Abstract
Primary ovarian insufficiency (POI), also known as premature ovarian failure, is a disorder of infertility characterized by amenorrhoea, low estrogen levels and increased gonadotropin levels in women aged <40 years. POI is the result of premature exhaustion of the follicle pool or can be attributed to follicular dysfunction, for example, owing to mutations in the follicle-stimulating hormone receptor or steroidogenic cell autoimmunity. Moreover, advances in cancer therapeutics over the past decades have led to increasing survival rates for both paediatric and adult malignancies. Given the gonadotoxic effect of many cancer treatments, more women develop POI. A marker that predicts whether women are at risk of POI would, therefore, aid in early diagnosis and fertility counselling. Anti-Müllerian hormone (AMH), a growth factor produced solely by small, growing follicles in the ovary, might constitute such a marker, as serum levels of this hormone correlate strongly with the number of growing follicles. In addition, AMH could potentially help assess the progression of ovarian senescence, as serum AMH levels are independent of hypothalamic–pituitary–gonadal axis function and decrease to undetectable levels at menopause. In cancer survivors, serum AMH levels correlate with the extent of gonadal damage. In this Review, we provide an overview of the current studies that have measured AMH in women with POI of various aetiologies and discuss its possible application as a marker to determine ovarian reserve.
Key Points
-
Primary ovarian insufficiency (POI) is a disorder of infertility caused by cessation of ovarian function before the age of 40 years
-
The number of women that develop POI is growing owing to the increased success of cancer treatments
-
Anti-Müllerian hormone (AMH) is an ovary-specific growth factor, the expression of which is independent of hypothalamic–pituitary–gonadal axis function
-
Serum AMH levels correlate with the size of the primordial follicle pool and can be used in the early assessment of a diminished ovarian reserve, which most patients with POI are affected by
-
Serum AMH levels correlate with the degree of ovarian damage—induced by the gonadotoxic effect of cancer treatment—in cancer survivors and might aid in fertility counselling of these patients
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Conway, G. S. Premature ovarian failure. Br. Med. Bull. 56, 643–649 (2000).
Albright, F., Smith, P. H. & Fraser, R. A syndrome characterized by primary ovarian insufficiency and decreased stature: Report of 11 cases with a digression on hormonal control of axillary and pubic hair. Am. J. Med. Sci. 204, 625–648 (1942).
Welt, C. K. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin. Endocrinol. (Oxf.) 68, 499–509 (2008).
Nelson, L. M. Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med. 360, 606–614 (2009).
De Vos, M., Devroey, P. & Fauser, B. C. Primary ovarian insufficiency. Lancet 376, 911–921 (2010).
te Velde, E. R. & Pearson, P. L. The variability of female reproductive ageing. Hum. Reprod. Update 8, 141–154 (2002).
Coulam, C. B., Adamson, S. C. & Annegers, J. F. Incidence of premature ovarian failure. Obstet. Gynecol. 67, 604–606 (1986).
Anasti, J. N. Premature ovarian failure: an update. Fertil. Steril. 70, 1–15 (1998).
Persani, L., Rossetti, R. & Cacciatore, C. Genes involved in human premature ovarian failure. J. Mol. Endocrinol. 45, 257–279 (2010).
Matzuk, M. M. & Lamb, D. J. The biology of infertility: research advances and clinical challenges. Nat. Med. 14, 1197–1213 (2008).
Bakalov, V. K. et al. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil. Steril. 84, 958–965 (2005).
Aittomäki, K. et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82, 959–968 (1995).
Latronico, A. C. et al. Brief report: testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N. Engl. J. Med. 334, 507–512 (1996).
Araki, S. et al. Arrest of follicular development in a patient with 17 alpha-hydroxylase deficiency: folliculogenesis in association with a lack of estrogen synthesis in the ovaries. Fertil. Steril. 47, 169–172 (1987).
Conte, F. A., Grumbach, M. M., Ito, Y., Fisher, C. R. & Simpson, E. R. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J. Clin. Endocrinol. Metab. 78, 1287–1292 (1994).
