Anti-Müllerian hormone

anti-Müllerian hormone
Identifiers
Symbol AMH
Entrez 268
HUGO 464
OMIM 600957
RefSeq NM_000479
UniProt P03971
Other data
Locus Chr. 19 p13.3
anti-Müllerian hormone receptor, type II
Identifiers
Symbol AMHR2
Entrez 269
HUGO 465
OMIM 600956
RefSeq NM_020547
UniProt Q16671
Other data
Locus Chr. 12 q13

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, whose key roles are in growth differentiation and folliculogenesis.[1] In humans, the gene for AMH is AMH, on chromosome 19p13.3,[2] while the gene AMHR2 codes for its receptor on chromosome 12.[3]

AMH is activated by SOX9 in the Sertoli cells of the male fetus.[4] Its expression inhibits the development of the female reproductive tract, or Müllerian ducts (paramesonephric ducts), in the male embryo, thereby arresting the development of fallopian tubes, uterus, and upper vagina.[5][6][7][8] AMH expression is critical to sex differentiation at a specific time during fetal development, and appears to be tightly regulated by nuclear receptor SF1, transcription GATA factors, sex-reversal gene DAX1, and follicle-stimulating hormone (FSH).[9][10][11] Mutations in both the AMH gene and the type II AMH receptor have been shown to cause the persistence of Müllerian derivatives in males that are otherwise normally masculinized.[12]

AMH is also a product of granulosa cells of the preantral and small antral follicles in women. As such, AMH is only present in the ovary until menopause.[13] Production of AMH regulates folliculogenesis by inhibiting recruitment of follicles from the resting pool in order to select for the dominant follicle, after which the production of AMH diminishes.[13][14] As a product of the granulosa cells, which envelop each egg and provide them energy, AMH can also serve as a molecular biomarker for relative size of the ovarian reserve.[15] In humans, this is helpful because the number of cells in the follicular reserve can be used to predict timing of menopause.[16] In bovine, AMH can be used for selection of females in multi-ovulatory embryo transfer programs by predicting the number of antral follicles developed to ovulation.[17] AMH can also be used as a marker for ovarian dysfunction, such as in women with polycystic ovary syndrome (PCOS).

Structure

AMH is a dimeric glycoprotein with a molar mass of 140 kDa.[18] The molecule consists of two identical subunits linked by sulfide bridges, and characterized by the N-terminal dimer (pro-region) and C-terminal dimer.[1] AMH acts with receptors, AMH-RI and AMH-RII, upon which, after a series of conformational changes and phosphorylation steps, gene expression is regulated in the cell.[1]

Function

Embryogenesis

In mammals, AMH prevents the development of the Müllerian ducts into the uterus and other Müllerian structures.[5] The effect is ipsilateral, that is each testis suppresses Müllerian development only on its own side.[19] In humans, this action takes place during the first 8 weeks of gestation. If no hormone is produced from the gonads, the Müllerian ducts automatically develop, while the Wolffian ducts, which are responsible for male reproductive parts, automatically die.[20] 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 (anti-Müllerian hormone receptors). 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 Müllerian ducts).

Ovarian

AMH is expressed by granulosa cells of the ovary during the reproductive years, and limits the formation of primary follicles by inhibiting excessive follicular recruitment by FSH.[15][21] AMH expression is greatest in the recruitment stage of folliculogenesis, in the preantral and small antral follicles. This expression diminishes as follicles develop and enter selection stage, upon which FSH expression increases.[22] Some authorities suggest it is a measure of certain aspects of ovarian function,[23] useful in assessing conditions such as polycystic ovary syndrome and premature ovarian failure.[24]

Other

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,[25] and changing AMH levels (rising in females, falling in males) may be involved in the onset of puberty in both sexes. Functional AMH receptors have also been found to be expressed in 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.[26]

Pathology

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 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, ambiguous genitalia, and cryptorchidism.

