A C TA Obstetricia et Gynecologica

AOGS REVIE W A R T I C L E

The role of anti-Müllerian hormone in female fertility

and infertility – an overview
ANNA GARCIA–ALIX GRYNNERUP1,2 , ANETTE LINDHARD1 & STEEN SØRENSEN2
1
Fertility and Endocrinology Unit, Department of Gynecology and Obstetrics, Roskilde Hospital, University of Copenhagen,
Roskilde, and 2 Department of Clinical Biochemistry, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark

Key words Abstract

Anti-Müllerian hormone, ovarian reserve,
polycystic ovary syndrome, ovarian
hyperstimulation syndrome, low responder,
granulosa cell tumor
Correspondence
Steen Sørensen, Department of Clinical
Biochemistry, Hvidovre Hospital, University of
Copenhagen, DK-2650 Hvidovre, Denmark.
E-mail: steen.soerensen@hvh.regionh.dk
Conflict of interest
The authors have stated explicitly that there
are no conflicts of interest in connection with
this article.
Please cite this article as: Grynnerup AG,
Lindhard A, Sørensen S. The role of
anti-Müllerian hormone in female fertility and
infertility – an overview. Acta Obstet Gynecol
Scand 2012;91:1252–1260.
Received: 28 October 2011
Accepted: 10 May 2012
Anti-Müllerian hormone (AMH) plasma levels reflect the continuous non-cyclic
growth of small follicles, thereby mirroring the size of the resting primordial follicle
pool and thus acting as a useful marker of ovarian reserve. Anti-Müllerian hormone
seems to be the best endocrine marker for assessing the age-related decline of the
ovarian pool in healthy women; thus, it has a potential ability to predict future repro-
ductive lifespan. The most established role for AMH measurements is before in vitro
fertilization is initiated, because AMH can be predictive of the ovarian response,
namely poor and hyper-responses. However, recent research has also highlighted
the use of AMH in a variety of ovarian pathological conditions, including polycystic
ovary syndrome, granulosa cell tumors and premature ovarian failure. A new com-
mercial enzyme-linked immunosorbent assay for measuring AMH levels has been
developed, making results from different studies more comparable. Nevertheless,
widespread clinical application awaits an international standard for AMH, so that
results using future assays can be reliably compared.
Abbreviations: AMH, anti-Müllerian hormone; DSL, Diagnostic System Labo-
ratories; ELISA, enzyme-linked immunosorbent assay; FSH, follicle-stimulating
hormone; IBC, Immunotech-Beckman-Coulter; IVF, in vitro fertilization; NPV,
negative predictive value; OHSS, ovarian hyperstimulation syndrome; PCOS,
polycystic ovary syndrome; PPV, positive predictive value.

DOI: 10.1111/j.1600-0412.2012.01471.x

ovarian reserve in order to provide proper counseling and

Introduction
In Western societies during the last 50 years, increasing fe-
male educational level and participation in the labor force
have resulted in a rise in the mean age at which women de-
liver their first child. Female fertility starts to decline from the
early twenties because of decreasing ovarian reserve; a term
that refers to both the quality and the quantity of the ovar-
ian follicle pool. Consequently, many women will be faced
with unexpected fertility problems (1,2). The rate at which
the ovarian reserve declines varies greatly among women
(2), making it a challenge to estimate an individual woman’s
remaining reproductive lifespan. There is therefore a grow-
ing demand for the development of sensitive biomarkers of
treatment of infertile women.
Anti-Müllerian hormone (AMH) is a new, promising
marker of ovarian reserve. Anti-Müllerian hormone, also
known as Müllerian-inhibiting substance, is a dimeric glyco-
protein of the transforming growth factor-β superfamily that
is involved in growth and differentiation (3). Anti-Müllerian
hormone was originally described as a gonadal factor in males
that causes regression of the Müllerian ducts, which are pre-
cursors to the female reproductive tract in early mammalian
embryos (4). In males, AMH is expressed by the Sertoli cells
from the eighth week of gestation until the onset of puberty.
In females, however, AMH is expressed in granulosa cells
and secreted into the circulation from the time of birth until


C 2012 The Authors

1252 Acta Obstetricia et Gynecologica Scandinavica 

C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
A.G.-A. Grynnerup et al. Anti-Müllerian hormone in female fertility and infertility

Table 1. Sensitivity and specificity of AMH for prediction of poor response to in vitro fertilization treatment.

Cut-off
values Sensitivity Specificity PPV NPV Definition of AMH
Reference n Type of study (pmol/L) (%) (%) (%) (%) poor response assay

Muttukrishna et al. (2005; 63) 108 Retrospective 1.43 87 64 – – ≤4 oocytes IBC

Tremellen et al. (2005; 64) 75 Prospective 8.10 80 85 67 92 ≤4 oocytes IBC
La Marca et al. (2007; 65) 48 Prospective 5.36 80 93 – – ≤4 oocytes IBC
McIlveen et al. (2007; 66) 84 Prospective 8.93 85 63 – – ≤4 oocytes IBC
Lekamge et al. (2007; 67) 126 Retrospective 14.0 73 73 – – ≤4 oocytes IBC
Gnoth et al. (2008; 68) 132 Prospective 9.00 97 41 36 98 ≤4 oocytes DSL
Riggs et al. (2008; 69) 123 Retrospective 5.93 83 79 30 97 ≤4 oocytes DSL
Barad et al. (2009; 70) 76 Retrospective 3.57 87 84 79 90 ≤4 oocytes DSL
Nardo et al. (2009; 71) 165 Prospective 7.14 87 67 – – ≤4 oocytes DSL
Al-Azemi et al. (2011; 72) 352 Prospective 9.71 76 75 – – ≤4 oocytes IBC
Honnma et al. (2011; 79) 1026 Retrospective 10.0 72 76 – – ≤4 oocytes IBC

Note: Abbreviations: AMH, anti-Müllerian hormone; DSL, Diagnostic System Laboratories; IBC, Immunotech-Beckman-Coulter; NPV, negative predictive
value; and PPV, positive predictive value.

