Few words on “Ovarian Volumes in
asymptomatic clinically normal Indian women”
Dr Srimanta
Kumar Pal.
The human ovary is a dynamic organ which continually changes
in size and activity through life, as an integral part of the changes that the
female is going through before during and after her reproductive life.
Following the rapid increase in the use of transvaginal scan in recent years,
the measurement of ovarian volume has become quick, accurate and
cost-effective. Ovarian volume is an
important tool in the screening, diagnosis and monitoring the treatment of
conditions such as benign cysts, endometriomata, polycystic ovarian syndrome,
ovarian cancer and adolescent abnormalities and excessive response to ovarian
stimulation protocols which some time lead to life threatening
complications like OHSS.
The imaging
science has made a monumental progress in last three decades. Medical fraternity have therefore very
rightly utilized sonography as one the important and reliable tool in diagnosis
of many of the diseases of abdominal
organs and abnormalities of other soft tissues of body like breasts, thyroid, scrotum
and the like. Being a noninvasive procedure and more so without exposing the
patient to any harmful effect like
radiation hazards this modality of investigation have uncarpeted a new
avenue for diagnosis of different diseases
and syndromes of many gynecological diseases in addition to long term
follow up of some tumours and neoplastic diseases of gonads .
We are aware
that there is exponential rise of ovarian volume from prepubertal period to
third decades of life. Thereafter as
number of nongrowing follicles decrease with advancement of age the volume of
ovaries decreases at a slow pace. In the following study we have tried to establish nomogram of ovarian volume in
healthy asymtomatic women between the age group 14 year to 70 yrs of age so
that any variation from the norm is picked up and further evaluated. There
have been almost similar studies where ovarian volume was assessed relationship of ovarian
volume in relation to age, height, and
weight in women undergoing transvaginal sonography.
So far as ovarian diseases are concerned many
endocrine (polycystic ovarian diseases) , functional ( follicular cyst) ,
beningn and malignant diseases of ovaries
exhibit some volumetric aberrations and any deviation from
the nomogram will alert the concerned clinician about some pathological
changes, .
In addition
to abovementioned syndromes some other uncommon diseases also exhibit an
increase or decrease in volumes of ovaries. Such syndromes which yield altered
ovarian volumes are a) women with diminished ovarian reserve b) premenopausal
and menopausal ovaries c) estimation of
NGF (nongrowing follicles) from ovarian volume d) primary amenorrhoea like
Turners syndrome e) Ovarian hyperstimulation Syndrome (OHSS). It is therefore
felt necessary to have a nomogram or population based reference range of
ovarian volume across the ages amongst Indian women. To our knowledge ours study is the first kind of such survey in
asymtomatic women in our country.
For reasons not clear to us the there are very few publications on ovarian volume in
the recent past though such volumetric studies were assessed by dozen of
investigators in last century. In fact there were about a dozen studies on
estimation of ovarian volumes amongst healthy fertile non-polycystic ovary
women in their reproductive life. Such studies were done by dozen of
investigators like Lass and Brinsden, Andolf
et al, Granberg, et al, Christensen et
al, Pavlik et al .
The normal volumes of ovaries across the
decades of a woman have also been duly assed and charted by Pache et al,
1992 and Cohen et al .
. The aim of present study too was aimed at to determine
the relationship of ovarian volume with age, height, and weight of asymptomatic
healthy women, who consented for such estimations. In our study we estimated
volumes of ovaries by
. Measuring each ovary in three dimensions, and ovarian
volume was calculated using the prolate ellipsoid formula (L x H x W x 0.523).
Mean ovarian volume according to age was calculated for each decade of life.
