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 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 - 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 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 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 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. hCG level4 Blood group and antibody screen4 full blood count4 Coagulation studies4
9.5 Hydatidiform Mole Section C Clinical Guidelines King Edward Memorial Hospital Perth Western Australia Page 2 of 6

Date Issued: Date Revised: January 2010 Review Date: January 2013 Written by:/Authorised by: OGCCU Review Team: OGCCU DPMS Ref: 8471

All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual

2. 3.

U & Es 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. 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 HCG should be obtained until the levels are normal. Ideally the womans serum HCG 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 HCG. 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. 2. 3. 4. Avoid the use of the OCP / HRT following molar evacuation until normal hCG values are obtained. 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 Check hCG levels 6 weeks after any subsequent or future pregnancies regardless of that pregnancys outcome to ensure there is no persistent trophoblastic activity.

5.

FOLLOW UP MANAGEMENT PARTIAL HYDATIDIFORM MOLE 1. Weekly serum HCG 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 Page 3 of 6

All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual

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)
9.5 Hydatidiform Mole Section C Clinical Guidelines King Edward Memorial Hospital Perth Western Australia Page 4 of 6

Date Issued: Date Revised: January 2010 Review Date: January 2013 Written by:/Authorised by: OGCCU Review Team: OGCCU DPMS Ref: 8471

All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual

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 Mole <4 < 103 Lung 0 -

1 > 39 Abortion 4-6 103 - 104 3-4 cm Spleen , kidney 1-4 -

2 Term pregnancy 7-12 104 - 105 5cm Gastro intestinal 5-8 Single drug

4 > 12 > 105 Brain , liver >8 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 Page 5 of 6

All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual

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.
2. 3. 4. 5. 6. 7. Sebire NJ, Seckl MJ. Gestational trophoblastic disease: current management of hydatidiform mole. British Medical Journal. 2008; 337(453-337). Shih IM. Gestational trophoblastic neoplasia - pathogenesis and potential therapeutic targets. Lancet Oncology. 2007; 8:642-50. 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. Soper JT. Gestational Trophoblastic Disease. Obstetrics & Gynecology. 2006; 108(1):176-87. 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.
9. 10.

FIGO Oncology Committee FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee Int J Gynaecol Obstet. 2002 Jun;77(3):285-7. Charing Cross Hospital.2007. Charing Cross Hospital Trophoblast Disease Clinic Guide:Info for Clinicians. Avail at www.hmole-chorio.org.uk 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 Page 6 of 6

All guidelines should be read in conjunction with the Disclaimer at the beginning of this manual