Nelson, L. M. et al. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J. Clin. Endocrinol. Metab. 79, 1470–1475 (1994).
Nelson, L. M., Covington, S. N. & Rebar, R. W. An update: spontaneous premature ovarian failure is not an early menopause. Fertil. Steril. 83, 1327–1332 (2005).
Hubayter, Z. R. et al. A prospective evaluation of antral follicle function in women with 46, XX spontaneous primary ovarian insufficiency. Fertil. Steril. 94, 1769–1774 (2010).
Karimov, C. B. et al. Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function. Hum. Reprod. 26, 2077–2083 (2011).
Goswami, D. & Conway, G. S. Premature ovarian failure. Hum. Reprod. Update 11, 391–410 (2005).
Skillern, A. & Rajkovic, A. Recent developments in identifying genetic determinants of premature ovarian failure. Sex. Dev. 2, 228–243 (2008).
Knauff, E. A. et al. Genome-wide association study in premature ovarian failure patients suggests ADAMTS19 as a possible candidate gene. Hum. Reprod. 24, 2372–2378 (2009).
van Dooren, M. F., Bertoli-Avellab, A. M. & Oldenburg, R. A. Premature ovarian failure and gene polymorphisms. Curr. Opin. Obstet. Gynecol. 21, 313–317 (2009).
Oldenburg, R. A. et al. A genome-wide linkage scan in a Dutch family identifies a premature ovarian failure susceptibility locus. Hum. Reprod. 23, 2835–2841 (2008).
Christin-Maitre, S. & Tachdjian, G. Genome-wide association study and premature ovarian failure. Ann. Endocrinol. (Paris) 71, 218–221 (2010).
Bondy, C. A. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J. Clin. Endocrinol. Metab. 92, 10–25 (2007).
Saenger, P. et al. Recommendations for the diagnosis and management of Turner syndrome. J. Clin. Endocrinol. Metab. 86, 3061–3069 (2001).
Sherman, S. L. Premature ovarian failure in the fragile X syndrome. Am. J. Med. Genet. 97, 189–194 (2000).
Verkerk, A. J. et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905–914 (1991).
Fu, Y. H. et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67, 1047–1058 (1991).
Allingham-Hawkins, D. J. et al. Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study—preliminary data. Am. J. Med. Genet. 83, 322–325 (1999).
Conway, G. S., Payne, N. N., Webb, J., Murray, A. & Jacobs, P. A. Fragile X premutation screening in women with premature ovarian failure. Hum. Reprod. 13, 1184–1187 (1998).
Conway, G. S., Kaltsas, G., Patel, A., Davies, M. C. & Jacobs, H. S. Characterization of idiopathic premature ovarian failure. Fertil. Steril. 65, 337–341 (1996).
Novosad, J. A., Kalantaridou, S. N., Tong, Z. B. & Nelson, L. M. Ovarian antibodies as detected by indirect immunofluorescence are unreliable in the diagnosis of autoimmune premature ovarian failure: a controlled evaluation. BMC Womens Health 3, 2 (2003).
La Marca, A. et al. Primary ovarian insufficiency: autoimmune causes. Curr. Opin. Obstet. Gynecol. 22, 277–282 (2010).
Gatta, G., Capocaccia, R., Coleman, M. P., Ries, L. A. & Berrino, F. Childhood cancer survival in Europe and the United States. Cancer 95, 1767–1772 (2002).
Gatta, G. et al. Childhood cancer survival trends in Europe: a EUROCARE Working Group study. J. Clin. Oncol. 23, 3742–3751 (2005).
Edgar, A. B., Morris, E. M., Kelnar, C. J. & Wallace, W. H. Long-term follow-up of survivors of childhood cancer. Endocr. Dev. 15, 159–180 (2009).