In all previous studies done abroad it was observed that mean
ovarian volume was 6.6 +/- 0.19 cm in
women less than 30 years of age; 6.1 +/- 0.06 cm in women 30-39 yers of age ; 4.8 +/- 0.03 cm
in women 40-49; 2.6 +/- 0.01 cm3 in women 50-59; 2. 1 +/- 0.01 cm3
in women 60-69; and 1.8 +/- 0.08 cm in women >/=70. Mean ovarian volume was 4.9
+/- 0.03 cm in premenopausal women and 2.2 +/- 0.01 cm in
postmenopausal women (P < 0.001). Lass and Brinsden concluded that there is a statistically
significant decrease in ovarian volume with each decade of life from age 30 to
age 70. Mean ovarian volume in premenopausal women is significantly greater
than that in postmenopausal women. The upper limit of normal for ovarian volume
is 20 cm in premenopausal women and 10 cm3 in
postmenopausal women.
The overall information received from
studies mentioned above boiled down to
the fact that normal ovarian
volume in the menstruating females is 5-15 cc, with an approximate mean of
10 cc. However,
measurements as high as 22 cc have
been reported in normal ovaries.
Each weighs between 5-8 g. The volume
in cc is roughly equal to the grams in weight. This review summarizes the current available data in
the literature on ovarian volume in the different stages in the life of a
healthy asymtomatic female.
. Normal ovarian volume in the menstruating females is
5-15 cc, with an approximate mean of 10 cc; however, measurements as high as 22
cc have been reported in normal
ovaries. Each weighs between 5-8 g. The volume in cc is roughly equal to the grams in weight +/-
0.01 cm(3) in women 60-69; and 1.8 +/- 0.08 cm(3) in women >/=70. In the
study carried ut by Ahmed et al 8 the mean ovarian volume in premenopausal women was like
previous foreign studies but the volume of ovaries amongst Indian women were
significantly greater than that in postmenopausal women of foreign countries8.
The upper limit of normal for ovarian
volume, according to
Ahmed et al was 20 cm in premenopausal women and 10 cm
in postmenopausal women.
|
The
issue of intraobserver & interobserver variations: in estimating Ovarian
volume -In the present study for every women who were
assessed for ovation volumes estimation both the first author (JP) and the
third author(S K P) did the evaluation
in each case but separately
at a single institution and each author
was blind about the estimations made by the other
coworker. Relevance of such interobserver
analysis in estimation of ovarian volumes
were highlighted by other
workers9. The
issue of 3-D sonography for accuracy: in estimating Ovarian volume - Three dimensional sonography of
ovaries were not carried out in this study. Whatever informations on ovarian
volumes were collected in the present study from the age groups of 14 years
to 70 years were done by Wipro GE Versana
Pro machine which is essentially 2-D machine . But some researchers
have time and again paid importance on the relevance of 3 D imaging so far as
estimation of ovarian volume was concerned. Such 3-D imaging have been stressed by some
authors |
The issue
of endovaginal sonography in estimating Ovarian volume -- Some
researchers have claimed the superiority of transvaginal route for assessing
volumes of ovaries. In the present study we used both the methods as when
written consent was available. In our hands there were no such difference
between TAS (transabdominal route of sonography) vs TVS (transvaginal route of
sonography).
The issue
of automated volume estimation of ovaries: : in estimating Ovarian volume VOCAL methodology of estimating ovarian volume is preferred by some
researchers18
.Automation
in measuring ovarian volume is however rarely warranted. But to us it becomes
sensible to be acquanatied with VOCAL program
which warrants that the observer
should manually define the
contour of the ovary while the dataset
is rotated through 180 degree.
Raine-Fenning et al compared
the two techniques and observed that that measurements with VOCAL
program are superior to conventional , through some researchers have mentioned that either way of estimation of volumes of
ovaries were comparable .
.Raine-Fenning et al compared the two
techniques and found that measurements with VOCAL program
are superior to conventional USG. Few
researchers have gone further and claim that automated volume estimation is far
superior to 3-D USG
The issue
of sonography in CHILDREN & ADOLESCENTS: in estimating Ovarian
volume -
Like all other organs of body there are some
coordinated developmental changes that take place around the genital organs. .
The prepubertal uterus is thin, with a fundus equal in size to the cervix.
