Molar pregnancy

Gestational trophoblastic disease

1. Molar pregnancy Presented By Nirsuba Gurung Masters in nursing Women health and development

2. Gestational Trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta.

3. Gestational trophoblastic disease is a prolifirative disorder of trophoblastic cells It can be benign, premalignant or malignant

4. Classification of gestational Trophoblastic disease WHO Classification Malignant neoplasms of various types of trophoblats Malformations of the chorionic villi that are predisposed to develop trophoblastic malignacies Benign entities that can be confused with with these other lesions Choriocarcinoma Complete Hydatidiform moles Placental site nodule Exaggerated placental site Epithilioid trophoblastic tumors Placental site trophoblastic tumor Partial Invasive

5. Non-metastatic disease: confined to the uterus Metastatic A- low risk-good prognosis B – high risk-poor prognosis

6. Low risk Disease present in less than 4 mooths duration Initial serum hCG level < 40,000 IU/ml Metastasis limited to lung and vagina No prior chemotherapy No preceding term pregnancy

7. High risk Long duration of disease Initial serum hCG level > 40,000 IU/ml Brain or liver metastasis Failure of prior chemotherapy Following term pregnancy

8. Hydatidiform Mole Definition: In latin "hydatid" means "drop of water” "mole" means "spot” Pathologically, Hydatidiform moles represents placentas with abnormally developed chorionic villi (enlarged, edematous and vesicular villi with variable amounts of proliferative trophoblast)

9. Macroscopic of Hydatidiform mole Hydropic villi Grapelike vesicles filled clear material usually 1 to 3cm diameter proliferation of the trophoblast

10. Hydatidiform mole(molar pregnancy) Molar pregnancy is an abnormal form of pregnancy, wherein a non viable , fertilized egg implants in the uterus, and thereby converts pregnancy process into pathological ones. It is characterized by presence of hyadatidiform moles.

11. It is an abnormal condition of the placenta where there are partly degenerative and partly proliferative changes in the young chorionic villi.

12. These results in the formation of clusters of small cysts of varying size It is regarded as a begin neoplasia of the chorion with malignant potential

13. INCIDENCE There is considerable geographical and environmental influences in incidence. The incidence is higher in eastern than western countries. Its incidence in India is 1:160 and 1:2000 in UK .

14. Hydatidiform Mole Incidence: In the United States, 1in 600 therapeutic abortions 1 in 1,500 pregnancies Internationally: In Japan & China, 1-2 in 1,000 pregnancies In Indonesia & India, 12 in 1,000 pregnancies In the United Arab of Emirates, 2 in 1000 deliveries (population-based study; Graham IH, Fajardo AM; 1988) In Saudi Arabia; 1.48 in 1000 live births (hospital-based study; Felemban AA, et al; 1969)

15. In the United States, 1in 600 therapeutic abortions 1 in 1,500 pregnancies In Asian countries, The rate is 10 times higher than in Europe and North America In Saudi Arabia;, 1.48 in 1000 live births (hospital-based study; Felemban AA, et al; 1969)

16. Contd……. It is prevalent among teenage and elderly patient with high parity.

17. TYPES COMPLETE PARTIAL

18. Complete mole A complete mole is caused by a single sperm combining with an egg which has lost its DNA. The genotype is typically 46XX due to subsequent mitosis of fertilizing sperm but can also be 46XY.