Blood levels

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.[27] The rise during childhood and adolescence is likely reflective of different stages of follicle development.[21] From 25 years of age AMH declines to undetectable levels at menopause.[27]

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.[28]

Weak evidence suggests that AMH should be measured only in the early follicular phase because of variation over the menstrual cycle. Also, AMH levels decrease under current use of oral contraceptives and current tobacco smoking.[29]

Reference ranges

Reference ranges for Anti-Müllerian hormone, as estimated from reference groups in the United states, are as follows:[30]

Females:

Age Unit Value
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

Males:

Age Unit Value
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.[31] Note that males are born with higher AMH levels than females in order to initiate sexual differentiation, and in women, AMH levels decrease over time as fertility decreases as well.[31]

Clinical usage

General fertility assessment

Comparison of an individual's AMH level with respect to average levels[27] is 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.[32] A higher level of anti-Müllerian hormone when tested in women in the general population has been found to have a positive correlation with natural fertility in women aged 30–44 aiming to conceive spontaneously, even after adjusting for age.[29] However, this correlation was not found in a comparable study of younger women (aged 20 to 35 years).[29]

In vitro fertilization

AMH is a useful tool 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.[33] Additionally, AMH levels are used to estimate a woman's remaining egg supply.[34]

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.[35] 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.[28] Subsequently, higher AMH levels are associated with greater chance of live birth after IVF, even after adjusting for age.[29][36] AMH can thereby be used 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).[37][38] AMH can predict an excessive response in ovarian hyperstimulation with a sensitivity and specificity of 82% and 76%, respectively.[39]

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[40] and ovarian volume.[41]

Women with cancer

In women with cancer, radiation therapy and chemotherapy can damage the ovarian reserve. In such cases, a pre-treatment AMH is useful in predicting the long-term post-chemotherapy loss of ovarian function, which may indicate fertility preservation strategies such as oocyte cryopreservation.[29] A post-treatment AMH is associated with decreased fertility.[21][29]

Granulosa cell tumors of the ovary secrete AMH, and AMH testing has a sensitivity ranging between 76 and 93% in diagnosing such tumors.[29] AMH is also useful in diagnosing recurrence of granulosa cell tumors.[29]

Neutering status in animals

In veterinary medicine, AMH measurements are used to determine neutering status in male and female dogs and cats. AMH levels can also be used to diagnose cases of ovarian remnant syndrome.[42]

Biomarker of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is an endocrine disorder most commonly found in women of reproductive age that is characterized by oligo- or anovulation, hyperandrogenism, and polycystic ovaries (PCO).[43] This endocrine disorder increases AMH levels at nearly two to three times higher in women with PCOS than in normal type women. This is often attributed to the increased follicle count number characteristic of PCOS, indicating an increase in granulosa cells since they surround each individual egg.[44][45] However, increased AMH levels have also been attributed not just to the increased number of follicles, but also to an increased amount of AMH produced per follicle.[44][46] The high levels of androgens, characteristic of PCOS, also stimulate and provide feedback for increased production of AMH, as well.[22] In this way, AMH has been increasingly considered to be a tool or biomarker that can be used to diagnose or indicate PCOS.

Potential future usage

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. If there were more standardized AMH assays, it could potentially be used as a biomarker of polycystic ovary syndrome.[47]

Names

The adjective "Müllerian" is written either "Müllerian" or "müllerian", depending on the governing style guide; the derived term with the prefix of "anti-" is then "anti-Müllerian", "anti-müllerian", or "antimüllerian". The Müllerian ducts are named after Johannes Peter Müller.[48]

A list of the names that have been used for the antimüllerian hormone is as follows. For the sake of simplicity, this list ignores some orthographic variations; for example, it gives only one row for "Müllerian-inhibiting hormone", although there are 4 acceptable stylings thereof (cap M or lowercase m, hyphen or space).

Protein name styling Protein symbol
Anti-Müllerian hormone AMH
anti-müllerian hormone AMH
antimüllerian hormone AMH
Müllerian-inhibiting factor MIF
Müllerian-inhibiting hormone MIH
Müllerian-inhibiting substance MIS
müllerian duct inhibitory factor MDIF
müllerian regression factor MRF
anti-paramesonephric hormone APH
antiparamesonephric hormone APH