menopause (5); hence, it is measurable in the plasma. Plasma
levels of AMH are barely detectable at birth, but increase
significantly at puberty and thereafter decline slowly during
the reproductive period, until AMH becomes undetectable
at menopause (6).
As a marker of ovarian reserve, AMH may be useful both to
estimate the reproductive lifespan of healthy young women
and to predict the ovarian response to stimulation for in vitro
fertilization (IVF), namely poor and hyper-responses. Besides
assessment of ovarian reserve, AMH has several potential
roles in the diagnosis and management of various ovarian
pathologies, including polycystic ovary syndrome (PCOS),
granulosa cell tumors and early ovarian aging. This review
will focus on the background for and use of AMH measure-
ments in assessing female fertility and infertility.
Material and methods
The PubMed database was systematically searched for studies
published until November 2011, using the following medical
subject heading (MeSH) terms, major topics: “anti-müllerian
hormone” (entry terms: Anti Mullerian Hormone, Antim-
ullerian Hormone, Mullerian Inhibiting Hormone, Mulle-
rian Inhibiting Substance, Mullarian-Inhibitory Substance,
Mullerian Inhibitory Substance, Mullerian-Inhibiting Fac-
tor, Mullerian Inhibiting Factor, Mullerian-Inhibiting Hor-
mone, Anti-Mullerian Factor, Anti Mullerian Factor, Mul-
lerian Regression Factor) alone and in combination with
“analysis,” “blood,” “diagnostic use,” “physiology,” “secre-
tion” and “therapeutic use.” This strategy yielded 235 publi-
cations, including both original articles and reviews, whereas
hardly any randomized controlled trials were identified. Of
these 235 publications, 96 were excluded because they were
not in English, were not related to humans or were not related
to females. The remaining 139 publications were examined
and assessed for methodological quality and their relevance to
the following predefined themes: AMH in female infertility,
ovarian physiology, ovarian reserve, IVF and PCOS. Prefer-
ence was given to original clinical studies over review articles.
References of retrieved publications were also reviewed to
identify potentially relevant studies missed in the PubMed
search.
Furthermore, in order to evaluate AMH as a predictor of
IVF outcome (Tables 1–3), any article that could possibly
be of value for the association between AMH and the IVF
outcomes, i.e. poor ovarian response, pregnancy or hyper-
response, was preselected. Secondly, studies were included
if adequate data could be obtained (specificity, sensitivity,
cut-off values and assay used for AMH measurements). Pub-
lications reporting single cases or small case series were not
considered to represent sufficiently strong evidence, and were
excluded. Only studies that defined poor ovarian response as
four or fewer oocytes were included, in order to make the
results more reliably comparable. Ultimately, 12 prospec-
tive and seven retrospective cohort studies, along with one
case–control study, were included to evaluate AMH as a pre-
dictor of IVF outcome (Tables 1–3). Altogether, the final re-
view was based on predominantly original publications and
a few reviews (in total 80 publications) that were considered
to be of sufficiently high scientific standard as well as of high
relevance for the topic.
Results
Anti-Müllerian hormone in ovarian physiology
The follicles represent the basic functional unit in the ovaries.
During fetal life, germ cells populate the ovary and become
surrounded by somatic cells, forming primordial follicles.


C 2012 The Authors

Acta Obstetricia et Gynecologica Scandinavica 

C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260 1253
Anti-Müllerian hormone in female fertility and infertility A.G.-A. Grynnerup et al.

Table 2. Sensitivity and specificity of AMH for prediction of pregnancy following in vitro fertilization treatment.

Cut-off
values Sensitivity Specificity PPV NPV Definition of AMH
Author n Type of study (pmol/L) (%) (%) (%) (%) pregnancy assay

Lekamge et al. (2007; 67) 126 Retrospective 14.0 50 62 – – Cumulative clinical pregnancy IBC
Elgindy et al. (2008; 73) 29 Prospective 19.28 83 82 77 87 Clinical pregnancy IBC
Lee et al. (2009; 36) 123 Prospective 12.0 60 66 49 75 Live birth DSL
Barad et al. (2009; 70) 76 Retrospective 7.14 62 75 48 84 Clinical pregnancy DSL
Li et al. (2010; 74) 189 Retrospective 13.0 77 44 – – Cumulative live birth IBC
Majumder et al. (2010; 75) 97 Prospective 19.3 66 55 31 84 Live birth DSL
Kini et al. (2010; 76) 170 Retrospective 5.0 86 28 – – Cumulative clinical pregnancy DSL

Note: Abbreviations are as for Table 1.

Table 3. Sensitivity and specificity of AMH for prediction of hyper-response to in vitro fertilization treatment.

Cut-off
values Sensitivity Specificity PPV NPV Definition of AMH
Author n Type of study (pmol/L) (%) (%) (%) (%) hyper-response assay

Nelson et al. (2007; 48) 340 Prospective 15.0 88 77 – – >21 oocytes DSL
Lee et al. (2008; 77) 262 Prospective 24.0 91 81 30 99 Moderate to severe ovarian DSL
hyperstimulation syndrome
Riggs et al. (2008; 69) 123 Retrospective 11.4 84 67 22 98 >15 oocytes DSL
Nardo et al. (2009; 71) 165 Prospective 25.0 88 70 – – >20 oocytes and/or estradiol DSL
> 21.000 pmol/L
Alfatoonian et al. (2009; 78) 159 Prospective 34.5 93 78 65 96 >15 oocytes IBC
Honnma et al. (2011; 79) 1026 Retrospective 17.6 69 75 – – ≥20 oocytes IBC
Ocal et al. (2011; 80) 82 Case–control 23.6 90 71 61 94 Ovarian hyperstimulation DSL
syndrome

Note: Abbreviations are as for Table 1.

