Management of adnexal masses in pregnancy

2017 TOG

Introduction

Adnexal masses in pregnancy are common, with a prevalence
of 0.19–8.8%. The incidence of ovarian malignancy is 1 in 1500–32 000 pregnancies.

Clinically significant adnexal masses in pregnancy

Corpus luteal cyst
Corpus luteal cysts produce progesterone and support
pregnancy in the early first trimester.

Usually, they
spontaneously regress by the 8th week of pregnancy
when the placenta takes over progesterone production.

These cysts are highly vascular and
prone to spontaneous haemorrhage or rupture.

Persistent
corpus luteal cysts may appear like simple cysts later in
pregnancy and will disappear during follow-up.

Follicular cyst
A physiologically mature follicle is typically less than 2 cm in
diameter.

Failure of involution, or failure of a mature follicle to spontaneously rupture, results in a follicular cyst, which is usually 2.5–6 cm in diameter.

typically resolves before 16 weeks of gestation.

Haemorrhagic cyst

Acute haemorrhage into an ovarian cyst presents as sudden abdominal pain, which usually resolves within a few days.

In clinically stable women, this is best managed conservatively with simple analgesia.

Haemorrhagic cysts are usually benign but have varied sonographic appearances, and may be
difficult to distinguish from malignant lesions.

The presence of a clot, for example, may be confused for a solid nodule. Colour Doppler will show no vascularity within the clot, whereas blood flow may be evident in a solid or papillary lesion (Figure 2).

Hyperstimulated ovaries

Bilateral enlarged ovaries may be part of ovarian
hyperstimulation syndrome (OHSS).

In conventional in vitro fertilisation, mild OHSS affects approximately one-third of cycles, while the combined incidence of moderate or severe OHSS varies from 3.1 to 8%.

In severe cases, the ovaries may be enlarged to greater than 12 cm, and as such
are at high risk of torsion and haemorrhage.

In most cases, OHSS is self-limiting and requires supportive management while awaiting resolution.

Cyst drainage is not normally recommended, and surgery is only indicated in women with
associated adnexal torsion or ovarian rupture.
Hyper stimulated ovaries are highly vascular and liable to damage on handling

Hyperreactio luteinalis
The sonographic appearance of ovaries with this condition is
similar to that seen in hyper stimulated ovaries.

This results from an exaggerated response to circulating levels of beta human chorionic gonadotrophin in the absence of ovulation induction.

Maternal virilisation may occur in 14–25% of cases.

Luteoma of pregnancy
This is a rare and benign condition in which luteinised stroma cells replace the ovarian parenchyma.

These cells produce androgens causing maternal virilisation in 25–30% of cases.

When maternal virilisation occurs, there is a 50% risk of virilisation of a female fetus.

Heterotopic pregnancy

This is a rare event in pregnancy, but in assisted reproductive techniques have a 1–2% risk of heterotopic pregnancy.

There should be a high index of suspicion in patients with an adnexal mass (Figure 3).

Mature cystic teratoma (dermoid cyst)

Dermoid cysts are the most common adnexal cystic lesions diagnosed after 16 weeks of gestation.

Dermoid cysts less than 6 cm in diameter are generally asymptomatic in pregnancy.

Dermoid cysts greater than 6 cm are prone to torsion.

In their review, Yen et al. suggest the risk of torsion to be about 27%.

Where ultrasound scans reveal indeterminate lesions, magnetic resonance imaging (MRI) is useful for
identifying features that suggest ‘fat content’, which are typical of a mature dermoid cyst (Fig4,Fig 5).

Malignant germ cell tumours

With the exclusion of borderline or low malignant potential
ovarian tumours, these account for about 38% of invasive ovarian tumours in pregnancy.

Dysgerminomas are the most common and have a good prognosis.

They are sensitive to chemotherapy and radiotherapy,

should be discussed as part of the patient plan in the cancer multidisciplinary team (MDT) meeting.
Borderline or low malignant potential masses
Borderline or low malignant potential (LMP) masses are
usually cystic lesions with malignant cytological features, but without invasion of the ovarian stroma.

In pregnancy, most LMPs are either mucinous or serous epithelial tumours.
The ovarian ‘crescent sign’ seen in ultrasound imaging refers to a rim of normal ovarian tissue adjacent to the lesion.

helpful sign in excluding invasive ovarian cancer, but does not exclude an LMP lesion.

Pelvic inflammatory disease
Pelvic inflammatory disease (PID) is rare in pregnancy.

The thick cervical mucus formed in pregnancy is thought to act as an effective mechanical barrier against ascending infection.

