AMH Ovarian Reserve
For the last several years, there has been a large amount of interest in a hormone called Anti-Müllerian hormone (AMH) as a measure of ovarian reserve. Some older studies referred to this hormone as Müllerian inhibiting substance (MIS) or factor (MIF). They are all names for the same hormone.
In men, AMH is produced only in the testicles and in women it is produced only in the ovaries. This article will focus on using blood AMH levels as an indicator of ovarian reserve.
Ovarian reserve is a term used by fertility specialists to estimate a woman’s chances for having a healthy live born baby using her own eggs. To understand how AMH works as an indicator of ovarian reserve, it is important to first understand a little about how the eggs are stored in the ovary. Early in pregnancy, a female fetus starts to form eggs in her ovaries. Each egg is surrounded by a group of cells called granulosae cells. The eggs and its surrounding granulosae cells are collectively referred to as a follicle.
As the female fetus matures, more follicles are produced. At about the 20th week of pregnancy, the female fetus now has several million follicles. At that point however, the fetus stops making new follicles and the existing follicles start to degenerate. By the time a female is born, the number of follicles has dropped to only a few hundred thousand. After birth, the follicles continue to degenerate. This process of degeneration is constant and will continue until there are no follicles (eggs) remaining in the ovary.
Just prior to puberty, a woman’s follicles will start to develop to prepare for the initiation of ovulation, this is known as folliculogenesis. Folliculogenesis lasts for approximately 375 days. It coincides with thirteen menstrual cycles. The process is continuous so at any given moment, a woman will have follicles at various stages of development inher ovaries.
Primordial – The only type of follicle present in the fetus.The majority of follicles in the adult ovary are in the primordial stage. The follicle size is very small and cannot be seen on ultrasound. The eggs are immature. Theses follicles are dormant and can remain dormant for up to 50 years in humans. These follicles do not respond to hormones. At some point, the primordial follicles are “awakened”. The process by which primordial follicles are awakened is poorly understood. AMH is not produced by primordial follicles.
Primary – Once a primordial follicle is awakened, itis known as a primary follicle. The egg has now started on a 375 day journey toward either ovulation or destruction. Primary follicles are not yet responsive to hormones. They are not seen on ultrasound and they do not produce AMH.
Secondary – Approximately 290 days of growth and development after the primordial follicle was awakened, the primary follicle will become a secondary follicle. At the end of this stage, the follicle starts to produce AMH and is referred to as a pre-antral follicle. While still too small to see on ultrasound, these follicles will now respond to hormones. A pre-antral follicle is about 0.2 mm in diameter and is about 65 days away from ovulation.
Antral – This stage lasts about 50 days. The egg and follicle are both growing and developing. Antral follicles are visible on ultrasound and range in size from 2-10 mm. Counting of the antral follicles during an ultrasound forms the basis of another test of ovarian reserve, the antral follicle count . At a given moment, a woman may have only a few antral follicles or a large number. This group of antral follicles is known as acohort. The size of the cohort will rarely exceed 50 or 60 follicles and is often less.
Antral follicles produce AMH as well as estrogen. Receptors on the surface of the granulosae cells of the antral follicle are very sensitive to hormone stimulation from the pituitary especially FSH (follicle stimulating hormone ). FSH causes the follicles to produce increasing amounts of estrogen. Both estrogen and FSH are necessary for continued development of the follicle. Typically, only one follicle from the group will become dominant and proceed towards ovulation, the rest will degenerate. The dominant follicle and the degenerating follicle have stopped producing AMH.
Pre-ovulatory – By 8-10 days before ovulation, one dominant follicle will have been selected for continued development. A pre-ovulatory follicle will eventually reach a size of 20 – 22 mm just prior to ovulation.
Remember this: AMH is produced solely in the granulosae cells of pre antral and antral ovarian follicles. Measuring the AMH levels gives an indication of the size of the cohort.
AMH decreases with age
As women age, the pool of primordial follicles shrinks due to degeneration. As a result, the number of follicles which are awakened from the dormant state decreases. As the size of the cohort of antral follicles decreases, the total amount of AMH produced by those follicles also decreases.Thus older women will have lower AMH levels than younger women.
Although women in each age group can have a range of AMH levels, the average AMH level in younger women is higher than the average level in older women. The older the group studied, the lower the average AMH.
A young woman with a very low AMH may have a similar level to an “average” older woman.
|Age range||10th Percentile||50th Percentile|
|42 and over||0.09||0.50|
An 18 year old woman who has an AMH of 1.0 has very poor ovarian reserve. compared to other women her age, an AMH less than 1.10 means that 905 of owmen her age have a better AMH level.
a 32 year old with an AMH of 2.1 would be considered average for age. 50% of women in her age category have a better AMH and 50% have a worse AMH.
A 40 year old woman with an AMH of 3.2 has a much better ovarian reserve than women her age.
Remember this: The number of antral follicles (the cohort) size, correlates with fertility potential. Young women, who normally have better fertility, will normally have a larger number of antral follicles visible on ultrasound and higher AMH levels.
AMH and ovarian reserve
The central concept for the measurement of blood levels of AMH to determine ovarian reserve is this: women with lower AMH levels have a lower ovarian reserve than women with high AMH levels. AMH is currently being used by fertility specialists to help predict women who may respond poorly to fertility medications and in general, couples who are less likely to be successful with fertility treatment.
AMH and fertility
Up until recently, most of the research into AMH involved women who had already been diagnosed with infertility. It was unclear whether AMH was a good predictor of pregnancy in women who were just starting to attempt pregnancy. A recent study found, however, that in a group of women without infertility, those with a low AMH became pregnant less frequently than those with a higher AMH.
AMH and fertility treatment
Women with poor ovarian reserve as evidenced by a low AMH do not respond to fertility medications as well as normal women. These women are known as “poor responders”. Even with the use of aggressive medication protocols using high doses of fertility medications, these women respond poorly, and as a result, have a high rate of treatments which are cancelled for poor or absent response.
Even when eggs are stimulated to develop, the quality ofthose eggs seems poorer. For example, in our IVF program, women with an AMH less than 0.5 do not reach embryo transfer 1/3 of the time. Women with an AMH level over two, however, will have an embryo transfer 99% of the time.
If we look only at women who were able to have an embryo transfer, women with an AMH less than 0.5 had a pregnancy rate of 18% but women with a level over 2.0 had a pregnancy rate of 45%. This argues strongly for abnormality in the eggs of women with poor ovarian reserve.
Remember this: A low AMH indicates a problem in both the quantity and quality of the remaining eggs.
Some other facts about AMH
AMH levels show much less fluctuation over the course of the menstrual cycle compared to other measures of ovarian reserve such as the FSH blood test. There is some fluctuation, however. The higher the AMH level that greater the percentage of fluctuation can be seen.
Obese women tend to have lower AMH levels. It is not clearwhy this occurs. It is known that obese women have poorer fertility than normal weight women; it is possible that the reason is due to poorer ovarian reserve.
Women with PCOS commonly have a large pool of antral follicles and therefore often have higher than normal AMH levels.