Ovarian function

Is the ovarian function of women and girls who received cancer treatment reduced in comparison to women and girls in the general population?

It is generally accepted that some chemotherapeutic agents and radiotherapy treatment have a gonadotoxic effect, including a reduction in ovarian reserve which can impact fertility and long-term bone, cardiovascular and cognitive health.^[1] Ovarian reserve is an indirect measure of the primordial follicle pool within the ovary, and an indicative marker of the temporal risk of an early menopause. Ovarian reserve is assessed by the serum marker anti-mullerian hormone (AMH) which is routinely used in fertility practice. Ovarian reserve can also be assessed by measuring the small, antral follicles within the ovary, or less commonly by the ovarian volume or surface area^[2] in post pubertal patients.

The strongest evidence of the impact of cancer treatment on ovarian function comes from prospective cohort studies. Studies that are part of the "Ovarian Reserve After Cancer: Longitudinal Effects (ORACLE)" (NCT02467231) study, reported young patients with cancer experienced more symptoms of menopause after treatment compared to similar age-matched controls.^[3] Another cohort study also found that reproductive-aged women with a history of cancer were more likely to experience menopausal symptoms such as vaginal dryness than their similar-aged peers.^[4]

The ORACLE study also found that decreased AMH levels were associated with an increase in menopausal symptoms in women ^[3], however the rate of change of AMH after cancer treatment was not significantly different than similar-aged controls.^[5] Late reproductive-aged patients with breast cancer also had significantly lower AMH compared with age-matched controls, particularly in menstruating patients who subsequently developed chemotherapy-related amenorrhea.^[6] Newer AMH assays are available that are a highly sensitive measure of ovarian activity and may better predict future menses or amenorrhoea.^[7][8]

The fact that women are more likely to have reduced ovarian reserve after cancer treatment is sufficient evidence to prompt the discussion of the impact of cancer treatment on fertility with all women diagnosed with cancer. It is important to state that ovarian reserve (as measured by serum AMH) is not a predictor of oocyte quality or the chance of conception, it is purely a measure of the pool of remaining follicles.

In the interpretation of the serum AMH concentration, it should be conveyed to the patient that a ‘high’ or ‘low’ concentration is not a predictor of the chance of having a healthy baby. Should IVF be required, a ‘higher’ concentration of serum AMH is more predictive of a better response to ovarian stimulation, than a woman with a ‘low’ serum AMH.^[9] Additionally, AMH in the immediate post chemotherapy phase, and in patients on treatments such as GnRHa may be difficult to asses. Therefore follow up for ovarian reserve should be delayed for at least 6-12 months.