The primary impact of chemotherapy on fertility is related directly to the loss of ovarian function secondary to the gonadotoxicity of many chemotherapeutic agents (Pic. 3). The greatest risk is in women over age 40 years receiving alkylating agents with up to 80% of patients having permanent amenorrhea (absent period) after treatment. However, in women under 30 years, the risk of permanent amenorrhea is substantially decreased to less than 20%.
The effect of chemotherapy will also depend on whether it is radical (seeks to control rather than destroy tumours) or adjuvant, single agent, or combination. Unfortunately, estimates in the impact on fertility vary widely dependent on various factors, and, therefore, there is no definitive predictor prior to treatment making counseling on future fertility challenging for health care providers.
The peak number of oocytes is found in females at 20 weeks of fetal life, and this number declines until menopause. The number of primordial follicles (first stage in follicle development) is approximately 500,000 at menarche; menopause occurs once that pool is nearly depleted. Although chronologic age is the most important predictor of oocyte quality and quantity, there is variability in the rate of ovarian aging. The term “ovarian reserve” is used to describe remaining ovarian oocyte quantity. Although menstrual cycles do not start to become irregular until a mean age of 45 to 55 years, endocrinologic changes associated with ovarian aging have been demonstrated for women age 35 to 40 years and at earlier ages after cancer treatment. Assessment of a patient’s ovarian reserve both before and after cancer treatment may provide valuable information for patients in discussion of fertility preserving option prior to treatment and future fertility after treatment.
Further research is needed to determine the impact of cancer treatments on markers of ovarian reserve and any correlation with future fertility. It is important to consider that most research has evaluated these markers in relation to success of ovarian stimulation for IVF (in vitro fertilization); therefore, caution must be used in counseling patients on the likelihood of spontaneous pregnancy or with other fertility treatments.
In male patients, prepubertal status does not provide protection from gonadal damage and alkylating agents at high doses induce germ cell injury although Leydig cell (produces testosterone in testes) function is commonly preserved. Because most chemotherapy agents are given as part of a combination regimen, it has been difficult to quantify the gonadotoxicty of individual drugs.