Ovarian reserve is a term that is used to determine the capacity of the ovary to provide egg cells that are capable of fertilization resulting in a healthy and successful pregnancy. Diminished ovarian reserve (DOR) is a fairly common cause of infertility and testing for DOR is a routine part of an infertility work up. Various tests have been proposed for assessing ovarian reserve and these have been discussed in detail in a previous blog.
Measuring the basal follicle-stimulating hormone (FSH) level (cycle days 2, 3 or 4) has been considered the “gold standard” test for assessing ovarian reserve for many years now. It, however was far from perfect and has several limitations – a) it had to be measured at a specific time of the cycle, b) an estradiol level had to be measured along with the FSH level, c) it varied from cycle-to-cycle. Also, d) although a high FSH level was predictive of a low response, a low FSH level was not a marker of high response.
Anti-mullerian hormone (AMH) is a hormone that is produced by the granulosa-cells that surround small (early preantral stage) follicles and is directly correlated with egg supply. AMH has the following advantages a) AMH levels can be measured at any time of the cycle. b) There is no need to measure estradiol levels along with an AMH level. c) there is less cycle-to-cycle variation d) AMH is a much more sensitive marker of DOR as AMH levels decrease much earlier than FSH levels rise. e) AMH levels are a much better predictor of ovarian response than FSH. f) Low AMH levels predict a poor response and elevated AMH levels predict high response.
The question therefore arises; “Should basal follicle-stimulating hormone (FSH) testing be abandoned in favor of measuring anti-mullerian hormone (AMH) in determining ovarian reserve?”
This very question was debated in a series of letters in the journal Fertility and Sterility. Dr’s Toner and Siefer (Fertil Steril 2013;99:1825-30) suggest the following guideines:
- AMH less than 0.5 ng/mL predicts difficulty in IVF getting more than three follicles to grow. These patients should be stimulated with an aggressive stimulation protocol.
- AMH less that 1.0 ng/mL suggests a limited egg supply at any age. These patients also should be counseled to pursue pregnancy aggressively
- AMH greater than 1.0 ng/mL but less than 3.5 ng/mL are the “normal’ responders and may be stimulated with “routine” protocols
- AMH greater than 3.5 ng/mL indicates an ample egg supply. These patients may be “high” responders at risk for ovarian hyperstimulation syndrome (OHSS) and may have polycystic ovary syndrome (PCOS).
They believe that AMH is superior to FSH in identifying high and good responders. A low AMH level in combination with a moderately elevated FSH level may have a better prognosis than when the FSH level is markedly elevated.
Rosenwaks and Reichman responded to the above opinion paper with the following critique. They recently published their data on 1,052 patients with low AMH levels and showed a pregnancy rate of 25.7% per retrieval. They also showed a pregnancy rate of 19% per retrieval in 224 patients with undetectable AMH levels. They thus caution against using AMH “cut-off” levels to prevent patients from trying IVF with their own eggs.
AMH levels do vary and their experience at Cornell was that they have observed a variation of as much as 1.0 ng/mL measured within several months.
They recommend that an AMH level should not be used by itself as a marker of ovarian reserve. It should be used in conjunction with other markers including basal FSH level, antral follicle count, antral follicle count and age. I agree.
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