See also

References

  1. 1 2 3 Rzeszowska, Marzena; Leszcz, Agnieszka; Putowski, Lechosław; Hałabiś, Magdalena; Tkaczuk-Włach, Joanna; Kotarski, Jan; Polak, Grzegorz (2016). "Anti-Müllerian hormone: structure, properties and appliance". Ginekologia Polska. 87 (9): 669–674. ISSN 2543-6767. doi:10.5603/gp.2016.0064.
  2. ↑ Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP (June 1986). "Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells". Cell. 45 (5): 685–98. PMID 3754790. doi:10.1016/0092-8674(86)90783-X.
  3. ↑ Imbeaud S, Faure E, Lamarre I, Mattéi MG, di Clemente N, Tizard R, Carré-Eusèbe D, Belville C, Tragethon L, Tonkin C, Nelson J, McAuliffe M, Bidart JM, Lababidi A, Josso N, Cate RL, Picard JY (December 1995). "Insensitivity to anti-müllerian hormone due to a mutation in the human anti-müllerian hormone receptor". Nature Genetics. 11 (4): 382–8. PMID 7493017. doi:10.1038/ng1295-382.
  4. ↑ Taguchi, Osamu; Cunha, Gerald R.; Lawrence, W.Dwayne; Robboy, Stanley J. "Timing and irreversibility of Müllerian duct inhibition in the embryonic reproductive tract of the human male". Developmental Biology. 106 (2): 394–398. doi:10.1016/0012-1606(84)90238-0.
  5. 1 2 Behringer RR (1994). "The in vivo roles of müllerian-inhibiting substance". Current Topics in Developmental Biology. Current Topics in Developmental Biology. 29: 171–87. PMID 7828438. doi:10.1016/S0070-2153(08)60550-5.
  6. ↑ Rey R, Lukas-Croisier C, Lasala C, Bedecarrás P (December 2003). "AMH/MIS: what we know already about the gene, the protein and its regulation". Molecular and Cellular Endocrinology. 211 (1-2): 21–31. PMID 14656472. doi:10.1016/j.mce.2003.09.007.
  7. ↑ Taguchi O, Cunha GR, Lawrence WD, Robboy SJ (December 1984). "Timing and irreversibility of Müllerian duct inhibition in the embryonic reproductive tract of the human male". Developmental Biology. 106 (2): 394–8. PMID 6548718. doi:10.1016/0012-1606(84)90238-0.
  8. ↑ "Serum Anti-Müllerian hormone (AMH) levels are differentially modulated by both serum gonadotropins and not only by serum Follicle Stimulating Hormone (FSH) levels - ScienceDirect" (PDF). ac.els-cdn.com. Retrieved 2017-05-25.
  9. ↑ Shen WH, Moore CC, Ikeda Y, Parker KL, Ingraham HA (June 1994). "Nuclear receptor steroidogenic factor 1 regulates the müllerian inhibiting substance gene: a link to the sex determination cascade". Cell. 77 (5): 651–661. PMID 8205615. doi:10.1016/0092-8674(94)90050-7.
  10. ↑ Nachtigal MW, Hirokawa Y, Enyeart-VanHouten DL, Flanagan JN, Hammer GD, Ingraham HA (May 1998). "Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression". Cell. 93 (3): 445–454. PMID 9590178. doi:10.1016/s0092-8674(00)81172-1.
  11. ↑ Viger RS, Mertineit C, Trasler JM, Nemer M (July 1998). "Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter". Development. 125 (14): 2665–2675. PMID 9636081.
  12. ↑ Belville C, Josso N, Picard JY (December 1999). "Persistence of Müllerian derivatives in males". American Journal of Medical Genetics. 89 (4): 218–223. PMID 10727997. doi:10.1002/(sici)1096-8628(19991229)89:4<218::aid-ajmg6>3.0.co;2-e.
  13. 1 2 Pellatt, Laura; Rice, Suman; Mason, Helen D. (2010-05-01). "Anti-Müllerian hormone and polycystic ovary syndrome: a mountain too high?". Reproduction. 139 (5): 825–833. ISSN 1470-1626. PMID 20207725. doi:10.1530/REP-09-0415.
  14. ↑ Kollmann, Zahraa; Bersinger, Nick A.; McKinnon, Brett D.; Schneider, Sophie; Mueller, Michael D.; von Wolff, Michael (2015). "Anti-Müllerian hormone and progesterone levels produced by granulosa cells are higher when derived from natural cycle IVF than from conventional gonadotropin-stimulated IVF". Reproductive Biology and Endocrinology. 13: 21. ISSN 1477-7827. PMC 4379743 Freely accessible. PMID 25889012. doi:10.1186/s12958-015-0017-0.
