Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2013

AMH: it’s use in prediction of ART outcome and reproductive lifespan (#176)

Frank J Broekmans 1
  1. Department for Reproductive Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

In the past decades postponement of childbearing has led to increased rates of age related female subfertility. Reproductive ageing in the female is almost exclusively based on changes in the ovaries. The decrease in follicle numbers and reduction of oocyte quality dictate both the occurrence of menopause as well as the natural loss of fecundity, respectively. The decline in fertility with age has been clearly shown in assisted reproduction technology (ART) programs.

The rate of ovarian ageing is highly variable among women. Identification of subfertile women who have severely decreased ovarian reserve for their age is therefore clinically relevant. Tests for ovarian reserve (ORT) relate mainly to the quantitative aspect of ovarian reserve. Basal endocrine, ultrasound morphological and challenge tests all have been proposed as possible outcome predictors enabling patient tailored treatment. Tailored treatment may imply refusing IVF treatment, applying adjusted dosages of gonadotropins or treatment schedules or just counselling on reduced prospects.

From recent systematic reviews and meta-analyses the accuracy and true clinical value of ORTs to predict poor ovarian response and the occurrence of pregnancy after IVF have become more apparent. It was shown that the best performing tests to date (AFC, AMH, basal FSH) have a rather good accuracy in predicting poor ovarian response. However, the value of the prior identification of a poor responder remains to be established for two reasons. First, poor response is not unequivocally related to a poor prospect for pregnancy. Second, measures like FSH dosage increase, co medication or agonist/antagonist schedule adaptations in predicted poor responders may neither increase response nor the chances for pregnancy. Moreover, current comparative trials suggest that FSH doses of 225 and over will not further improve ovarian response.

Accuracy of ORTs in the prediction of the occurrence of pregnancy appeared almost absent. Only if an extreme cutoff is used, in order to prevent couples from wrongly being refused IVF, a very small minority of IVF indicated cases (~3%) is identified as having unfavourable prospects in a first IVF treatment cycle. Based on these analyses the use of any ovarian reserve test for outcome prediction prior to starting IVF, although mostly cheap and not very demanding, can not be supported. Recent studies have indicated that ovarian reserve tests such as AMH or the AFC could help fine tuning prognosis estimates for pregnancy based on female age alone. Still, the designation of a very poor prognosis remains difficult, so that other than for counseling purposes routine testing may be only helpful in specific patient groups, such as older patients.

In view of all these issues, there may exist a need to have advance notice on the stretch of the reproductive lifespan for an individual woman. 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. Markers that could inform in advance on the individual timing of natural infertility and menopause may be family history and quantitative ovarian reserve markers like AMH and the AFC. Results of longitudinal studies may provide predictive models for individual application. Moreover, application of genetic profiles may add to the predictive accuracy of the currently known endocrine and ultrasound markers. As studies sofar have failed to provide a set of genetic markers that explain the individual variation in the timing of this ageing process, to date information on the mother’s age at menopause, combined with a quantitative test such as AMH for confirmation, may provide the most valuable information.