|Locus||Chr. 19 p13.3|
|anti-Mullerian hormone receptor, type II|
|Locus||Chr. 12 q13|
Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts (paramesonephric ducts) in the male embryo. It has also been called Müllerian inhibiting factor (MIF), Müllerian-inhibiting hormone (MIH), and Müllerian-inhibiting substance (MIS). It is named after Johannes Peter Müller.
In mammals, AMH prevents the development of the mullerian ducts into the uterus and other mullerian structures. The effect is ipsilateral, that is each testis suppresses Müllerian development only on its own side. In humans, this action takes place during the first 8 weeks of gestation. If no hormone is produced from the gonads, the Mullerian ducts automatically develop, while the Wolffian ducts, which are responsible for male reproductive ducts, automatically die. Amounts of AMH that are measurable in the blood vary by age and sex. AMH works by interacting with specific receptors on the surfaces of the cells of target tissues. The best-known and most specific effect, mediated through the AMH type II receptors, includes programmed cell death (apoptosis) of the target tissue (the fetal mullerian ducts).
In healthy females AMH is either just detectable or undetectable in cord blood at birth and demonstrates a marked rise by three months of age; while still detectable it falls until four years of age before rising linearly until eight years of age remaining fairly constant from mid-childhood to early adulthood - it does not change significantly during puberty; from 25 years of age AMH declines to undetectable levels at menopause. AMH is expressed by granulosa cells of the ovary during the reproductive years, and controls the formation of primary follicles by inhibiting excessive follicular recruitment by FSH. It, therefore, has a role in folliculogenesis, and some authorities suggest it is a measure of certain aspects of ovarian function, useful in assessing conditions such as polycystic ovary syndrome and premature ovarian failure. It is useful to predict a poor ovarian response in in vitro fertilization (IVF), but it does not appear to add any predictive information about success rates of an already established pregnancy after IVF.
AMH production by the Sertoli cells of the testes remains high throughout childhood in males but declines to low levels during puberty and adult life. AMH has been shown to regulate production of sex hormones, and changing AMH levels (falling in females, rising in males) may be involved in the onset of puberty in both sexes. Functional AMH receptors have also been found to be expressed on neurons in the brains of embryonic mice, and are thought to play a role in sexually dimorphic brain development and consequent development of gender-specific behaviours.
In men, inadequate embryonal AMH activity can lead to the Persistent Müllerian duct syndrome (PMDS), in which a rudimentary uterus is present and testes are usually undescended. The AMH gene (AMH) or the gene (AMH-RII) for its receptor are usually abnormal. AMH measurements have also become widely used in the evaluation of testicular presence and function in infants with intersex conditions, ambiguous genitalia, and cryptorchidism.
The standard measurement of AMH follows the Generation II assay. This should give the same values as the previously used IBC assay, but AMH values from the previously used DSL assay should be multiplied with 1.39 to conform to current standards because it used different antibodies.
|Younger than 24 months||ng/mL||Less than 5|
|pmol/l||Less than 35|
|24 months to 12 years||ng/mL||Less than 10|
|pmol/l||Less than 70|
|13–45 years||ng/mL||1 to 10|
|pmol/l||7 to 70|
|More than 45 years||ng/mL||Less than 1|
|pmol/l||Less than 7|
According to NICE guidelines of in vitro fertilization, an anti-Müllerian hormone level of less than or equal to 5.4 pmol/l (0.8 ng/mL) predicts a low response to ovarian hyperstimulation, while a level greater than or equal to 25.0 pmol/l (3.6 ng/mL) predicts a high response. Other cut-off values found in the literature vary between 0.7 and 20 pmol/l (0.1 and 2.97 ng/ml) for low response to ovarian hyperstimulation.
|Younger than 24 months||ng/mL||15 to 500|
|pmol/l||100 to 3500|
|24 months to 12 years||ng/mL||7 to 240|
|pmol/l||50 to 1700|
|More than 12 years||ng/mL||0.7 to 20|
|pmol/l||5 to 140|
AMH measurements may be less accurate if the person being measured is vitamin D deficient.