Pelvic infection can arise from ascending infection; from infection of an ovarian cyst, ovarian endometrioma or hydrosalpinx; or a superimposed infection of necrotic tissue (e.g. from adnexal torsion).

An ovarian abscess is a recognised complication of transvaginal oocyte retrieval and
transcervical embryo transfer.

A confined abscess usually presents with an indolent onset of abdominal pain and
swinging pyrexia. A woman with a ruptured abscess will usually have features of diffuse peritonitis, although this can be masked in pregnancy.

Acute PID in pregnancy is managed in a similar way as in nonpregnant women. doxycycline (a tetracycline) is contraindicated beyond the
15th week of gestation because it causes tooth and bone discolouration and inhibits bone growth.

Inadvertent use of tetracyclines in the first trimester is not associated with an increased risk of congenital malformations .

Appendiceal mass

Acute appendicitis occurs in an estimated 1 in 1500 pregnancies. Appendicectomy is the most common non obstetric operative procedure in pregnant women.
The enlarging uterus causes displacement and lateral rotation of the caecum and appendix.

The appendix remains in the right iliac fossa
during the first trimester, moves to the pelvic brim during the second trimester, and reaches the lower right upper quadrant in the third trimester.

The change in position of the appendix, and the fact that pregnant women often have
nonspecific abdominal pain, can result in delayed diagnosis, which increases the incidence of appendiceal perforation and increased maternal and fetal morbidity and mortality.

An appendiceal mass is caused by a walled-off appendiceal
perforation and represents a pathological spectrum ranging
from phlegmon to an abscess.

Outside of pregnancy, an appendiceal mass is found in 2–6% of patients with acute appendicitis .

Assessment of adnexal masses

Ultrasound
Greyscale ultrasound scan remains the first-line imaging
tool for evaluating adnexa.

It is adequate for the
characterisation of ovarian masses and assessment of
tumour size.

It is as accurate as computed tomography
(CT) and MRI for the diagnosis of ovarian cancer, with a
sensitivity of 86–95% and a specificity of 68–90%.

Factors suggestive of malignancy include:

the presence of solid components within the cysts papillary projections >6 mm, a high colour score of blood flow detected within papillary projections

increasing size of mass during pregnancy (increase in size by 20% on subsequent
scan) presence of septations and free fluid extending beyond the pouch of Douglas.

It is also useful to determine whether a mass is intra-ovarian or extra-ovarian, as most extra-ovarian cystic masses are benign.

Three-dimensional ultrasound scan does not appear to significantly change the accuracy of diagnosis of ovarian malignancy.

Colour Doppler
This allows the assessment of tumour vascularity and can
help to differentiate between benign and malignant ovarian
masses.

Malignant lesions are typically more vascular, with
a decreased blood flow resistance and increased blood flow
velocity compared with benign cysts.
(IOTA) group recommend a
subjective assessment of colour Doppler blood flow, with
no flow representing a benign feature and strong flow a
malignant feature;

The combination of morphological features with Doppler
evaluation allows more accurate initial characterisation and differentiation of benign from malignant masses, with a pooled sensitivity of 86% and specificity of 91%.

The role of colour Doppler in assessing ovarian malignancy
in pregnancy is debatable, as the decreased vascular resistance
seen and attributed to angiogenesis in a tumour may be seen in
normal pregnancy ovarian physiology.

Magnetic resonance imaging and computerised
tomography scans

MRI appears to be safe in pregnancy, although the use of
gadolinium contrast medium, which is used to enhance
vascularity seen in malignant tissue, remains uncertain.

MRI is useful in the management of indeterminate masses
following an ultrasound scan and in cases of suspected
malignancy.

It is also able to better characterise tissue
composition (as in ovarian endometriomas), fat (as in
dermoid cysts of the ovary) and to assess metastasis.

It is expensive and is not readily available in some healthcare
systems.

The use of CT and MRI is superior to ultrasonography in the prediction of peritoneal and nodal
metastases in nonpregnant women.

In pregnancy, MRI is preferable to CT as it avoids radiation exposure.

However, CT is useful for assessing thoracic metastases and can be done with abdominal shielding

Tumour marker studies
Pregnancy may alter the serum levels of tumour markers making the interpretation of results in pregnancy difficult.

CA125

The serum titre of CA125 is raised in over 80% of women with epithelial ovarian cancer.

It is also produced in pregnancy by the decidua, which makes interpreting this
tumour marker test difficult.

The level of serum CA125 peaks in the first trimester and slowly declines with advancing
gestation.