Bath, L. E., Wallace, W. H. & Critchley, H. O. Late effects of the treatment of childhood cancer on the female reproductive system and the potential for fertility preservation. BJOG 109, 107–114 (2002).
van Dorp, W. et al. Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review. Hum. Reprod. Update http://dx.doi.org/10.1093/humupd/dmr038.
Brougham, M. F. & Wallace, W. H. Subfertility in children and young people treated for solid and haematological malignancies. Br. J. Haematol. 131, 143–155 (2005).
Shelling, A. N. Premature ovarian failure. Reproduction 140, 633–641 (2010).
Josso, N. et al. Anti-müllerian hormone: the Jost factor. Recent Prog. Horm. Res. 48, 1–59 (1993).
Lee, M. M. & Donahoe, P. K. Müllerian inhibiting substance: a gonadal hormone with multiple functions. Endocr. Rev. 14, 152–164 (1993).
Josso, N., Picard, J. Y. & Tran, D. The anti-Müllerian hormone. Birth Defects Orig. Artic. Ser. 13, 59–84 (1977).
Durlinger, A. L., Visser, J. A. & Themmen, A. P. Regulation of ovarian function: the role of anti-Müllerian hormone. Reproduction 124, 601–609 (2002).
Rajpert-De Meyts, E. et al. Expression of anti-Müllerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J. Clin. Endocrinol. Metab. 84, 3836–3844 (1999).
Weenen, C. et al. Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol. Hum. Reprod. 10, 77–83 (2004).
Shi, J. et al. Bone morphogenetic protein-6 stimulates gene expression of follicle-stimulating hormone receptor, inhibin/activin beta subunits, and anti-Müllerian hormone in human granulosa cells. Fertil. Steril. 92, 1794–1798 (2009).
Salmon, N. A., Handyside, A. H. & Joyce, I. M. Oocyte regulation of anti-Müllerian hormone expression in granulosa cells during ovarian follicle development in mice. Dev. Biol. 266, 201–208 (2004).
Grøndahl, M. L. et al. Anti-Müllerian hormone remains highly expressed in human cumulus cells during the final stages of folliculogenesis. Reprod. Biomed. Online 22, 389–398 (2011).
McGee, E. A. & Hsueh, A. J. Initial and cyclic recruitment of ovarian follicles. Endocr. Rev. 21, 200–214 (2000).
Durlinger, A. L. L. et al. Control of primordial follicle recruitment by anti-Müllerian hormone in the mouse ovary. Endocrinology 140, 5789–5796 (1999).
Carlsson, I. B. et al. Anti-Müllerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro. Hum. Reprod. 21, 2223–2227 (2006).
Durlinger, A. L. L. et al. Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 143, 1076–1084 (2002).
Gigli, I., Cushman, R. A., Wahl, C. M. & Fortune, J. E. Evidence for a role for anti-Müllerian hormone in the suppression of follicle activation in mouse ovaries and bovine ovarian cortex grafted beneath the chick chorioallantoic membrane. Mol. Reprod. Dev. 71, 480–488 (2005).
Kevenaar, M. E. et al. A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity. Hum. Reprod. 22, 2382–2388 (2007).
Durlinger, A. L. L. et al. Anti-Müllerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 142, 4891–4899 (2001).
Visser, J. A. et al. Increased oocyte degeneration and follicular atresia during the estrous cycle in anti-Müllerian hormone null mice. Endocrinology 148, 2301–2308 (2007).
di Clemente, N. et al. Inhibitory effect of AMH upon the expression of aromatase and LH receptors of granulosa cells of rat and porcine immature ovaries. Endocrine 2, 553–558 (1994).
Grossman, M. P., Nakajima, S. T., Fallat, M. E. & Siow, Y. Müllerian-inhibiting substance inhibits cytochrome P450 aromatase activity in human granulosa lutein cell culture. Fertil. Steril. 89, 1364–1370 (2008).
Andersen, C. Y. & Byskov, A. G. Estradiol and regulation of anti-Müllerian hormone, inhibin-A, and inhibin-B secretion: analysis of small antral and preovulatory human follicles' fluid. J. Clin. Endocrinol. Metab. 91, 4064–4069 (2006).
