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Anti Mllerian Hormone (AMH) is produced by granulosa cells of ovarian follicles during the early stages of follicle development. AMH level may vary significantly in women of the same age. AMH is a good indicator of ovarian reserve and help diagnose PCOS thus helping in diagnosing a woman's reproductive lifespan.
A woman's reproductive system is built with several organs which function with the assistance of several crucial hormones. AMH is one of the most important hormones which contributes to the proper working of the system in every woman. Anti-Mullerian Hormone (AMH) is a hormone secreted by cells in developing egg sacs or follicles. Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor-beta superfamily. Their key roles are in growth differentiation and folliculogenesis. In humans, the gene for AMH is AMH, on chromosome 19p 13 while the gene AMHR2 codes for its receptor on a chromosome. Anti-Mullerian Hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles, mirroring the size of the resting primordial follicle pool. It acts as a useful marker of ovarian reserve. AMH maybe the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women.
AMH has the potential ability to predict future reproductive lifespan in women. The most accepted role for measuring AMH is before the initiation of In Vitro Fertilization (IVF) as AMH can be predictive of the ovarian response, namely poor, and hyper-responses. However, some research suggests that AMH can be used in a variety of ovarian pathological conditions. They can be used for detecting the presence of Polycystic Ovary Syndrome (PCOS), Granulosa cell tumors, and Premature Ovarian Failure. A new commercial enzyme-linked immunosorbent assay for measuring AMH levels has been developed, making results from different studies more efficient and comparable. Nevertheless, widespread clinical application awaits an international standard for Anti Mullerian Hormone, so that results using future assays can be reliably compared. (1)
In this article we will look at:
- What are the functions of Anti Mullerian Hormone (AMH)?
- What is the Anti-Mullerian Hormone Test?
- What is AMH Test used for?
- What is the process involved in AMH Tests?
- When to get tested with AMH test?
- What are the factors that influence AMH levels?
- What is the significance of AMH Tests?
- What are the effects of IVF procedure with low AMH level?
- How to increase an AMH level in the body?
- Why is AMH more preferred over FSH?
- How is age and AMH related to each other?
In male mammals, AMH prevents the development of the Müllerian ducts into the uterus and other Müllerian structures. The effect is ipsilateral, that is each testis has the ability to suppress Müllerian development only on its own side. In humans, this action occurs during the first 8 weeks of the gestational period. If no hormone is produced from the gonads, the Müllerian ducts automatically develop. Wolffian ducts, which are responsible for male reproductive parts, automatically die. Amounts of AMH that are measurable in the blood vary by age and gender. It works by interacting with specific receptors on the surface of the cells of target tissues (anti-Müllerian hormone receptors). The best-known and most specific effect, mediated through the AMH type II receptors, including programmed cell death (apoptosis) of the target tissue (the fetal Müllerian ducts).
- Ovarian Functioning:
Anti Mullerian Hormone is expressed by granulosa cells of the ovary during the reproductive years. It limits the formation of primary follicles by inhibiting excessive follicular recruitment by FSH. AMH expression is often maximum in the recruitment stage of folliculogenesis which primarily occurs in the small antral, and preantral follicles. This AMH expression diminishes as follicles develop and enter the selection stage, upon which FSH expression increases. Some authorities suggest it is a measure of certain aspects of ovarian function, useful in assessing conditions such as Polycystic Ovary Syndrome (PCOS) and premature ovarian failure.
- Other Functions:
Anti Mullerian Hormone (AMH) production by the Sertoli cells of the testes remains high throughout childhood stage in males. However, it may decline to a certain extent during puberty and adult life. AMH has been shown to regulate the production of sex hormones and changing AMH levels may be involved in the onset of puberty in both sexes. It has also been observed in one of the latest performed medical researches that functional AMH receptors are expressed in neurons in the brains of embryonic mice. They are thought to play a crucial role in the development of gender-specific behaviors and sexually dimorphic brain development.
