Age and infertility (2) by Prof. Oladapo Ashiru OFR
Assessment of ovarian aging
Ovarian reserve testing has been explored as a means to determine a woman’s fertility potential and to provide an assessment of ovarian aging.
Although chronological age alone serves as a good marker of ovarian reserve, some women will experience a decline in their natural fertility sooner than average, while some older women may maintain above average ovarian function.
The identification of these two groups, in which ovarian reserve is inconsistent with chronological age, may be useful in counselling and planning treatment.
The most commonly used test of ovarian reserve is the three-day cycle or the Basal Follicle Stimulating Hormone level. This is one of the essential reproductive hormones in humans.
An elevated Basal FSH level is the first sign of ovarian aging that can be detected in women. It usually occurs in women aged between 35 and 40. Physiologically, the follicular pool is reduced to approximately 10 per cent of the levels present at puberty.
The rise in Basal FSH is due to a loss in another set of reproductive hormones responsible for ovarian feedback called inhibin-A and B when the available follicular cohort diminishes.
Basal FSH levels are easy to obtain and no special skills are required to perform the test or interpret the results. However, it is good to also note that Basal FSH levels have been shown to be predictive for poor response to ovarian stimulation and for non-pregnancy only when the levels are extremely elevated.
Elevated basal FSH levels are also less predictive of pregnancy for women aged 35. An ovarian antral follicle count can be performed early in the menstrual cycle. Antral follicles between 2 mm and 10 mm can be identified by trans-vaginal ultrasound. They are sensitive to FSH and considered to be representative of the available follicle pool.
The number of antral follicles seems to correlate with the number of primordial follicles in the ovary, with a decline in primordial follicles being reflected in a lower number of antral follicles. The decline in AFC may not be as steep as the decline in fertility but decline in AFC is also correlated with both the menopause transition and ovarian response to stimulation.
Antimüllerian hormone is produced by the granulosa cells of pre-antral and small antral follicles but NOT dominant follicles. AMH levels decrease with decreasing AFC, which in turn is a marker of the possible eggs available at the early stage. Primordial follicle count levels remain consistent throughout the menstrual cycle and become undetectable in women after menopause. Although AMH provides moderate value in prediction of ovarian response in IVF, it is a poor predictor of pregnancy.
The clomiphene challenge test is performed by administering 100 mg of clomiphene daily from day 5 to day 9 of the cycle. FSH is measured on day 3 and on day 10. If an adequate response to clomiphene is generated, the rise in FSH will be suppressed by the release of estradiol and inhibin-B by developing follicles. Systematic reviews have not shown a benefit to the clomiphene challenge test over basal FSH or AFC. Inhibin-B and basal estradiol have not been shown to be more useful predictors of poor response or pregnancy than basal FSH.
However, basal estradiol levels are often screened in conjunction with FSH and can confirm correct timing in the menstrual cycle. An elevated estradiol level may also falsely suppress FSH levels.
In summary, as a rule of thumb, the fertility potential of a woman can be determined by the Antral follicle Count (AFC), the Day3 FSH.