19. Partial mole Partial mole occurs when an egg is fertilized by 2 sperm or by ,sperm which reduplicates itself yielding the genotype of 69 XXY or 92XXXY

20. Hydatidiform mole Complete mole Partial mole Partial mole Partial mol ( fetal tissue) Grossly placenta a mixture of normal and hydropic villi Fetus Severe growth restriction Multiple congenital anomalies

21. Risk Factors hydatidiform mole   Strongest risk factors are Age and a history of prior hydatidiform mole Both extremes of reproductive age adolescents twofold risk Older than 40 tenfold risk

22. History of Prior mole High parity Disturbed maternal immune mechanism suggested by: Rise in gammaglobulin level in absence of hepatic disease Increased association with AB blood group which possess no ABO antibody

23. An ethnic predisposition Diet (Deficiencies of protein or) (Vitamin A deficiency) Animal fat Smoking Increased paternal age

24. The risk of another mole Complete mole is 1.5 percent Partial mole is 2.7 percent Two prior molar pregnancies the risk is 23 percent

25. Pathogenesis and Cytogenetics of HM Genetic Constitution Diploid Triploid/ teraploid Patho-genesis 4% Fertilization of an empty ovum by two sperms “Diandric dispermy” 90% Triploid fertilization of a normal ovum by two sperms “Dispermic triploidy” 96% Fertilization of an empty ovum by one sperms that undergoes duplication “Diandric diploidy” 10% Tetraploid fertilization of a normal ovum by three sperms “Dispermic triploidy” Karyotype 46XX 69XXX 69YXX 69YYX 46XX 46XY Complete Partial

26. Complete Mole, Pathogenesis Duplication 46XX Empty ovum 23X Diandric diploidy Androgenesis Paternal chromosomes only

27. Complete Mole, Pathogenesis 46XX Empty ovum 23X Dispermic diploidy Paternal chromosomes only 23X 23X 23X

28. Partial Mole, Pathogenesis 69XXY Normal ovum 23X Dispermic triploidy Paternal extra set 23Y 23X 23Y 23X 23X

29. Hydatidiform Mole Alterations in gene expression profiles Up-regulation and down-regulation of proteins committed to cell growth control e.g. Up-regulation of growth factor and cytokine mediated pathways, and antiapoptosis genes Trophoblastic hyperplasia e.g. Down-regulation of insulin growth factor binding proteins and tumor necrosis factor receptor

30. Pathogenesis Principally a disease of the chorion Death of the ovum ir failure of the embryo to grow is essential to develop complete H. mole The secretion from the hyperplastic cells and transferred substances from the maternal blood accumulates in the stroma of the villi which are deviod of blood vessels

31. This results in distension of the villi to form small vesicles The distension may also be due to edema and liquification of the stroma Vesicle fluid is interstitial fluid and is almost similar to ascitic or edema fluid but rich in hCG

32. Naked eye appearance The mass filling the uterus is made of multiple chains and clusters of cysts of varying sizes No trace of embryo or the amniotic sac Hemorrhage, if occurs, takes place in the decidual space

33. Microscopic appearance Marked prolifiration of syncitial and cytotrophoblastic epithelium Marked thining of the sromal tissue due to hydropoc degeneration Absence of blood vessels

34. FEATURES COMPLETE MOLE PARTIAL MOLE karyotype 46XX, paternal Triploid or quadriploid Embryo/fetus absent Present Villious edema All villi Some villi Trophoblastic proliferation Diffuse, circumferential Focal, slight Uterine size More than the date Less than the date Beta hCG High(>50000) Slight elevation Behaviour 2% choriocarcinoma Rare

35. Clinical features Amenorrhea 8-12 weeks with following manifestation Vaginal bleeding Varying degree of abdominal pain Constitutional symptoms Patient become sick without any apparent reason Vomiting of pregnancy becomes excessive Breathlessness Thyrotoxic symptoms

36. Expulsion of grape like vesicles per vaginum History of quickening absent

37. Clinical Presentation: Complete mole: Vaginal bleeding Severe anemia Passage of hydropic villi

38. Signs Features suggestive of early pregnancy Pallor Features of pre-eclampsia Per abdomen Uterus –more than gestational period (70%) Uterus feels firm elastic(doughy ) Fetal parts not palpable Absence of fetal movement and FHS

39. Vaginal examination Internal ballotement cannot be elicited Unilaternal or bilaternal enlargement of ovary (25-50%) Finding of vesicles in the vaginal discharge Open cervical os

