The Role of AMH in Female Reproduction, and Beyond…?

In the past decades, postponement of childbearing has led to increasing rates of age-related female infertility, which is almost exclusively owing to changes in the ovaries. In order to have a chance of at least 90% to realize a two-child family, couples should start trying to conceive when the female partner is 27 years of age or younger. Unfortunately, medical treatment modalities such as IVF may only partly solve these problems, such that with the availability of IVF this age limit may be pushed towards 31 years.
The pacing of the ovarian ageing process is highly variable among women. This is evident from the large variation in age at menopause. Very early menopause, as in premature ovarian failure (ovarian arrest before the age of forty years), may represent the extreme of this variation. In view of this large variation in reproductive ageing, the identification of women who have severely decreased ovarian reserve for their age is clinically relevant, as it may identify specifically those women who cannot afford to postpone their pregnancy until their thirties.
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 (mother’s age at menopause) and quantitative ovarian reserve markers, like AMH and the AFC.
AMH is a dimeric glycoprotein produced by granulosa cells in the ovaries. It primarily has a paracrine action towards limiting the transition of primordial follicles into primary follicles and thereby plays a large role in the ovarian ageing process. It should not be forgotten however that AMH is of crucial importance in preventing the formation of uterus, fallopian tubes and the upper vagina in the male. There, produced in the Sertoli cells of the developing male gonad, it may have had a more endocrine role, with distant effects in other organs. The release of AMH from the ovaries and the testes into the circulation can be picked up by assay systems directed at uncleaved and bioactive cleaved forms of AMH. Among recent assay systems no full similarity is present when measurements are compared. Also, the potential role for circulating AMH in distant signalling remains to be elucidated, with potential roles in cardiovascular disease and the development of the PCO syndrome. The expression of the antral follicle number present at any time moment in the ovaries has been one of the most researched roles for AMH.
AMH has shown to be a quite accurate marker for such follicle quantity, especially in assisted reproduction, although its beneficial effect when coupled to an altered treatment approach still needs to be demonstrated. Serum AMH also has been claimed to be predictive of natural fertility, but these claims have not been confirmed in most studies.
Studies on the relation between AMH and age at menopause have so far been very promising. However, the correct prediction of extreme ages at menopause, as well as a lack in precision of the forecasts, may prove problematic. Recent studies on serial AMH measurements seem to demonstrate that the decline rate for AMH may be varying between individuals, and that in women with high age specific AMH, decline may accelerate in later life so that discrimination for the occurrence of the end state of menopause may be more troublesome than expected. Family history, as an expression of genetic makeup, may well remain the simple factor to take notice of.
In assisted reproduction technology, AMH has failed to discriminate the pregnant from the not pregnant IVF patient. It may however help to modulate the probability prediction for ongoing pregnancy within age classes.