The primordial follicle formation begins at mid-gestation
and is complete shortly after birth, by which time about one
million primordial follicles are present. Throughout life, until
their numbers are exhausted, primordial follicles leave the
primordial follicle pool to enter the growing pool; a process
named initial recruitment. This is a continuous process, not
controlled by the pituitary–gonadal endocrine axis.
The majority of these growing follicles will undergo
atresia, unless they are rescued by follicle-stimulating
hormone (FSH). The rescue of a cohort of grow-
ing follicles by FSH starts after puberty when the
hypothalamic–pituitary–gonadal endocrine axis is activated,
and is called cyclic recruitment. Among the cohort of rescued
follicles, only one follicle is selected to become the dominant
follicle, which will ovulate under the influence of luteinizing
hormone (7).
Anti-Müllerian hormone cannot be detected in resting pri-
mordial follicles, but the expression rapidly increases once a
follicle reaches the preantral and antral stages (Figure 1). The
highest level of AMH expression is seen in granulosa cells in
preantral and small antral follicles of no more than 4 mm
diameter, and the expression disappears as follicles develop
to the larger antral and preovulatory stages (8).
Anti-Müllerian hormone-knockout mice exhibit a more
rapid rate of primordial follicle recruitment and conse-
quently, the primordial follicle pool becomes prematurely
exhausted (9), indicating that AMH exerts a negative, re-
straining influence on initial recruitment. In vitro culture of
neonatal ovaries in the presence of AMH confirmed its in-
hibitory effect on initial recruitment (10). In addition, AMH
also seems to inhibit the cyclic recruitment of follicles by
lowering their FSH sensitivity (11), thereby controlling the
number of preantral and small antral follicles that do not
undergo atresia and continue to grow to reach the preovu-
latory stage. Thus, AMH seems to be a strong suppressor
of both initial and cyclic recruitment, preventing premature
depletion of the follicle pool.
Methods for measuring AMH in plasma
Anti-Müllerian hormone is secreted by granulosa cells into
the circulation and is therefore measurable in plasma. Two
commercial enzyme-linked immunosorbent assays (ELISAs)
have been available since 2004, one from Immunotech (Mar-
seille, France) and the other from Diagnostic Systems Labo-
ratories (DSL; Webster, Texas, USA). The Beckman Coulter


C 2012 The Authors

1254 Acta Obstetricia et Gynecologica Scandinavica 

C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
A.G.-A. Grynnerup et al. Anti-Müllerian hormone in female fertility and infertility

Figure 1. Anti-Müllerian hormone (AMH) and folliculogenesis. Anti-Müllerian hormone is secreted by the growing follicles: primary, secondary,
preantral and small antral follicles. The AMH secretion increases as the follicles develop (shown in the figure by thickening of the arrows). The highest
level of AMH secretion is by preantral and small antral follicles. Anti-Müllerian hormone has two major mechanisms of action in the ovary, as follows:
firstly, AMH inhibits the initial recruitment of primary follicles from the resting pool of primordial follicles (step 1); and secondly, AMH inhibits the
sensitivity of antral follicles to follicle-stimulating hormone (FSH) during cyclic recruitment (step 2). Anti-Müllerian hormone thereby prevents premature
depletion of the follicle pool. (This figure was produced using Servier Medical Art, www.servier.com.)

Company now owns both. High correlation exists between
values obtained by the two kits, although the absolute values
are around four times lower with DSL (12,13). No interna-
tional reference standard has yet been established for AMH.
Widespread clinical use awaits the availability of an inter-
national standard for AMH so that results using different
assays may be reliably compared. Results may be reported in
nanograms per milliliter or picomoles per liter (1 ng/mL cor-
responds to 7.14 pmol/L). Caution must be used when com-
paring results from different publications, bearing in mind
that different ELISAs may have been used.
The Beckman Coulter Company has now developed a
second-generation ELISA for the measurement of AMH in
plasma, the AMH Gen II assay, which will most probably
replace the earlier two assays (14). No automated assays have
yet been developed, although it is possible that an automated
platform will be available in the near future.
Anti-Müllerian hormone as a marker for ovarian
reserve
The term “ovarian reserve” describes the number and the
quality of the remaining oocytes in the ovaries, while ovarian
aging describes the age-related decline in the ovarian reserve.
The number of resting primordial follicles that are left in
the ovary is an important parameter in assessing the ovarian
reserve (15), but it is difficult to measure directly. However,
the size of the resting primordial follicle pool seems to cor-
relate with the number of follicles that enter the pool of
growing follicles (1,16). As only the growing follicles pro-
duce AMH, plasma AMH levels seem to reflect the size of the
resting primordial follicle pool. Studies in mice and monkeys
have shown a strong correlation between AMH levels and
the number of primordial follicles (17,18). The role of AMH
in predicting oocyte quality is still to be clarified, but the
age-related decrease of the follicle pool is associated with a
decrease in oocyte quality (19,20).
Other current ovarian reserve tests include hormonal
markers (FSH, estradiol and inhibin B) and ultrasonographic
markers (antral follicle count and measurement of ovarian
volume). These tests reflect, directly or indirectly, the size of
the antral follicle pool. Antral follicle count is a direct ultra-
sound measure of this pool, whereas more indirectly, in the
early follicular phase inhibin B and estradiol levels are consid-
ered to be dependent on the number of antral follicles. Levels
of FSH are regulated by a negative feedback action of these
two granulosa cell products; hence, they are a more indirect
reflection of the antral follicle pool. The age-related decline
in the number of oocytes leads to a decline in estradiol and
inhibin B levels and, consequently, a rise in FSH (21). Com-
pared with these hormonal markers, plasma levels of AMH
seem to reflect the longitudinal decline in the oocyte/follicle
pool better over time, even before irregular cycles occur (22)
and, in contrast to cyclic fluctuations that are characteris-
tic of FSH, estradiol and inhibin B, AMH shows little or
no intracycle fluctuation (23–25). Thus, AMH reflects the
continuous non-cyclic growth of small follicles. Consistently,
AMH levels are affected relatively little by conditions that sup-
press the later FSH-dependent stages of follicle development,
such as pregnancy (26), use of hormonal contraceptives (27)
and treatment with gonadotropin-releasing hormone ago-
nist (28). Furthermore, AMH does not seem to be affected
by other clinical and behavioral variables, such as body mass
index and smoking status (29).
The predictive value of AMH for ovarian reserve is still un-
certain, but several prospective longitudinal studies involving
up to 11 years follow-up of normo-ovulatory women have
found that AMH seems to be the best endocrine marker in as-
sessing ovarian aging (22,30,31) and that plasma AMH levels,
with reasonable accuracy, can predict the onset of menopause


