While the ability of ovarian reserve to predict outcome after one ART cycle remains ‘unclear’, this latest meta-analysis shows that higher values of serum AMH increase cumulative live birth rate following an initial ART cycle. However, because the study found no AMH level below which live birth could not be achieved, the authors advise that AMH should not be the sole reason for opposing ART treatment, especially in young women.
Anti-Mullerian hormone continues to raise controversy, not in its ability to predict response to ovarian stimulation for IVF (for which evidence is strong) but in its association with live birth, either conceived naturally or with ART. Now, a new meta-analysis has confirmed what many earlier studies have suggested, that, serum AMH level is positively associated with cumulative LBR after IVF/ICSI but ‘no discriminating threshold can be established’ below which live birth cannot be achieved; as a result a low serum AMH level ‘should not be used as the sole criterion for rejecting IVF treatment’, especially in young patients.(1)
AMH has emerged as an undisputed biomarker of ovarian reserve and is closely correlated with the number of mature oocytes retrieved following stimulation. This seems increasingly important with more evidence emerging to suggest a direct link between LBR and the number of oocytes retrieved per cycle.(2) These recent results seemed to confirm those of the landmark paper of Sunkara et al of 2011, which had similarly found LBRs improving as the number of eggs retrieved increased (to a plateau of 15), though with additional dependence on the age of the woman.(3) The findings, said the authors at the time, suggested ‘that the number of eggs in IVF is a robust surrogate outcome for clinical success’.
However, while AMH levels may well be indicative of response to stimulation - and in terms of oocyte yield offer some kind of prediction of success - it remains unclear whether AMH can actually predict pregnancy or live birth in spontaneous or assisted conception. This, say the authors of the new meta-analysis, is especially so in predicting cumulative live birth, which with the ever-increasing application of FET in treatment today is deemed a ‘more relevant’ outcome. Their meta-analysis was thus to investigate whether serum AMH levels can predict the chances of live birth and/or cumulative live birth in women who conceive naturally or in infertile women having IVF/ICSI or IUI.
Thirty-two eligible studies were analysed, with just seven applicable to AMH and cumulative LBR. A ‘positive trend’ was evident in most of these studies, but in a non-linear relation. However, after the exclusion of two studies at risk of bias, the mean serum AMH level was indeed significantly higher in women with at least one live birth than in those without. Similar conclusions (from 19 studies) were drawn from analysis of live birth alone, with a positive trend but non-linear relation in some but not all studies, and no AMH threshold evident. There were insufficient data on the ability of AMH to predict cumulative LBR after IUI or natural conception in women without a history of infertility (five studies).
Thus, most studies were related to ART, where a positive trend in LBR was found with AMH but without linear relation and without any indication of a discriminating (upper or lower) threshold. A majority of studies found that serum AMH level does not appear to affect live births per transfer or per cycle, as even very low AMH levels were associated with live birth - while 11 retrospective studies concluded that AMH level is a good prognostic marker of live birth per cycle or transfer.
However, although the number of studies considering AMH and cumulative LBR was ‘small’, the result, say the authors, ‘indicate that the serum AMH level has some value in predicting cumulative LBR in IVF/ICSI’. Explaining why this might be, the authors add: ‘In accordance with these results, having a higher serum AMH level would confer a quantitative advantage in women that is associated with a greater number of oocytes retrieved and a higher number of cryopreserved embryos available for subsequent transfers.’
The link between AMH and cumulative LBR, suggest the authors, thus lies in AMH as a ‘quantitative marker’ of ovarian response to stimulation and its prediction of the number of oocytes and embryos obtained. However, the authors stress that the serum AMH level is not the sole predictor of cumulative LBR. And, because there was no AMH level below which live birth could not be achieved after ART, they advise that serum AMH level should not be the sole criterion for counselling against ART treatment, especially in young women.
1. Peigne M, Bernard V, Dijols L, et al. Using serum anti-Mullerian hormone levels to predict the chance of live birth after spontaneous or assisted conception: a systematic review and meta-analysis. Hum Reprod 2023;
2. See https://www.focusonreproduction.eu/article/News-in-Reproduction-Oocyte-retrieval-LBR
3. Sunkara SK, Rittenberg V, Raine-Fenning N, et al. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011; 26: 1768–1774.