Molar pregnancy

Molar pregnancy is very common in south east Asia. so this slide will give some knowledge regarding this topic.

1. CASE SUMMARY 18 years , primi presented in ER with complain of amenorrhoea for 3 months followed by PV bleeding for 2 days with passage of grape like vesicles ,on examination uterus 24 weeks size and vitals stable and hemoglobin 8gm /dl %. WHAT COULD BE THE DIAGNOSIS?

2. Molar Pregnancy Dr Hem Nath Subedi IInd year Resident OBGYN COMSTH

3. CONTENTS DEFINITION INCIDENCE TYPES CLINICAL FEATURES INVESTIGATIONS DIAGNOSIS MANAGEMENT COMPLICATIONS

4. DEFINITION Gestational Trophoblastic Disease (GTD) is a spectrum of abnormal growth and proliferation of the trophoblasts that continue even beyond the end of pregnancy

5. INCIDENCE The reported incidence of GTD varies widely worldwide, from a low of 23 per 100,000 pregnancies (Paraguay) to a high of 1,299 per 100,000 pregnancies (Indonesia). The malignant potential of GTD is also higher in South Asia (10-15%) compared to western countries (2-4%)

6. Types Gestational trophoblastic disease Molar pregnancy ( hydatidiform mole) or premalignant Complete mole Incomplete or partial mole Gestational trophoblastic neoplasia or malignant Invasive mole Choriocarcinoma Placental site trophoblastic tumor Epitheloid trophoblastic tumor

7. COMPLETE VS INCOMPLETE HYDATIDIFORM MOLE

8. Spectrum of Gestational Trophoblastic Disease Premalignant Malignant COMPLETE MOLE INVASIVE MOLE PARTIAL MOLE CHORIOCARCINOMA PLACENTAL SITE TROPHOBLASTIC TUMOR ABORTION OR NORMAL PREGNANCY 15%* 0.5%* Seckl mj , fisher RA. Choriocarcinoma and partial partial hydatidiform mole . Lancet 2000;356:688

9. Genetic basis of developing Gestatinal Trophoblastic Disease Defective locus at 19q13.4 in five families and this abnormalities excitingly, been localized to a single gene NALP7. Choriocarcinoma has been found to be developed after delation of 7p12-q11.2,amplification of 7q21-q31, and loss of 8p12-p21. Murdoch S,djuric U et al . Mutation I NALP7 cause hydatidiform moles and reproductive wastage in human. Mustada T , sasaki M et al .human Chromosome 7 carries a putative tumor suppressor gene(s) involved in choriocarcinoma . Oncogene 1997;15: 2773-2781

10. Clinical features Vaginal bleeding Excessive uterine growth Hyperemesis gravidarum Hyperthyroidism Preeclampsia Embolization of trophoblastic tissue Theca lutein cyst Metastatic features pulmonary- cough, chest pain, hemoptysis , dyspnoea , chest x ray finding -80% Vaginal – growth in vagina irregular bleeding per vagina - 30% Hepatic- Epigastric pain -10% CNS – acute focal neurologic deficit. - 10% -Gestational Trophoblastic Disease,in Bereks And Novaks Gynecology ,15 th Edition, Walter Wilkinson, Newyork 2012, Pp ,

11. VAGINAL METASTASIS

12. LUNG METASTASIS

13. Diagnosis Clinical features History Physical examination Investigation Lab investigation – Beta- hCG , LFT, RFT, CBC, urine R/E USG abdomen and pelvis Chest x ray CT scan Histopathological examination

14. USG Showing snow strom patttern

15. Staging of Gestational Trophoblastic Neoplasia Stage I - Disease confined to uterus Stage II -GTN extending outside uterus but limited to genital structures ( adnexa , vagina, broad ligament) Stage III -GTN extending to lungs with or without known genital tract involvement Stage IV -All other metastatic sites Goldstein DP, Vzanten-Przybysz I, Bernstein MR, et al. Revised FIGO staging system for gestational trophoblastic tumors: recommendations regarding therapy. J Reprod Med 1998;43:37–43.

