Transcript Mostafa Eissa

ANTIMULLERIAN HORMONE LEVEL IN
PERSISTENT DYSFUNCTIONAL OVULATION CYST:
A POSSIBLE ROLE IN NORMAL AND ABNORMAL
FOLLICULOGENESIS
Moustafa K Eissa MD FRCOG,
Hussam Shawkey MD,
Ahmad Samir MD,
Yasser el-Mazney MBChB
Department of Obstetrics & Gynaecology,
Minia University and Minia Infertility
Research & Treatment Center.
INTRODUCTION (1)

During ovulatory menstrual cycles, follicles
develop and rupture releasing mature ova.
Dysfunctional ovulation cysts arise when this
physiologic release fails and follicular growth
continues (Eissa etal 1986). This occurs either
from excessive stimulation by follicle
stimulating hormone (FSH) or from lack of the
normal preovulatory luteinizing hormone (LH)
surge (Altchek et al 2003 and Prat et al 2004).
Others suggest abnormal follicle (Eissa etal
1987)
INTRODUCTION (2)

Follicular cysts grow larger than 28 mm and
most are asymptomatic. Larger cysts may
cause pelvic discomfort or heaviness. If the
granulosa cells lining the follicular cyst
produce excessive oestradiol, menstrual
irregularities occur (DiSaia and Creasman
2002 and Altchek et al 2003).
INTRODUCTION (3)

Treatment of simple follicular cyst varies from
expectant management (Nardo etal 2003),
medical treatment (Turan et al., 1994). ,
transvaginal aspiration under ultrasound
guidance (Shawekey etal 2011), laparoscopic
aspiration or excision (Lin et al., 1995) and
surgical ovarian cystectomy (Flynn and Niloff,
1999).
INTRODUCTION (4)
 Durlinger
(1999) suggested that in
the absence of AMH, follicles may
be more sensitive to FSH. In vitro
and in-vivo studies confirmed this
hypothesis (Durlinger et al., 2001).
INTRODUCTION (5)

The inhibitory effects of AMH on FSH-sensitivity of follicles may
play an important role in the process of selection. During
selection a group of follicles is selected from the group of AMHproducing growing follicles to continue growth up to the
preovulatory stage. It is thought that, depending on its
developmental stage. Each follicle requires a certain
concentration of FSH to continue growth and this concentration
has to be exceeded to ensure selection. Since AMH affects
FSH-sensitivity of the follicles, it may play a role in the
determination of follicles to undergo selection or be removed
through atresia (Baarends 1995).
AIM OF THE WORK
 The
primary aim of the study is to see if
the AMH plays a role in cyst formation.
The secondary aim is to test if AMH may
be used as a predictor for response to
medical treatment in patients with simple
dysfunctional ovulation cyst.
PATIENTS AND METHODS (1)

This prospective randomized controlled study
was conducted in the Department of Obstetrics
and Gynecology, Faculty of Medicine, El-Minia
University and El-Minia infertility research unit
during the period from November 2009 to June
2010, after being approved by the
Department’s Ethical Committee.
PATIENTS AND METHODS (2)

This study included 35 patients, divided into two
groups. The control group included 10 infertile
patients prepared for ICSI procedure. The study
group included 25 patients, presented with simple
dysfunctional ovulation cyst resistant to medical
treatment for three months. They had transvaginal
ultrasound criteria for cyst benignity being
unilateral, less than 10 cm, thin walled with no
internal trabiculae or septations and clear
contents. They were subjected to transvaginal
ultrasound aspiration as a method of treatment as
previously described (Shawkey etal 2011).
PATIENTS AND METHODS (3)

Levels of AMH, testosterone and oestradiol were
measured. These hormones were withdrawn from
follicles aspirated during ovum pick up (group1) and
from simple follicular cyst during therapeutic cyst
aspiration (group 2). Levels of serum AMH and FSH
were measured in all patients. Correlations between
these hormones were done in a trial to explain
pathophysiology of anovulation and cyst formation
and to match between the pathophysiology and mode
of treatment for each ovarian cyst.
Results1
To our knowledge, this study is the first to measure
AMH in fluid aspirated from human simple ovarian cyst
Table (1): Patients' characteristics in both study groups
Patients'
characteristics
Group I
(n= 25)
Group II
(n= 10)
P value--
Range
Mean ± SD
range
Mean ± SD
Age (years)
20-40
28.04±6.1
22-40
32.8±4.7
0.3 (NS)
Height (cm)
154-170
162.7±7.6
150-170
163.9±5.8
0.6 (NS)
Weight (kg)
60-80
70.5±5.1
66-80
72.6±4.6
0.2 (NS)
19.3-30.4
26.7±2.5
22.8-32
27.1±2.6
0.6 (NS)
BMI
RESULTS (2)
TABLE (2): CLINICAL PRESENTATIONS OF THE STUDY GROUP
Complaints
No
Percent
Primary infertility
13
52%
Secondary infertility
6
24%
Amenorrhea
2
8%
Metroragia
2
8%
Menoragia
2
8%
Table (2)shows patient's clinical presentations of the group2 (study)
more than half (52%) of the patients presented by primary infertility
followed by (24%) secondary infertility While the rest of them
presented by amenorrhea, metroragia and menoragia by (8%) for
each.
RESULTS (3)
TABLE (3): HORMONAL PROFILE IN BOTH GROUPS
Group 1
(n= 10)
Group 2
(n= 25)
Mean ± SD
Mean ± SD
Serum FSH (ng\ml)
4.65±1.5
5.41±1.9
0.2 (NS)
Serum AMH (ng\ml)
5.9±2.02
14.6±3.3
0.0001(S)
FF* AMH (ng\ml)
29.5±25.7
440.7±182.9
0.0001(S)
FF* Testosterones (ng\ml)
5.8±4.2
5.2±3.7
0.6(NS)
FF* Estradiol (ng\ml)
21.2±0.6
20.4±6.8
0.7(NS)
Hormone
P value
*FF: follicular fluid (means follicular fluid in group 1 and cyst fluid in group 2).
Table (3) shows hormonal profiles in group1 (control) and group 2
(study):Serum and follicular fluid AMH in group 2 are higher than group 1
and this difference is statistically significant, while there is no statistical
differences between the two groups as regard other hormones.
RESULTS (4)
HORMONAL RELATIONS IN GROUP 1 (CONTROL):
FIG (1): CORRELATION BETWEEN FOLLICULAR FLUID AND SERUM AMH
10.00
Serum AMH (ng/ml)
9.00
r= 0.38
p= 0.2
8.00
7.00
6.00
5.00
4.00
3.00
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
Intrafollicular AMH (ng/ml)
Fig(1) shows that there is a non significant fair positive association
between follicular fluid and serum AMH (r=0.38, p =0.2).
RESULTS (5)
FIG(2): CORRELATION BETWEEN FOLLICULAR FLUID AMH AND SERUM
FSH (CONTROL GROUP)
6.00
r= - 0.26
p= 0.4
Serum FSH (ng/ml)
5.50
5.00
4.50
4.00
3.50
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
Intrafollicular AMH (ng/ml)