Kevenaar, M. E. et al. Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women. Hum. Reprod. 22, 1547–1554 (2007).
te Velde, E. R., Scheffer, G. J., Dorland, M., Broekmans, F. J. & Fauser, B. C. Developmental and endocrine aspects of normal ovarian aging. Mol. Cell. Endocrinol. 145, 67–73 (1998).
Scheffer, G. J. et al. Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility. Fertil. Steril. 72, 845–851 (1999).
Bergada, I. et al. Time course of the serum gonadotropin surge, inhibins, and anti-Müllerian hormone in normal newborn males during the first month of life. J. Clin. Endocrinol. Metab. 91, 4092–4098 (2006).
Guibourdenche, J. et al. Anti-Müllerian hormone levels in serum from human foetuses and children: pattern and clinical interest. Mol. Cell. Endocrinol. 211, 55–63 (2003).
Hagen, C. P. et al. Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients. J. Clin. Endocrinol. Metab. 95, 5003–5010 (2010).
Lee, M. M. et al. Mullerian inhibiting substance in humans: normal levels from infancy to adulthood. J. Clin. Endocrinol. Metab. 81, 571–576 (1996).
van Rooij, I. A. et al. Anti-müllerian hormone is a promising predictor for the occurrence of the menopausal transition. Menopause 11, 601–606 (2004).
van Rooij, I. A. et al. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study. Fertil. Steril. 83, 979–987 (2005).
de Vet, A., Laven, J. S., de Jong, F. H., Themmen, A. P. N. & Fauser, B. C. Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil. Steril. 77, 357–362 (2002).
Fanchin, R. et al. Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum. Reprod. 18, 323–327 (2003).
van Rooij, I. A. et al. Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. Hum. Reprod. 17, 3065–3071 (2002).
Hansen, K. R., Hodnett, G. M., Knowlton, N. & Craig, L. B. Correlation of ovarian reserve tests with histologically determined primordial follicle number. Fertil. Steril. 95, 170–175 (2011).
Kevenaar, M. E. et al. Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology 147, 3228–3234 (2006).
Seifer, D. B., Baker, V. L. & Leader, B. Age-specific serum anti-Müllerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil. Steril. 95, 747–750 (2011).
Kelsey, T. W., Wright, P., Nelson, S. M., Anderson, R. A. & Wallace, W. H. A validated model of serum anti-müllerian hormone from conception to menopause. PLoS ONE 6, e22024 (2011).
Nelson, S. M. et al. External validation of nomogram for the decline in serum anti-Müllerian hormone in women: a population study of 15,834 infertility patients. Reprod. Biomed. Online 23, 204–206 (2011).
Hehenkamp, W. J. et al. Anti-Müllerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J. Clin. Endocrinol. Metab. 91, 4057–4063 (2006).
La Marca, A., Stabile, G., Artenisio, A. C. & Volpe, A. Serum anti-Müllerian hormone throughout the human menstrual cycle. Hum. Reprod. 21, 3103–3107 (2006).
Streuli, I. et al. Serum antimüllerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertil. Steril. 90, 395–400 (2008).
Tsepelidis, S. et al. Stable serum levels of anti-Müllerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women. Hum. Reprod. 22, 1837–1840 (2007).
Robertson, D. M., Hale, G. E., Fraser, I. S., Hughes, C. L. & Burger, H. G. Changes in serum antimüllerian hormone levels across the ovulatory menstrual cycle in late reproductive age. Menopause 18, 521–524 (2011).
Sowers, M. et al. Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles. Fertil. Steril. 94, 1482–1486 (2010).
Streuli, I. et al. Clinical uses of anti-Müllerian hormone assays: pitfalls and promises. Fertil. Steril. 91, 226–230 (2009).
Wunder, D. M., Bersinger, N. A., Yared, M., Kretschmer, R. & Birkhäuser, M. H. Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women. Fertil. Steril. 89, 927–933 (2008).