  15. 1 2 Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC, Themmen AP (February 2004). "Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment". Molecular Human Reproduction. 10 (2): 77–83. PMID 14742691. doi:10.1093/molehr/gah015.
  16. ↑ van Disseldorp J, Faddy MJ, Themmen AP, de Jong FH, Peeters PH, van der Schouw YT, Broekmans FJ (June 2008). "Relationship of serum antimüllerian hormone concentration to age at menopause". The Journal of Clinical Endocrinology and Metabolism. 93 (6): 2129–34. PMID 18334591. doi:10.1210/jc.2007-2093.
  17. ↑ Rico C, Médigue C, Fabre S, Jarrier P, Bontoux M, Clément F, Monniaux D (March 2011). "Regulation of anti-Müllerian hormone production in the cow: a multiscale study at endocrine, ovarian, follicular, and granulosa cell levels". Biology of Reproduction. 84 (3): 560–571. PMID 21076084. doi:10.1095/biolreprod.110.088187.
  18. ↑ Hampl R, Šnajderová M, Mardešić T (2011). "Antimüllerian hormone (AMH) not only a marker for prediction of ovarian reserve". Physiological Research / Academia Scientiarum Bohemoslovaca. 60 (2): 217–223. PMID 21114374.
  19. ↑ Page 1114 in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
  20. ↑ An Introduction to Behavioral Endocrinology, Randy J Nelson, 3rd edition, Sinauer
  21. 1 2 3 Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, Griesinger G, Kelsey TW, La Marca A, Lambalk C, Mason H, Nelson SM, Visser JA, Wallace WH, Anderson RA (2014). "The physiology and clinical utility of anti-Mullerian hormone in women". Human Reproduction Update. 20 (3): 370–385. PMID 24430863. doi:10.1093/humupd/dmt062.
  22. 1 2 Dumont, Agathe; Robin, Geoffroy; Catteau-Jonard, Sophie; Dewailly, Didier (2015). "Role of Anti-Müllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: a review". Reproductive Biology and Endocrinology. 13: 137. ISSN 1477-7827. PMC 4687350 Freely accessible. PMID 26691645. doi:10.1186/s12958-015-0134-9.
  23. ↑ Broer SL, Eijkemans MJ, Scheffer GJ, van Rooij IA, de Vet A, Themmen AP, Laven JS, de Jong FH, Te Velde ER, Fauser BC, Broekmans FJ (August 2011). "Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women". The Journal of Clinical Endocrinology and Metabolism. 96 (8): 2532–9. PMID 21613357. doi:10.1210/jc.2010-2776.
  24. ↑ Visser JA, de Jong FH, Laven JS, Themmen AP (Jan 2006). "Anti-Müllerian hormone: a new marker for ovarian function". Reproduction. 131 (1): 1–9. PMID 16388003. doi:10.1530/rep.1.00529.
  25. ↑ 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. PMID 15555913. doi:10.1016/j.jsbmb.2004.07.002.
  26. ↑ 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. PMC 2678437 Freely accessible. PMID 19359476. doi:10.1073/pnas.0902253106.
  27. 1 2 3 Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WH (2011). "A Validated Model of Serum Anti-Müllerian Hormone from Conception to Menopause". PLOS ONE. 6 (7): e22024. PMC 3137624 Freely accessible. PMID 21789206. doi:10.1371/journal.pone.0022024.
  28. 1 2 La Marca A, Sunkara SK (2013). "Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice". Human Reproduction Update. 20 (1): 124–40. PMID 24077980. doi:10.1093/humupd/dmt037.
  29. 1 2 3 4 5 6 7 8 Broer SL, Broekmans FJ, Laven JS, Fauser BC (2014). "Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications". Human Reproduction Update. 20 (5): 688–701. PMID 24821925. doi:10.1093/humupd/dmu020.
  30. ↑ For mass values: For molar values: Derived from mass values using 140,000 g/mol, as given in:
    • Hampl R, Šnajderová M, Mardešić T (2011). "Antimüllerian hormone (AMH) not only a marker for prediction of ovarian reserve". Physiological Research / Academia Scientiarum Bohemoslovaca. 60 (2): 217–223. PMID 21114374.
  31. 1 2 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. PMID 22508713. doi:10.1210/jc.2012-1213.