40. Classical symptom of a complete mole Abnormal vaginal bleeding Lower abdominal pain Hyperemesis gravidarum Features of early onset of pre-eclampsia Uterus > dates No fetal parts and FHS

41. Classical symptoms contd…. Expulsion of vesicular tissues Theca lutein cyst of ovaries Hyperthyriodism Serum hCG >1,00,000 IU/ml USG –snow strom appearance

42. Hydatidiform Mole Diagnosis: History Clinical examination Ultrasound examination Serum hCG levels Histopathological examination Cytogenetic and molecular biological examination

43. Hydatidiform Mole Diagnosis: Ultrasonography: * The diagnosis of molar pregnancy is nearly always made by ultrasonography Complete mole The classical finding is a “snow storm" pattern Theca lutein cysts are frequent findings on ultrasound

44. The snow storm appearance of complete hydatidiform mole

45. Theca lutein cysts, a frequent finding on ultrasound

46. Hydatidiform Mole Diagnosis: Ultrasonography: Partial mole Abnormal gestational sac The classic vesicular sonographic findings of a complete mole are usually not seen Focal sonographic cystic changes and/or hydropic changes in the placenta are significantly associated with the diagnosis of a partial molar pregnancy

47. Hydatidiform Mole Diagnosis: Ultrasonography : However, based on ultrasound, correct diagnosis can be suspected in only: 84% of patients with complete mole and 30% of patients with partial mole ( Lindholm and Flam, 1999) The accuracy of ultrasonogrophy is gestational age dependent In comlete mole: 100% of cases cane be diagnosed at a gestational age of 13 weeks or more 50% of cases cane be diagnosed in earlier pregnancies ( Lazarus et al , 1999)

48. Hydatidiform Mole Diagnosis: Serum hCG levels: Serum hCG levels of greater than 92 000 IU/l associated with absent fetal heart beat indicate a diagnosis of complete hydatidiform moles (Romero et al, 1985) Serum hCG level decreases quickly if the patient has an abortion, but it does not in molar pregnancy

49. Hydatidiform Mole Diagnosis: Histopathological examination: It should always be done as far as possible and samples should be kept for DNA analysis for a final diagnosis when histology can not differentiate molar pregnancy from abortion

50. Table3: Pathological features of complete and partial hydatidiform mole Complete Mole Partial Mole Macro-scopically A mass of large, edematous villi that are diffusely distributed, typically described as resembling a cluster of grapes The placental tissue is less bulky A few enlarged villi with a focal distribution A fetus may be identified grossly that often has multiple congenital anomalies including syndactyly of the fingers & toes

51. The grape like vesicles in gross appearance

52. Table3: Pathological features of complete and partial hydatidiform mole Complete Mole Partial Mole Micro- scopically Enlarged edematous villi which show a central acellular fluid-filled space referred to as a “ central cistern ” Abnormal trophoblastic proliferation that is circumferential in contrast to normal villi in which trophoblastic proliferation is at one end of the villus Absence of fetal tissue Two distinct populations of villi . One with large, edematous villi with central cisterns. The other contains small villi that show some degree of stromal fibrosis Abnormal circumferential trophoblastic proliferation Fetal tissue, RBSs

53. DIFFERENTIAL DIAGNOSIS Threatened abortion Fibroid or ovarian tumor with pregnancy. Multiple pregnancy Mistaken date ACUTE HYDRAMINOS

54. Complications associated with molar pregnacy: Those related to the increased trophoblastic tissue volume: Theca-lutein cysts Pregnancy-induced hypertension, hyperthyroidism, Respiratory distress Hyperemesis Those related to its management: Uterine perforation

