review article - polycystic ovaries

7/28/2019 Review Article - Polycystic Ovaries

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Review article

Polycystic ovaries

1K LAKHANI, MSc,

2A M SEIFALIAN, MSc, PhD,

3W U ATIOMO, MD, MRCOG and

3P HARDIMAN, MD, FRCOG

1Ultrasound Department, X-Ray, North Middlesex Hospital, Sterling Way, Edmonton, London N18 1QX and2University Department of Surgery and 3University Department of Obstetrics and Gynaecology, Royal Free

and University College Medical School, Pond Street, London NW3 2PF, UK

Abstract. Transvaginal ultrasound is currently the gold standard for diagnosing polycystic

ovaries. The results of studies using ultrasound suggest a prevalence in young women of at least

20%. Between 5% and 10% of these women with polycystic ovaries shown on ultrasound will have

the classical symptoms of polycystic ovary syndrome such as infertility, amenorrhoea or signs of

hirsutism and obesity, as originally described by Stein and Leventhal in 1935. However, the

significance of polycystic ovaries in asymptomatic women is still under investigation, as is the role

of Doppler (pulsed and colour) and three-dimensional ultrasound. Ultrasound has also con-tributed to our understanding of the local and systemic haemodynamic changes associated with

polycystic ovaries, although the relationship of these changes to morbidity and mortality is

unknown.

The condition now known as polycystic ovarian

syndrome (PCOS) was first described by Stein and

Leventhal in 1935 [1] as comprising amenor-

rhoea, hirsutism, obesity and sclerotic ovaries. It

is one of the most common human endocrino-

pathies, affecting 510% of women of reproductive

age [2]. The diagnosis of PCOS was previouslybased on a combination of clinical and endocrine

features, including raised serum concentrations of

luteinizing hormone (LH), testosterone (T) and

androstenedione and reduced levels of sex hor-

mone binding globulin [3, 4]. With the introduction

of pelvic ultrasound in the 1980s, non-invasive

assessment of ovarian morphology became pos-

sible. Ultrasound studies have demonstrated that

approximately 20% of young women have poly-

cystic ovaries (PCO) [5, 6], of whom around

2570% have symptoms of infertility, menstrual

irregularity or hirsutism, consistent with the

diagnosis of PCOS [2, 5, 6]. However, the finding

of PCO on ultrasound does not per se warrant

such a diagnosis. More recently, high frequency

transvaginal ultrasound (TVS) has superseded

transabdominal (TA) real-time scanning in the

diagnosis of PCO because of its superior resolu-

tion, whilst three-dimensional (3D) imaging and

colour Doppler blood flow studies have allowed

detailed evaluation of the stroma. The aim of this

review article is to address the development of

diagnostic ultrasound criteria of PCO with

successive advances in ultrasound technology

and to identify its salient associations.

Developments in ultrasound imaging

With advances in technology, in particular that

of TVS, ultrasound has replaced laparotomy

and X-ray pelvic pneumogynaecography in the

diagnosis of PCO [7, 8]. The static B-scanners of

the mid 1960s allowed visualization of ovarian

enlargement as well as of cysts measuring greater

than 1 cm in diameter [9]. The poor resolution of

the ultrasound equipment used in the early 1970s

permitted visualization of the ovarian outline

only, and the diagnosis of PCO was based upon

increased maximum length (.4.0 cm). However,

the use of a single dimension may lead to false

positive results when the full bladder compresses

the ovary, or false negative results when the

ovaries are spherical in shape. In fact PCO tend tobe more spherical in shape so that the sphericity

index (expressed as ovarian width to ovarian

length ratio) is greater than 0.7 in PCO. A

decreased uterine width to ovarian length ratio of

greater than 1.0 has also been reported in the

diagnosis of PCO. All these features are now used

less frequently because of their low sensitivity [10].

Thereafter, the development of grey scan equip-

ment in the 1970s and real-time sector scanners in

the 1980s improved resolution and, for the first

time, cysts less than 1 cm could easily be recog-

nized [11]. In 1981, Swanson et al [11] describedPCO as enlarged and rounded, with a mean

volume of 12 cm3 and containing an increasedReceived 11 June 2001 and in revised form 25 September

2001, accepted 16 October 2001.

