Can ovarian failure be predicted?
Several reasons exist for wishing to have advance notice of the timing of menopause. Since menopause relates strongly to the occurrence of natural infertility some 10 years earlier, long-term prediction of menopause may help women to timely start attempts to have children. If premature or early menopause could be predicted, preventive measures could be taken in order to minimise the related long-term health risks. Incipient ovarian failure in terms of the current inability to create a viable ongoing pregnancy could be another issue that has been the subject of numerous studies, especially directed in the field of assisted reproduction.
The process of ovarian ageing consist of the gradual decline in number and quality of the remaining follicles and oocytes in both ovaries at a given age. Decline in follicle numbers dictates the occurrence of irregular cycles and menopause, while quality decay of the oocytes results in decreasing fertility, defined as the capacity to conceive and give birth to a child. There is substantial individual variation in the onset of menopause, varying roughly between 40 and 60 years, with a mean age of 51. Along the same pattern, the rate of decline in fertility may vary considerably between women of the same age. These notions underline the need for tests (ovarian reserve tests, ORTs) that describe future and current ovarian reserve status.
Among these tests are calendar age, family history, AMH, poor response in IVF, basal FSH, antral follicle count and genetic variation for long-term prediction. From recent long-term follow up studies, only AMH has shown to provide some individual value in the prediction of time to menopause. The application of genetic profiles has so far been hampered by inconsistent findings and only very small effects of the associated variation on age at menopause.
Assessment of ovarian reserve status in ART patients has demonstrated to be inadequate when pregnancy prospects are concerned. From recent individual patient data analysis it has been demonstrated that ORTs do not add to the prediction based on female age alone. Response to ovarian hyperstimulation has appeared to be highly predictable, especially when AMH and the AFC are applied. The management options for predicted poor and high responders are still under study and debate. The combination of poor response in a first ART cycle and an abnormal AMH or AFC test result may identify a group of patients that have such a poor prognosis that further treatment may better be refused.