WOMEN AND NEWBORN HEALTH SERVICE 9 ABNORMALITIES OF EARLY PREGNANCY

Transcription

WOMEN AND NEWBORN HEALTH SERVICE 9 ABNORMALITIES OF EARLY PREGNANCY
WOMEN AND NEWBORN HEALTH SERVICE
King Edward Memorial Hospital
CLINICAL GUIDELINES
SECTION C: GYNAECOLOGY GUIDELINES
9 ABNORMALITIES OF EARLY
PREGNANCY
Date Issued:
Date Revised: January 2010
Review Date: January 2013
Authorised by: OGCCU
Review Team: OGCCU
9.5.Hydatifdiform Mole
Section C
Clinical Guidelines
King Edward Memorial Hospital
Perth Western Australia
9.5 HYDATIDIFORM MOLE
BACKGROUND INFORMATION
Gestational trophoblastic disease (GTD) occurs in 1 in 750 pregnancies. 15% of patients will need
treatment for persistent trophoblastic tissue, and a further 3% will develop choriocarcinoma. GTD
results from abnormal proliferation of trophoblasts due abnormal regulatory mechanisms. Benign
forms of GTD include complete or partial hydatidiform moles, while malignant forms of GTD include
invasive hydatidiform moles, choriocarcinoma, placental site trophoblastic tumours and epithelioid
trophoblastic tumours.1
A hydatidiform mole is also known as a molar pregnancy. It affects 1-3 women in every 1000
pregnancies, and about 10% of hydatidiform moles will develop into one of the persistent forms of
GTD. Partial moles are generally triploid (XXY) with two sets of chromosomes from the paternal
component and a haploid set from the maternal genetic component.2 One of the histological findings
with partial moles is the presence of fetal or embryonic tissue.3 The complete mole usually has the
genetic material exclusively derived for the paternal DNA.2, and goes on to duplicate its chromosomes
with a 46XX karyotype with no identifiable embryonic or fetal tissue present.3
The volume and amount of trophoblastic proliferation in complete molar pregnancy generally exceeds
the growth shown in partial moles. This is reflected in clinical presentation, although the management
for both types is similar.4 Early complete molar pregnancies are often associated with ultrasound
diagnosis of delayed miscarriage or an anembryonic pregnancy. Ultrasound use is limited in detection
of a partial molar pregnancy.5 Diagnosis is sometimes only made by pathological examination after
surgical evacuation for a suspected incomplete abortion.6
After surgical evacuation of molar pregnancy follow-up with β hCG levels are required to detect if
levels have returned to normal, or in cases of developing neoplasia the levels will plateau or rise.1, 4
Most episodes of persistent sequelae after molar pregnancy occur within approximately 6 months of
evacuation.4
DIAGNOSIS
Diagnosis of complete or partial molar pregnancy is by:
 Clinical signs and symptoms
 Ultrasound examination
 Histological findings
 Blood tests findings - β hCG levels
DPMS
Ref: 8471
All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual
Page 1 of 6
CLINICAL SIGNS AND SYMPTOMS
May include:

Abnormal vaginal bleeding – watery brown vaginal bleeding resembling ‘prune juice’ is a sign
found in complete molar pregnancy. Discharge may contain ‘grapelike’ clusters of tissues7 With a
partial mole a missed or spontaneous miscarriage may occur.7

Hyperemesis gravidarum – occurs due to high circulating levels of oestrogen in complete molar
pregnancies, but is rarely seen in partial molar pregnancies.3
Hyperthyroid – significant hyperthyroidism can be associated with high β hCG levels.3 Signs of
women who present with hyperthyroid may include tachycardia, warm skin and mild tremors.7
Other signs and symptoms present may include:


Abnormal uterine size – excessive uterine size may be seen with extensive trophoblastic
proliferation in a complete molar pregnancy.3 The uterine size can be up to 50% larger than
expected for the gestation.4, 6 The uterine size may be small for gestation in a woman with a
partial mole.6

Fetal heart sounds – absent in complete molar pregnancy, but often present in a partial molar
pregnancy.6

