Measuring ovarian function in young cancer survivors.

It is known that young female cancer survivors are at higher risk for decreased fertility and early menopause. Because the risk of these outcomes varies by age, cancer type, treatment regimen and other patient-specific characteristics, there is a need for valid tools for measuring and predicting reproductive function in this population. Ovarian reserve tests (ORT) include serum and ultrasound biomarkers used in characterizing healthy ovarian aging and predicting ovarian reserve prior to fertility treatment. This review summarizes efforts to translate ORT to use in female cancer patients. To date, small longitudinal and cross-sectional studies of young cancer patients demonstrate that gonadotoxic chemotherapy impact ORT. While follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume have all been demonstrated to change with exposure to gonadotoxic therapy, FSH, AMH and AFC appear to be the most sensitive. More data are needed to determine the long-term effect of hormonal agents from tamoxifen to GnRH agonists on ORT. The effect of unilateral oophorectomy acutely or in the long-term on ORT is not known. There are some early data postulating that cancer itself may impair ovarian reserve. Among cancer survivors, ORT correlate with amenorrhea. Even in young survivors with normal menstrual cycles, hormone and ultrasound measures of ovarian reserve suggest decreased underlying ovarian reserve than age-matched healthy women. More studies are needed to determine the optimal time to test ORT in the large number of young survivors on combined estrogen and progesterone contraceptives. A significant utility of ORT would be to be able to predict fertility for young survivors, and there are no data on this outcome to date. The goal of future studies of ORT in young girls and women with cancer is to determine their utility as surrogate measures of ovarian function or predictors of infertility or ovarian failure. To do so, large-scale data need to be collected through cooperative group mechanisms. Epidemiologically, studies need to move from association studies to develop ORT into appropriate screening and predictive tests.