Anti-Mullerian Hormone Why You Should be Asking for This Test

By: Susanna J Park, MD

Women are delaying pregnancy for a variety of reasons. Perhaps she is focusing on her career; perhaps she is enjoying the freedoms of an unattached life; perhaps she has not found the right person yet.  The ability to defer motherhood is a wonderful privilege. However, when should a woman start to be concerned about her ability to conceive? One test that may help women track their reproductive potential is the Ant-Mullerian Hormone.  This hormone is believed by many to be the best blood test currently available to assess a woman’s supply of follicles in her ovary.

A woman stores all of her eggs in small fluid-filled structures called follicles in her ovaries. A single follicle contains a single egg. Each woman has the greatest number of follicles when she is a 5 month old fetus in her mother’s womb.  At this time, she has 6-7 million follicles.  Subsequently, while still in the mother’s uterus, she will start to experience loss of follicles (and therefore eggs) via a process called atresia, defined as programmed cell death. By the time she is born, a baby girl will have only 1-2 million combined total follicles remaining in her ovaries. Through childhood, follicles continue to undergo atresia such that by puberty, the total number of follicles is approximately 400,000.  Puberty marks the start of ovulation. During ovulation, one follicle per month is released from the ovary into the fallopian tube. This process allows women to conceive via fertilization. It is a common misconception that only one follicle is lost per month. However while one follicle is being released through ovulation, many other follicles simultaneously are dying through atresia. Thus, every month, both ovaries lose a significant number of follicles. This continues throughout adulthood such that by the age of 52 (the average age of menopause), there are only approximately 1,000 follicles remaining in both ovaries combined.

The loss of follicles is permanent and irreversible. Unlike men who continue to produce new sperm, scientists believe that women do not produce new follicles.  Instead, women are born with a finite number of follicles. Fertility medications do not increase the follicle supply in an ovary.  Rather, fertility medications increase the number of follicles which ovulate from the ovary in a given cycle.

It used to be believed that the rate of loss of follicles due to atresia decreased at a gradual rate, until the age of 37, at which time the rate of loss of follicles accelerated.  Recent studies have demonstrated this is not the case, and that instead, the loss of follicles is continuous.  Thus, we used to reassure women in their early 30’s that they did not need to worry about their fertility until they were in their mid 30’s.  Now we know that it is possible for women in their early 30’s to have fertility issues due to a low supply of follicles in their ovaries.

Many physicians and researchers believe that the best blood test to assess the supply of follicles in a woman’s ovaries is Anti-Mullerian Hormone (AMH), also known as Mullerian Inhibiting Substance (MIS). In females, this hormone is secreted by a particular group of cells in the follicles called granulosa cells. Thus, the more follicles there are in the ovaries, the greater the amount of AMH in the blood. Conversely, the fewer follicles there are in the ovaries, the lower the amount of AMH in the blood.  Therefore, AMH is a reflection of the number of follicles in both ovaries. With time, as women become older, the level of AMH will naturally decrease.

Other tests are currently used to assess the supply of follicles in ovaries. The most common of these tests is Follicle Stimulating Hormone (FSH) and Estradiol, which are measured on the third day of the menstrual cycle (Day 3 FSH & Estradiol).  There are several disadvantages to this test.  First, the test is time sensitive – that is, it must be performed on either the second, third, or fourth day of the menstrual cycle.On the other hand, AMH can be measured any time of the menstrual cycle. Second, Day 3 FSH & Estradiol results become abnormal once the supply of follicles in the ovaries has diminished substantially. Therefore, it is possible to have a borderline low reserve of follicles but a normal Day 3 FSH & Estradiol result. This provides a woman with a false reassurance that she has an ample supply of follicles and thus, ample time to become pregnant. In contrast, AMH decreases with the gradual decline in the supply of follicles over time. Studies have shown that AMH is the earliest indicator that the supply of follicles is diminishing. Finally, Day 3 FSH & Estradiol levels from one menstrual cycle may be different from the levels repeated at a subsequent menstrual cycle. There is a lot of cycle-to-cycle variability. And while studies suggest that the highest FSH value is most predictive of egg quantity, a woman may be falsely reassured if she sees a subsequent lower FSH value. The value of AMH, however, remains rather constant cycle-to-cycle.

Another common test used to assess the reserve of follicles is measuring the number of antral follicles visible on transvaginal ultrasound. This test is called antral follicle count (AFC). The antral follicles are those which have the ability to grow into mature follicles each month. The greater the number of follicles in the ovary, the greater the number of antral follicles seen on ultrasound; therefore, AFC is a reflection of the reserve of follicles.  AFC is a rather good test of a woman’s ovarian supply of follicles. AFC measurement can be performed any time of the menstrual cycle.  However, there are some disadvantages to antral follicle count. First, acquiring the information requires a vaginal ultrasound, whereas AMH requires only a blood test. Second, because it is natural for the number of follicles that grow into antral follicles each month to vary monthly, the AFC number will accordingly change each month. In contrast, AMH levels show little monthly change. Third, AFC measurement is subjective because it is a count of the number of antral follicles seen. Therefore, different people measuring the same ovary at the same time may count slightly different numbers of antral follicles. AMH, however, is an objective measurement performed by measuring the level of the AMH hormone in the blood so the result is not subjectively determined.

Which women should be requesting an AMH test to assess their ovarian follicle reserve? Answer: Any woman who wants to know her follicle reserve may benefit from an AMH test. However, there are known factors which affect the reserve of follicles in the ovary: age, environment, and genetics. Therefore, women with the following conditions which may lower ovarian follicle supply, should consider asking their physicians for the AMH test:

(1)  any woman over 30 years of age;

(2)  any woman with a history of surgery on the ovary (removal of an ovarian cyst, removal of an ovary);

(3)  any woman with a history of any toxins which may have a negative impact on the ovary (smoking, chemotherapy, radiation);

(4)  any woman with a family history of menopause earlier than 50 years old;

(5) any woman whose family history includes female relatives who experienced a loss of ovarian function at less than 40 years old.

Regardless of AMH results, the greatest predictor of the ability to conceive is a woman’s age.  Women who are young have higher quantity and better quality eggs (also known as oocytes).  With increasing age, both the quantity and quality of eggs decrease. No test exists, not even AMH, which can measure the quality of an egg.  The AMH is only a measurement of the quantity, not quality, of eggs/follicles.  It is for this reason that the likelihood of conception decreases with age.  And while lifestyle choices such as maintaining a healthy weight and exercising regularly are essential in achieving optimal conditions for pregnancy, these factors do not slow down the rate of decrease of egg quantity or quality with time.

As more and more women make the decision to delay their child-bearing, it is critical that they be aware of the age-related decline in fertility. While all of us know a family member or a friend who became pregnant at an “older” age, not all women will be able to do so.  Therefore, it is important that women empower themselves with knowledge of their fertility so that they can make informed reproductive decisions. AMH is an important factor in determining a woman’s reproductive potential.

References:

[1] Faddy Hum Reprod 1996;11:1484
[2] Seifer and MacLaughlin F&S 2007;88:539