C 2012 The Authors

Acta Obstetricia et Gynecologica Scandinavica 

C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260 1255
Anti-Müllerian hormone in female fertility and infertility
(32–34). Taken together, these data suggest that plasma levels
of AMH can be used as a marker of ovarian reserve.
Anti-Müllerian hormone and in vitro fertilization
Assessment of ovarian reserve is important before IVF treat-
ment is initiated. The response to IVF treatment is highly
variable, even among women of similar ages (35). This un-
doubtedly reflects the variation in ovarian reserve. Identi-
fication of both low and high responders prior to ovarian
hyperstimulation allows physicians to optimize stimulation
protocols to reduce cycle cancellation rate and severe compli-
cations, such as ovarian hyperstimulation syndrome (OHSS).
In selected literature defining poor response as an oocyte
yield of four oocytes or fewer, AMH was found to be a pre-
dictor of poor response, with a reported sensitivity and speci-
ficity of 72–97 and 41–93%, respectively, at varying cut-off
values (Table 1). The varying cut-off values seem to be caused
by variations in study methods and study populations, espe-
cially age, inclusion criteria and the etiology of infertility
(36).
The ideal ovarian reserve test would identify women with
a practically zero chance of becoming pregnant owing to
diminished ovarian reserve. Those women could be advised
against undergoing treatment, thereby avoiding a disappoint-
ing outcome at high cost, in addition to adverse effects. In
contrast, false-positive tests (i.e. low AMH levels falsely pre-
dicting poor response) would cause women to be advised in-
correctly against treatment. As shown in Table 1, the positive
predictive values vary between 30 and 79%, and many false
positives would therefore be expected. In order to prevent
a high rate of false positives, extreme cut-off values must be
used. This would imply that only a small percentage of abnor-
mal tests would be found, and many poor responders would
pass unrecognized. The negative predictive values shown in
Table 1 are somewhat higher than the positive predictive val-
ues, ranging from 90 to 98%, implying that a negative test
(i.e. high AMH level) is less likely to be a false negative.
Prediction of live birth is the ultimate goal of any IVF
screening test, and application of AMH as a predictor of on-
going pregnancy following IVF appears to be limited in un-
selected infertile patients (Table 2). Studies have found that
a number of poor responders do achieve pregnancy (37).
In particular, poor responders at a young age have a better
prognosis than older ones (38), and successful pregnancies
have been reported in cases of very low and even undetectable
AMH levels (39). A recent study found that patients with ex-
tremely low serum AMH levels have moderate, but reasonable
chances of achieving pregnancy and live births (40). There
is reason to believe that the ability of AMH to predict IVF
pregnancy outcome may vary greatly with age. A retrospec-
tive study including 1558, women who had undergone IVF
treatment, demonstrated that the clinical pregnancy rate for
1256 Acta Obstetricia et Gynecologica Scandinavica 
C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
A.G.-A. Grynnerup et al.
women younger than 34 years did not differ with AMH levels.
At the same time, women 42 years or older had poor prog-
nosis regardless of AMH levels. The authors conclude that
serum AMH concentrations are associated with pregnancy,
only for women between the ages of 34 and 41 years (41).
This might reflect the fact that there may be different mecha-
nisms behind depletion of ovarian reserve. In older women,
the physiological aging of the oocytes (declining oocyte qual-
ity) may play an important role, whereas non-physiological
mechanisms may dominate in younger women, such as con-
genital reduced ovarian reserve and faster consumption of
primordial follicles without deterioration of oocyte quality
(42,43).
Anti-Müllerian hormone, along with other endocrine
markers, performs relatively poorly as a marker for with-
holding IVF treatment, and it is not feasible to suggest that a
woman should not undergo IVF treatment based solely on a
low AMH value. However, in the absence of a perfect predic-
tive marker, plasma AMH concentration could well serve as a
reference in pretreatment counseling, along with other factors
such as age. It is still not clear whether individualized treat-
ment strategies based on AMH values may increase oocyte
yield. Randomized clinical trails need to clarify whether dif-
ferent types and dosages of hormone stimulation influence
oocyte yield in poor responders. So far, published results on
the topic have been ambiguous (44–46).
Anti-Müllerian hormone also appears to be useful in the
prediction of OHSS subsequent to gonadotropin stimulation.
An excessive ovarian response to IVF treatment may lead to
OHSS, which is a potentially life-threatening condition (47).
Elevated mean basal AMH values are associated with the oc-
currence of an excessive response, and AMH measurements
prior to gonadotropin stimulation could provide valuable in-
formation in order to prevent OHSS. The reported sensitivity
for predicting hyper-response varies between 69 and 93% and
the specificity between 67 and 81%, at varying cut-off values
(Table 3). The corresponding positive predictive values and
negative predictive values range between 22 and 65, and 94
and 99%, respectively. Thus, AMH seems to be a fair predic-
tor of excessive response, and may improve the counseling of
patients and permit an individualization of treatment, with
the aim of reducing the incidence of OHSS (46,48).
Anti-Müllerian hormone and PCOS
Polycystic ovary syndrome is a heterogeneous syndrome af-
fecting 5–10% of the female population (49). The syndrome
is characterized by at least two of the following three key com-
ponents: oligo-/amenorrhea; clinical or biochemical hyper-
androgenism; and polycystic ovary morphology. In addition,
women suffering from PCOS will often present metabolic
disturbances, including obesity, insulin resistance and the
metabolic syndrome (50). Women with PCOS are known to