AMH has been synthesized. Its ability to inhibit growth of tissue derived from the Müllerian ducts has raised hopes of usefulness in the treatment of a variety of medical conditions including endometriosis, adenomyosis, and uterine cancer. Research is underway in several laboratories.
Comparison of an individual's AMH level with respect to average levels is also useful in fertility assessment, as it provides a guide to ovarian reserve and identifies women that may need to consider either egg freezing or trying for a pregnancy sooner rather than later if their long-term future fertility is poor. Measuring AMH alone may be misleading as high levels occur in conditions like polycystic ovarian syndrome and therefore AMH levels should be considered in conjunction with a transvaginal scan of the ovaries to assess antral follicle count and ovarian volume.
It also has the potential to rationalise the programme of ovulation induction and decisions about the number of embryos to transfer in assisted reproduction techniques to maximise pregnancy success rates whilst minimising the risk of ovarian hyperstimulation syndrome (OHSS) AMH can predict an excessive response in ovarian hyperstimulation with a sensitivity and specificity of 82% and 76%, respectively.
- Sexual differentiation
- Anti-Mullerian hormone receptor
- Alfred Jost discoverer.
- PMDS (Persistent Müllerian Duct Syndrome)
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- An Introduction to Behavioral Endocrinology, Randy J Nelson, 3rd edition, Sinauer
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- Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, Eijkemans MJ, Mol BW, Broekmans FJ (2013). "Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach". Human Reproduction Update 19 (1): 26–36. doi:10.1093/humupd/dms041. PMID 23188168. Retrieved 2013-04-23.
- Trbovich AM, Martinelle N, O'Neill FH, Pearson EJ, Donahoe PK, Sluss PM, Teixeira J (October 2004). "Steroidogenic activities in MA-10 Leydig cells are differentially altered by cAMP and Müllerian inhibiting substance". The Journal of Steroid Biochemistry and Molecular Biology 92 (3): 199–208. doi:10.1016/j.jsbmb.2004.07.002. PMID 15555913.
- Wang PY, Protheroe A, Clarkson AN, Imhoff F, Koishi K, McLennan IS (April 2009). "Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior". Proceedings of the National Academy of Sciences of the United States of America 106 (17): 7203–8. doi:10.1073/pnas.0902253106. PMC 2678437. PMID 19359476.
- La Marca, A.; Sunkara, S. K. (2013). "Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: From theory to practice". Human Reproduction Update 20: 124. doi:10.1093/humupd/dmt037.
- For mass values:
- Antimullerian Hormone (AMH), Serum from Mayo Medical Laboratories. Retrieved April 2012.
- Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013
- Dennis NA, Houghton LA, Jones GT, van Rij AM, Morgan K, McLennan IS (July 2012). "The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys". The Journal of Clinical Endocrinology and Metabolism 97 (7): 2450–5. doi:10.1210/jc.2012-1213. PMID 22508713. Retrieved 2013-04-23.
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- Seifer DB, Maclaughlin DT (September 2007). "Mullerian Inhibiting Substance is an ovarian growth factor of emerging clinical significance". Fertil. Steril. 88 (3): 539–46. doi:10.1016/j.fertnstert.2007.02.014. PMID 17559842.
- Wallace WHB, Kelsey TW (2004). "Ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography". Human Reproduction 19 (7): 1612–7. doi:10.1093/humrep/deh285. PMID 15205396.
- Nelson SM, Yates RW et al. (2007). "Serum anti-Mullerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles—implications for individualization of therapy". Human Reproduction 22 (9): 2414–2421. doi:10.1093/humrep/dem204. PMID 17636277.
- Nelson SM, Yates RW et al. (2009). "Anti-Mullerian hormone-based approach to controlled ovarian stimulation for assisted conception". Human Reproduction 1 (1): 1–9.
- Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ (2011). "AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis". Human Reproduction Update 17 (1): 46–54. doi:10.1093/humupd/dmq034. PMID 20667894. Retrieved 2013-04-23.