Infertility – AMH test.
Anti-Mullerian Hormone Testing of Ovarian Reserve
What is AMH?
- AMH, or anti-mullerian hormone is a substance produced by granulosa cells in ovarian follicles.
- It is first made in primary follicles that advance from the primordial follicle stage. At these stages follicles are microscopic and can not be seen by ultrasound.
- AMH production is highest in preantral and small antral stages (less than 4mm diameter) of development.
- Production decreases and then stops as follicles grow. There is almost no AMH made in follicles over 8mm.
- Therefore, the levels are fairly constant and the AMH test can be done on any day of a woman’s cycle.
AMH and fertility
How can AMH hormone levels be a fertility test?
Since AMH is produced only in small ovarian follicles, blood levels of this substance have been used to attempt to measure the size of the pool of growing follicles in women.
- Research shows that the size of the pool of growing follicles is heavily influenced by the size of the pool of remaining primordial follicles (microscopic follicles in “deep sleep”).
- Therefore, AMH blood levels are thought to reflect the size of the remaining egg supply – or “ovarian reserve”.
With increasing female age, the size of their pool of remaining microscopic follicles decreases. Likewise, their blood AMH levels and the number of ovarian antral follicles visible on ultrasound also decreases.
Women with many small follicles, such as those with polycystic ovaries have high AMH hormone values and women that have few remaining follicles and those that are close to menopause have low anti-mullerian hormone levels.
What is a normal AMH level?
Interpretation of anti-mullerian hormone levels and chances for conception
There are some problems involved with interpretation of AMH hormone levels. Because the test has not been in routine use for many years, the levels considered to be “normal” are not yet clarified and agreed on by the experts. Also, not all current commercial assays give equivalent results.
The table below has AMH interpretation guidelines from the fertility literature and our own experience. Do not get carried away with the cutoff values shown here. For example, the difference between a 0.6 and a 0.7 ng/ml test result puts a woman in a “different box” in this table – but there is very little real difference in fertility potential. In reality, it is a continuum – and not something that categorizes well.
AMH Blood Level
High (often PCOS)
Over 3.0 ng/ml
Over 1.0 ng/ml
Low Normal Range
0.7 – 0.9 ng/ml
0.3 – 0.6 ng/ml
Less than 0.3 ng/ml
More will be learned regarding anti-mullerian hormone levels and outcomes as we continue to use the AMH fertility test and study the relationship between AMH hormone values and fertility, ovarian responsiveness, chances for IVF success, etc.
Ovarian reserve testing methods
Anti mullerian hormone is one potential test of ovarian reserve. There are other tests that are currently used for evaluation of the remaining egg supply. None of the tests are perfect, and fertility specialists will often use a combination of tests to try to get a better estimate of the size of the remaining egg supply.
Note: Anti mullerian hormone has also been referred to (mostly in the past) as “mullerian inhibiting substance”, or MIS.
Day 3 FSH Fertility Testing of Ovarian Reserve – Follicle Stimulating Hormone Test
Page author Richard Sherbahn MD
|Background on Ovarian Reserve Testing
Antral follicle counts and response of the ovaries to stimulation with injectable gonadotropins are other variables that affect the overall chance for conception when we attempt IVF – in vitro fertilization.
Female age is a very important variable. However, a woman can be 42 and still have some good quality eggs (and still be fertile), or she can be 25 with poor quality eggs and be infertile, although this is rare.
In general, egg quantity and quality tends to decline slowly starting in the early 30’s, and then much faster in the late 30s and early 40s.
What does FSH hormone do?
Follicle stimulating hormone (FSH) is one of the most important hormones involved in the natural menstrual cycle as well as in pharmacological (drug-induced) stimulation of the ovaries. It is the main hormone involved in producing mature eggs in the ovaries..
FSH is the same hormone that is contained in the injectable gonadotropins which are used to produce multiple eggs for infertility treatment.
What produces FSH hormone?
Both FSH and LH hormone are produced by the pituitary gland at the base of the brain. When a women goes into menopause she is running out of eggs in her ovaries. The brain senses that there is a low estrogen environment – and signals the pituitary to make more FSH hormone. More FSH is released from the pituitary in an attempt to stimulate the ovaries to produce a good follicle and estrogen hormone.
Think of it like stepping on the gas pedal in the car to get going. The FSH is the gas, and the pituitary gland releases FSH to get a follicle “going” at the beginning of every menstrual cycle. If there are less follicles left (and perhaps lower quality follicles) the amount of “gas” has to be increased to get a follicle developing.
In a menopausal woman, the gas pedal is on the floor for the rest of her life – even though there are no follicles (or eggs) left. The woman’s body never gives up trying – FSH levels are permanently elevated.
Women in menopause have high FSH hormone levels – above 40 mIU/ml. As women approach menopause their baseline FSH levels (day 3 of their cycle) will tend to gradually increase over the years. When they run out of follicles capable of responding, their FSH will be high and they stop having periods.
- If this happens in a woman under age 40, we call it premature ovarian failure or primary ovarian insufficiency
Why do we measure the FSH level on day 3?
By measuring a woman’s baseline FSH on day 3 of the cycle (we do it on day 2, 3, or 4), we get an indication as to whether she has normal “ovarian reserve”. We are looking at how hard her body needs to “step on the gas” early in the menstrual cycle to get a follicle growing.