55. Hydatidiform Mole, complications Theca- lutein cysts : Prevalence: Clinically evident theca lutein cysts (usually >5 – 6 cm) are detected in about 25-35% of women with molar pregnancies Association: They usually correlate with marked elevation of serum hCG levels above 100,000 IU/l Complications: Pain or pressure that may require percutaneous aspirations. Torsion, rupture, or bleeding are rare complications that can require oophorectomy Bilateral theca letein cysts increase the risk of post-molar GTD Course: The mean time for theca luteal cysts to regress is approximately 8 weeks

56. Hydatidiform Mole, complications Respiratory distress syndrome: Prevalence: Rare Pathophysiology: Embolization of trophoblastic tissue Transient impairment of left ventricular function during induction of anesthesia for suction D&C of molar pregnancy coexisting conditions such as anemia, hyperthyroidism, hypertension from preeclampsia Risk factors: Uterine size larger than 14 to 16 weeks ’ High levels of hCG

57. Hydatidiform Mole, complications Respiratory distress syndrome: Presentation: Tachypnia and tachycardia following evacuation Bilateral pulmonary infiltrates on chest x-ray Management: Central venous monitoring Ventilatory support Course: It should resolve within 24 to 48 hours after molar evacuation

58. Hydatidiform Mole, complications Hyperthyroidism: Prevalence: Clinical hyperthyroidism is seen in less than 10% of patients with molar pregnancies A small number of patients may have elevated thyroid function tests without clinical evidence of disease Management: Beta-blockers should be administered prior to molar evacuation to prevent thyroid storm that may be induced by anesthesia and surgery.

59. A hydatidiform mole and a co-existent fetus: Prevalence: Rare (1 in 22,000 – 100,000) partial moles and twin gestations with co-existent fetuses and molar gestations Diagnosis: Usually, by ultrasound Few, after examination of the placenta following delivery Complications: Increased risk of medical complications Increased risk for postmolar gestational trophoblastic disease Management: No clear guidelines for management

60. Risk Factors for post-molar gestational trophoblastic disease: Advanced maternal age Factors that reflect the volume of trophoblastic tissue:Clinical factors that are associated with high hCG levels (>100,000 mIU/mL) uterus large for date, bilateral theca lutein cysts, Respiratory distress syndrome after molar evacuation, eclampsia, hyperthyroidism, Uterine subinvolution with post evacuation hemorrhage. (With any one of these factors or a combination of many, the risk of post-molar GTD has ranges from 25% to 100%)

61. Hydatidiform Mole Risk Factors for post-molar gestational trophoblastic disease: The presence of “ invasive trophoblast antigen (ITA) ” which has 100% sensitivity and specificity for invasive trophoblastic tumors (Cole et la, 2003) *There is no correlation between the degree of anaplasia and the risk of post-molar GTD

62. COMPLICATIONS IMMEDIATE Hemorrhage and shock Sepsis Perforation of uterus Pre- eclampsia Acute pulmonary insufficiency Coagulation failure

63. LATE Development of choriocarcinoma (2 to 20%) Risk factors of malignant change: Patient’s age>40 or <20 Parity >3 Serum hCG> 100000 mIU/mL Uterine size> 20 wk Previous history of molar pregnancy Thece leutin cysts: large(>6cm diameter)

64. MANAGEMENT The principle of the management: Suction evacuation of the uterus Supportive therapy Counselling for regular follow up

65. The patient are grouped into two: Group A:the mole is in the process of expulsion Group B:the uterus remains inert

66. Management Complete history and physical examination Investigations Medical and surgical care 1 3 2

67. History and physcal examination: Should aim to rule out the classic symptoms and signs that would lead to a diagnosis of: severe anemia dehydration preeclampsia thyrotoxicosis  The patient should be stabilized hemodynamically

68. Management: Investigations: Laboratory: Pre-evacuation hCG Complete blood count Electrolytes, BUN, creatinine Liver function tests Thyroid function tests Imaging: Pelvic ultrasound Chest x-ray

69. Hydatidiform Mole Management: Medical care: Correction of: Anemia Dehydration Hyperthyroidism hypertension

70. Management:Surgical Suction curettage (with oxytocin or prostaglandin infusion) Hysterectomy The method of choice Increased risk of medical complications Associated with a markedly decreased rate of malignant sequelae (3.5%) when compared with suction evacuation.