Owing to the hormonal stimulation of puberty, the uterus enlarges and the
fundus becomes prominent. The ovaries which are demonstrated with
ultrasonography (USG) at all ages now with release of pulsatile gonadototrophin
ovarian volume start increasing after 6 years of age. Microcystic follicles are
normally seen throughout childhood. USG is the modality of choice for imaging
the pediatric female pelvis.
.
Though very
uncommon but still precocious puberty of
Issosexual type are heralded by the enlargement of ovaries due to premature
activation of hypothalamo hypophyseal axis. A nomogram of ovarian volume at
this age say 5 -8 yrs will be of immense help to pick up such rare disorders in
addition to demonstration raised basal gonadotrophins Ovaries of such age group have been plotted
against the age group by Maciej Mazgaj24.
Polycystic
ovarian syndrome (PCO) and relevance of
ovarian volumes”:-The polycystic ovarian syndrome was initially based on
the diagnosis of ovarian volumes, abnormal hair growth and Oligomenorrhoea and
subfertility. There have been many amendments, consensus opinions,
recommendations by different task forces and positional and positional
statements of digamous and treatement of PCOS . Ovarian volume is an
important parameter in diagnosing polycystic
ovarian syndrome. When the volume of any one the ovary exceeds 10 ml then there will be always a suspicion of
having polycystic ovarian syndrome (PCO). The other morphological features of
so called PCO are 1) peripheral
arrangement of small follicles each
measuring 2 mm 10 mm in diameter
numbering more than 12 per ovary and echogenic stroma. The typical ring like
arrangement of atretic follicles in the outer part of ovaries is often termed
as necklace sign
Though many
morphological characteristics of ovary have been included in the definition,
diagnosis and long term prognostication of PCO still volume of ovaries remain an important parameter of diagnosing PCO.
As our study was limited to healthy asymptomatic women therefore we didn’t
include PCO women who mainly present with subfertility and menstrual disorders.
However , where there were incidental morphological appearances of ovaries like increased echogenecity,
excess number of follicles then we immediately excluded those asymtomatic
fertile women from our study because we know that not all PCO women have
menstrual disorders neither all ate infertile.
However it
is fair to remember for us that an ovarian volume was
11 mL in PCOS women and 5.75 mL in controls are normal .The volumes ovaries in cases of polycystic
ovaries have been discussed in detail by many authors,
Ovarian volume and diagnosis of
premature ovarian failure: We are aware of the
fact that the ovaries are full of thousands of non- growing follicles
which are often termed as “NGF” by
reproductive physicians .These lie in dormant state but do contribute significantly to volumes of ovaries .Diminished ovarian reserve is
defined as reduced capacity
of the ovaries to
produce oocytes or the oocytes produced are of poorer quality leading to the
formation of poor quality
embryos. The most severe form of DOR can be represented clinically as premature ovarian failure (POF) . The condition may result from disease or injury, but
most commonly occurs as a result of normal aging..
A
small volume ovary in childbearing age will usually but not always speak of
diminished ovarian reserve . Not only low per centile of ovarian volume but a
low Antral Follicular Count (AFC) will support the diagnosis of premature
ovarian follicle. There are some recognized
serum markers of dwindling ovarian reserve. Such markers are low anti
Mullerian hormone (AMH),) and high basal follicular Stimulating hormone .
Ovarian volume has an important predictive value in prevention and also in diagnosis of OHSS. If ovarian volumes are high enough then
ovarian stimulation protocol should be
cautiously planned by an
experienced reproductive physician lest there can be ovarian hyperstimulation
syndrome which is an life threatening condition (OHSS). Prediction of OHSS in most cases can be made by prior
estimation of ovarian volumes.