Inadequate AMH activity in men may lead to Persistent Mullerian Duct Syndrome (PMDS) in which a rudimentary uterus is present and testes are usually undescended. The AMH gene or the gene for its receptor (AMH-RII) are usually abnormal. AMH measurements have also become widely used in the evaluation of testicular presence and function in infants with intersex conditions, cryptorchidism, and ambiguous genitalia. According to a study, it was found that there was a link between a hormonal imbalance in the womb and Polycystic ovary syndrome (PCOS), specifically prenatal exposure to Anti-Mullerian hormone. For the study, the researchers injected pregnant mice with AMH, so that they had a higher than normal concentration of the Anti-Mullerian Hormone. Indeed, they gave birth to daughters who later developed PCOS-like tendencies. These include conditions like delayed puberty, infertility, and erratic ovulation. To reverse it, the researchers dosed the polycystic mice with an IVF drug called cetrorelix, which made the symptoms to go away. These experiments should be confirmed in humans, but it could be the first step in understanding the relationship between Polycystic Ovary Syndrome (PCOS) and the Anti-Mullerian hormone (AMH). (2)
- Blood levels:
In healthy females, AMH is either just detectable in cord blood at birth. This indicates a marked rise by three months of age. AMH level falls until four years of age before rising linearly until eight years of age. It remains fairly constant from mid-childhood to early adulthood. It does not change significantly during puberty. The rise during childhood and adolescence is likely reflective of different stages of follicle development. AMH declines to undetectable levels at the menopause stage of the respective woman's life. The standard measurement of AMH follows the Generation II assay. This gives the same values as the previously used IBC assay. AMH values from the previously used Diagnostic Systems Lab (DSL) assay should be multiplied with 1.39 to conform to current standards because it used a different set of antibodies for the chosen tests. It is generally suggested that AMH should be measured only in the early follicular phase because of variation over the menstrual cycle. Also, AMH levels decrease if the individual is presently using oral contraceptives and tobacco smoking.
The level of AMH in a woman's blood is usually a very good indicator of her ovarian reserve. AMH concentrations slowly decrease with increasing age after an initial increase until early adulthood. It becomes undetectable 5 years before the woman has passed the menopause stage when the stock of primordial follicles is exhausted. There is sufficient variability in the pace of follicle pool depletion when several women are taken into consideration. The initial size of the follicle pool is reflected by a wide range of age at menopause. Individual AMH serum concentration does accurately reflect the size of the pool of antral follicles. This represents the quantity of the remaining primordial follicles. AMH is made in the reproductive tissues of both males and females. The role of AMH and whether levels are normal depending on the age and gender factor. (3)
An Anti-Mullerian Hormone (AMH) test is generally used to check a woman's ability to produce eggs that can be fertilized for pregnancy. A woman's ovaries can make thousands of eggs during her childbearing years. The number declines as a woman gets older. The levels of AMH indicates the appropriate number of potential egg cells a woman is left with, this is known as the ovarian reserve. If a woman's ovarian reserve is high, she may have a better chance of getting pregnant. She may also be able to wait for months or years before trying to get pregnant depending on the ovarian reserve of the woman. If the ovarian reserve is low, it may mean a woman will have trouble getting pregnant. In this case, she should not take very long to decide on trying to have a baby. (4)
AMH tests may also be used for the following purposes:
- To predict the start of menopause. A time in a woman's life when her menstrual periods have stopped and she cannot conceive anymore. It usually starts when a woman is around 50 years old.
- In order to find out the reason for early menopause.
- Helps in finding out the reason for amenorrhoea, the lack of menstruation. It is most often diagnosed in girls who have not started menstruating by the age of 15 and among those women who have missed several periods.
- Help diagnose Polycystic Ovary Syndrome (PCOS), a hormonal disorder that is a common cause of female infertility, the inability to get pregnant.
- Check infants with genitals that are not clearly identified as male or female.
- Monitor women who have already been diagnosed with ovarian cancer.
A health care professional firstly takes a blood sample from a vein in the patient's arm, using a small needle. After the needle is inserted, a small amount of blood is collected into a test tube or vial with care. Patients may feel some kind of discomfort when the needle is inserted by the professional or removed out after collecting the blood. The procedure usually takes less than five minutes. There is very little risk associated with a blood test. Patients may experience slight pain or bruise at the spot where the needle was put in. Most of the symptoms vanish at a quicker pace. It may not necessarily be a part of routine fertility blood testing. Patients may not need to fast or take other special actions prior to the test. The test results are very helpful in guiding which procedure one needs to choose for their respective case.
To get the best overall picture of a woman's fertility, AMH testing works best when done in combination with an antral follicle count test. The doctor may advise other tests as well, particularly if patients have not undergone extensive hormonal tests. This means that they may need to undergo testing at a specific point in their cycle, even though the AMH test can be performed as and when required.
