malignancy now makes it important to assess the long-term adverse effects of cancer therapy. Loss of fertility is reported by cancer survivors to be a major concern. In women, this largely relates to gonadotoxicity of chemotherapy or local radiotherapy; uterine damage is less common and follows pelvic surgery or radiotherapy. All chemotherapeutic agents are gonadotoxic, but particularly the alkylating agents such as cyclophosphamide. After the acute insult there is a limited capacity for ovarian recovery, and there is a spectrum of effect ranging through reduced fertility to premature menopause, which is strongly associated with age at treatment. This fits well with the model of age-related decline in ovarian function whereby the fixed pool of oocytes (determined in fetal life) is continually depleted.
Ovarian reserve is a concept familiar to fertility clinicians, indicating ovarian functional capacity. This is assessed prior to fertility treatment using biochemical markers (FSH, oestradiol, inhibin), ultrasound (antral follicle count, ovarian volume) or dynamic testing (clomiphene, FSH or GnRHa stimulation). The application of these tests to assess gonadal toxicity is novel but shows potential in predicting long-term outcome. Patients with chemotherapy-induced ovarian damage may be helped to optimise their “window of fertility” (or, conversely, warned of the need for contraception) and some may be able to utilise the new technologies of egg or embryo freezing to preserve fertility.
Faddy, MJ & Gosden, RG.
A model conforming the decline in follicle numbers to the age of menopause in women
Human Reproduction 1996; 11: 1484–1486
Lutchman Singh, K; Davies, M & Chatterjee, R.
Fertility in female cancer survivors: pathophysiology, preservation and the role of ovarian reserve testing
Human Reproduction Update 2004; 11: 69–89
04 - 06 Apr 2005
British Endocrine Societies