Pregnancy induced hypertension – although uncommon it may present in the first half of the
pregnancy.4

Respiratory distress6

Anaemia6
ULTRASOUND EXAMINATION
Ultrasound examination may reveal:

A ‘snow-storm’ appearance on the scan. The molar tissue presents as a mixed echogenic pattern
which is produced by the presence of villi and intrauterine clots replacing the normal placental
image.6

Theca lutein cysts may be seen is 25-30% of women with a complete mole, but rarely for a partial
molar pregnancy.6 These cysts are associated with β hCG stimulation of the ovaries and may
take several months to resolve after molar evacuation.4

Ovarian enlargement more than 6 cm.4
HISTOLOGY EXAMINATION
BLOOD TESTS
β hCG levels are often markedly elevated in complete molar pregnancies, but significant increased
levels are less common with partial molar pregnancies.3
MANAGEMENT
See Clinical Guidelines, Section 9.1.2 Assessment in the Emergency Centre for initial assessment of
all women presenting for review.
A Consultant must be notified about all suspected or confirmed molar pregnancies.
INTIAL MANAGEMENT
Perform initial bloods tests for:
1.
 β hCG level4



Blood group and antibody screen4
full blood count4
Coagulation studies4
Date Issued:
Date Revised: January 2010
Review Date: January 2013
Written by:/Authorised by: OGCCU
Review Team: OGCCU
DPMS Ref: 8471
9.5 Hydatidiform Mole
Section C
Clinical Guidelines
King Edward Memorial Hospital
Perth Western Australia
All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual
Page 2 of 6
 U & E’s
 Renal and liver function tests4
 Thyroid function test
Order a Chest X-ray prior to surgery.4 This is performed to exclude pulmonary invasive mole.
2.
3.
Arrange surgical intervention with suction dilatation and curettage (D&C) Ultrasound guidance
may be clinically indicated. Routine repeat evacuation after diagnosis of molar pregnancy is
not necessary. Any surgery for incomplete evacuation is decided on an individual basis after
Consultant review.1
Avoid the use of oxytocic infusions until surgery has been completed. This reduces the risk of
causing trophoblastic embolism to the placental bed.1, 5 If there is significant haemorrhage
prior to the procedure the use of oxytocin is determined on an individual basis.5
Send all products of conception for histology examination.
Administer RhD immunoglobulin to Rh-negative patients after surgery.4
Register with the Oncology Unit if molar pregnancy is confirmed.
4.
5.
6.
7.
FOLLOW UP MANAGEMENT – COMPLETE HYDATIDIFORM MOLES (CHM)
1.
Weekly serum βHCG should be obtained until the levels are normal. Ideally the womans
serum βHCG should be performed at the same laboratory for the duration of the follow up as
different laboratories may utilise different ways of measuring the serum βHCG. Where the
womans general practitioner is responsible for monitoring their follow up, copies of the results
should be forwarded to the emergency centre / Oncology Unit at KEMH.
2.
If the hCG normalises within 8 weeks, no further testing is required.
3.
If the hCG takes longer than 8 weeks to return to normal, monitor the hCG monthly for 12
months.
4.
If the hCG rises > 10% or falls < 10%, the patient must be referred for an appointment at the
Oncology Clinic for consideration of adjuvant therapy.
5.
Send a discharge letter to the GP. Provide information of discharge, the follow-up
management and include management if the woman presents with a future pregnancy.
LONGER TERM MANAGEMENT
1.
Avoid the use of the OCP / HRT following molar evacuation until normal hCG values are
obtained.
2.
With subsequent pregnancies the patient should have and early ultrasound scan to confirm a
normal pregnancy.
Pregnancy should be avoided until after the completion of the surveillance period
In subsequent or future pregnancies the placenta should be sent to histopathology to be
examined for the presence of molar disease
3.
4.
5.
Check βhCG levels 6 weeks after any subsequent or future pregnancies regardless of that
pregnancy’s outcome to ensure there is no persistent trophoblastic activity.
FOLLOW UP MANAGEMENT – PARTIAL HYDATIDIFORM MOLE
1. Weekly serum βHCG should be obtained until normal levels are obtained. Once achieved
follow up can be discontinued.
Date Issued:
Date Revised: January 2010
Review Date: January 2013
Written by:/Authorised by: OGCCU
Review Team: OGCCU
DPMS Ref: 8471
9.5 Hydatidiform Mole
Section C
Clinical Guidelines
King Edward Memorial Hospital
Perth Western Australia
All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual
Page 3 of 6
COUNSELLING FOR THE PATIENT

