Moustafa Eissa MD FRCOG
Cyberjaya University College of Medical
Sciences, Malaysia
In this subject facts are
disperse and hypotheses
and speculations are the
 Anti Mullerian Hormone (AMH) is a
dimeric glycoprotein. It is secreted
from granulosa cells of antral and
preantral follicles.
(Pepinsky et al 1988).
 Its expression in females starts as
early as 32 weeks of gestational age
(Rajpert-DeMeyts et al 1999)
It is secreted from granulosa cells of
antral and preantral follicles before
selection for dominance. It's
secretion declines in preovulatory
(Durlinger et al 2002).
 This is a widely accepted fact. However, in a
study done by our group comparing AMH level
in follicular fluid (FF) and serum in a study
group of dysfunctional ovulation cysts and a
control group of mature graffian follicles, we
found high levels of AMH and it was not
declining (Table 1). There was a strong
correlation between follicular and serum AMH
in the study group and inverse significant
correlation between AMH (FF) and serum FSH
(Figure 1).
(Eissa et al 2013)
Table (1): Hormonal profile in Control and Cyst formation groups.
*FF: follicular fluid (means follicular fluid in group 1 and cyst fluid in group 2).
Group 1
(n= 10)
Mean ± SD
Group 2
Study (Cyst)
(n= 25)
Mean ± SD
Serum FSH(ng\ml)
0.2 (NS)
Serum AMH(ng\ml)
FF* AMH (ng\ml)
FF* Estradiol(ng\ml)
P value
Figure (1) correlation between serum and follicular fluid
concentration of AMH in cyst group
r= - 0.65 p= 0.0001
Serum FSH (ng/ml)
Intrafollicular AMH (ng/ml)
 Polycystic Ovarian Syndrome (PCOS) is one of
the most common endocrinopathies affecting
5-10% of women of reproductive age.
(Amer 2006)
 PCOS is a multifactorial complex
characterized by chronic anovulation,
polycystic ovarian appearance, biochemical
and clinical manifestations of
hyperandrogenism. Figure (2 and 3).
(Rotterdam Consensus 2004).
Figure 3
The cause of anovulation in PCOS
 Stein & Leventhal (1935): the sclerocystic thickened
capsule is the primary cause of anovulation
 Amer (2006): chronic anovulation is the result of
abnormal folliculogenesis and steroidogenesis.
 Homburg et al (2009): the basic lesion is excessive
secretion of androgens. Hyperinsulinaemia and high LH
exacerbate the problem.
 La Marca et al (2009): The failure to find a
causative gene, although its familial nature,
suggested a developmental theory based on
Barker theory.
The excessive exposure to androgens
in utero of rhesus monkeys programs
the offending genes. This theory is
not proved in human yet.
(Abbott et al 2002).
So it is now known that the main
pathology of PCOS lies in the ovaries
itself and the excessive production of
androgens by the ovaries is the main
endocrinological disturbance. However,
insulin resistance and hyperinsulinaemia
and increased LH secretion play a role in
the pathogenesis of PCOS. Figure (4)
(Homburg and Crawford 2014)
Figure 4
Laparoscopic PCOS drilling
Figure 5
Figure 6
Laparoscopic ovarian drilling
Figure 7
Numerous theories of the aetiology
of the associated anovulation have
been speculated as
hyperinsulinaemia and
dysfunctional feedback mechanism
However, there is no clear evidence that
excessive insulin or androgen has a direct
inhibitory effect on ovulation. While
there is a good correlation between
severity of hyperandrogenemia and
anovulation, there is no clear evidence
that excessive androgen inhibit ovulation.
(Homburg and Crawford 2014).
Also, there is no convincing evidence
that insulin has an inhibitory effect
on ovulation. The dysfunctional
feedback mechanisms are widely
thought to be secondary to the
primary pathophysiological change
in the ovary itself
(Franks et al 2006).
AMH and anovulation in PCOS
In PCOS patients, ovaries have large
number of pre-antral and small antral
follicles compared to normal ovary, the
concentration of AMH is markedly
increased compared to the control.
(Pigny et al 2006).
Since in vivo and in vitro studies showed that
growth of the primordial follicles to growing
follicles occurs in absence of AMH (Durlinger
2001), so this is may be the main role of AMH to
prevent the growth of primordial follicles and
prevent exhaustion of primordial follicle pool.
Hence ovarian aging may be delayed in women
with PCOS since high AMH levels may inhibit
the selection and growth of primordial follicles
(Mulders et al 2004).
This may be the initial step of
understanding the causative relationship
of AMH to anovulation in PCOS patients.
On the other hand and in normal ovary,
the growing follicles (>10mm) are
deprived of AMH, so they become more
responsive to circulating FSH and follicle
selection occurs.
(Pellatt et al 2007).
In studies of McGee and Hsueh (2000)
and Durlinger et al (1999), it was found
that AMH decreases the sensitivity of
growing follicles to the secreted FSH.
These studies are not proved in
humans and further studies are
Kevenaar et al (2007) suggested a role of
AMH in FSH induced steriodogenesis
in human. This may explain the high
oestradiol and the normal or
relatively subnormal level of FSH in
PCOS patients.
The main pathophysiological
disturbance of failure of ovulation in
PCOS patients leads to accumulation of
pre-antral and antral follicles and
increased secretion of AMH. So, this in a
vicious circle, leads to further
(Wang et al 2007).
 Level of AMH, although, high in PCOS
patients, it depends on the severity of the
condition. The density of pre-antral follicles is six
times in amenorrheic PCOS patients compared with
the normal ovary
(Webber et al, 2003).
 It’s concentration in amenorrheic PCOS is high
compared to oligomenorrheic and regularly
menstruating patients
(La Marca et al 2009)
 Also, it is higher in insulin resistant
PCOS patients than insulin sensitive
patients. These findings may strengthen
the role of AMH in causing anovulation
in PCOS patients.
(Fleming et al 2006).
Role of AMH in diagnosis and monitoring
treatment of PCOS patients
 AMH measurement is useful in
diagnosis and monitoring treatment in
PCOS patients with high sensitivity and
 . In absence of ultrasound diagnosis,
measurement of AMH might be used
accurately in diagnosis of PCOS.
(Pigny et al 2006)
 PCOS women with high circulating AMH (≥
3.4 ng/mL) seem to be resistant to CC and
may require a higher starting dose
(Mahran et al 2013).
 PCOS women with markedly raised
circulating AMH seem to be resistant to
HMG ovulation induction and may require
a higher starting dose. The good response
seems to be inversely proportional to AMH
level (Figure 6).
(Amer et al 2013).
Figure (8) Good response rates in 34 cycles of HMG ovarian
stimulation in PCOS women with different serum AMH levels
.Amer et al 2013
Further studies are needed to know if this
high AMH in PCOS patients is a result of
the accumulation of small antral follicles
because of the failure of ovulation or it is
a cause of disruption of folliculogenesis.
If this proved in humans an AMH
antagonist may be the key treatment.
The use of AMH measurement in
evaluation of PCOS patients need a large
and well designed trial. More studies are
needed to evaluate the role of measuring
AMH in adolescent girls to identify those
at high risk for developing PCOS. Also,
further studies are needed to identify
those who may respond to treatment as
weight loss, clomiphene citrate and
insulin desensitizers.
Thank you

AMH in pre-pubertal girls Crisosto et al, JCEM, 2007