In addition to diagnosing PCO and
premature ovarian failure as mentioned above
there are other important indication of estimation of ovarian
volume such as different kinds of beningn and malignant cysts of ovaries. In
such cases not only follicular diameters are important as a follow up
protocol but serial estimation of volumetric enlargement is also relevant
. Ovarian cystic masses include a spectrum of benign,
borderline and high grade malignant neoplasms. Imaging plays a crucial role in
characterization and pretreatment planning of incidentally detected or
suspected adnexal masses, as diagnosis of ovarian malignancy at an early stage
is correlated with a better prognosis. Knowledge of differential diagnosis,
imaging features, management trends and an algorithmic approach of such lesions
is important for optimal clinical management. This article illustrates a
multi-modality approach in the diagnosis of a spectrum of ovarian cystic masses
and also proposes an algorithmic approach for the diagnosis of these lesions
Ovarian
cysts may be of various etiologies. Such
ovarian cysts do commonly have an effect on ovarian volume and planned imaging
of ovarian volume is an important tool in follow up of different kinds of
ovarian cysts. Though presence of functional cysts do alter the volume of
ovaries minimally still any slight
increase in ovarian volumes in an asymtomatic women will raise a
suspicion of presence of follicular or lutein cysts. As mentioned , presence of
any cyst in the ovary often warrant long
term follow up about progression or
regression of so called functional cysts.
.
Cysts in
ovary vary widely in etiology, from physiologic, to complex benign,
to neoplastic with internal echoes. An ovarian cyst which is < 1 cm
cysts is commonly seen in this age group and is considered clinically unimportant.
Ovarian cystic lesions constitute a spectrum from benign to malignant
pathology. Imaging can confidently characterize the majority of cystic lesions
as benign, thereby avoiding an aggressive surgical approach.
Anechoic
unilocular simple cysts (no septations or solid component) less than 5 cm in
diameter and seen on ultrasound have a very low malignant potential. Cysts more
than 1 cm and less than 7 cm should have a yearly follow up ultrasound to
document stability. If more than 7 cm,
either surgical evaluation or further imaging with MRI should be considered.
Any complex cystic mass demonstrating
thick, irregular septations and a solid component with or without intralesional
vascularity is mostly malignant and should undergo surgical evaluation. Some of
these patients may undergo CT or MRI imaging prior to surgery to define the
nature and extent of the disease and also as baseline study for post treatment
follow up . However, a fluid-fluid level and foci of calcification (posterior
acoustic shadowing) is likely to represent a dermoid/ possibly beningn
teratoma. In such fluid filed cases volumetric assement may not be diagnostic
about the nature of the tumour .For confirmation of any such so called
functional cyst serum tumour markers are of immense help as is CT or MRI which
hopefully will confirm the diagnosis .
Coming back to the issue of dermoids which exhibits the presence of fat and it
is also necessary to evaluate the extent of the lesion (as many dermoids with
calcification can represent just the tip of iceberg) and all such reports like
ovarian imaging, MRI and serum tumour markers taken together should formulate a
standard treatement plan as applicable for a given case. Incidentally, a
detected lesion on CT with foci of fat attenuation, fat-fluid level and
calcification is diagnostic of a dermoid. .
Sonographic
complex cystic lesions will certainly alter the volume of the ovary in the
affected side. Complex cysts with solid components and/or mural nodules and/or
thickened irregular septa remains a concern for a malignant neoplastic process and surgical evaluation or imaging
with contrast enhanced MRI is recommended for characterization and evaluation
of the extent of the disease .
Those
ovarian lesions that remain indeterminate can be closely followed or surgically
resected with a relatively conservative approach. Imaging cases of ovarian malignant
lesions can not only raise a high diagnostic concern but it can also evaluate
the extent of disease, thereby guiding appropriate treatment planning.,
Quantification
of the risk of malignancy of ovarian cysts or tumours as imaged based on the Simple Rules has good diagnostic performance both
in oncology centres and other centres. A simple classification based on these
risk estimates may form the basis of a clinical management system. Patients
with a high risk may benefit from surgery by a gynecological oncologist, while
patients with a lower risk may be managed locally. Over the years, researchers have
developed different models to accurately characterize adnexal masses as benign
or malignant preoperatively. A recent meta-analysis confirmed that the International Ovarian
Tumor Analysis (IOTA)
algorithms such as the Simple Rules are very effective to
preoperatively classify adnexal masses as benign or malignant.