Inform the patient the risk of reoccurrence for molar pregnancy is 1 in 55. Advise the patient
to present to the GP early if she should have any further pregnancies to arrange for an early
pregnancy ultrasound to confirm a normal intrauterine pregnancy.

Provide the woman with details of follow-up management plan and appointments to attend at
the Emergency Centre at KEMH or alternative arrangements where appropriate
MOLAR PREGNANCY INDICATIONS FOR CHEMOTHERAPY TREATMENT DURING
SURVEILLANCE
1. Brain, liver, GI metastases or lung metastases > 2cm on chest x-ray.
2. Histological evidence of choriocarcinoma
3. Heavy vaginal bleeding or gastrointestinal/ intraperitoneal bleeding.
4. Pulmonary, vulval or vaginal metastases unless the hCG level is falling.
5. rising hCG in two consecutive serum samples
6. hCG > 20,000IU / L more than 4 weeks after evacuation
7. hCG plateau in 3 consecutive serum samples
8. Raised hCG level 6 months after evacuation (even if falling)
FIGO INDICATIONS FOR CHEMOTHERAPY TREATMENT
1. hCG plateau of 4 values +/< 10% decline over at least 3 weeks; days 1,7,14 and 21
2. hCG increase of >10% or greater for three values or longer over at least 2 weeks.
3. The presence of histologic choriocarcinoma.
4. Any detectable serum hCG 4- 6 months after molar evacuation. The level of hCG plateau is to
be determined at the discretion of the treating physician.
5. Evidence of metastases.
INITIAL ASSESSMENT FOR WOMEN ADMITTED FOR CHEMOTHERAPY TREATMENT AFTER A
DOCUMENTED MOLAR PREGNANCY



Full history to include: details of the antecedent and all other pregnancies, LMP date,
evacuation date and method, OCP usage, bleeding and other symptoms particularly
respiratory and CNS.
Investigations: FBC, biochemistry, clotting, HIV, HBV serology, hCG serum levels are
measured twice a week during the treatment, group and save.
Doppler ultrasound of the pelvis to confirm disease presence and volume and to rule out the
possibility of a new pregnancy and chest x-ray.
For women admitted for treatment for presumed choriocarcinoma or PSTT

As above plus
o CT scan thorax, abdomen and pelvis (if the chest x-ray is negative)
o MRI brain scan (if pulmonary metastasis is present)
Date Issued:
Date Revised: January 2010
Review Date: January 2013
Written by:/Authorised by: OGCCU
Review Team: OGCCU
DPMS Ref: 8471
9.5 Hydatidiform Mole
Section C
Clinical Guidelines
King Edward Memorial Hospital
Perth Western Australia
All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual
Page 4 of 6
o
o
Diagnostic CSF hCG level (If pulmonary metastasis is present and the CT brain scan
is negative).
GFR prior to EP/ EMA or CNS EMA/ CO chemotherapy
PROGNOSTIC FACTORS AND TREATMENT GROUPS
There is a relationship between the level of elevation of hCG at presentation, the presence of distant
metastases and the reducing chances of cure with single agent chemotherapy.
FIGO (2000) staging / scoring
SCORES
0
< 39
AGE
Antecedent
pregnancy
Months from
index
pregnancy
Pre treatment
hCG(milli IU/mL)
Largest tumour
size
Site of
metastases
Number of
metastases
Previous
chemotherapy
1
> 39
2
-
4
-
Mole
Abortion
Term pregnancy
<4
4-6
7-12
> 12
< 103
103 - 104
104 - 105
> 105
-
3-4 cm
5cm
-
Lung
Spleen , kidney
Gastro intestinal
Brain , liver
0
1-4
5-8
>8
-
-
Single drug
Two or more drugs
-
From these parameters estimate the risk category and offer the woman initial therapy either with
single agent chemotherapy if their score is 6 or less or multi agent combination chemotherapy for
scores of seven and over (FIGO 2002).
0-6 low risk
> 7 high risk
CHEMOTHERAPY TREATMENT REGIME FOR TROPHOBLASTIC DISEASE (PROGNOSTIC
SCORE < 6)
Methotrexate / Folinic acid treatment schedule
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Methotrexate 50mg intramuscularly at noon
Folinic acid 15mg orally at 6pm
Methotrexate 50mg intramuscularly at noon
Folinic acid 15mg orally at 6pm
Methotrexate 50mg intramuscularly at noon
Folinic acid 15mg orally at 6pm
Methotrexate 50mg intramuscularly at noon
Folinic acid 15mg orally at 6pm
Repeat every 2 weeks, plus 2 cycles beyond a negative hCG
Date Issued:
Date Revised: January 2010
Review Date: January 2013
Written by:/Authorised by: OGCCU
Review Team: OGCCU
DPMS Ref: 8471
9.5 Hydatidiform Mole
Section C
Clinical Guidelines
King Edward Memorial Hospital
Perth Western Australia
All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual
Page 5 of 6
POST CHEMOTHERAPY FOLLOW UP