Most of the researches suggest that birth control pills do not affect AMH levels in women. However, they can have an impact on the level of other hormones. The doctor may request their patients to go off of birth control for up to three months. If patients are dependent on other fertility drugs, it is important to inform the doctor before undergoing any fertility tests. (5)
Getting an AMH test is most appropriate when a healthcare practitioner wants to evaluate a woman's fertility, predict the onset of menopause, confirm the presence of PCOS. The AMH test is also recommended when there is a requirement of evaluation of the cause of male characteristics in a female (also known as virilization). Sometimes, it is required prior to some assisted reproductive procedures, periodically when a woman is undergoing treatment for an AMH-producing ovarian cancer. It is helpful in suspecting that testicles of an infant boy are absent, hidden, or not functioning properly. (6)
Variation in AMH levels could also be explained by biological variance. Results may be contradictory regarding intra and inter-cycle variability of AMH levels. Some studies show these to be limited and merely represent fluctuations by chance. These could be possibly related to gradual changes in the number of antral follicles present in both ovaries. However, other studies have demonstrated substantial fluctuations in the menstrual cycle, which would argue in favor of measuring AMH levels at the early follicular phase only. Especially in young women, this fluctuation in AMH over a time period of several weeks may be quite extensive. It needs to be taken into consideration if applied in clinical conditions. It has been suggested that AMH levels remain constant under the influence of exogenous sex steroids used for contraception. In a recent large cohort study which was conducted in more than 2000 women, it was demonstrated that AMH levels decrease under current use of oral contraceptives. Such an effect was also demonstrated in other studies. Previous use of oral contraception was not associated with lower AMH levels. AMH levels may stay at the increased level even after discontinuation of oral contraceptives. Both findings support the notion of a reversible suppressive subtle effect of oral contraceptives on AMH. It was also demonstrated that under mid-luteal GnRH (Gonadotropin-releasing hormone) agonist administration AMH levels changed significantly across the initial 4 weeks. Such observations suggest that a patient is presently receiving GnRH agonist medication. For example in cancer treatment, AMH may not be a reliable marker of ovarian reserve. Finally, various other factors were recently described to influence absolute AMH concentrations, including overweight, ethnicity, Vitamin D status, polymorphisms of AMH hormone. If a patient presently has a habit of smoking then also there are high chances of having low AMH levels in the body. The clinical relevance of the given observations remains to be determined. (7)
Here is some AMH levels reference:
- An AMH level over 3,0 ng/ml, is usually an indicator of Polycystic Ovarian Syndrome (PCOS). It means that there are lots of growing follicles in the ovaries. This potentially puts a woman at risk of Ovarian Hyperstimulation Syndrome (OHSS), if she is planning to go for Assisted Reproductive Treatment (ART).
- The level of AMH between 3 and 0.7 ng/ml means that ovarian reserve is normal. There may be other reasons for infertility as well. If AMH levels are normal and a woman still has not succeeded in getting pregnant, she might need further examination with the assistance of other recommended medical tests. Besides she has to improve her overall health with better nutrition, exercise, and increased relaxation.
- Anywhere between 0 and 0.6, ng/ml will require IVF or FSH stimulation. This score might help the doctor to understand if the patient has a low ovarian reserve. The ovarian reserve is also a potential indicator of the outcome of pregnancy treatment. With this test result, patients are most likely to receive additional treatment to increase their AMH levels.
- If a woman is trying to conceive, and there are no issues with sperm count, a doctor who discovers that AMH levels are optimum usually advises treatment to remove other health factors that might negatively affect the occurrence of conception. If both the patient and her partner are theoretically able to conceive, the doctor might then move on to advise additional medical treatments and lifestyle changes to improve the chances of getting pregnant.
The probability of success with an In Vitro Fertilization (IVF) cycle largely depends on a woman's ovarian reserve. It also depends on her ability to produce a decent number of high-quality eggs in a cycle. In some of the abnormal cases, the high FSH levels along with low AMH levels, suggests a compromised ability of the ovaries to produce a good number of high-quality eggs. It denotes a relatively poor fertility prognosis and low probability of success with IVF procedure.