Ultrasound
has always been pivotal in diagnosing pelvic masses and can fairly differentiate
cystic vs solid lesions provide accurate assessment of size, follow changes in
appearance, and assess vascular supply and flow. The International Ovarian Tumor Analysis (IOTA)
algorithms framed a “Simple Rules from the International Ovarian
Tumor Analysis” to differentiate benign vs malignant adnexal masses. Clinicians
have incorporated such simple rules in practice and the Royal College of
Obstetricians and Gynacologists in the United Kingdom has included the Simple
Rules in their Green Top guideline on the assessment and management of ovarian
masses in premenopausal women .
A recent study
published in the American Journal of Obstetrics and Gynecology April, 2016
issue aims to develop and validate a model based on IOTA Simple Rules to estimate
the risk of malignancy in adnexal masses. The 12 variables
used in predicting low risk of ovarian cancer (LR1) were: (1) personal history of ovarian cancer;
(2) current hormonal therapy; (3) age of the patient; (4) maximum diameter of
the lesion; (5) pain during examination; (6) ascites; (7) blood flow within a
solid papillary projection; (8) a purely solid tumor; (9) the maximum diameter
of the solid component; (10) irregular internal cyst walls; (11) acoustic
shadows; and (12) color score.
A
simple unilocular cyst was most predictive of a benign tumor, while presence of
ascites was most predictive of malignancy and (irregular multilocular-solid
tumor with largest diameter ≥100 mm) was least predictive. When an ovarian mass
is detected on clinical examination, the risk of malignancy at an oncology
center is 48.7% and 27.5% for patients at other centers. After sonography
if more of M-features(malignant features) than B-features(benign features) were present the risk of malignancy was 42%
and was at most 0.29% when ≥2 B-features and no M-features were present. Based
on these findings a simple classification of adnexal masses can be used in
clinical practice to determine the risk of malignancy for an individual patient
and her management subsequently.
Over the years’ various mathematical models
based on clinical and pathological markers are being used to aid in clinical
decision making. In 2014 a metaanalysis by Kaijser Jet al
confirmed the superiority of IOTA simple rules and
5 simple rules to suggest benign tumor (B-rules):
(1) Unilocular cyst;
(2) Presence of solid components
where the largest solid component is < 7 mm in largest diameter;
(3) Acoustic shadows;
(4) Smooth multilocular tumor less
than 100 mm in largest diameter; and
(5) No detectable blood flow on
Doppler examination.
5 simple rules to predict malignancy (M-rules):
(1) Irregular solid tumor;
(2) Ascites;
(3) at least four papillary
structures;
(4) irregular multilocular-solid
tumor with a largest diameter of at least 100 mm; and
(5) Very high color content on color
Doppler examination.
The cancer antigen-125 is not one of the
variables in the Simple Rules, it is not included in the Simple
Rules risk classification and adding serum levels of CA 125 to the
Logistic regression model does not help us to discriminate between benign and
malignant adnexal masses. In phase 3 the model was validated and it seen that
it works well both in hands of oncologists as well as general gynaecology
practitioners. In low risk patients a ‘wait and watch’ policy could be adapted,
with close monitoring and avoiding unnecessary surgeries whereas in high risk
patients it leads to early diagnosis and improved survival .
There was an
international cross-sectional cohort study involving 22 oncology centers,
referral centers for ultrasonography, and general hospitals. We included
consecutive patients with an adnexal tumor who underwent a standardized
transvaginal ultrasound examination and were selected for surgery. Data on 5020
patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor
(B-features) and the 5 features indicative of malignancy (M-features) are based
on the presence of ascites, tumor morphology, and degree of vascularity at
ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal
mass (pathologist blinded to ultrasound findings). Logistic regression analysis
was used to estimate the risk of malignancy based on the 10 ultrasound features
and type of center. The diagnostic performance was evaluated by area under the
receiver operating characteristic curve, sensitivity, specificity, positive
likelihood ratio (LR+), negative likelihood ratio (LR–), positive predictive
value (PPV), negative predictive value (NPV), and calibration curves.