Fanchin, R. et al. High reproducibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status. Hum. Reprod. 20, 923–927 (2005).
Sowers, M. R. et al. Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition. J. Clin. Endocrinol. Metab. 93, 3478–3483 (2008).
van Disseldorp, J. et al. Relationship of serum antimüllerian hormone concentration to age at menopause. J. Clin. Endocrinol. Metab. 93, 2129–2134 (2008).
Broer, S. L. et al. Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women. J. Clin. Endocrinol. Metab. 96, 2532–2539 (2011).
Tehrani, F. R., Shakeri, N., Solaymani-Dodaran, M. & Azizi, F. Predicting age at menopause from serum antimüllerian hormone concentration. Menopause 18, 766–770 (2011).
Tehrani, F. R., Solaymani-Dodaran, M. & Azizi, F. A single test of antimullerian hormone in late reproductive-aged women is a good predictor of menopause. Menopause 16, 797–802 (2009).
Hendriks, D. J., Mol, B. W., Bancsi, L. F., Te Velde, E. R. & Broekmans, F. J. Antral follicle count in the prediction of poor ovarian response and pregnancy after in vitro fertilization: a meta-analysis and comparison with basal follicle-stimulating hormone level. Fertil. Steril. 83, 291–301 (2005).
Seifer, D. B., MacLaughlin, D. T., Christian, B. P., Feng, B. & Shelden, R. M. Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil. Steril. 77, 468–471 (2002).
La Marca, A. et al. Anti-Müllerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum. Reprod. 22, 766–771 (2007).
Nelson, S. M., Yates, R. W. & Fleming, R. Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles—implications for individualization of therapy. Hum. Reprod. 22, 2414–2421 (2007).
Nelson, S. M. et al. Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception. Hum. Reprod. 24, 867–875 (2009).
Broer, S. L. et al. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum. Reprod. Update 17, 46–54 (2011).
Broer, S. L., Mol, B., Dolleman, M., Fauser, B. C. & Broekmans, F. J. The role of anti-Müllerian hormone assessment in assisted reproductive technology outcome. Curr. Opin. Obstet. Gynecol. 22, 193–201 (2010).
Broer, S. L., Mol, B. W., Hendriks, D. & Broekmans, F. J. The role of antimüllerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil. Steril. 91, 705–714 (2009).
Fadini, R. et al. Anti-mullerian hormone as a predictive marker for the selection of women for oocyte in vitro maturation treatment. J. Assist. Reprod. Genet. 28, 501–508 (2011).
Gnoth, C. et al. Relevance of anti-Müllerian hormone measurement in a routine IVF program. Hum. Reprod. 23, 1359–1365 (2008).
Lie Fong, S. et al. Anti-Müllerian hormone: a marker for oocyte quantity, oocyte quality and embryo quality? Reprod. Biomed. Online 16, 664–670 (2008).
Smeenk, J. M. et al. Antimüllerian hormone predicts ovarian responsiveness, but not embryo quality or pregnancy, after in vitro fertilization or intracyoplasmic sperm injection. Fertil. Steril. 87, 223–226 (2007).
La Marca, A. et al. Serum anti-müllerian hormone levels in women with secondary amenorrhea. Fertil. Steril. 85, 1547–1549 (2006).
Méduri, G. et al. Serum anti-Müllerian hormone expression in women with premature ovarian failure. Hum. Reprod. 22, 117–123 (2007).
Bachelot, A. et al. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur. J. Endocrinol. 161, 179–187 (2009).
Knauff, E. A. et al. Anti-Müllerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J. Clin. Endocrinol. Metab. 94, 786–792 (2009).
Sullivan, A. K. et al. Association of FMR1 repeat size with ovarian dysfunction. Hum. Reprod. 20, 402–412 (2005).
Rohr, J. et al. Anti-Mullerian hormone indicates early ovarian decline in fragile X mental retardation (FMR1) premutation carriers: a preliminary study. Hum. Reprod. 23, 1220–1225 (2008).
