N.S. Macklon, M.D., Ph.D.; B.C.J.M. Fauser, M.D., Ph.D.


Semin Reprod Med. 2005;23(3):248-256. 

In This Article


Evidence is accumulating that menopausal age (and resulting sterility) is preceded by a period of reduced fertility related to a decreased follicle pool, a reduced cohort of growing follicles, and diminished oocyte quality.[12] Poor response to ovarian hyperstimulation with exogenous gonadotropins during IVF therapy is a manifestation of this phenomenon, and may precede the development of cycle abnormalities.[76] The poor responder reveals a diminished ovarian reserve by producing few follicles despite prolonged administration of high doses of exogenous gonadotropins. Although quantity and quality of oocytes are considered to be related to each other in constituting the ovarian reserve, it is becoming clear that poor quantity does not always mean poor quality. This is illustrated by the limitations of basal FSH levels as a predictor of ongoing pregnancy in younger patients. Moreover, when a small cohort of oocytes is obtained after mild stimulation, oocyte quality is maintained or even enhanced.[77]

The limitations of present tests of ovarian responsiveness and reserve mandate caution in their application.[74] Their clinical value depends on the context of their use and the cut-off levels selected. If tests of ovarian reserve are used for counseling rather than excluding patients from treatment, chosen cut-off levels may be nearer normal values. In this case, false-positive results, which occur when a patient conceives despite an abnormal value for a marker of ovarian reserve, will be perceived as a happy surprise rather than an indictment of an exclusive patient selection policy.

In the future, markers of ovarian reserve may have an important role in aiding the counseling of women undergoing cancer treatment with regard to their reproductive prognosis. Retrospective studies indicate that AMH levels are reduced in childhood cancer survivors.[78] Prospective studies are required to investigate the value of endocrine and biophysical markers of ovarian reserve in predicting which patients can expect ovulatory cycles after cancer treatment, and those for whom invasive therapies such as ovarian cryopreservation may be indicated.

A better understanding of the control of follicular development from the fetal stage through to the menopause will offer the prospect of identifying more sensitive and specific markers of ovarian reserve. Additional research into the concept that human ovaries may contain germ line stem cells may open the way to novel therapeutic interventions aimed at manipulating the age-related decline in quantity and quality of oocytes.


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