AMH below 1.05 ng/ml, has been associated with extremely low pregnancy rates and many IVF centers deny treatment to women with such low levels of AMH. However, recent research suggests that even women with undetectably low AMH levels (below 0.16 ng/ml) can still conceive and successfully carry a pregnancy after she implements the suggested measures. Many women are able to carry their pregnancy to term if given proper treatment involving DHEA supplementation along with well-designed ovarian stimulation protocols. (8)
Patients with low AMH typically benefit the most from well-managed IVF protocols when performed by the infertility specialist. DHEA supplementation has been shown to be effective in improving IVF pregnancy rates in women with low AMH. Studies over the last 8-9 years have shown significant improvements in AMH levels after DHEA supplementation. Women who are reaching their late thirties saw a significant improvement in AMH concentrations after DHEA treatment, compared to older women. With the introduction of DHEA supplementation and research-driven treatment plans are modified to best suit individual patients, diagnosis and treatment are more effective for diminished ovarian reserve. An umbrella term encompassing both premature ovarian aging and natural, age-related loss of ovarian reserve. (9)
The FSH level is not as reliable as the AMH level for the following 3 reasons.
- The FSH level varies according to the menstrual cycle dates.
- It depends upon the estradiol level (a high estradiol level will artificially suppress a high abnormal FSH level into the normal range).
- It varies from cycle to cycle. It is not always reliable or dependable.
An Anti-Mullerian Hormone level is a much better marker for ovarian reserve. AMH is much more stable than the FSH level. It does not vary from cycle to cycle. Even better, it can be measured on any day of the cycle. This is why most infertility specialists today prefer AMH to check ovarian reserve, rather than the old FSH level.
One crucial aspect of AMH is that there are at least 2 scales and innumerable clinic definitions of what is "normal". It depends on which assay and study need to be used. One scale is ng/ml and one is pmol/l. The pmol/l scale runs from 0 to 48, the ng/ml runs from about 0-10. On the ng/ml scale, less than 2 ng/ml is considered to be a low AMH.
It is important to remember that FSH levels increase as women age while AMH levels decline. In other words, normal FSH and AMH and levels vary depending on a woman’s age. For example, a normal AMH level for a woman at 41 could suggest premature ovarian aging (POA) if the same AMH level was found in a 32-year-old woman. Focusing on age-specific AMH and FSH levels is the best way to assess a woman’s ovarian reserve. It is also the best way to devise an appropriate treatment plan and estimate her IVF pregnancy chances.
An AMH level can also be very useful for young women who want to check their fertility levels or want to postpone childbearing. Some women these days are postponing having a baby in order to pursue a career. The good news is that while usually, fertility does not decline too much below the age of 32, for some women the decision to postpone childbearing can prove to be one they may regret later. Fertility declines as a woman grow older and the problem is that it is not possible to predict the rate of fertility decline for an individual woman. Most women are lulled into a false sense of security if they have a regular period. They assume that if their periods are regular, this automatically means that their egg quality is very good for a successful conception. This is not always true for some women. While their egg quality is up to the mark for them to produce enough hormones to get regular periods, they may not be able to conceive. If the AMH level is low, patients might want to re-think their priorities. If it is normal, then one usually has a possible option of postponing their childbearing years. (10)
Several medical tests like AMH are performed during infertility treatments which aid in the success of the same. You can take the assistance of OVO Fertility right from the start of your fertility treatment journey. You can also browse some of the blogs in the pregnancy section of OVO Fertility. You can also contact us on +918268260808 to solve your queries.
SOURCES AND REFERENCES:
- ^ The Role of Anti-Mllerian Hormone in Female Fertility and Infertility | NCBI Ncbi.nlm.nih.gov, 15 June 2019
- ^ Anti-Mllerian Hormone | Wikipedia En.wikipedia.org, 15 June 2019
- ^ Ovarian Reserve (AMH) Test | IVF Australia Ivf.com.au, 15 June 2019
- ^ What Is an Anti-Mllerian Hormone (AMH) Test | Medline Plus Medlineplus.gov, 15 June 2019
- ^ AMH Testing | Infertility Texas Infertilitytexas.com, 15 June 2019
- ^ Anti-Mllerian Hormone | AACC Labtestsonline.org, 15 June 2019
- ^ Anti-Mllerian Hormone: Ovarian Reserve Testing and Its Potential Clinical Implications | OXFORD Academic Academic.oup.com, 15 June 2019
- ^ Ivf Results in Patients with Very Low Serum Amh Are Significantly Affected by Chronological Age Ncbi.nlm.nih.gov, 15 June 2019
- ^ Treatment for Low AMH | Center for Human Reproductive Centerforhumanreprod.com, 15 June 2019
- ^ AMH Testing | Infertility Texas Infertilitytexas.com, 15 June 2019
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