Spath, M. A. et al. Intra-individual stability over time of standardized anti-Müllerian hormone in FMR1 premutation carriers. Hum. Reprod. 26, 2185–2191 (2011).
Gleicher, N., Weghofer, A., Oktay, K. & Barad, D. H. Correlation of triple repeats on the FMR1 (fragile X) gene to ovarian reserve: a new infertility test? Acta Obstet. Gynecol. Scand. 88, 1024–1030 (2009).
Gleicher, N., Weghofer, A., Oktay, K. & Barad, D. Relevance of triple CGG repeats in the FMR1 gene to ovarian reserve. Reprod. Biomed. Online 19, 385–390 (2009).
Gleicher, N., Weghofer, A. & Barad, D. H. A pilot study of premature ovarian senescence: I. Correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Müllerian hormone. Fertil. Steril. 91, 1700–1706 (2009).
Bennett, C. E., Conway, G. S., Macpherson, J. N., Jacobs, P. A. & Murray, A. Intermediate sized CGG repeats are not a common cause of idiopathic premature ovarian failure. Hum. Reprod. 25, 1335–1338 (2010).
Abir, R. et al. Turner's syndrome and fertility: current status and possible putative prospects. Hum. Reprod. Update 7, 603–610 (2001).
Toniolo, D. & Rizzolio, F. X chromosome and ovarian failure. Semin. Reprod. Med. 25, 264–271 (2007).
Borgström, B. et al. Fertility preservation in girls with turner syndrome: prognostic signs of the presence of ovarian follicles. J. Clin. Endocrinol. Metab. 94, 74–80 (2009).
Purushothaman, R., Lazareva, O., Oktay, K. & Ten, S. Markers of ovarian reserve in young girls with Turner's syndrome. Fertil. Steril. 94, 1557–1559 (2010).
Tsigkou, A. et al. High serum inhibin concentration discriminates autoimmune oophoritis from other forms of primary ovarian insufficiency. J. Clin. Endocrinol. Metab. 93, 1263–1269 (2008).
La Marca, A. et al. Primary ovarian insufficiency due to steroidogenic cell autoimmunity is associated with a preserved pool of functioning follicles. J. Clin. Endocrinol. Metab. 94, 3816–3823 (2009).
Gleicher, N., Weghofer, A. & Barad, D. H. A pilot study of premature ovarian senescence: II. Different genotype and phenotype for genetic and autoimmune etiologies. Fertil. Steril. 91, 1707–1711 (2009).
Clowse, M. E. et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J. Womens Health 18, 311–319 (2009).
Nitzschke, M. et al. GnRH analogs do not protect ovaries from chemotherapy-induced ultrastructural injury in Hodgkin's lymphoma patients. Arch. Gynecol. Obstet. 282, 83–88 (2010).
Sánchez-Serrano, M. et al. Twins born after transplantation of ovarian cortical tissue and oocyte vitrification. Fertil. Steril. 93, 268.e11–268.e13 (2010).
Meirow, D. et al. Monitoring the ovaries after autotransplantation of cryopreserved ovarian tissue: endocrine studies, in vitro fertilization cycles, and live birth. Fertil. Steril. 87, 418.e7–418.e15 (2007).
Janse, F. et al. Limited value of ovarian function markers following orthotopic transplantation of ovarian tissue after gonadotoxic treatment. J. Clin. Endocrinol. Metab. 96, 1136–1144 (2011).
Schmidt, K. T. et al. Autotransplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience. Fertil. Steril. 95, 695–701 (2011).
Lie Fong, S. et al. Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone. Hum. Reprod. 24, 982–990 (2009).
Rosendahl, M. et al. Ovarian function after removal of an entire ovary for cryopreservation of pieces of cortex prior to gonadotoxic treatment: a follow-up study. Hum. Reprod. 23, 2475–2483 (2008).
van Beek, R. D. et al. Anti-Mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin's lymphoma during childhood. J. Clin. Endocrinol. Metab. 92, 3869–3874 (2007).
