Ovarian reserve is an expression of the number and quality of eggs available for conception. As a parameter for predicting pregnancy, ovarian reserve testing is often part of a fertility evaluation. Such testing requires specific measurement, and clinical judgment to interpret the results.
Egg numbers are at a maximum before birth, at around 20 weeks gestation. After birth, there is a progressive decline in the number of eggs from roughly one million at birth to 300,000 at puberty. Through the reproductive years the remaining eggs are lost, with the rate accelerating around the mid-30s, resulting in few eggs left at menopause, around age 50-52. The number of eggs available for reproduction at a certain age is the ovarian reserve, which is the target of the diagnostic tests described here.
Age is the most accurate predictor of egg health, but within age groups, there is considerable variation in the number of eggs remaining for reproduction. Age alone as a predictor of ovarian reserve is not sufficient, since, for individuals, fertility may be better or worse than the average for that age. Extreme examples of this variability include the teenager in menopause and the 59 year-old that delivered a natural pregnancy in 1997. This variability in pregnancy rates within an age group is present in all reproductive age groups.
To predict an individual woman’s fertility rate, in addition to her age, both clinical and laboratory methods are available to evaluate ovarian reserve. The best tests are direct measures of the ovary, such as the Antral Follicle Count (AFC) and Anti-mullerian Hormone (AMH) level; indirect measures, such as clinical history and levels of pituitary hormones, are common tools for prediction of ovarian reserve.
The simplest method of predicting fertility rates is clinical history, of both the individual and her closely related family. The number of months spent attempting to conceive predicts fertility. A couple that has been trying for some time will naturally have a lower fertility rate than a woman that has not had unprotected intercourse. Response to ovarian stimulation can also be used as a marker, as it is fairly consistent between cycles. Family history, i.e., the fertility of the woman’s mother or sisters reflected in age at menopause and age at conception are useful predictors. Such factors from clinical history can help define the risk of a problem with ovarian reserve.
Ultrasound is a useful tool for predicting ovarian reserve, as in measuring the Antral Follicle Count (AFC). Antral follicles are the smaller follicles, visible on ultrasound, between 2 and 10 mm, that are lost as a woman ages. In younger women, the AFC is 10-20, declining by 5% per year through age 37, and then accelerating to a loss of 10% per year thereafter. Women show a fairly consistent AFC loss rate of one follicle every two years.
AFC predicts the response to ovarian stimulation at least as well as blood tests, but its ability to predict pregnancy outcomes is limited, particularly when low. A woman with a higher AFC will show a better response to fertility drug treatments. A high AFC seems to predict pregnancy rates, but data remains limited, as there are no prospective studies published. A low AFC seems to be a less accurate predictor of ovarian reserve, particularly in older age groups. AFC may help predict outcomes, but should not be used to exclude patients from treatment.
Anti-mullerian hormone (AMH) is a blood test that directly measures ovarian reserve. Produced directly by early stage ovarian follicles, high levels (over 1.0) are favorable, while low levels (less than 1.0) indicate decreased ovarian reserve. AMH may be the best measure of the menopausal transition and ovarian age. It may also be useful in predicting ovarian hyperstimulation syndrome, the effects of chemotherapy, and in determining the treatment of PCOS.
AMH seems a superior predictor of ovarian response compared to other markers, including age, and day 3 FSH and estradiol. It offers similar predictive value compared to AFC. AMH can be drawn at any time in the menstrual cycle, and is not affected by hormonal therapy, including oral contraceptives.
AMH still requires further study. The range of normal variation is still being determined, and the true predictive value of the test requires a great deal more analysis. The specific range of reliability and predictive value by age is yet to be established.
Cycle day three FSH and estradiol, and, to a lesser extent, the clomiphene challenge test, remain viable tests for estimating ovarian reserve. These tests are established as predictors of response to ovarian stimulation. Prediction of pregnancy rates is more difficult. Recent studies concentrating on the predictive value of these tests have shown that they cannot be used to determine which patients cannot conceive, but are useful for screening and counseling.
All in all, these tests are only rough predictors of ovarian reserve. They are moderately good predictors of ovarian response to stimulation, and relatively poor predictors of pregnancy outcome. In a particular patient, the tests can be used to counsel about potential response to ovulation induction, but it remains difficult to predict pregnancy outcome based on the test results.
The ultimate test of ovarian reserve is response to treatment and whether a pregnancy results from that treatment. Stay tuned as we evaluate further research to establish the validity of ovarian reserve testing methods.