A higher cut-off level of 112 U/ml to dictate the normal range has been suggested in pregnancy between 11 and 14 weeks of gestation.

In pregnancy, the evaluation of CA125 is still advised in the presence of a suspicious or
indeterminate adnexal mass – at least as a baseline test, but
also to highlight potential malignancy when the CA125
titre is grossly elevated.

Its serum level is also useful in monitoring treatment responses in women with known ovarian cancer.

Lactate dehydrogenase

Elevated serum titres are seen in cases of dysgerminoma.
Pregnancy does not seem to alter the lactate dehydrogenase

(LDH) serum level and, therefore, it remains a
useful tumour marker.

Alpha feto-protein and human chorionic
gonadotropin

Values of AFP and hcg marker tests may be raised in some germ cell tumours.

However, they are of limited use in
pregnancy as both are altered by pregnancy physiology, the most obvious is hCG

HE4
HE4 is a glycoprotein expressed by the epididymal epithelium.

Increased serum levels are seen in ovarian
cancer but also in mesothelioma, lung, endometrial, breast,
gastrointestinal, renal and transitional cell tumours.

HE4 is not increased in endometriosis and has fewer false-positive results with benign disease compared with CA125.

HE4 is thought to be more sensitive and specific than CA125 in distinguishing between benign and malignant ovarian masses.

The combination of CA125 and HE4 may also improve sensitivity from 73% to 76.4%.

The serum level of HE4 in pregnancy is lower than in the nonpregnant state.

Currently HE4 assays are not readily available in the UK

The RMI 1 tool combines the use of ultrasonographic features with CA125 and menopausal status.

It is particularly useful in the management of postmenopausal women with ovarian cysts.

It is of limited use in pregnancy, as CA125 can be elevated in normal pregnancy.

IIOTA tool is a model based on the morphological features of ovarian masses
identified with ultrasound examination.

It has a reported sensitivity of 95% and specificity of 91%.

Referral to the gynaecological oncology service is indicated in women with any of the M rules (Box 1).

Risk of Ovarian Malignancy Algorithm

The Risk of Ovarian Malignancy Algorithm (ROMA)
combines the results of HE4, CA125 and menopausal status
to generate a single numerical score correlating with the
likelihood of malignancy.

It classifies patients as being at low or high risk for malignant disease.

Its use is limited in pregnancy as the serum titre of CA125 and HE4 can vary significantly.

Management

Conservative management
Up to 76% of adnexal masses in pregnancy will be simple ovarian cysts of less than 5 cm in diameter.

These are often functional cysts that resolve spontaneously by 16 weeks of
gestation and require no follow-up in pregnancy.

A follow-up ultrasound scan should be offered for larger or complex cysts at around 14–16 weeks of gestation.

Intervention should be delayed until 14–16 weeks to allow spontaneous resolution of functional cysts and, more importantly, to prevent surgery on a luteal cyst that might be supporting the pregnancy.

Persistent ovarian or para ovarian simple cysts have a low risk of malignancy and can be
managed conservatively.

Complex adnexal masses, which on uss appear to be benign, such as ovarian
dermoid tumours, can be managed conservatively in the
absence of symptoms, although patients should be made aware of the increased risk of ovarian torsion in pregnancy

There is a patient-centred decision to be made between the risk of intervention and conservative management, based on size of the mass, morphology and the likely diagnosis.

Role of ultrasound-guided fine needle aspiration
There are a few small case series of the successful
management of simple ovarian cysts in pregnancy using
ultrasound-guided fine needle aspiration (FNA).

The procedure is well tolerated with few complications.

It requires no hospitalisation or general anaesthesia.

Cyst aspiration is useful in relieving acute pain and can reduce the risk of cyst torsion and rupture.

Cyst aspiration near term has been described when a large cyst is at risk of obstructing labour.

There is a high rate of cyst recurrence after the procedure (33–40%), and FNA may need to be repeated later in pregnancy.

Some authors consider FNA no better than placebo as many of these simple cysts resolve spontaneously
with time.

FNA is only suitable for simple cysts.

Role of surgery
Indications for surgery

Adnexal torsion
The estimated incidence of ovarian torsion in pregnancy is
1–5 in 10 000 pregnancies, and may be as high as 16% in pregnant women with OHSS.

It can occur at any time in pregnancy, but is more common in the first and early second
trimesters.

It can occur without an adnexal mass (torsion of a normal-sized ovary) in pregnancy.

The clinical presentation of adnexal torsion is similar in pregnant and nonpregnant women.