The British Journal of Radiology, 75 (2002), 916 E 2002 The British Institute of Radiology

9The British Journal of Radiology, January 2002


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number of small follicles (28 mm) encircling the

ovarian cortex. However, the importance of

ovarian size in diagnosis has lessened as variousgroups [1214] have shown a considerable overlap

between PCO and normal ovaries and as the

upper limit of normal has decreased from greater

than 10 cm3 to 5.5 cm3 [15]. This decrease may

also reflect the broader inclusion criteria in the

latter studies compared with Swanson et al who

only included patients with enlarged ovaries and

classic SteinLeventhal syndrome at the extreme

end of the clinical spectrum.

In 1985, Adams et al [16] published new criteria

based on TA ultrasound, which required 10 or more

cysts of 28 mm in diameter arranged peripherally

around an echo dense stroma. However, thesecriteria have remained in widespread use even

after the introduction of TVS a decade later. The

high resolution of the technique allows visual-

ization of follicles less than 5 mm in diameter as

well as echogenic stroma (Figure 1), which corre-

sponds closely to the characteristic histopatho-

logical changes (Figure 2), and this is now

accepted as the gold standard for diagnosis of

PCO (Table 1). There have been at least four

definitions of PCO using TVS. The most recent

criteria were defined by Fox [17] and Atiomo et al

[18]. These criteria differ slightly in the number of

Figure 1. Transvaginal image of a polycystic ovaryshowing peripheral distribution of follicles (arrows).

Figure 2. Stained longitudinal section of a polycysticovary showing numerous small peripheral follicles.

Table 1. Results of some ultrasound studies described in the literature

Reference UER Ultrasound variable Criteriaindicativeof PCO

% of patientswith clinicalPCOS

% of controlshaving thecriteria

No. ofpatientsstudied

No. ofstudiedcontrols

Adams et al1985 [16]

TA Ovarian volume .15 cm3 33 0 76 17No. of follicles 410 mm .10 72 0

Yeh et al1987 [53]

TA Ovarian volume .10 cm3 70 0 108 25No. of follicles 58 mm .5 74 11 68 18Uterine width/ovarian

length.1 7 6 100 24

Pache et al1992 [54]

TV Ovarian volume .8 cm3 About 70 0 52 29No. of follicles .6 mm .11 About 50 0 52 29

Mean ovarian size ,4 mm About 70 7 52 29Increased echogenicity

of OSPresent 94 10 52 29

Robert et al1995 [15]

TV Increased stromal area a.8 cm3 61 4 69 48Increased maximal

ovarian area

a

.10.8 cm3 55 2 69 48

Fox et al1999 [17]

TV Ovarian volume 17.6 cm3 60 0 29 35No. of follicles 25 mm .15 46 0 25 0Increased echogenicity

of OSPresent 60 0 29 2

Atiomo et al2000 [18]

TV Ovarian volume .9 cm3 Around 70No. of follicles 28 mm .10 Around 80 Not mentioned 32 40Increased echogenicity

of OSPresent Around 60

UER, ultrasound examination route; TA, transabdominal; TV, transvaginal; OS, ovarian stroma; PCO, asymptomatic women withpolycystic ovaries; PCOS, polycystic ovarian syndrome.

aTotal of both ovaries.

K Lakhani, A M Seifalian, W U Atiomo and P Hardiman

10 The British Journal of Radiology, January 2002


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follicles and their size. However, Fox does not

stipulate that the requisite numbers of follicles are

seen in a single plane of the ovary. In clinical

practice the ultrasonographer forms an impres-

sion of the ovary from the images obtained in

three planes. Therefore, there is still a degree of

subjectivity in this diagnosis. The ultrasound

diagnostic criteria of PCO have been refined

with advances in technology. Diagnostic accuracy

has evolved from increased ovarian length to the

recognition of the distribution of follicles and

textural changes in the ovarian stroma. The most

consistent feature of PCO, which is not seen in a

normal cycling ovary, is the presence of small

follicles around an echodense ovarian stroma,

although recognition of the latter is highly sub-

jective and depends upon equipment settings.