C 2012 The Authors
A.G.-A. Grynnerup et al.
have an excessive amount of preantral and small antral folli-
cles in the ovaries and to have increased plasma AMH con-
centrations (51,52). The elevated AMH levels are not only
due to the excessive accumulation of preantral follicles, but
also to increased granulosa cell AMH production (53). The
major inhibitory role of AMH during folliculogenesis may
contribute to anovulation in PCOS. The reason for the raised
AMH in women with PCOS is still largely unknown, but both
excessive androgen production (52,54) and insulin insensi-
tivity (55) may play a role. Understanding the reason for the
raised AMH might give clues concerning the mechanism of
anovulation in PCOS.
Anti-Müllerian hormone concentrations appear to corre-
late well with the severity of the syndrome (56) and resistance
to treatment (51,57). Hence, it has been proposed that AMH
may be used as a marker for the extent of the disease (51).
Additionally, AMH measurements have been found to offer a
relatively high specificity and sensitivity (92 and 69%, respec-
tively) as a diagnostic marker for PCOS (58); thus, it has been
proposed that in situations where accurate ultrasound data
are not available, AMH could be used instead of the follicle
count as one of the diagnostic criteria for PCOS (58).
Other clinical applications
Improved methods for cancer treatment in young people
have led to an increase in the number of long-term survivors.
However, many of the chemotherapeutic regimens used in
the treatment of pediatric cancers are gonadotoxic, increasing
the risk of premature ovarian failure in young women. Anti-
Müllerian hormone seems to be an early and sensitive plasma
marker of gonadal damage after chemotherapeutic treatment
(59).
Finally, AMH has been applied as a biomarker of granu-
losa cell tumors, with high sensitivity ranging between 76 and
93%. Anti-Müllerian hormone may be used postoperatively
as a marker for the efficacy of surgery and for disease re-
currence. It still remains to be clarified which levels of AMH
should be used for this purpose (60). Based on the physiolog-
ical inhibitory role of AMH, it has been proposed that AMH
may inhibit epithelial ovarian cancer cells. These observations
will be the basis for future research aiming to investigate the
possible clinical role of AMH as adjuvant therapy for ovarian
cancer (61,62).
Discussion
Anti-Müllerian hormone is a promising new marker of ovar-
ian reserve, because AMH levels are believed to reflect the size
of the resting follicle pool. Anti-Müllerian hormone levels do
not change significantly during the menstrual cycle, making
AMH measurements more convenient than other endocrine
markers of ovarian reserve, such as early follicular phase FSH.