Bath, L. E., Wallace, W. H., Shaw, M. P., Fitzpatrick, C. & Anderson, R. A. Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound. Hum. Reprod. 18, 2368–2374 (2003).
Lie Fong, S. et al. Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies. Hum. Reprod. 23, 674–678 (2008).
Su, H. I. et al. Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors. Cancer 116, 592–599 (2010).
Partridge, A. H. et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil. Steril. 94, 638–644 (2010).
Lutchman Singh, K. et al. Predictors of ovarian reserve in young women with breast cancer. Br. J. Cancer 96, 1808–1816 (2007).
Anderson, R. A., Themmen, A. P., Al-Qahtani, A., Groome, N. P. & Cameron, D. A. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum. Reprod. 21, 2583–2592 (2006).
Yu, B. et al. Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy. Cancer 116, 2099–2105 (2010).
Rosendahl, M. et al. Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age. Fertil. Steril. 94, 156–166 (2010).
Anders, C. et al. A pilot study of predictive markers of chemotherapy-related amenorrhea among premenopausal women with early stage breast cancer. Cancer Invest. 26, 286–295 (2008).
Anderson, R. A. & Cameron, D. A. Pretreatment serum anti-müllerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. J. Clin. Endocrinol. Metab. 96, 1336–1343 (2011).
Kaipia, A. & Hsueh, A. J. Regulation of ovarian follicle atresia. Annu. Rev. Physiol. 59, 349–363 (1997).
Massagué, J. TGF-β signal transduction. Annu. Rev. Biochem. 67, 753–791 (1998).
Massagué, J. & Wotton, D. Transcriptional control by the TGF-beta/Smad signaling system. Embo. J. 19, 1745–1754 (2000).
Visser, J. A. AMH signaling: from receptor to target gene. Mol. Cell. Endocrinol. 211, 65–73 (2003).
Erickson, G. F. & Shimasaki, S. The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod. Biol. Endocrinol. 1, 9 (2003).
Author information
Authors and Affiliations
Contributions
J. A. Visser researched the data and wrote the article. All authors provided a substantial contribution to discussions of the content and reviewed and/or edited the manuscript before submission.
Corresponding author
Ethics declarations
Competing interests
J. A. Visser declares an association with the following company: MSD (speakers bureau/honoraria). J. S. E. Laven declares an association with the following companies: Genovum (grant/research support; stockholder/director), Merck-Serono (grant/research support), MSD (grant/research support). A. P. N. Themmen declares an association with the following company: ANSH Labs (consultant). I. Schipper declares no competing interests.
Rights and permissions
About this article
Cite this article
Visser, J., Schipper, I., Laven, J. et al. Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency. Nat Rev Endocrinol 8, 331–341 (2012). https://doi.org/10.1038/nrendo.2011.224
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrendo.2011.224
This article is cited by
-
DNMT1-mediated lncRNA IFFD controls the follicular development via targeting GLI1 by sponging miR-370
Cell Death & Differentiation (2023)
-
Investigating the relationship between body composition, lifestyle factors, and anti-Müllerian hormone serum levels in women undergoing infertility assessment
Irish Journal of Medical Science (1971 -) (2023)
-
Dose-dependent effects of ghrelin and aberrant anti-Mullerian hormone levels in the prevention of ovarian damage caused by cisplatin in Wistar-albino rats
Archives of Gynecology and Obstetrics (2022)
-
Evaluation of safety, feasibility and efficacy of intra-ovarian transplantation of autologous adipose derived mesenchymal stromal cells in idiopathic premature ovarian failure patients: non-randomized clinical trial, phase I, first in human
Journal of Ovarian Research (2021)
-
Prevention of chemotherapy-induced premature ovarian insufficiency in mice by scaffold-based local delivery of human embryonic stem cell-derived mesenchymal progenitor cells
Stem Cell Research & Therapy (2021)