Fig (2 ) shows that there is non significant fair negative
association between follicular fluid AMH and serum FSH
with (r =-0.26, p =0.4)
RESULTS (6)
FIG(3): CORRELATION BETWEEN AMH AND ESTRADIOL LEVELS IN
FOLLICULAR FLUID
r= - 0.60
p= 0.06
Intrafollicular Estradiol (ng/ml)
22.00
21.50
21.00
20.50
20.00
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
Intrafollicular AMH (ng/ml)

Fig (3 ) shows that there is non significant
moderate negative association between
AMH and estradiol levels in follicular fluid (r
=-0.60, p =0.6).
RESULTS (7)

Also in this group (Control group) there is no
association between AMH and testosterone in
follicular fluid (r =0.09, p =0.8), no association
between serum AMH and serum FSH (r=0.17 ,p =0.6),
non significant moderate negative association
between serum AMH and follicular fluid esrtadiol (r =0.52, p =0.1) and no association between serum AMH
and follicular fluid Testosterone ( r=-0.11,p=0.7).
RESULTS (8)
HORMONAL RELATIONS IN GROUP 2 (STUDY GROUP)
FIG(4) : CORRELATION BETWEEN FOLLICULAR FLUID AND
SERUM AMH
20.00
r= 0.07
p= 0.7
Serum AMH (ng/ml)
18.00
16.00
14.00
12.00
10.00
8.00
0.00
300.00
600.00
900.00
1200.00
1500.00
Intrafollicular AMH (ng/ml)

Fig(4)shows that there is no association between
follicular fluid and serum AMH (r=0.07, p =0.7).
RESULTS (9)
FIG(5): CORRELATION BETWEEN FOLLICULAR
FLUID AMH AND SERUM FSH (STUDY GROUP)
r= - 0.65
p= 0.0001
Serum FSH (ng/ml)
8.00
6.00
4.00
2.00
0.00
300.00
600.00
900.00
1200.00
1500.00
Intrafollicular AMH (ng/ml)

Fig (5 ) shows that there is a significant negative
association between follicular fluid AMH and serum
FSH (r =0.65, p =0.0001).
RESULTS (10)
FIG(6): CORRELATION BETWEEN AMH AND ESTRADIOL
LEVELS IN FOLLICULAR FLUID (STUDY GROUP)
40.00
Intrafollicular Estradiol (ng/ml)
r= - 0.47 p= 0.01
30.00
20.00
10.00
0.00
0.00
300.00
600.00
900.00
1200.00
1500.00
Intrafollicular AMH (ng/ml)
Fig (6) shows that there is a significant fair negative association between
AMH and estradiol levels in follicular fluid with (r =-0.47, p =0.01).
RESULTS (11)

Hormonal relation in this group revealed no
association between AMH and testosterone in
follicular fluid (r=0.24, p =0.3), no association
between serum AMH and serum FSH (r=0.008,
p=0.9), no association between serum AMH
and follicular fluid esrtadiol (r=0.14, p =0.5)
and no association between serum AMH and
follicular fluid Testosterone (r=-0.16, p =0.4).
CONCLUSIONS (1)

In the present study it was noted that there is a
statistically significant higher levels of serum and
follicular fluids’ AMH in study group than the controls.
AMH alters FSH-sensitivity of the follicles leading to
disturbance in the expression of the LH receptors of
the growing follicle. So AMH prevents the FSH
mediated selection of the follicle, prevents its removal
and causes failure of its lutenization and rupture. This
phenomenon may guide the growing follicle to lose its
FSH-dependent maturation and lutenisation and to be
transformed into cyst.
CONCLUSIONS (2)


This explanation may shed some light about the
resistance of these cysts to hormonal treatment.
High serum levels of AMH is a reflection of high FF
AMH. High serum levels of AMH in cases with ovarian
cyst may be used to distinguish cases that will
respond to hormonal treatment from those which fail
to achieve complete remission of their pathology.