C 2012 The Authors
Acta Obstetricia et Gynecologica Scandinavica 
C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
Anti-Müllerian hormone in female fertility and infertility
Anti-Müllerian hormone seems to be the best endocrine
marker for assessing the age-related decline of the ovarian
pool in healthy women; thus, it has a potential ability to
predict the reproductive lifespan. However, it must be high-
lighted that only sparse longitudinal prospective data exist in
this field, and the clinical use of AMH in advising individual
women outside the context of IVF is not well supported. Nev-
ertheless, societal influences will continue to result in women
delaying childbearing until their later reproductive years, and
it is predictable that AMH will be measured increasingly in
women wishing to know their future reproductive lifespan.
The most established role for AMH measurement is before
the start of IVF treatment, when AMH can be predictive of
the ovarian response, especially when combined with age.
The cycle stability and operator independency make AMH
a very attractive single predictor of both poor and excessive
ovarian response to IVF treatment and can be useful to tai-
lor expectations to the treatment. However, similar to other
ovarian reserve tests, AMH has not proved to be a good pre-
dictor of pregnancy, reflecting the fact that factors other than
the quantitative aspects of ovarian reserve may influence the
chances of pregnancy.
A new field of application for AMH measurement may be
its use in the individualization of ovarian stimulation regi-
mens in IVF in order to reduce the incidence of cycle cancella-
tion and OHSS. Whether individualized treatment based on
AMH testing will lead to improved outcome and/or higher
safety in IVF treatment regimens must be further elucidated.
Anti-Müllerian hormone has a potential role in the diag-
nosis and management of several ovarian pathologies, in-
cluding PCOS. Anti-Müllerian hormone is often consider-
ably elevated in patients with PCOS, but thus far AMH is not
one of the diagnostic criteria. It has been proposed that in
situations where accurate ultrasound data are not available,
AMH could be used instead of the antral follicle count as a
diagnostic criterion for PCOS. The markedly elevated AMH
concentrations contrast to the often normal values of other
reproductive hormones in PCOS, thus adding a biochemical
aspect to the diagnosis.
Last but not least, a possible role as a biomarker of gran-
ulosa cell tumors combined with the above-mentioned im-
plications of measuring AMH makes this hormone a most
interesting item for further investigation.
Funding
No specific funding.
References
1. Gougeon A, Ecochard R, Thalabard JC. Age-related changes
of the population of human ovarian follicles: increase in the
disappearance rate of non-growing and early-growing
follicles in aging women. Biol Reprod. 1994;50:653–63.
1257
Anti-Müllerian hormone in female fertility and infertility
2. te Velde ER, Pearson PL. The variability of female
reproductive ageing. Hum Reprod Update. 2002;8:141–54.
3. Massagué J. The transforming growth factor-beta family.
Annu Rev Cell Biol. 1990;6:597–641.
4. Jost A. Reserches sur la differenciation de l’embryon de lapin.
Nat Microsc Morphol Exp. 1947;36:271–289.
5. Rajpert-De Meyts E, Jørgensen N, Graem N, Müller J, Cate
RL, Skakkebaek NE. Expression of anti-Müllerian hormone
during normal and pathological gonadal development:
association with differentiation of Sertoli and granulosa cells.
J Clin Endocrinol Metab. 1999;84:3836–44.
6. Lee MM, Donahoe PK, Hasegawa T, Silverman B, Crist GB,
Best S, et al. Mullerian inhibiting substance in humans:
normal levels from infancy to adulthood. J Clin Endocrinol
Metab. 1996;81:571–6.
7. McGee EA, Hsueh AJ. Initial and cyclic recruitment of
ovarian follicles. Endocr Rev. 2000;21:200–14.
8. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome
NP, Visser JA, et al. Anti-Müllerian hormone expression
pattern in the human ovary: potential implications for initial
and cyclic follicle recruitment. Mol Hum Reprod.
2004;10:77–83.
9. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek
JT, Grootegoed JA, et al. Control of primordial follicle
recruitment by anti-Müllerian hormone in the mouse ovary.
Endocrinology. 1999;140:5789–96.
10. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham
HA, Nachtigal MW, et al. Anti-Müllerian hormone inhibits
initiation of primordial follicle growth in the mouse ovary.
Endocrinology. 2002;143:1076–84.
11. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Kumar TR,
Matzuk MM, et al. Anti-Müllerian hormone attenuates the
effects of FSH on follicle development in the mouse ovary.
Endocrinology. 2001;142:4891–9.
12. Fréour T, Mirallié S, Bach-Ngohou K, Denis M, Barrière P,
Masson D. Measurement of serum anti-Müllerian hormone
by Beckman Coulter ELISA and DSL ELISA: comparison and
relevance in assisted reproduction technology (ART). Clin
Chim Acta. 2007;375:162–4.
13. Bersinger NA, Wunder D, Birkhäuser MH, Guibourdenche J.
Measurement of anti-mullerian hormone by Beckman
Coulter ELISA and DSL ELISA in assisted reproduction:
differences between serum and follicular fluid. Clin Chim
Acta. 2007;384:174–5.
14. Kumar A, Kalra B, Patel A, McDavid L, Roudebush WE.
Development of a second generation anti-Müllerian
hormone (AMH) ELISA. J Immunol Methods.
2010;362:51–9.
15. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson
JF. Accelerated disappearance of ovarian follicles in mid-life:
implications for forecasting menopause. Hum Reprod.
1992;7:1342–6.
16. Scheffer GJ, Broekmans FJ, Dorland M, Habbema JD,
Looman CW, te Velde ER. Antral follicle counts by
1258 Acta Obstetricia et Gynecologica Scandinavica 
C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
A.G.-A. Grynnerup et al.
transvaginal ultrasonography are related to age in women
with proven natural fertility. Fertil Steril. 1999;72:845–
51.
17. Kevenaar ME, Meerasahib MF, Kramer P, van de Lang-Born
BM, de Jong FH, Groome NP, et al. Serum anti-Müllerian
hormone levels reflect the size of the primordial follicle pool
in mice. Endocrinology. 2006;147:3228–34.
18. Appt SE, Clarkson TB, Chen H, Adams MR, Christian PJ,
Hoyer PB, et al. Serum antimüllerian hormone predicts
ovarian reserve in a monkey model. Menopause.
2009;16:597–601.
19. Pellestor F, Andréo B, Arnal F, Humeau C, Demaille J.
Maternal aging and chromosomal abnormalities: new data
drawn from in vitro unfertilized human oocytes. Hum
Genet. 2003;112:195–203.
20. Lie Fong S, Baart EB, Martini E, Schipper I, Visser JA,
Themmen AP, et al. Anti-Müllerian hormone: a marker for
oocyte quantity, oocyte quality and embryo quality? Reprod
Biomed Online. 2008;16:664–70.
21. Burger HG, Dudley EC, Hopper JL, Shelley JM, Green A,
Smith A, et al. The endocrinology of the menopausal
transition: a cross-sectional study of a population-based
sample. J Clin Endocrinol Metab.1995;80:3537–45.
22. de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC.
Antimüllerian hormone serum levels: a putative marker for
ovarian aging. Fertil Steril. 2002;77:357–62.
23. La Marca A, Stabile G, Artenisio AC, Volpe A. Serum
anti-Mullerian hormone throughout the human menstrual
cycle. Hum Reprod. 2006;21:3103–7.
24. Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, Te
Velde ER, Broekmans FJ. Anti-Müllerian hormone levels in
the spontaneous menstrual cycle do not show substantial
fluctuation. J Clin Endocrinol Metab. 2006;91:4057–63.
25. Zec I, Tislarić-Medenjak D, Bukovec-Megla Z, Harni V, Kusić
Z. Serum levels of antimüllerian hormone in women with
regular menstrual cycles. Acta Clin Croat. 2010;49:405–9.
26. La Marca A, Giulini S, Orvieto R, De Leo V, Volpe A.
Anti-Müllerian hormone concentrations in maternal serum
during pregnancy. Hum Reprod. 2005;20:1569–72.
27. Li HW, Wong CY, Yeung WS, Ho PC, Ng EH. Serum
anti-müllerian hormone level is not altered in women using
hormonal contraceptives. Contraception. 2011;83:582–5.
28. Mohamed KA, Davies WA, Lashen H. Antimüllerian
hormone and pituitary gland activity after prolonged
down-regulation with goserelin acetate. Fertil Steril.
2006;86:1515–7.
29. Shaw CM, Stanczyk FZ, Egleston BL, Kahle LL, Spittle CS,
Godwin AK, et al. Serum antimüllerian hormone in healthy
premenopausal women. Fertil Steril. 2011;95:2718–21.
30. Mulders AG, Laven JS, Eijkemans MJ, de Jong FH, Themmen
AP, Fauser BC. Changes in anti-Müllerian hormone serum
concentrations over time suggest delayed ovarian ageing in
normogonadotrophic anovulatory infertility. Hum Reprod.
2004;19:2036–42.

