Assessment of current and future ovarian reserve status

Abstract

Ovarian ageing is the gradual decline in the number of oocytes and the simultaneous decrease of the quality of the remaining oocytes. The changes in quantity and quality will lead to four milestones in the reproductive lifespan: subfertility, the end of natural fertility, menopausal transition and menopause. It is hypothesized that a fixed interval exists between these milestones, with the end of natural fertility occurring 10 years before menopause. The normal process of ovarian ageing varies considerably among women, with an age range of about 20 years. Therefore, accurate prediction of the current and future fertility status is desirable. This thesis evaluates the true value of ovarian reserve tests (ORTs) in the assessment of the current fertility status in assisted reproduction treatment (ART) as well as their potential in forecasting future fertility status. For the prediction of the current fertility status we evaluated the available evidence through both conventional and individual patient data meta-analysis. For the quantitative aspect of the current fertility status status, it could be demonstrated that the ORTs AFC and AMH are highly capable of predicting the ovarian response to hyperstimulation, and that the predictive ability is age independent. For the prediction of an ongoing pregnancy ovarian reserve tests demonstrated a poor accuracy and did not add to the limited predictive capacity of female age. Also, no clinical subgroup could be identified in which the performance of one of the ovarian reserve tests clearly is improved to a level at which correct prediction of pregnancy would become possible. This emphasizes that assessment of the quality aspect of ovarian reserve remains troublesome. Based on these findings, the clinical value of ovarian reserve tests will depend on the implications for management of predicting a poor or excessive response to ovarian hyperstimulation. Current literature suggests possibilities especially for dosage reduction in predicted excessive responders, while prediction of poor response may help in timely decisions on refraining from further ART treatment. For the prediction of the future ovarian reserve status, a long term follow up study was performed in normo-ovulatory women, with assessment of menopausal status 12 years after initial evaluation of ovarian reserve status. A nomogram of age specific AMH values could be constructed, from which it appeared that the normal distribution of age at menopause will shift considerably depending on the age specific AMH value. This implies that by correct prediction of the age range of menopause, individual assessment of the reproductive lifespan may become possible. From there, avenues for primary prevention of age related infertility and menopause related conditions may open