3D ultrasound

To avoid the difficulties in outlining or mea-

suring ovarian size, 3D ultrasound has been

proposed using a dedicated volumetric probe or

a manual survey of the ovary [19]. 3D ultrasound

has been used to measure ovarian and stromal

volumes, providing information that is not

available from two-dimensional (2D) ultrasound

[19]. Data are transferred to a computer and can

be analysed later. From the stored data, measure-

ments can be made from the image that is re-

constructed and the ovarian and stromal volumes

are displayed on the screen in three adjustable

orthogonal planes; subsequently the volume canbe more accurately evaluated. In a study by Kyei-

Mensah et al [19], the difference in ovarian size

was accounted for by the differences in stromal

volumes, there being no differences in follicular

volume between normal ovaries and PCO. How-

ever, 3D ultrasound is governed by the same

principles as 2D ultrasound and hence its resolu-

tion is reduced in obese women. Expertise and

experience is therefore important, as numerous

volume measurements of sufficient quality may be

necessary to permit meaningful analysis.

Doppler ultrasound

Transvaginal colour and pulsed Doppler ultra-

sound in combination with B-mode imaging is

used as a non-invasive method to assess blood

flow in both obstetrics and gynaecology. Colour

or power Doppler allows detection of the uterine

and ovarian vessels as well as the network within

the ovarian stroma; power Doppler is more sensi-

tive to slow flow and allows the detection of blood

flow within the ovarian stroma [20]. However,

power Doppler does not as yet allow quantitative

measurement of blood flow. The spectral Dopplerassessment of vascular changes in the ovarian and

uterine arteries in women with PCO has improved

our understanding of the pathogenesis of this

common condition and provides an additional

variable to the traditional endocrinological and

more recent ultrasound features for its diagnosis.

Colour Doppler allows the ovarian artery to be

identified at the lateral border of the ovary as well

as the ascending branch of the uterine artery at

the cervicouterine junction [21]. This technique

has been used to study the haemodynamic changes

in the uterine and/or ovarian arteries during the

menstrual cycle in women with normal ovaries

[21]. Battaglia et al [20] reported a higher uterine

artery pulsatility index (PI) in women with PCOS

and a decreased resistance index (RI) within the

ovarian stroma in PCOS (suggestive of increased

downstream resistance) and a positive correlation

with LH levels. The capillary area increases after

the LH surge, causing an increase blood flow

attributed to vasodilatation and resulting in flow

detection with Doppler ultrasound [22]. However,using colour Doppler and spectral waveform

analysis we did not find any significant differences

in the ovarian artery PI or RI in PCO/PCOS

women compared with women with normal

ovaries (unpublished data). The mechanism res-

ponsible for these haemodynamic changes in

PCOS is not known, but it may be significant

that stromal blood flow in PCO (Figure 3) has

been attributed to increased concentrations of

serum vascular endothelial growth factor [23]. The

clinical significance of these changes is also under

investigation and it is of interest that a higher

uterine artery PI has been associated with lower

conception rates during embryo transfer in in vitro

fertilization [24].

MRI

Data on MRI for PCO is still limited [25]. MRI

allows easier localization of the ovaries because of

its multiplanar scanning of the pelvis. The image

Figure 3. A typical flow velocity diagram at thestroma shows higher velocity in a 35-year-old poly-cystic ovary syndrome patient.

Review article: Polycystic ovaries



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quality of MRI is improved by the use of a pelvic

dedicated phased array coil receiver. The most

useful planes are transverse and coronal and the

T2 weighted sequence is best for assessing ovarian

morphology as the cysts are displayed as high

signal (white) and the stroma as low signal (black)

(Figure 4). T1 weighted sequences are less infor-

mative, although following gadolinium injection

there is enhancement of the stroma, suggesting

that the stroma is highly vascularized in PCO.

The external features of PCO (increased ovarian

volume, increased roundness index (ovarian width/

ovarian length ratio) and decreased uterine width

to ovarian length ratio) are easily recognized on

transverse cuts. Although the T2 weighted se-

quence displays the increased number of follicles,

their detection is less easy than with ultrasound

because of the poor resolution of MRI, unless

using high magnetic fields of 11.5 T. In clinical

practice, MRI is rarely used for the diagnosis ofPCO as it does not provide any more information

than TVS and is also an expensive modality [25].

It may be helpful in difficult situations when

ultrasound either is not possible or is unhelpful

(in virgin or obese women, respectively).

How PCO differ from multifollicularovaries

Multifollicular ovaries (MFO) were first des-

cribed by Adams and colleagues in 1985 [16], and

are encountered in mid to late normal puberty,hyperprolactinaemia, hypothalamic anovulation

and weight-related amenorrhoea. They differ

from PCO, having fewer cysts (610 per ovary;

Figure 5), which tend to be larger (up to 10 mm

in diameter) and distributed throughout the ovary

with no stromal hypertrophy [16]. MFO result

from incomplete pulsatile gonadotrophin (GnRH)

stimulation of ovarian follicular development [26].