C 2012 The Authors
A.G.-A. Grynnerup et al.
31. van Rooij IA, Broekmans FJ, Scheffer GJ, Looman CW,
Habbema JD, de Jong FH, et al. Serum antimullerian
hormone levels best reflect the reproductive decline with age
in normal women with proven fertility: a longitudinal study.
Fertil Steril. 2005;83:979–87.
32. Tehrani FR, Solaymani-Dodaran M, Azizi F. A single test of
antimullerian hormone in late reproductive-aged women is a
good predictor of menopause. Menopause. 2009;16:797–802.
33. Tehrani FR, Shakeri N, Solaymani-Dodaran M, Azizi F.
Predicting age at menopause from serum antimüllerian
hormone concentration. Menopause. 2011;18:766–70.
34. Broer SL, Eijkemans MJ, Scheffer GJ, van Rooij IA, de Vet A,
Themmen AP, et al. Anti-mullerian hormone predicts
menopause: a long-term follow-up study in normoovulatory
women. J Clin Endocrinol Metab.2011;96:2532–9.
35. Fauser BC, Diedrich K, Devroey P. Predictors of ovarian
response: progress towards individualized treatment in
ovulation induction and ovarian stimulation. Hum Reprod
Update. 2008;14:1–14.
36. Lee TH, Liu CH, Huang CC, Hsieh KC, Lin PM, Lee MS.
Impact of female age and male infertility on ovarian reserve
markers to predict outcome of assisted reproduction
technology cycles. Reprod Biol Endocrinol. 2009;7:100.
37. Klinkert ER, Broekmans FJ, Looman CW, Te Velde ER. A
poor response in the first in vitro fertilization cycle is not
necessarily related to a poor prognosis in subsequent cycles.
Fertil Steril. 2004;81:1247–53.
38. Ulug U, Ben-Shlomo I, Turan E, Erden HF, Akman MA,
Bahceci M. Conception rates following assisted reproduction
in poor responder patients: a retrospective study in 300
consecutive cycles. Reprod Biomed Online. 2003;6:439–43.
39. Cordes T, Schultze-Mosgau A, Diedrich K, Griesinger G.
Ongoing pregnancy after human menopausal gonadotropin
stimulation and timed intercourse in a 40-year-old woman
with undetectable antimüllerian hormone levels. Fertil Steril.
2010;94:e70; author reply e71–2.
40. Weghofer A, Dietrich W, Barad DH, Gleicher N. Live birth
chances in women with extremely low-serum anti-Mullerian
hormone levels. Hum Reprod. 2011;26:1905–9.
41. Wang JG, Douglas NC, Nakhuda GS, Choi JM, Park SJ,
Thornton MH, et al. The association between anti-Müllerian
hormone and IVF pregnancy outcomes is influenced by age.
Reprod Biomed Online. 2010;21:757–61.
42. Barad DH, Weghofer A, Gleicher N. Utility of age-specific
serum anti-Müllerian hormone concentrations. Reprod
Biomed Online. 2011;22:284–91.
43. Sun W, Stegmann BJ, Henne M, Catherino WH, Segars JH. A
new approach to ovarian reserve testing. Fertil Steril.
2008;90:2196–202.
44. Klinkert ER, Broekmans FJ, Looman CW, Habbema JD, te
Velde ER. Expected poor responders on the basis of an antral
follicle count do not benefit from a higher starting dose of
gonadotrophins in IVF treatment: a randomized controlled
trial. Hum Reprod. 2005;20:611–5.