  32. ↑ Cupisti S, Dittrich R, Mueller A, Strick R, Stiegler E, Binder H, Beckmann MW, Strissel P (December 2007). "Correlations between anti-müllerian hormone, inhibin B, and activin A in follicular fluid in IVF/ICSI patients for assessing the maturation and developmental potential of oocytes". European Journal of Medical Research. 12 (12): 604–8. PMID 18024272.
  33. ↑ 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. PMID 23188168. doi:10.1093/humupd/dms041.
  34. ↑ Indichova J. "Does a Low AMH Level (Anti-Mullerian Hormone) Indicate Infertility?". http://www.fertileheart.com. Retrieved 6 February 2015. External link in |website= (help)
  35. ↑ Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013
  36. ↑ Iliodromiti S, Kelsey TW, Wu O, Anderson RA, Nelson SM (2014). "The predictive accuracy of anti-Müllerian hormone for live birth after assisted conception: a systematic review and meta-analysis of the literature". Human Reproduction Update. 20 (4): 560–570. PMID 24532220. doi:10.1093/humupd/dmu003.
  37. ↑ Nelson SM, Yates RW, Fleming R (September 2007). "Serum anti-Müllerian 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. PMID 17636277. doi:10.1093/humrep/dem204.
  38. ↑ Nelson SM, Yates RW, Lyall H, Jamieson M, Traynor I, Gaudoin M, Mitchell P, Ambrose P, Fleming R (April 2009). "Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception". Human Reproduction. 24 (4): 867–875. PMID 19136673. doi:10.1093/humrep/den480.
  39. ↑ 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. PMID 20667894. doi:10.1093/humupd/dmq034.
  40. ↑ Seifer DB, Maclaughlin DT (September 2007). "Mullerian Inhibiting Substance is an ovarian growth factor of emerging clinical significance". Fertility and Sterility. 88 (3): 539–46. PMID 17559842. doi:10.1016/j.fertnstert.2007.02.014.
  41. ↑ Wallace WH, Kelsey TW (July 2004). "Ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography". Human Reproduction. 19 (7): 1612–7. PMID 15205396. doi:10.1093/humrep/deh285.
  42. ↑ Place, Ned J.; Hansen, Betty S.; Cheraskin, Jeri-Lyn; Cudney, Sarah E.; Flanders, James A.; Newmark, Andrew D.; Barry, Bridget; Scarlett, Janet M. (2011-05-01). "Measurement of serum anti-Müllerian hormone concentration in female dogs and cats before and after ovariohysterectomy". Journal of Veterinary Diagnostic Investigation. 23 (3): 524–527. ISSN 1040-6387. PMID 21908283. doi:10.1177/1040638711403428.
  43. ↑ Azziz, Ricardo (2006-03-01). "Diagnosis of Polycystic Ovarian Syndrome: The Rotterdam Criteria Are Premature". The Journal of Clinical Endocrinology & Metabolism. 91 (3): 781–785. ISSN 0021-972X. doi:10.1210/jc.2005-2153.
  44. 1 2 Zahid, Nida (2014-09-01). "Role of Anti-Mullerian Hormone (AMH) in Polycystic Ovary Syndrome (PCOS)? A Mini Review". Reproductive System & Sexual Disorders. 3 (4). ISSN 2161-038X. doi:10.4172/2161-038X.1000143.
  45. ↑ Dewailly, Didier (2016-11-01). "Diagnostic criteria for PCOS: Is there a need for a rethink?". Best Practice & Research Clinical Obstetrics & Gynaecology. 37: 5–11. ISSN 1521-6934. doi:10.1016/j.bpobgyn.2016.03.009.
  46. ↑ Verma, Anil Kumar; Rajbhar, Sarita; Mishra, Jyoti; Gupta, Mayank; Sharma, Mratunjai; Deshmukh, Geeta; Ali, Wahid (2017-05-25). "Anti-Mullerian Hormone: A Marker of Ovarian Reserve and its Association with Polycystic Ovarian Syndrome". Journal of Clinical and Diagnostic Research : JCDR. 10 (12): QC10–QC12. ISSN 2249-782X. PMC 5296514 Freely accessible. PMID 28208941. doi:10.7860/JCDR/2016/20370.8988.
  47. ↑ Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, Escobar-Morreale HF (2013). "Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society". Human Reproduction Update. 20 (3): 334–352. PMID 24345633. doi:10.1093/humupd/dmt061.
  48. ↑ Minkoff E, Baker P (2004). Biology Today: An Issues Approach (Third ed.). New York: Garland Science. p. 296. ISBN 1136838759.

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