Furthermore, MFO resume a normal appearance

following weight gain or treatment with pulsatile

GnRH, whilst PCO retain their appearance

throughout reproductive life, irrespective of time

of cycle, pregnancy or drug treatment [26], and

women with MFO have normal levels of LH

and T and reduced levels of follicle stimulating

hormone (FSH) compared with women with PCO

[27].

Pelvic pain and PCO

Cystic ovaries have also been described [28] in

women with venous congestion resulting in pelvic

pain (Figure 6). This condition is thought to arise

from abnormal relaxation of the pelvic veins and

may respond to progesterone therapy. Adams and

co-workers [29] evaluated ovarian morphology

using TA ultrasound in 55 women with chronic

pelvic pain and reported that women with chronic

pelvic pain due to venous congestion not only had

a larger uterus and thicker endometrium com-

pared with age- and parity-matched controls but

also had cystic ovaries. Of these women, 56% had

cystic changes, which ranged from the classic

polycystic pattern to the appearance of clusters of

46 cysts.

Early pregnancy loss

Early miscarriage has been associated with

increased LH [30] and increased T [31] levels

(both of which are in turn associated with PCOS).

Figure 4. MRI of polycystic ovaries (arrows) in a 37-year-old woman.

Figure 5. Transvaginal image of a multifollicularovary.




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The prevalence of early pregnancy loss ranges

from 2040% [32, 33] in women with PCOS

following treatment for anovulation. Studies have

shown a clear relationship between the raised

serum LH level often found in women with PCOS

and early pregnancy loss [34]. Because of the

presumed link between PCOS and early preg-

nancy loss in induced cycles, the relationship

between PCO and early miscarriage in women

with spontaneous ovulatory cycles was studied in56 women with three or more miscarriages. This

study showed that 82% of women had ultrasound

appearances of PCO [33]. However, a recent study

found no increase in miscarriage rate in women

with polycystic ovary morphology and a history

of early embryo loss compared with women with

the same history but normal ovarian morphology

on ultrasound [35].

Are PCO present in post-menopausal

women?The clinical diagnosis of PCOS is convention-

ally restricted to pre-menopausal women; con-

versely, histopathologists do not usually identify

PCO in post-menopausal women. However, in a

cross-sectional study of 18 post-menopausal

volunteer women and 94 post-menopausal women

who had undergone coronary angiography,

Birdsall and Farquhar [36] identified PCO in 8/18

of the volunteer group and 35/94 women in the

angiography group. Moreover, the women with

PCO had increased serum concentrations of T, a

feature of PCO in young women. The results ofthis study raise the possibility that the morpho-

logical and endocrine features of PCOS may not

resolve at the time of the menopause and thus

highlight the need for long-term longitudinal data.

PCO in asymptomatic women

PCO are not confined to women with the

classical symptoms of the syndrome described by

Stein and Leventhal [1]. On the contrary, with the

advent of TVS, PCO are commonly seen in

asymptomatic women. In a study of hospital staff

volunteers using TA ultrasound, the prevalence of

PCO was 23% [6]. Three further studies have

shown a prevalence of between 16% and 33%

[5, 37, 38]. At present, however, the clinical

significance of PCO in asymptomatic women is

unclear, although there is evidence of biochemical

abnormalities in these women similar to those

present in PCOS, but to a lesser degree. In 1977,

Carmina et al [39] reported LH and androgenlevels between those found in normal subjects and

those found in patients with PCOS. Similarly, we

found a linear trend in ultrasound and endocrine

variables from controls through PCO to PCOS

[40].

The relationship between ovarian morphology

and symptomatology is further complicated by

the assertion that some women with classical

symptoms of PCOS may have normal ovaries on

ultrasound. One study of five women with clinical

features of PCOS and cystic ovaries and five

women with clinical features of PCOS and normal

ovaries on TVS reported no significant endocrine

differences between the two groups [41].

Although obesity was included in the original

description of the syndrome [1], not all women

with PCOS are obese. Obesity itself can lead to

many changes ascribed to PCOS, thus it may be

possible that obesity unmasks or even potentiates

the endocrine changes of asymptomatic women

with PCO to PCOS.