71. Hysterectomy Hysterectomy: is indicated in: a)Patient with over 35, b)Patient complete her family irrespective of age, c)Uncontrolled hemorrhage or perforation during surgical evacuation,

72. Counselling Counselling for follow up: Routine follow up is mandatory for all cases for at least 1 year. Intervals: initially the check up must be made at an interval of 1 week till the serum hCG levels become negative.This usually happen by 4-8 weeks. once negative within 56 days,the patient is followed up at every 1 month intervals for 6 months.

73. Women undergone chemotherapy should be followed up for 1 year after hCG has been normal. Methods employed in each visit: a)enquire about each symptoms b)abdomino vaginal examination c)investigations:hCG,chest x-ray

74. PROPHYLACTIC CHEMOTHERAPY If the hCG levels fails to normal by the stipulated time(10-12) weeks or relevation at 4-8 weeks. Post evacuation hemorrhage. Where follow up facilities are not adequate. Evidence of metastasis irrespective of the level of hCG.

75. Prophylactic Chemotherapy: In one randomized clinical trial, a single course of methotrexate and folinic acid reduced the incidence of postmolar trophoblastic disease from 47.4% to 14.3% (P <.05) in patients with high-risk moles: hCG levels greater than 100,000 mIU/mL, uterine size greater than gestational age, ovarian size greater than 6 cm),

76. However, the incidence was not reduced in patients with low-risk moles On the other hand, the use or prophylactic chemotherapy increases the risk of drug resistance Because of the excellent primary cure rates among women with post-molar GTD, and mortality achieved by monitoring patients with serial hCG determinations and instituting chemotherapy only in patients with postmolar gestational trophoblastic disease outweighs the potential risk and small benefit of routine prophylactic chemotherapy.

77. Pregnancy after Hydatidiform Mole: Risk of another molar pregnancy: Increased by 10-fold (1 – 2% incidence) Current recommendations for management of subsequent pregnancies: an early ultrasound to confirm normal gestational development and dates A chest x-ray to screen for occult metastasis masked by the hCG rise of pregnancy Examination of the placenta or products of conception histologically at the time of delivery or evacuation for evidence of occult trophoblastic disease An hCG level should be obtained 6 weeks post evacuation or delivery to confirm normalization.

78. CONTRACEPTIVE ADVICE The patient is advised not to be pregnant for at least 1 year. Use of contraception IUD is contraindicated. OCP:after hCG value have been normal. Barrier method.

79. Hydatidiform Mole Prognosis: Post-molar gestational trophoblastic disease: Risk: Following complete mole: 20% Following partial mole: 5% Type: 70% to 90% are persistent or invasive moles 10% to 30% are choriocarcinomas Diagnosis: A rising, plateauing, or persistent elevation of human chorionic gonadotropin after evacuation of a hydatidiform mole or an ectopic or term pregnancy

80. PROGNOSIS More than 80% of H. moles are benign. The outcome after treatment is usually excellent. Highly effective means of contraception are recommended to avoid pregnancy for at least 6 to 12 months. About 15 to 20% of cases may develop into persistent GTD. In 2 to 10% of cases it may change into choriocarcinoma .

81. Over 90% of women with malignant, non spreading cancer are able to survive and retain their ability to conceive and bear children. In those with metastatic cancer, remission remains at 75 to 85%, although their childbearing ability is usually lost.

82. NURSING DIAGNOSIS Acute pain related to uterine contraction. Risk for fluid volume deficit related to execessive vascular loss. Ineffective uteroplacental tissue perfusion related to abnormal trophoblastic proliferation. Risk for maternal injury related to blood loss,abnormal blood profile,impaired immune system.

83. Fear related to fetal loss and outcome of pregnancy.