C 2012 The Authors
Acta Obstetricia et Gynecologica Scandinavica 
C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
Anti-Müllerian hormone in female fertility and infertility
45. Popovic-Todorovic B, Loft A, Bredkjaeer HE, Bangsbøll S,
Nielsen IK, Andersen AN. A prospective randomized clinical
trial comparing an individual dose of recombinant FSH
based on predictive factors versus a ‘standard’ dose of 150
IU/day in ‘standard’ patients undergoing IVF/ICSI
treatment. Hum Reprod. 2003;18:2275–82.
46. Nelson SM, Yates RW, Lyall H, Jamieson M, Traynor I,
Gaudoin M, et al. Anti-Müllerian hormone-based approach
to controlled ovarian stimulation for assisted conception.
Hum Reprod. 2009;24:867–75.
47. Practice Committee of American Society for Reproductive
Medicine. Ovarian hyperstimulation syndrome. Fertil Steril.
2008;90:S188–93.
48. Nelson SM, Yates RW, 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. 2007;22:
2414–21.
49. Broekmans FJ, Knauff EA, Valkenburg O, Laven JS,
Eijkemans MJ, Fauser BC. PCOS according to the Rotterdam
consensus criteria: change in prevalence among WHO-II
anovulation and association with metabolic factors. BJOG.
2006;113:1210–7.
50. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus
workshop group. Revised 2003 consensus on diagnostic
criteria and long-term health risks related to polycystic ovary
syndrome (PCOS). Hum Reprod. 2004;19:41–7.
51. Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH,
Fauser BC. Anti-Müllerian hormone serum concentrations
in normoovulatory and anovulatory women of reproductive
age. J Clin Endocrinol Metab. 2004;89:318–23.
52. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C,
Jonard S, et al. Elevated serum level of anti-Mullerian
hormone in patients with polycystic ovary syndrome:
relationship to the ovarian follicle excess and to the follicular
arrest. J Clin Endocrinol Metab. 2003;88:5957–62.
53. Pellatt L, Hanna L, Brincat M, Galea R, Brain H, Whitehead
S, et al. Granulosa cell production of anti-Müllerian
hormone is increased in polycystic ovaries. J Clin Endocrinol
Metab. 2007;92:240–5.
54. Eldar-Geva T, Margalioth EJ, Gal M, Ben-Chetrit A, Algur N,
Zylber-Haran E, et al. Serum anti-Mullerian hormone levels
during controlled ovarian hyperstimulation in women with
polycystic ovaries with and without hyperandrogenism. Hum
Reprod. 2005;20:1814–9.
55. La Marca A, Orvieto R, Giulini S, Jasonni VM, Volpe A, De
Leo V. Mullerian-inhibiting substance in women with
polycystic ovary syndrome: relationship with hormonal and
metabolic characteristics. Fertil Steril. 2004;82:970–2.
56. Piouka A, Farmakiotis D, Katsikis I, Macut D, Gerou S,
Panidis D. Anti-Müllerian hormone levels reflect severity of
PCOS but are negatively influenced by obesity: relationship
with increased luteinizing hormone levels. Am J Physiol
Endocrinol Metab. 2009;296:E238–43.
1259
Anti-Müllerian hormone in female fertility and infertility
57. Moran LJ, Noakes M, Clifton PM, Norman RJ. The use of
anti-müllerian hormone in predicting menstrual response
after weight loss in overweight women with polycystic ovary
syndrome. J Clin Endocrinol Metab. 2007;92:3796–
802.
58. Pigny P, Jonard S, Robert Y, Dewailly D. Serum
anti-Müllerian hormone as a surrogate for antral follicle
count for definition of the polycystic ovary syndrome. J Clin
Endocrinol Metab. 2006;91:941–5.
59. van Beek RD, van den Heuvel-Eibrink MM, Laven JS, de Jong
FH, Themmen AP, Hakvoort-Cammel FG, et al.
Anti-Müllerian hormone is a sensitive serum marker for
gonadal function in women treated for Hodgkin’s lymphoma
during childhood. J Clin Endocrinol Metab.
2007;92:3869–74.
60. Jamieson S, Fuller PJ. Molecular pathogenesis of granulosa
cell tumors of the ovary. Endocr Rev. 2012;33:109–44.
61. La Marca A, Volpe A. The anti-Mullerian hormone and
ovarian cancer. Hum Reprod Update. 2007;13:265–73.
62. Pieretti-Vanmarcke R, Donahoe PK, Szotek P, Manganaro T,
Lorenzen MK, Lorenzen J, et al. Recombinant human
Mullerian inhibiting substance inhibits long-term growth of
MIS type II receptor-directed transgenic mouse ovarian
cancers in vivo. Clin Cancer Res. 2006;12:1593–8.
63. Muttukrishna S, McGarrigle H, Wakim R, Khadum I, Ranieri
DM, Serhal P. Antral follicle count, anti-mullerian hormone
and inhibin B: predictors of ovarian response in assisted
reproductive technology? BJOG. 2005;112:1384–90.
64. Tremellen KP, Kolo M, Gilmore A, Lekamge DN.
Anti-müllerian hormone as a marker of ovarian reserve. Aust
N Z J Obstet Gynaecol. 2005;45:20–4.
65. La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella
S, et al. Anti-Müllerian hormone measurement on any day of
the menstrual cycle strongly predicts ovarian response in
assisted reproductive technology. Hum Reprod.
2007;22:766–71.
66. McIlveen M, Skull JD, Ledger WL. Evaluation of the utility of
multiple endocrine and ultrasound measures of ovarian
reserve in the prediction of cycle cancellation in a high-risk
IVF population. Hum Reprod. 2007;22:778–85.
67. Lekamge DN, Barry M, Kolo M, Lane M, Gilchrist RB,
Tremellen KP. Anti-Müllerian hormone as a predictor of IVF
outcome. Reprod Biomed Online. 2007;14:602–10.
68. Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P,
Godehardt E. Relevance of anti-Mullerian hormone
measurement in a routine IVF program. Human Reprod.
2008;23:1359–65.
69. Riggs RM, Duran EH, Baker MW, Kimble TD, Hobeika E,
Yin L, et al. Assessment of ovarian reserve with
anti-Müllerian hormone: a comparison of the predictive
value of anti-Müllerian hormone, follicle-stimulating
1260 Acta Obstetricia et Gynecologica Scandinavica 
C 2012 Nordic Federation of Societies of Obstetrics and Gynecology 91 (2012) 1252–1260
A.G.-A. Grynnerup et al.
hormone, inhibin B, and age. Am J Obstet Gynecol.
2008;199:202.e1–8.
70. Barad DH, Weghofer A, Gleicher N. Comparing
anti-Müllerian hormone (AMH) and follicle-stimulating
hormone (FSH) as predictors of ovarian function. Fertil
Steril. 2009;91:1553–5.
71. Nardo LG, Gelbaya TA, Wilkinson H, Roberts SA, Yates A,
Pemberton P, et al. Circulating basal anti-Müllerian
hormone levels as predictor of ovarian response in women
undergoing ovarian stimulation for in vitro fertilization.
Fertil Steril. 2009;92:1586–93.
72. Al-Azemi M, Killick SR, Duffy S, Pye C, Refaat B, Hill N,
et al. Multi-marker assessment of ovarian reserve predicts
oocyte yield after ovulation induction. Hum Reprod.
2011;26:414–22.
73. Elgindy EA, El-Haieg DO, El-Sebaey A. Anti-Müllerian
hormone: correlation of early follicular, ovulatory and
midluteal levels with ovarian response and cycle outcome in
intracytoplasmic sperm injection patients. Fertil Steril.
2008;89:1670–6.
74. Li HW, Yeung WS, Lau EY, Ho PC, Ng EH. Evaluating the
performance of serum antimullerian hormone concentration
in predicting the live birth rate of controlled ovarian
stimulation and intrauterine insemination. Fertil Steril.
2010;94:2177–81.
75. Majumder K, Gelbaya TA, Laing I, Nardo LG. The use of
anti-Müllerian hormone and antral follicle count to predict
the potential of oocytes and embryos. Eur J Obstet Gynecol
Reprod Biol. 2010;150:166–70.
76. Kini S, Li HW, Morrell D, Pickering S, Thong KJ.
Anti-mullerian hormone and cumulative pregnancy
outcome in in-vitro fertilization. J Assist Reprod Genet.
2010;27:449–56.
77. Lee TH, Liu CH, Huang CC, Wu YL, Shih YT, Ho HN, et al.
Serum anti-Müllerian hormone and estradiol levels as
predictors of ovarian hyperstimulation syndrome in assisted
reproduction technology cycles. Hum Reprod.
2008;23:160–7.
78. Aflatoonian A, Oskouian H, Ahmadi S, Oskouian L.
Prediction of high ovarian response to controlled ovarian
hyperstimulation: anti-Müllerian hormone versus small
antral follicle count (2–6 mm). J Assist Reprod Genet.
2009;26:319–25.
79. Honnma H, Baba T, Sasaki M, Hashiba Y, Oguri H,
Fukunaga T, et al. Different ovarian response by age in an
anti-Müllerian hormone-matched group undergoing in vitro
fertilization. J Assist Reprod Genet. 2011;29:117–25.
80. Ocal P, Sahmay S, Cetin M, Irez T, Guralp O, Cepni I. Serum
anti-Müllerian hormone and antral follicle count as
predictive markers of OHSS in ART cycles. J Assist Reprod
Genet. 2011;28:1197–1203.

C 2012 The Authors