The unilateral polycystic ovaryThe development of TVS has also identified a

small group of women with one polycystic ovary

in whom the contralateral ovary can be clearly

visualized and appears normal. In 1999, in an

observational study of 16 women with unilateral

PCO and 20 women with bilateral PCO, Battaglia

and co-workers [42] reported that the women in

the latter group had higher concentrations of

androstenedione and LH to FSH ratios. Further-

more, in women with unilateral PCO, grey scale

and Doppler ultrasound showed different features

in the affected and the unaffected ovary, similarto the appearance of the polycystic and the

normal ovary, respectively [42].

Figure 6. Pelvic venous congestion in a young womanwith polycystic ovary syndrome (for details see text).




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Wider health implications of PCOS

PCOS is common among women of reproduc-

tive age and in clinical practice these women are

seen for three major reasons: infertility (74%),

menstrual irregularity (66%) and androgen excess

(48%). PCOS should no longer be considered a

purely gynaecological condition, as many of thesewomen may be at an increased risk of cardio-

vascular disease in later life [4345] owing to the

associated risk factors of obesity, insulin resis-

tance, hypertension and altered lipid profiles often

observed in these women [46]. Using risk model

analysis, Dahlgren et al [45] has estimated a 7.4-

fold increase in mortality, however in the only

follow-up study cardiovascular mortality was not

increased [47]. The reason for this discrepancy is

unknown, but it has been suggested that protec-

tive mechanisms may be operative or that this

cohort was in some way not representative of the

general population with PCO.

Haemodynamic changes have also been reported

in women with PCOS. Prelevic et al reported

lower flow over the aortic arch [48], higher rest-

ing forearm flow during reactive hyperaemia and

lower incremental forearm flow [49] in PCOS than

in age-matched control women. In a study using

Doppler ultrasound, we found reduced PI and

back-pressure (a better indicator of interpreting

the PI in low impedance vascular beds such as

the cerebral circulation [50, 51]), suggestive of

reduced vascular tone in the internal carotid

artery in women with PCOS and PCO comparedwith young healthy controls. These differences

were independent of blood pressure, insulin resis-

tance and other endocrine and metabolic factors

[40]. In a subsequent study we reported a para-

doxical constrictor response to 5% carbon dioxide

(a known cerebrovasodilator) in the internal car-

otid artery in women with PCOS compared with

women with normal ovaries [51]. We are currently

investigating the possibility that this represents an

abnormality in endothelial function in women

with PCO. Interestingly, Lees et al [52] reported a

constrictor response to transdermal glyceryl tri-nitrate (a potent vasodilator), which acts through

the endothelial nitric oxide system in women with

PCO. The clinical significance of these changes in

the cerebral circulation requires further inves-

tigation, but they are indicative of widespread

changes in cardiovascular function in these women,

which may influence morbidity and mortality.

Although it is not quite clear whether the

estimated risk of health problems in women with

PCOS actually translate into long-term morbidity

and/or mortality, asymptomatic women with

PCO must indeed have an increased likelihoodof adverse health outcomes as a result of their

PCO status. As clinicians it is ethical to advise

and suggest that women with PCO/PCOS (espe-

cially the obese ones) lose weight and adopt

healthy life-style practices that could reduce their

risk of developing hypertension, non-insulin

dependent diabetes mellitus (NIDDM) and the

associated cardiovascular consequences.

Conclusion

The ultrasound criteria for diagnosing PCO

have evolved from simply increased dimensions to

the recognition of a characteristic follicular pattern

and textural changes in the ovarian stroma.

3D ultrasound, together with pulsed and colour/

power Doppler ultrasound, have also been used to

visualize PCO, but their clinical role is not yet

established. Using TVS scanning and applying

strict criteria, the prevalence of PCO in the female

population is at least 20%, although only betweenone-quarter and one-half of these women have the

classic symptoms of the syndrome. The signifi-

cance of this finding in asymptomatic women is

currently under investigation. Women with clin-

ical features of the syndrome are at increased risk

of developing NIDDM, but concerns about

cardiovascular risks have not yet been clearly

confirmed. Ultrasound is also being used to

identify systemic haemodynamic changes in these

women, but the clinical significance of these

changes and the mechanisms responsible have

yet to be established.

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review article - polycystic ovaries

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