Estimation
of ovarian volume is very relevant in cases of menopausal women .The normal
ovary of a postmenopausal woman is a small structure (mean volume 1.25ml)
usually situated lateral to the uterine fundus and in close relation to the
internal iliac vein. .
But
the problem in imaging ovaries in this age group is that there are some
limitations of imaging ovaries in postmenopausal women.. In as many as 40% of
transvaginal ultrasound (TVS) examinations the ovary may not been
seen as typically they shrink with age and are sometimes very difficult to
locate . In some studies however researchers were able to able to localize
the ovaries in each case of postmenopausal women. ”. Nonvisibility of ovaries
by TVS raised a pragmatic approach of imaging ovaries and people were worried
about reliability of an annual screening examination in postmenopausal women.
The report however didn’t mention about inability of imaging ovaries by
abdominal route. In postmenopausal women there is an increased risk of a
pelvic mass malignancy. However one study showed that up
to 15% of asymptomatic postmenopausal women had cystic masses up to 3 cm in size 68. If followed for 6 months over half regress and approximately one fourth enlarge
and one fourth stay the
same in size. Clinical judgment in these
cases is needed to determine which patients may benefit
from surgery aspiration and cytology or observation . Serum CA 125 has only
a limited role because of
its poor sensitivity
and specificity . Signs
indicating the possibility of malignancy are enlargement , development of irregular solid areas
and ascites .
. For
this reason of nonvisibility of ovaries there was an study in the United
Kingdom which was named as “Collaborative Trial of Ovarian Cancer Screening
(UKCTOCS) and other screening trials.
The study group affirmed that the sonographer should always attempt to
visualize both ovaries as this provides the maximum assurance that an early
ovarian cancer. Here lies the relevance of this article. Our study however
could image all such postmenopausal cases
.Persistent
vs Regressing Masses : In the pre or
perimenopausal women a follow up examination may be indicated 6-8
weeks after the initial
sonographic finding, in those masses
though to be benign even though
some may persist up to 2-3
months. About 70 % of cysts in premenopausal women will
demonstrate regression in 2-3
months . If regression does not
take place , one should consider other
etiologies. Acute
enlargement can result from intraluminal hemorrhage and torsion.
. Asymptomatic postmenopausal women with ultrasound‐detected adnexal abnormalities with solid elements have a 1
in 22 risk for EOC. Despite the higher prevalence of Type II EOC, the risk of
borderline or Type I cancer in women with ultrasound abnormalities seems to be
higher than does the risk of Type II cancer. This has important immediate
implications for patients with incidental adnexal findings as well as for any
future ultrasound‐based
screening. There have been studies which
aimed at estimation of the risk of primary epithelial ovarian cancer
(EOC) and slow growing borderline or Type I and aggressive Type II
EOC(epithelial ovarian cancer) in
postmenopausal women with adnexal abnormalities on ultrasound. There was a
prospective cohort study in the ultrasound group of the UK Collaborative Trial
of Ovarian Cancer Screening of postmenopausal women with ultrasound‐detected abnormal adnexal (unilocular, multilocular,
unilocular solid and multilocular solid, solid) morphology on their first scan.
Women were followed up through the national cancer registries and by postal
questionnaires. Absolute risks of EOC and borderline, Type I and Type II EOC
within 3 years of initial scan were calculated. In such studies out of 48 053
women who underwent ultrasound examination and had complete scan data, 4367 had
abnormal adnexal morphology. The overall absolute risk of EOC associated with
abnormal adnexal morphology was 1.08% (95% CI, 0.79–1.43%); for borderline and
Type I it was 0.73% (95% CI, 0.5–1.03%); and for Type II it was 0.34% (95% CI, 0.33–0.79%)74.
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