Review the woman 6 weeks after the completion of therapy.
At this visit
o Recheck the sites of original disease
o Doppler ultrasound of the pelvis
o Chest x-ray or CT / MRI if abnormal at presentation
o Advise on the need for contraception for 12 months
o Advise re the avoidance of excess sunlight exposure
o Outline the risk of relapse following methotrexate (5%), following EMA-CO (3%) or the
chance of a new molar pregnancy (1:75)
Post treatment hCG follow up
Year 1 2 weekly serum and urine hCG for 1-6 months
Year 2 4 weekly urine hCG
Year 3 8 weekly urine hCG
Year 4 3 monthly urine hCG
Year 5 4 monthly urine hCG
Year 6 – life
6 monthly urine hCG
REFERENCES
1.
Sebire NJ, Seckl MJ. Gestational trophoblastic disease: current management of hydatidiform mole.
British Medical Journal. 2008; 337(453-337).
2.
Shih IM. Gestational trophoblastic neoplasia - pathogenesis and potential therapeutic targets. Lancet
Oncology. 2007; 8:642-50.
3.
Garner EIO, Goldstein DP, Feltmate CM, Et al. Gestational Trophoblastic Disease. Clinical Obstetrics
and Gynecology. 2007; 50(1):112-22.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number 53 Diagnosis and
Treatment of Gestational Trophoblastic Disease. Obstetrics & Gynecology. 2004; 103(6):1365-77.
Royal College of Obstetricians and Gynaecologists. The management of Gestational Trophoblastic
Neoplasia. Green Top Guideline No 38. 2004.
4.
5.
6.
Soper JT. Gestational Trophoblastic Disease. Obstetrics & Gynecology. 2006; 108(1):176-87.
7.
Bess KA, Wood TL. Understanding Gestational Trophoblastic Disease. How Nurses Can Help
Those Dealing With A Diagnosis. AWHONN Lifelines. 2006; 10(4):322-26.
8.
FIGO Oncology Committee FIGO staging for gestational trophoblastic neoplasia 2000. FIGO
Oncology Committee Int J Gynaecol Obstet. 2002 Jun;77(3):285-7.
9.
Charing Cross Hospital.2007. Charing Cross Hospital Trophoblast Disease Clinic
Guide:Info for Clinicians. Avail at www.hmole-chorio.org.uk
10.
Kerkmeijer et al.2006. Aust NZ Obstet Gynaecol.46(2):112-8.
Date Issued:
Date Revised: January 2010
Review Date: January 2013
Written by:/Authorised by: OGCCU
Review Team: OGCCU
DPMS Ref: 8471
9.5 Hydatidiform Mole
Section C
Clinical Guidelines
King Edward Memorial Hospital
Perth Western Australia
All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual
Page 6 of 6