AMH and ovarian disfunction

Prof. Bart CJM Fauser

Dept. Reproductive Medicine

& Gynecology
University Medical Center
Utrecht, The Netherlands

WHO Classification
(Insler & Lunenfeld’72; WHO’93; ESHRE Capri’96)

Serum Gonadotropins
&
Serum Estradiol levels

(5-10%) (~80%) (5-10%)

FSH & LH FSH ~ FSH & LH

& & &
Estradiol Estradiol ~ Estradiol

WHO I WHO II WHO III

PCOS

Ovulation Induction Ovulation Induction IVF/oocyte

IVF IVF donation

The complex and long

trajectory of follicle development

McGee, Endocr Rev 2000

follicle development
in relation to AMH, Inh B, FSH

FSH dependence

Inhibin B

AMH
Estradiol

McGee, Endocr Rev 2000

Ovarian disfunction
in relation to AMH, Inh B, FSH

FSH dependence
Inhibin B

AMH
WHO 2:
advanced follicle maturation arrest

WHO 1: no FSH stimulation

WHO 3: no follicles
 Ovarian disfunction
in relation to AMH, Inh B, FSH

FSH dependence
Inhibin B

AMH
WHO 2:
advanced follicle maturation arrest
AMH (ug/L)

30
* P < 0.001
*

20
*

10

0
N= 41 64 64
JCEM,
Controls non-PCOS PCOS
2004 WHO-2

AMH in PCOS and hypothalamic amenorrhea

La Marca,
FS 2006
Elevated AMH in PCOS
- studies published so far -

Author Year No Controls PCOS

Cook 2002 47 2.4 ± 0.2 µg/l 5.3 ± 0.7 µg/l
Pigny 2003 104 2.9 ± 0.3 µg/l 6.6 ± 0.4 µg/l
Laven 2004 109 2.1 ± 0.6 µg/l 7.6 ± 1.8 µg/l
Piltonen 2005 170 2.4 ± 0.2 µg/l 8.1 ± 0.8 µg/l
Eldar-Geva 2005 52 1.6 ± 0.8 µg/l 5.1 ± 1.3 µg/l
La Marca 2006 34 3.5 ± 1.5 µg/l 7.4 ± 1.7 µg/l
Wachs 2007 27 2.1 ± 0.4 µg/l 7.2 ± 0.5 µg/l

Broekmans, 2008, submitted

2-3 fold increase

PCOS Hyperandrogenemia

PCO Oligo/anovulation
(WHO 2 type)

Accuracy of AMH to predict PCO

Pigny, JCEM 2006

Ovarian disfunction
in relation to AMH, Inh B, FSH

FSH dependence
Inhibin

AMH

WHO 1: no FSH stimulation

F&S, 2007
Ovarian disfunction
in relation to AMH, Inh B, FSH

FSH dependence
Inhibin B

AMH

WHO 3: no follicles

2.6 yrs

P < 0.001

Longitudinal ----- Cross sectional

Preliminary own findings
in POF and POF-like conditions

Control

Imminent ovarian
failure
´Broad´ ovarian failure
True POF

(Knauff 2008)
 Ovarian disfunction
in relation to AMH, Inh B, FSH

FSH dependence
Inhibin B

AMH
WHO 2:
advanced follicle maturation arrest

WHO 1: no FSH stimulation

WHO 3: no follicles

Conclusions
AMH seems like a useful marker to assess ovarian
disfunction in women presenting with oligo/amenorrhea

AMH in PCOS
- may be used to assess the extent of ovarian disfunction
- may replace ultrasound for PCO diagnosis
- may predict response to intervention
(weight reduction, OI, IVF?)
- may identify affected sibs of patients

AMH may predict and monitor extent of

ovarian damage due to chemotherapy

High quality commercially available AMH assay !!

 Correlation between AMH and other
Disease Characteristics in PCOS
AMH (ug/L)

50 50
R = 0.477 R = 0.421
AMH (ug/L)

P < 0.001 P < 0.001

40 40

30 30

20 20

10 10

0 0
0 1 2 3 4 5 6 7 0 10 20 30
Testosterone (nmol/L) Mean Ovarian Volume (mL)

Good Correlation with:

Age, Cycle duration, LH, Adion, Free IGF-I, Follicle number
No correlation with:
CC resistance, Duration or rFSH dosage during Ovulation Induction

FS 2005
2006