16. WHO PROGNOSTIC SCORING SCORES 1 2 4 AGE IN YRS <40 >40 - - ANTECEDENT PREGNANCY H.MOLE ABORTION TERM - INTERVAL SINCE LAST PREGNANCY <4 MONTHS 4-6 7-12 >12 BHCG <1000 10^3-10^4 10^4-10^5 >10^5 LARGE SIZE TUMOR 3-4 5 - - SITE OF METATSTASIS SPLEEN,KIDNEY GI LIVER, BRAIN NUMBER OF METASTASIS 1-4 5-8 >8 PREVIOUS FAILED CHEMO SINGLE DRUG TWO OR MORE DRUG Adapted from FIGO Low risk score <6 ,High risk score >7

17. Management of gestational trophoblastic disease Hydatidiform mole Evacuation Serial hCG levels FIGO scoring GTN LOW RISK SINGLE AGENT CHEMO HIGH RISK COMBINATION OF CHEMO SERAIL HCG MONITORING RELAPLSED AND RESISTANT DIEASE SECOND LINE CHEO THARAPY Resolution 6 months HCG follow up RESOLUTION LIFE LONG Hcg follow up Adapted from , management of trophoblastic disease ,in resent advances in obstetrics and gynecology, 24 th edition,jeypee brothers , india pp 135-151

18. Indications for chemotherapy in GTD Histological evidence of choriocarcinoma Evidence of metastases in brain, liver or gastrointestinal tract or radiological opacities >2 cm on chest x ray. Pulmonary , vulval or vaginal metastates unless hcg falling Heavy Vaginal Bleeding Or Evidence Of Gasrointestinal Or Intraperitoneal Hemorrhage Rising Hcg After Evacuation Serum Hcg >20,000 Iu /L More Than 4weeks After Evacuation, Because Of Risk Of Uterine Perforation. Elevated hcg 6months after evacuation even if still falling. Adapted from , management of trophoblastic disease ,in resent advances in obstetrics and gynecology, 24 th edition,jeypee brothers , india pp 135-151

19. Low risk treatment regimen Methotrexate 1mg/kg /day for 1 st , 3 rd ,5 th ,7 th day. Folinic acid rescue 0.1mg/kg/day for 2 nd ,4 th ,6 th ,8 th day Typical side effects Stomatitis Conjunctivitis Abdominal pain Chest pain Alazzam M, Tidy J, Hancock BW, et al.: First line chemotherapy in low risk gestational trophoblastic neoplasia . Cochrane Database Syst Rev (1): CD007102, 2009

20. High risk treatment regimen EMA/CO E toposide M ethotrexate A ctinomycin d C yclcophosphamide O ncovin / vincristine Week 1, Days 1-2 : EMA With Folinic Acid Rescue. Week 2, Day 8: CO Typical Side Effects Myelosuprpression -granulocyte Colony Stimulatin Factor Used To Prevent Neutropenia And Maintain Dose Intensity Nausea/Vomiting Mucositis Reversible Alopecia Neuropathy Bagshawe KD, Harland S. Immunodiagnosis and monitoring of gonadotropin -producing metastases in the centraL nervous system . Cancer 1976;38:112–118.

21. Follow up of patient Year 1 2-weekly serum and urine hCG for 1-6 months            2 weekly urine hCG for 7-12 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 Available at: http://www.hmole-chorio.org.uk/clinicians_info_post_chemo_followup.html

22. Pregnancy after GTN Live births (66.9%), Preterm deliveries (6.7%), Ectopic pregnancies (1.1%), Stillbirths (1.4%) Repeat molar pregnancies (1.7%) Garrett LA, Garner EO, Feltmate CM, et al. Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia . J Reprod Med 2008;53:481–486.

23. Recurrence rate of GTN 1.5 % of patient with prior complete mole . 2.7 % of patient with prior partial mole. 23% of patient with two prior molar pregnancies. 2.5% of patients with no metastatic disease. 3.7% of patients with good-prognosis metastatic disease. 13% of patients with poor-prognosis metastatic disease. Mutch DG, Soper JT, Babcock CJ, et al.: Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer 66 (5): 978-82, 1990 Gestational trophoblastic disease in: Williams obstetrics, 24 th edition, newyork , magraw hill.

24. COMPLICATIONS IMMEDIATE Massive hemorrhage Early onset preeclampsia and Eclampsia Hyperemesis Gravidarum Pulmonary embolism Uterine perforation IUGR of viable pregnancy Still birth Preterm birth REMOTE Choriocarcinoma

25. Questions Define types of molar pregnancy and write difference between complete hydatidiform mole and partial mole? What are the clinical features of molar pregnancy how will you manage a case of molar pregnancy? Write complications of molar pregnancy.