Therefore, if the baseline FSH is elevated the ovarian reserve (how many eggs are left) is reduced (sometimes the egg quality is also reduced).
Some practical problems with the day 3 FSH test:
- The cut off values used to say that egg quantity is good, OK, or poor is laboratory dependent. For example, and FSH of 11 in one laboratory may reflect good ovarian reserve – whereas a level of 11 in another lab using a different assay may indicate diminished ovarian reserve. See below for more.
- While an abnormal result (high baseline FSH) tends to be very predictive of low egg quantity, a normal result does not necessarily mean that the egg quantity is good. There are a significant number of women with normal FSH values that have a reduced egg supply. The lower egg supply is not being reflected in their FSH value. This is why doing antral follicle counts and AMH levels can be useful. By doing multiple ovarian reserve tests, we are more likely to find an ovarian reserve problem if there is one.
This is particularly true for women in their 40s. An infertile 44 year old woman with a normal FSH (for example 6) still has a very low probability of conceiving and delivering a baby with in vitro fertilization – or with any other fertility treatment. The fact that she is 44 greatly diminishes her chances – even if her FSH is normal. This is why IVF programs have age cutoffs.
The oldest women accepted by IVF programs varies somewhat – most programs have a cutoff somewhere between age 42-45. Infertile women older than 44 will very rarely be successful using their own eggs. However, these women are excellent candidates for in vitro fertilization with donor eggs.
Interpreting day 3 FSH blood test results – what are normal FSH levels?
In our fertility center we currently use an assay made by DPC that is run on an Immulite machine. We consider normal FSH level to be anything less than 9. As levels go above 9 we often see a reduction in response to ovarian stimulating drugs – as described in the table below.
If your FSH levels were run using a different assay, you can not compare your results to those shown below with confidence. For example, with some assays an FSH of 12 is normal.
|Day 3 FSH level||FSH interpretation for DPC Immulite assay|
|Less than 9||Normal FSH level. Expect a good response to ovarian stimulation.|
|9 – 11||Fair. Response is between normal and somewhat reduced (response varies widely). Overall, a slightly reduced live birth rate.|
|11- 15||Reduced ovarian reserve. Expect a reduced response to stimulation and some reduction in embryo quality with IVF. Reduced live birth rates on the average.|
|15 – 20||Expect a more marked reduction in response to stimulation and usually a further reduction in embryo quality. Low live birth rates. Antral follicle count is an important variable.|
|Over 20||This is pretty much a “no go” level in our center. Very poor (or no) response to stimulation. “No go” levels should be individualized for the particular lab assay and IVF center.|
More issues regarding day 3 FSH testing
In general, your ovarian reserve is as bad as your worst FSH. If you have an FSH of 15 in one cycle and then a a 7 in another cycle – the situation is not improving. Some women “bounce around” with FSH levels in the normal to abnormal range. However, they tend to respond and have chances for pregnancy as predicted by their highest FSH level.
Waiting for a menstrual cycle with a lower FSH level and then stimulating right away for IVF is not of any proven benefit.
Young women (under 35) with elevated FSH levels tend to stimulate better and have a much higher IVF success potential than “older” women. The better egg quality in the younger women can compensate for the quantity problem.
Day 3 estradiol testing
A blood estradiol level on day 3 (we do it on any day between days 2 and 4) of the menstrual cycle is a way to potentially discover some of those women with a normal day 3 FSH that may in fact have decreased egg quantity and quality.
What we want on day three is a low FSH level in conjunction with a low estradiol level. If the FSH is normal but the estradiol level is elevated, the elevated estradiol will often be artificially “suppressing” the FSH level down to the normal range.
The idea of using day 3 estradiol levels as an adjunct in evaluating egg quantity and quality is relatively recent. Clearly defined cutoff values for normal are not well established. We like to see the day 3 estradiol less than about 80. We repeat borderline or abnormal results in another menstrual cycle to try to get a “true” FSH.
There is some evidence that an elevated day 3 estradiol indicates a problem with ovarian reserve. This is sometimes the case, but often the issue is just that the elevated estrogen level is “masking” the potential for detecting low reserve by suppressing FSH into the normal range.
Clomiphene challenge test
A clomiphene challenge test is a dynamic type of test that can discover some cases of poor ovarian reserve that are still showing a normal day 3 FSH.
This test is done by:
- Obtaining a day 3 FSH and estradiol
- Take 2 tablets of clomiphene (100 mg) on days 5-9 of the cycle
- Repeat an FSH level on day 10 of the cycle
The normal Clomid challenge test result is a low FSH on day 3, a low estradiol on day 3 and a low FSH on day 10.
Cut off values for the day 3 and the day 10 FSH values are assay dependent and must be determined by experience with the lab being used.
In vitro fertilization – IVF
In vitro fertilization is a treatment for infertility, not a test. However, the IVF cycle details can give useful information about egg and embryo quality. By careful examination of the eggs and embryos during in vitro culture we can get clues about why pregnancy has not occurred previously.
For example, the eggs may demonstrate poor morphology, may have problems with maturation, with fertilization, or with proper cleavage, etc..