Acute abdominal pain is the most common symptom; there are similar rates of
nausea, vomiting, abdominal tenderness and signs of
peritoneal irritation in both groups.

Nausea and vomiting may be present in up to 85% of cases of ovarian torsion.
However, pregnant women are more likely to present earlier following the onset of acute pain.

They are twice as likely to have recurrent ovarian torsion compared to nonpregnant
women.

The WBC in pregnant women is often mildly elevated.

CRP is a nonspecific marker that is raised in most tissue injuries, including
infarction, haemorrhage and infection.

The CRP value starts to rise 6–8 hours after the onset of torsion and peaks at 24–72 hours.

It has a very limited role in the early disease
process, therefore clinical assessment and a high index of suspicion is important.

Ultrasound can aid diagnosis by identifying a tender mass that has a thickened and
oedematous capsule with a bland and often avascular centre.

Once a diagnosis is made then surgery should immediately follow ideally, laparoscopy with adnexal detorsion, aspiration of an ovarian cyst, ovarian cystectomy
or salpingo-oophorectomy.

Prompt surgery allows adnexal detorsion to revascularise and preserve the ovary.

Other surgical aims include reducing the size of the ovary to lower the risk of torsion recurrence.

In many cases the ovary may be ischaemic, friable and oedematous, so the simple puncture
and drainage of the ovarian cyst may suffice to treat acute pain with minimum risk to the pregnancy.

In cases of obvious necrosis with no revascularisation after detorsion, unilateral salpingo-oophorectomy may be required.

Suspected malignant mass
The majority of such lesions are either borderline or early
stage disease (FIGO stage IA) with a good prognosis. Non epithelial tumours (germ-cell and sex-cord) and epithelial ovarian cancers are the most frequently diagnosed invasive ovarian cancers.

investigations include an MRI scan of the abdomen, chest and pelvis.

MRI is clearly preferable, but it is an extensive procedure for the patient to endure.

The MRI team must be mindful of the risk of
pregnant women lying supine for long periods and the risk of the pregnant uterus compromising venous return.

A protocol, including a support ‘wedge’ to ensure a left
lateral tilt of the abdomen and an appreciation of the
difficulties of a pregnant woman undergoing a long
procedure, must be in place.

A chest X-ray or chest CT with abdominal shielding is an alternative to a chest MRI.

The gynaecological cancer MDT should discuss these tests to
plan management, bearing in mind the woman’s age, gestation, parity, desire for fertility and – importantly – the stage of the disease.
Women in the late second or third
trimester may consider early delivery by caesarean section at the time of surgery.

However, some chemotherapy protocols are safe in the second and third trimester.

Primary surgery can be limited to unilateral salpingo oophorectomy and surgical staging (cytology, omentectomy, peritoneal biopsy, and appendicectomy if it is abnormal).

Restaging, including CT imaging or laparoscopic assessment, should be undertaken after delivery for invasive epithelial type tumours because extra-ovarian disease may not have been adequately assessed during pregnancy surgery.

Surgical approach

Laparoscopy has evolved and is now considered safe in pregnancy.

A randomised control trial demonstrated less blood loss, improved visualisation of pelvic organs and a reduced risk of uterine irritability in laparoscopy compared with laparotomy.

These relate to the risks of hypercarbia
causing fetal acid-base disturbance and the risk of reduced
uterine blood flow, which may reduce placental flow
following pneumoperitoneum.

However, studies have revealed that pneumoperitoneum does not modify human uteroplacental flow.

There is no difference in intrauterine fetal growth restriction or stillbirth rates between laparoscopy
and laparotomy-managed cases.

There is no adverse fetal outcome when laparoscopy is performed with
pneumoperitoneum of 12–15 mmHg intra-abdominal pressure.

There is the potential risk of injury to the uterus during insertion of the primary port or the Veress
needle.

Alternative entry techniques such as the Hasson’s and
Palmer’s entry point may be considered, especially when
surgery is performed in the second trimester.

As such, a laparoscopic approach becomes increasingly more
difficult from about 12 weeks of gestation to almost impractical in the third trimester.

Laparotomy may be preferred to minimise inadvertent cyst rupture, tumour
cell dissemination and port site metastases when malignancy is suspected.

If a patient requires a
laparotomy then the site of incision may change with
gestation, from suprapubic transverse or lower midline in
the first trimester, to lower and upper midline or para midline on the side of the mass in later pregnancy.

Clearly, if a laparotomy is planned in the third trimester, then
delivery of the baby by caesarean section in the same operation should be considered (Figure 7)